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Biosecurity in UK research laboratories

Memoranda of Evidence

Memo No Submission from: Page No

01 Government response 1

02 Veterinary Laboratories Agency 27

03 Agri-Food & Biosciences Institute 31

04 Institute of Safety in Technology and Research 34

05 Merial Animal Health 39

06 Andrew Thompson, Oxford University 44

07 Robert W Osborne, University Biological Safety Adviser 49

08 Prospect 56

09 The Wellcome Trust (with annex BRL 09A) 58

10 Research Councils UK 74

11 Advisory Committee on Dangerous Pathogens 83

12 Pfizer Ltd 84

13 Institute of Biology and the Biosciences Federation 88

14 Institute for Animal Health 94

15 Biotechnology and Biological Sciences Research Council 101

16 Universities UK 109

17 Academy of Medical Sciences 116

18 Health Protection Agency 120

19 Astrazeneca 127

20 Chief Sanitary Inspectorate in Poland 132

21 British Embassy, Seoul, South Korea 135

22 British Embassy, Berlin, Germany 137

23 British Consulate, Italy 141

24 British Embassy, The Hague, Netherlands 143

25 British High Commission, Canada 147

26 British Embassy, Japan 151

27 British Embassy, Copenhagen, Denmark 154

28 British Embassy, Washington, United States 156

29 British High Commission, Wellington, New Zealand 163

30 British Embassy, Czech Republic 168

31 British Embassy, Switzerland 171

32 Association of the British Pharmaceutical Industry 181

33 British Embassy, Paris, France 185

34 Society for General Microbiology 188

35 Science & Education Department, Ministry of Health 194

36 HSE 198

37 HSE supplimentary 203

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Memorandum 1

Submission from the Government, submitted by the Department for Innovation, Universities and Skills

‘Biosecurity in UK Research Laboratories’

Introduction

1.1 Work with dangerous pathogens enables us to understand better how infectious diseases of human and animals develop and spread, which is essential if we are to develop effective treatments and vaccines against them. In addition to protection against naturally-occurring disease outbreaks, research involving dangerous pathogens provides the UK and its Armed Forces with safe and effective protection against the hazards of exposure to biological warfare agents.

1.2 The UK university and research sectors are very strong, and have a good international reputation. For example the Health Protection Agency (HPA) is a world leading contributor to research on human pathogens and the National Institute of Biological Standards and Control (NIBSC) is the world leader in many areas of biological standardisation. Both organisations play a crucial role in frontline defence against future threats such as pandemic influenza. Their work maintains UK capabilities in a vital area for national security.

1.3 Research on animal pathogens has also made a positive contribution to our ability to diagnose and understand disease occurrence, spread and future disease threats:

• Research has developed methods using full genome sequencing of Foot and Mouth Disease (FMD) viruses that have facilitated the tracking of the spread of FMD and identication of the order in which farms become infected within a complex outbreak.

• A simple molecular test to detect FMD virus has been developed, which can be used as the basis of a rapid and disposable device for field diagnosis.

• Work on the transmission dynamics of avian influenza virus will add to the evidence base on suitable control measures and risks to commercial poultry production from wild birds.

1.4 UK industry has built on this work by developing commercially successful vaccines against diseases such as anthrax and smallpox.

1.5 As Sir Bill Callaghan noted in his Review of the Regulatory Framework for Handling Animal Pathogens1: “The ability to handle animal pathogens in laboratories is essential if we

1 http://www.defra.gov.uk/animalh/diseases/fmd/pdf/callaghan-reviewreport071213.pdf

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are to fully understand infectious diseases and to develop effective vaccines against them. The [………] research carried out in UK laboratories plays an important role in the international fight against existing and emerging diseases. Without this research, there would be a significant adverse impact on the well being of both people and animals around the world.”

This point also applies to the ability to handle human pathogens.

1.6 It is thus imperative that we continue to maintain the capacity for research on dangerous pathogens in the UK. But we also need to minimise the risks from that work. This was highlighted in August 2007, when an outbreak of FMD was traced to a site at Pirbright in Surrey where the virus was being used in research and vaccine production.

1.7 Following this incident, two reviews have been published which bear on the containment of dangerous pathogens in UK research facilities. Both the ‘Independent Review of the safety of UK facilities handling foot-and-mouth disease virus’ by Professor Brian Spratt2 and ‘A Review of the Regulatory Framework for Handling Animal Pathogens’1 chaired by Sir Bill Callaghan made recommendations to improve containment and biosecurity. The Government has fully accepted all recommendations applicable to Government, most recently in a written statement3 to the House on 13 December, when Sir Bill Callaghan’s report was published. In particular, the Government has agreed that the role of the regulator of laboratories handling animal pathogens should move from Defra to the Health and Safety Executive. In addition, relevant Government Departments and Agencies are working together to establish a single regulatory framework to rationalise the control of human and animal pathogens.

1.8 This memorandum explains controls that apply in research laboratories. It covers the situation in Great Britain. Where relevant, it explains the changes being made in response to the recent recommendations.

1.9 The legislation described in this memorandum is concerned only with ensuring the biosafety and biosecurity of research facilities. Such facilities will additionally have to comply with any other relevant legislation, for example the Animal (Scientific) Procedures Act 1986 for research involving animals protected by the Act.

1.10 This memorandum represents the contributions of the following Government departments and agencies:

• Home Office • Department for Transport • The Health and Safety Executive (HSE) • Department of Health

2 http://www.defra.gov.uk/animalh/diseases/fmd/investigations/pdf/spratt_final.pdf 3 Government statement: http://defraweb/corporate/ministers/statements/hb071213.htm

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• Department for Innovation Universities and Skills • The Foreign and Commonwealth Office (FCO) • Department for the Environment, Food and Rural Affairs (Defra) • Ministry of Defence (MoD)

1.11 The FCO’s Science and Innovation Network will be responding to the Committee separately, as will the Devolved Administrations and RCUK (a partnership of seven UK Research Councils).

2 The current capacity for research on dangerous pathogenic material in the UK and the capability to conduct research on the causative agents of disease that may emerge at a future time

2.1 The sector working with dangerous pathogens includes a workforce of approximately 250,000 scientists working in a range of laboratory premises in healthcare, academia and industry. The UK has a large network of research facilities and diagnostic laboratories where work is undertaken with dangerous pathogens. Details are given below of the number of facilities which hold licences or are regulated to allow them to work on dangerous pathogens.

2.2 We will describe separately laboratory biosafety and laboratory biosecurity. Biosafety will be used to refer to the appropriate containment of pathogens in the laboratory environment, both to prevent exposure of workers within the laboratory, and exposure of people, animals and other vulnerable organisms in the external environment. Biosecurity will be used to refer to the secure storage, use and transport of dangerous pathogens and toxins to reduce the risk of malicious use.

2.3 Biosafety

2.3.1 Biosafety in laboratories is covered by three separate pieces of legislation:

• Control of Substances Hazardous to Health Regulations 2002 (COSHH) – regulated by HSE

• Specified Animal Pathogens Order 1998 (SAPO) – currently regulated by Defra, Scottish Executive & National Assembly for Wales

• Genetically Modified Organisms (Contained Use) Regulations 2000 (GMO(CU)). There is a joint Competent Authority – HSE and Defra in England and Wales, and HSE and the Scottish Executive in Scotland. HSE acts as the lead Competent Authority, and enforces the legislation in Great Britain.

2.3.2 With minor differences, each piece of legislation indicates the appropriate Containment Level (CL) for each facility, the level being dependent on the nature of the micro-organisms in use:

• CL 1 – appropriate for micro-organisms posing no or negligible risk

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• CL 2 - appropriate for micro-organisms posing low risk • CL 3 - appropriate for micro-organisms posing moderate risk • CL 4 - appropriate for micro-organisms posing high risk.

The legislation specifies which micro-organisms require which levels of containment. This is covered in more detail in section 4. Effectively, work with dangerous pathogens is restricted to CL 2, 3 & 4 laboratories, and the following information applies to only these.

2.3.3 Pathogens for which CL1 is appropriate are not considered to pose a risk to human health or the wider environment, and the regulatory framework is minimal under COSHH and SAPO. The Importation of Animal Pathogens Order 1980 as amended (IAPO) prohibits the importation into Great Britain from third countries of all risk groups of animal pathogens or carriers except under the authority of a valid licence issued by Defra, the Scottish Executive or Welsh Assembly. Under the GMO(CU) Regulations, all centres working with genetically modified organisms (GMOs) must notify the Competent Authority before commencing work for the first time, including work at CL1. However, once a centre is notified, no further notification is required for work requiring only CL1.

2.4 In this memorandum, the term ‘dangerous pathogens’ will be used throughout, and covers human and animal pathogens as well as genetically modified micro-organisms (GMMs) which require CLs 2, 3 and 4.

2.5 Organisations working with dangerous pathogens at containment level 2, 3 and 4 under regulation by HSE and/or SAPO.

2.5.1 As Table 1 below shows, most work with dangerous pathogens is done in Government and Research Council laboratories, and is regulated by HSE only.

2.5.2 Similar work is carried out in 70 different universities (those working at level 3 are also included in the 70 listed at level 2 – i.e. all that handle CL3 pathogens also handle CL2 pathogens).

Table 1 Organisation or site4 type5 Containment level Government Private

Research Council University

2 212 230 17 70 3 202 98 7 40 4 5 2 3 0

4 For containment level 4, category of sites is given; for containment level 2 and 3, the category of organisations is given. 5 This was difficult to assign with a high degree of confidence, particularly separating out Government & Research Council (plus others e.g. charities).

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2.5.3 The numbers of organisations working with dangerous pathogens in Great Britain are presented in Table 2 below. The term ‘organisation’ is used at the employer level, e.g. The University of Oxford. Organisations may have multiple facilities for work with dangerous pathogens. For example, one university has over 50 containment level 3 laboratories located on different sites. The term ‘site’ is used for the different departments/locations/campuses where the laboratories are housed.

Table 2 Number of organisations in Great Britain

Containment level

COSHH and / or GMO(CU) regulated only

SAPO regulated only

HSE & SAPO combined Total

2 494 7 28 529 3 323 5 19 347 Number of sites 46 1 2 7 10

These data represent the situation at December 2007 and cover a dynamic sector with frequent changes to organisations, facilities and projects. As such, these figures may be subject to change.

2.6 Biosecurity

2.6.1 Biosecurity is covered by measures set out in the Anti-terrorism Crime and Security Act 2001 (ATCSA), which are implemented by the National Counter-Terrorism Security Office (NaCTSO). Part 7 of the ATCSA provides the police with powers to impose security measures at laboratories in the UK that hold certain dangerous pathogens and toxins (as listed in Schedule 5 of the Act).

2.6.2 There are just over 100 pathogens and toxins caught by Part 7 and Schedule 5 of ATCSA. Approximately 400 laboratories in the UK are required to register under the legislation. This includes university and hospital laboratories but not necessarily diagnostic laboratories (which are an exception under the Security of Pathogens and Toxins (Exceptions to Dangerous Substances) Regulations 2002 (Statutory Instrument 1281).

6 For organisations with capacity to work at containment level 4, the number of sites is given; for organisations with capacity to work at containment level 2 and 3, the number of organisations is given.

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2.7 Emerging diseases

2.7.1 Many of these licensed facilities are involved in work on diseases that may emerge at a future time, such as NIBSC’s work on pandemic influenza. There is a significant amount of work carried out by the HPA, Medical Research Council and universities on pathogens which may pose a threat to the UK in the future, for example due to climate change or population movement.

2.7.2 Horizon scanning to identify existing and emerging infectious disease threats to public health in the UK is undertaken by the HPA's Microbial Risk Assessment team, supported by specialist diagnostic expertise in the Special Pathogens Reference Laboratory.

2.7.3 The HPA is a key player in the European Commission's public health infectious disease networks and provides consistent UK surveillance data for many diseases, based on its specialist microbiological services. It is the UK portal for the European Union Early Warnings and Alerts and for Assistance Calls, and its Centre for Emergency Preparedness and Response (CEPR) works closely with other centres, particularly in Europe, North America and Australasia.

2.7.4 Many staff at the CEPR are internationally renowned experts in their field and often provide advice and consultancy for the World Health Organization (WHO) and other international agencies. The HPA also houses many WHO Collaborating Centres and WHO Reference Laboratories for various infections (including polio and SARS).

2.7.5 On behalf of the MoD and the Government, the Defence Science and Technology Laboratory has the capability to safely undertake both in vivo and in vitro research with dangerous pathogens. The scope of the research programme is to provide effective protective measures against the range of potential biological and toxin agents which may be used aggressively by terrorists or in times of conflict.

2.7.6 Horizon scanning for future animal disease threats is conducted in different ways. Outbreaks of disease in the member countries of the Office Internationale des Epizooties (OIE) are reported through a notification system and this gives valuable information to allow global tracking of infectious diseases of significance. An additional system, placing obligations on the Member States to report outbreaks, is operated via the European Commission.

2.7.7 In addition, both the Veterinary Laboratories Agency (VLA) and the Biotechnology and Biological Sciences Research Council

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sponsored Institute for Animal Health at Pirbright act as World Reference Laboratories. In this capacity, they have regular dialogue with the veterinary authorities and diagnostic laboratories in many countries which, when pieced together with the consultancy advice they provide, enable emerging trends to be identified. The VLA has a well established programme of scanning surveillance covering farmed livestock and wildlife disease diagnosis, to provide baseline data on disease occurrence and assessment of potential emerging diseases or infections.

2.7.8 Defra carries out veterinary risk assessments of outbreaks overseas to inform their policies, and publishes Quarterly International Disease Surveillance reports.

3 The state of biological containment facilities in the UK

3.1 Assessment by HSE

3.1.1 HSE is responsible for inspection and enforcement at facilities in Great Britain where work is undertaken with dangerous pathogens and GMOs. The work is carried out by staff from Staff from HSE’s Biological Agents Unit.

3.1.2 The standard of compliance with regulations in the UK is generally good. The standard of laboratories has improved in recent years, and there is clear evidence of investment in infrastructure.

3.1.3 Table 3 below shows that 514 inspections were carried out by HSE between 2004 and September 2007. A small number of improvement notices was served in that period, reflecting the generally high standards of containment and management control at biological containment facilities.

Table 3 Enforcement Summary in Biological Agents Sector

Category Type Detail ‘02/‘03 ‘03/‘04 ‘04/‘05 ‘05/‘06 ‘06/‘07 Mid Year ‘07/‘08

Grand Total

ENFORCEMENT Prohibition Notice 1 1

Crown Censure 1 1 Improvement Notice 4 3 5 2 8 2 Notice Count 4 4 5 2 8 22

ENFORCEMENT Total 4 5 5 2 8 23 Interventio

n Inspection Inspection Count 179 121 145 69 514

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Category Type Detail ‘02/‘03 ‘03/‘04 ‘04/‘05 ‘05/‘06 ‘06/‘07 Mid Year ‘07/‘08

Grand Total

Investigation RIDDOR7 Accident 1 3 3 2 9 Complaint 1 1 RIDDOR Disease 2 2 RIDDOR Dangerous Occurrence 5 7 12 4 28 GMO Accident 2 2 GMO Report of Disease 1 1 RIDDOR Count 6 10 21 6 43

Intervention Total 185 131 166 75 557

3.2 Assessment of biological containment facilities by National Counter-Terrorism Security Office (NaCTSO)

3.2.1 NaCTSO assesses all laboratories required to register under ATCSA using a "Traffic Light" system. Currently, no laboratories are rated as 'red' (of concern). There are many new laboratories being built in the UK which will be incorporating the 'gold standard' of security measures in their design, as defined in the Home Office document 'Security Standards for Laboratories’. This ensures a continuing improvement in laboratory security across the UK.

3.3 Compliance with the Carriage of Dangerous Goods and Use of Transportable Pressure Equipment Regulations 2007

3.4 The HSE is the enforcement authority for these safety regulations, aided by the Vehicle Operators and Services Agency and the police at the roadside. HSE inspectors undertake inspections at premises often in conjunction with other enforcement activities. Generally, there is no evidence of non-compliance with these requirements.

3.5 Inspection activity since the accidental release of FMD Virus from Pirbright.

3.5.1 Following the publication of the investigation report following the 2007 outbreak of FMD, HSE and Defra released a Safety Alert on 7th September 2007. This was aimed at all high containment laboratories, to draw attention to the issues arising from the investigation. In addition, HSE and Defra committed to undertake a programme of inspections.

3.5.2 The first phase of the Safety Alert inspection programme focussed on CL4 facilities where work is undertaken with Hazard Group (HG) 4 dangerous pathogens, including both human and animal pathogens.

3.5.3 The inspections revealed no breaches of the legislation and no formal enforcement action was taken. This process has provided

7 Reporting of Injuries, Diseases and Dangerous Occurrences Regulations 1995

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both the regulatory bodies and the operators of the laboratories with the assurance that their facilities are well managed. The inspections have also provided a useful opportunity to provide advice and guidance on good practice. HSE will continue this series of Safety Alert inspections to consider CL3 facilities based on risk. The inspections will begin in January 2008 and will be completed by the end of the year.

4 Laboratory inspection regimes and the rationale and practicalities of the licensing system

4.1 Regulation and Licensing of work with dangerous pathogens

4.1.1 There is currently a complex regulatory framework for work with dangerous pathogens with different regimes for different types of pathogens, and the individual regimes are covered below. However, the Callaghan review recommended that a single regulatory framework should be developed to govern work with human and animal pathogens. Work is in progress to establish how this can be achieved in the recommended timescale. The following gives details of the current systems.

4.2 Human Pathogens: Control of Substance Hazardous to Health 2002 (COSHH)

4.2.1 HSE is responsible for COSHH, and regulates compliance in respect of deliberate work with human pathogens. Deliberate work means carrying out activities such as propagation, for example, as would occur in bacteriology, virology, mycology and parasitology laboratories. HSE develops policy in consultation with other Government Departments, including the Department of Health and Defra.

4.2.2 The COSHH regulations are wide ranging, covering all workplace exposure to substances that are hazardous to health. These include carcinogens, chemicals and other substances, such as microorganisms and toxins. Specific requirements relating to microorganisms are covered in Schedule 3 of the regulations, which apply, primarily, to laboratory and large-scale work with dangerous pathogens. The choice of control measures in laboratories is largely based on the HG of the pathogen that is being used (or that may be present). Pathogens are classified into one of four hazard groups from HG1 (the lowest) to HG4 (highest, e.g. Ebola virus) based on their ability to infect healthy adults. The classification is set out in the Approved List of Biological Agents, which is published on the HSE Website at http://www.hse.gov.uk/pubns/misc208.pdf

4.2.3 The HGs equate to the CLs – containment level 4 is required for hazard group 4 pathogens, etc.. The list is updated when new

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pathogens emerge, or when new evidence accrues on the pathogenicity of individual strains.

4.2.4 In addition to using specific control measures, those working with dangerous pathogens need to notify HSE at least 20 days in advance of any planned work where HG2, HG3 and HG4 are used for the first time, at particular premises. Notification is also required of the subsequent use of certain organisms (i.e. those in HG3 and HG4 and those in HG2 that are listed in Part V of Schedule 3 of COSHH are used for the first time).

4.2.5 Although this is not an approval system, HSE requires the notification to include sufficient information to demonstrate that duty holders have identified hazards associated with the organism which might arise from carrying out the work. This includes circumstances where staff (and others) could be exposed to a source of infection during the work, and the measures that will be applied to prevent or control exposure. The supporting documentation can include a risk assessment, a local code of practice or standard operating procedures/protocols. Where sufficient information is not provided, it may be requested.

4.2.6 Where necessary, technical advice can be obtained from the Advisory Committee for Dangerous Pathogens (ACDP), whose remit is to advise on risks to workers and others from exposure to pathogens. The ACDP is an independent committee which advises the Health and Safety Commission, HSE, Health and Agriculture Ministers and their counterparts under devolution in Scotland, Wales and Northern Ireland, as required, on all aspects of hazards and risks to workers and others from exposure to pathogens. The committee is made up from experts in microbiology and infectious diseases recruited from academia, the health service, industry and trade unions. It is serviced by a joint secretariat (HSE, Defra, and the HPA).

4.2.7 Inspection under COSHH

4.2.7.1 Although notification does not automatically entail an inspection, the notification is used to inform inspection activities. The expectation is that CL4 laboratories are inspected annually and CL3 laboratories are inspected at least once every three years.

4.3 Animal Pathogens: Specified Animal Pathogens Order 1998 (SAPO)

4.3.1 The containment and transport of animal pathogens is controlled by SAPO in Great Britain. Responsibility for the Order rests with

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Defra in England and the devolved administrations in Scotland and Wales (although there are no SAPO-approved laboratories in Wales).

4.3.2 The purpose of SAPO is to prevent animals and poultry in Great Britain being exposed to specified animal pathogens which could cause serious disease and economic loss to the British livestock and poultry industries. The Order does not apply to any animal pathogen or carrier contained in licensed veterinary or human medicines.

4.3.3 SAPO requires those working with any specified animal pathogen (listed in the Schedule to the Order) to apply for and obtain a licence. This stipulates the way in which the specified animal pathogens must be handled to ensure their safe containment and disposal, the areas of the laboratory in which various types of work may be done and the persons responsible for supervising the work.

4.3.4 Under SAPO, "specified animal pathogen" means an animal pathogen listed in the schedule to SAPO, including:

(a) intact pathogens; (b) pathogens which have been attenuated or genetically modified by any means, and (c) any nucleic acid derived from an animal pathogen listed in the Schedule which could produce that pathogen when introduced into a biological system in which the nucleic acid is capable of replicating.

4.3.5 Defra classifies animal pathogens for the purpose of operating IAPO and SAPO. The classification is made for the purpose of protecting animal health from escapes of organisms from a laboratory. (IAPO is described in section 6.2.)

4.3.6 Specified animal pathogens are classified into four categories: • Group 1 - Disease-producing organisms which are enzootic (i.e.

already present in the livestock population at a low or stable level) and do not produce notifiable disease.

• Group 2 - Disease producing organisms which are either exotic (i.e. not present in the UK livestock population) or produce notifiable disease, but have a low risk of spread from the laboratory.

• Group 3 - Disease producing organisms which are either exotic or produce notifiable disease and have a moderate risk of spread from the laboratory.

• Group 4 - Disease producing organisms which are either exotic or produce notifiable disease and have a high risk of spread from the laboratory.

• Rabies - Special containment conditions exist for Rabies and Rabies related viruses.

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4.3.7 The animal pathogens in Groups 2, 3 and 4 and containment requirements for Groups 2, 3 and 4 are described on the Defra website (http://www.defra.gov.uk/animalh/diseases/pathogens/classification.htm, http://www.defra.gov.uk/animalh/diseases/pathogens/category4.htm). They are based on those described in the COSHH regulations, with additional measures and procedures added to cover biosafety.

4.3.8 These containment requirements are intended only as a guide, as decisions on the facilities and procedures required to contain specified animal pathogens safely at individual establishments are made on a case-by-case basis.

4.3.9 Licensing and Inspection under SAPO

4.3.9.1 The SAPO licensing process includes inspection of the applicants’ laboratories and review of supporting documentation (i.e. the operating procedures for work, risk assessment and appropriate containment measures) prior to the licence being issued. Licences are usually valid for 5 years. Inspections of laboratories licensed under SAPO may be carried out at any time to ensure full compliance with licence conditions and the Order.

4.3.9.2 These inspections are currently carried out by Defra, the VLA and HSE. However, from April 2008, HSE becomes lead inspector and will assume these functions, under new regulatory powers which are currently being developed. This will apply across Great Britain, with separate arrangements being developed for Northern Ireland.

4.4 Genetically Modified Organisms (Contained Use) Regulations 2000 (as amended 2002, 2005)

4.4.1 Genetic modification of pathogens (human, animal or plant) where barriers are necessary to prevent their release is subject to compliance with the GMO(CU). GMO(CU) applies across Great Britain, with parallel regulations in Northern Ireland. The key requirement of GMO(CU) is that such pathogens may not be created or brought into the laboratory until the regulator is satisfied that the operator has assessed the risks of all activities and made sure that any necessary controls are put in place. There is a high priority given to the hazard identification of potentially novel GMMs.

4.4.2 The containment levels and criteria are defined in the European Directive 90/219/EC, and the amending Directive 98/81. These are detailed in the GMO(CU) Regulations. They differ from COSHH in a number of areas, primarily because the GM

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regulations are intended to protect both human health and the environment, whereas COSHH only covers human health.

4.4.3 Responsiblity for the GMO(CU) has not been devolved to Wales, although it has been devolved to Scotland. Thus in England and Wales the Competent Authority is Defra and the HSE acting jointly, while in Scotland it is the Scottish Ministers and the HSE acting jointly. HSE acts as the lead competent authority on risks to human health, and Defra / Scottish Executive on environmental issues. HSE is responsible for inspecting and enforcing on all aspects of GMO(CU).

4.4.4 The GMO(CU) Regulations require users to assign containment on the basis of risk assessment. Once the containment required to minimise human and environmental exposure has been determined, the activity is assigned a ‘risk class’ based on that containment. The four risk classes essentially equate to the containment level – CL1 is required for Class 1 activities, CL2 for Class 2, etc..

4.4.5 Prior to Class 2, 3 or 4 activities commencing, the notifier must submit a notification, including an assessment of the hazardous properties of the GMMs and the proposed containment for the planned activity. Specialist Inspectors at HSE and Defra review these notifications for technical content and compliance with the legislation placing an emphasis on the adequacy of the risk assessment and requesting additional information where necessary.

4.4.6 For high hazard organisms (Class 3 and 4) the operator may not proceed without the written consent of the Competent Authority.

4.4.7 Inspection under GMO(CU)

4.4.7.1 All Class 4 or novel genetic modification activities are brought to the attention of the Scientific Advisory Committee for Genetic Modification (SACGM), to provide independent scientific advice to the Competent Authority on the adequacy and scientific content of the hazard assessment. Where necessary, site inspection may be required where novel containment requirements are proposed. Once satisfied with the assessment of the hazard properties of the proposed GMM and proposed containment, the Competent Authority issues consent for the work to proceed.

4.5 Anti-Terrorism Crime and Security Act 2001 (ATCSA)

4.5.1 The secure storage and use of dangerous pathogens and toxins to reduce the risk of malicious use is regulated by ATCSA. Part 7 of ATCSA applies across the UK and provides the police with powers to impose security measures at laboratories that hold

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certain dangerous pathogens and toxins (as listed in Schedule 5 of the Act). The ATCSA list does not correspond directly to the classifications used in COSHH, SAPO or GMO(CU), as it has been drawn up specifically with malicious use in mind. These powers were introduced to improve the security of dangerous substances that may be targeted or used by terrorists. Schedule 5 has recently been updated to include further pathogens and toxins that could cause serous harm to human health or damage, disruption and alarm regarding animal pathogens (Part 7 of ATCSA (Extension to Animal Pathogens) Order 2007 and Schedule 5 to the ATCSA 2001 (Modification) Order 2007).

4.5.2 The list of registered laboratories, implementation policy and training for the police has been provided by NaCTSO. This is a national police unit co-located with the Centre for the Protection of the National Infrastructure.

4.5.3 Security procedures for laboratories differ according to containment level:

• CL 4 laboratories are subject to extensive security measures with extremely limited access. All staff granted access must undergo security clearance.

• CL 3 laboratories are subject to security measures required by ATCSA and receive bespoke advice regarding staff security checking.

• CL 2 laboratories are provided with bespoke advice regarding physical and personnel security by Counter-Terrorism Security Advisers (CTSAs).

4.5.4 Personnel Security Measures for Laboratories

4.5.4.1 The document ‘Personnel Security Standards for Laboratories’ was published by the Association of Chief Police Officers and the Home Office in April 2005. Since then it has been circulated to laboratories subject to Part 7 and Schedule 5 of ATCSA. The document delivers detailed personnel security advice to laboratories regarding new staff, existing staff, visitors and contractors.

4.5.4.2 The document delivers specific guidance on good practice relating to security checking of new staff, existing staff, contractors, visitors and students/short term appointments. The advice details how to check identities, checking references, checking qualifications, employment history and criminal convictions. It also provides guidance on what to do if concerns arise during the process.

4.5.4.3 This document was designed to deliver practical guidance without the false sense of security that can arise from a criminal

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records check alone. Managers are advised to maintain personnel security by way of good human resource management and reporting, the wearing of security passes and the creation of a ‘security aware’ environment.

4.5.5 Inspection under ATSCA

4.5.5.1 Since 2002 the legislation has been enforced by police CTSAs. Premises working with Schedule 5 agents need to notify the Home Office and will be visited by CTSAs. The CTSAs assess the security of the laboratories and have powers under part 7 of ATCSA to serve directions requiring security improvements. Failure to comply with these directions is a criminal offence.

4.5.6 Home Office review of Hazardous Substances

4.5.6.1 As the Prime Minister announced on 14 November 2007, the Home Office is carrying out further work to look at what more might be needed to strengthen protection against the use of hazardous substances for terrorist purposes. This review is being led by Lord West and will report to the Prime Minister later this year.

4.6 Inspection regimes

4.6.1 Regulatory activities in the sector

4.6.1.1 HSE, Defra and the Scottish Executive currently regulate work with dangerous pathogens in Great Britain. HSE is responsible for the regulation and manages the statutory notifications and permissioning schemes for work with human pathogens and GMMs under GMO(CU) and COSHH, whilst Defra and the Scottish Executive license work with animal pathogens under SAPO.

4.6.1.2 HSE provides technical and regulatory advice to other government departments, agencies and the bioscience & healthcare communities about working with dangerous pathogens. HSE also develops standards and guidance at national and international level on the control of dangerous pathogens, often based on advice from the SACGM and ACDP.

4.6.2 Inspection by under COSHH and GMO(CU)

4.6.2.1 HSE inspectors undertake inspection and enforcement activities at premises where work is undertaken with dangerous pathogens under GMO(CU) and COSHH. The inspection unit is made up of a team of specialists in the fields of microbiology and

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biotechnology with a broad collective experience in the research, clinical and industrial biosciences sectors.

4.6.2.2 Inspection of the physical containment of the laboratories is supplemented by review of documentation and interviewing staff to assess compliance with safety management systems. Where significant breaches of legislation are identified, Specialist Inspectors can use a full range of enforcement powers conferred by the Health and Safety at Work Act 1974, which include stopping work activities, issuing notices requiring specific improvements by specific dates and prosecution.

4.6.2.3 For larger sites involving extensive work with dangerous pathogens, an ‘Inspection Plan’ is developed. In essence this is a summary of the different interactions that HSE will utilise to engage a particular duty holder over a particular time period. The overall intention of the intervention plan is to facilitate a partnership approach to raising standards of biological safety. This approach can involve a range of activities including traditional inspections, topic-specific or all-encompassing biosafety audits, participation in training courses, and involvement in biosafety committee meetings and providing presentations.

4.6.3 Inspection under SAPO

4.6.3.1 In England up to March 2008, inspections of laboratories working with SAPO Group 4 pathogens are carried out by a senior veterinary official at Defra and HSE. From 2008, all other inspections are being carried out by the VLA and HSE. It is planned that HSE will take over sole responsibility for all inspections from April 2008. In Scotland, where there are no laboratories working with SAPO Category 4 pathogens, inspections are carried out by a Veterinary Advisor working in the Scottish Executive, assisted by veterinarians from Animal Health.

4.6.3.2 If, during an inspection, an inspector identifies non-compliance with the Order or the licence conditions, they may recommend that Defra or the Scottish Executive amend, suspend or revoke the licence. Any prosecution would be undertaken by the relevant local authority (usually the trading standards department) as local authorities are responsible for enforcement under SAPO. Since Local Authorities do not inspect laboratories, they will only become involved when the inspectors alert them to non-compliance that might warrant a prosecution.

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5 Biosafety training provision for staff working in containment facilities

5.1 The only specific requirements for biosafety training are made under the GMO(CU) regulations. However, there are general duties placed on employers to provide appropriate staff training and instruction.

5.2 All employers are bound under the Health and Safety at Work Act 1974 “…to provide such information, instruction, training and supervision as is necessary to ensure, so far as is reasonably practicable, the health and safety at work of his employees”. This requirement is a general one, demanding training but not specifying content.

5.3 The Management of Health and Safety at Work Regulations 1999, whilst not dictating content other than that it must be “adequate”, reinforce the general requirement specified in the Act, and extend this by specifying the regime for training (for example, on recruitment or on exposure to new or increased risk).

5.4 COSHH extend the general requirements to provide suitable and sufficient training with guidelines as to the content of this training. Training and information provided must provide the employee with details of the biological agent, including the risk presented to health; the significant findings of any relevant risk assessments; the appropriate precautions and actions to be taken by the employee to safeguard himself and other employees; results of any monitoring of exposure, and the collective results of any health surveillance. Furthermore, the training provided in the case of a HG4 pathogen or material which may contain such an organism, must provide for written instruction and procedures for the handling of such an agent specified in Regulation 12(2).

5.5 The above requirements for training are embedded further in:COSHH 2002 (as amended) Regulation 7(7) where it is indicated that, where there is exposure to a substance hazardous to health, control of that exposure will only be adequate if the principles of good practice (set out in Schedule 2A) are applied. This includes a necessity to inform and train all employees on the hazards and risk from the substances with which they work and the use of control measures developed to minimise the risks.

5.6 The GMO(CU) Regulations 2000 which require that written training records are kept for work at CLs 3 and 4. Inspections will cover training and instruction of staff, and involve a review of records. The lack of enforcement action in this area highlights a good level of compliance with the training requirements.

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6 The maintenance and recording practices surrounding the storage and transportation of dangerous pathogens

6.1 Storage

6.1.1 Safe storage of dangerous pathogens is a requirement of all the current regulatory systems. The degree of security of storage required depends on the nature of the organisms being used. For the high hazard organisms, the legislation stipulates “secure storage”. Accompanying guidance on what is expected is provided. At CL 4, organisms must only be stored within the CL 4 laboratory. Fridges, freezers and storage containers should be kept locked when not in use.

6.1.2 NaCTSO, through the CTSAs, have for some time been carrying out their own security audits at sites that handle infectious substances. Advice that has been given by CTSAs on these visits is in line with the requirements for storage and use at premises (Schedule 5 to ATCSA).

6.2 Transportation: under SAPO and the Importation of Animal Pathogens Order 1980 (IAPO)

6.3 Licences under SAPO stipulate the way in which the specified animal pathogens covered by the licence must be handled to ensure their safe transport, containment and disposal. SAPO applies to the specified animal pathogens, regardless of their origin (Great Britain, European Union (EU) or third country)

6.4 IAPO prohibits the importation into Great Britain from a third country (i.e. a country that is not a Member State of the EU) of any animal pathogen or carrier except under the authority of a licence and in accordance with the conditions of that licence.

6.5 Licences issued under IAPO contain conditions prohibiting any transfer of the imported animal pathogen and/or carrier and its derivatives to any other person or laboratory without the prior authority of the licensing authority.

6.6 Licences under IAPO usually stipulate the manner in which the animal pathogen or carrier must be prepared, treated and packed prior to importation, the containment conditions under which it must be handled and the method by which it and its derivatives must be disposed of, if it is not re-exported. The purpose of imposing these conditions is to protect animals and poultry from infection by animal pathogens imported into Great Britain from outside the EU. Licences are normally valid for two years, to provide for the importation of the material and the completion of work on the material in the laboratory, following importation.

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6.6.1 The Order also requires anyone who has in his possession an animal pathogen or carrier which he knows to have been imported in contravention of the provisions of the Order to report the fact to a veterinary inspector as quickly as possible. The Order does not apply to any animal pathogen or carrier contained in a licensed medicinal product, the importation of which is permitted under the Medicines Act 1968, or to importations made from other Member States of the European Communities.

6.7 Transport: The Carriage of Dangerous Goods and Use of Transportable Pressure Equipment Regulations 2007.

6.7.1 Infectious substances transported in Great Britain are subject to these Regulations, which transpose international regulations originating in the UN and cover both safety and security measures. The Regulations apply throughout Great Britain.

6.7.2 Classification of dangerous goods, including infectious substances

6.7.2.1 These Regulations set out nine classes of dangerous good. Infectious substances are Class 6, division 6.2. The regulations for infectious substances were developed by the UN Sub-Committee of Experts on the Transport of Dangerous Goods with input from specialised agencies including the WHO and the OIE.

6.7.2.2 Class 6.2 infectious substances are subdivided into Category A, the more dangerous pathogens, and Category B. Category A includes infectious agents which are capable of causing permanent disability, life threatening or fatal disease in otherwise healthy humans or animals. This category includes all the pathogens listed in the COSHH HG4 and SAPO Group 4, and many of those in HG3 and Group 3.

6.7.2.3 Category A substances are divided into those infectious substances affecting humans, and those affecting animals only. The Regulations give an indicative list of infectious substances for both humans and animals. For example, the list for humans includes Ebola virus and Lassa virus, while the list for animals includes FMD virus cultures, and Rinderpest virus cultures. Category B substances would typically include diagnostic specimens from doctors’ surgeries or veterinary surgeons where the consignor is confident the samples do not contain Category A substances.

6.7.2.4 The Regulations make it clear that the indicative lists are not exhaustive. New or emerging pathogens not on the list but meeting the criteria for Category A must be assigned to that

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category. Other infectious substances can be treated as Category B.

6.7.3 Safety requirements for dangerous goods

6.7.3.1 All Category A substances, regardless of quantity, have to be packaged, labelled and marked according to the rigorous safety requirements in the regulations and have the appropriate documentation, and for road transport, the driver needs to hold a vocational training certificate for Division 6.2.

6.7.3.2 The regulations for Category B substances recognise the reduced risk posed by these substances, and provided they are packaged in accordance with the regulations, most other provisions are dis-applied. Category B substances are accepted by Royal Mail for transport.

6.7.3.3 For road and rail transport the vehicle or rail wagon transporting Category A pathogens has in most cases to carry warning plates. All involved in the transport chain have to receive safety training appropriate to their responsibilities. For road transport, the driver has to have specific driver training when carrying any Category A substances or other dangerous goods in quantities above certain thresholds.

6.7.4 Security requirements for dangerous goods

6.7.4.1 The aim of the security elements of the Dangerous Goods Regulations is to seek to prevent dangerous goods from being stolen and misused by terrorists. The security measures apply to all dangerous goods, except those that are nuclear and are split into two levels:

i) a general level applicable to the carriage of all dangerous goods; and ii) a higher level for the carriage of high consequence dangerous goods.

6.7.4.2 High consequence dangerous goods are defined as those that, if misused, can cause a large loss of life or serious damage to the economy or environment, and include Category A substances as defined in section 6.7.2 above.

6.7.4.3 The security requirements apply to all those involved in the transport ‘chain’: consignors, loaders, carriers and unloaders. Anyone involved in the transport of dangerous goods must:

• Only offer dangerous goods to people, companies or organisations that have been properly identified;

• Ensure temporary storage sites are secure; • Implement a security awareness training programme for staff;

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• Create and put in place a detailed security plan (if carrying high consequence dangerous goods) which includes the need to maintain records of the specific goods carried and the quantities. In addition to the requirement that records are kept, it is recommended that they are retained for 4 years.

6.7.4.4 The Regulations are supported by comprehensive guidance which has been the product of a close working relationship between Government, Police and representatives of those who have some part to play in the transport chain of dangerous goods. Various Government departments are also represented where applicable. The Department for Transport continues to cooperate with this group (called the Industry Advisory Group) and holds regular liaison meetings with them. Further information on supporting guidance can be obtained from the Department for Transport’s website at http://www.dft.gov.uk/security/subdangerousgoods.

6.8 Review of Dangerous Goods Security

6.8.1 The Department for Transport is currently reviewing its Dangerous Goods Security regime to ensure the requirements remain effective and proportionate.

6.8.2 As part of this review, the Department has met with the other regulators of pathogen work and confirmed that their existing regulation and inspection regimes adequately cover the security requirements for pathogens and toxins stored in transit.

6.8.3 However, within the category of high consequence dangerous goods there are some substances which have greater potential for misuse in a terrorist attack (termed 'Very High Consequence Dangerous Goods' or VHCDGs). The Department for Transport is currently working with the Centre for Protection of National Infrastructure, Home Office and others to identify a list of VHCDGs, to assess the security measures currently in place to protect them in transit, and to consider the case for more stringent security requirements for these substances. This work will include pathogens and toxins within its scope and thus there is the potential for pathogens to be classified as VHCDGs and subject to enhanced containment levels accordingly.

6.9 Regulation of transport under COSHH

6.9.1 Notification to HSE is required under COSHH where HG4 pathogens are being moved from one site to another. Notification needs to be made at least 30 days in advance of any planned

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movement of the agent, although in practice, shorter times are often agreed to allow clinical diagnostic work to be carried out.

7 Measures implemented when pathogenic material cannot be accounted for

7.1 There are reporting systems in place under the Reporting of Injuries, Diseases and Dangerous Occurrences Regulations 1995 (RIDDOR) and the GMO(CU) Regulations which would apply in cases where material could not be accounted for.

7.2 The GMO(CU) Regulations require that accidents that ‘involve a significant and unintended release …which presents an immediate or delayed hazard to human health or to the environment’ are reported to the Competent Authority. This would include any situation where material could not be accounted for.

7.3 RIDDOR similarly requires notification to HSE as a ‘dangerous occurrence’, which would cover situations where samples containing HG 3 or 4 micro-organisms were lost or accidentally released. However, there is no specific requirement to keep an inventory of organisms held, although it would be expected as good practice. The requirement to ensure safe storage can only be effectively met by knowing what is held, and ensuring that it is kept safe.

7.4 HSE undertakes investigations of RIDDOR or GMO(CU) reportable incidents involving dangerous pathogens. Incidents range from dangerous occurrences which have the potential to expose employees to pathogens, such as laboratory spillages, to cases of laboratory acquired infections, via accidents such as needlestick injuries. The incidents are investigated in accordance with HSE’s enforcement policy and operational investigation policy and procedures.

7.5 Licence holders under SAPO CL4 have agreed procedures to notify the licensing authority (currently Defra) of either the accidental release of pathogenic material (as defined within SAPO) or of a "near miss". Defra would expect to be notified immediately by telephone, with a written report to follow within 24 hours. The responsibility for reporting rests with the Biological Safety Officer (where one has been appointed) or other competent individual at the licensed premises, who is required to make an assessment of the risk and formulate Standard Operating Procedures which set out the action to be taken. All such reports are assessed by senior veterinary officials in Defra and further action considered. For all relevant laboratories, provision for handling general and biological agents is contained in the COSHH, and for GM organisms in GMO(CU).

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8 The role of universities in overseeing security clearance for research students working with dangerous pathogens

8.1 In common with other Governments around the world, the British Government is working hard to stop the spread of knowledge and skills that could be used in the proliferation of weapons of mass destruction (WMD) and their means of delivery. The Academic Technology Approval Scheme (ATAS) is designed to ensure that people who are applying to study certain sensitive subjects in the UK do not have links to WMD programmes. The ATAS is administered by the FCO and was introduced on 1 November 2007.

8.2 Non-European Economic Area nationals who require leave to enter or remain in order to study in the UK and who are seeking to undertake postgraduate study in the UK in specific, limited subjects must hold an ATAS certificate before they can apply for an entry clearance or extension of stay. The Immigration Rules were amended on 30 November to make the possession of an ATAS certificate a mandatory requirement. Students seeking leave to enter or remain who require an ATAS certificate and who do not hold one will be refused leave to enter/remain.

8.3 The MoD provided technical advice on which subjects to include in fields such as engineering, technology, and the sciences; a full list is available at www.fco.gov.uk/ATAS. The scheme is focussed on those conducting postgraduate research (at both Doctoral and Masters level) although students taking taught Masters in the specific areas of Materials Science, Materials Technology, Physics, Mechanical Engineering and Aerospace Engineering also come within its remit.

8.4 An ATAS certificate can be applied for via a free, on-line form resembling a CV. No supporting documentation is required. The FCO aims to take decisions on the vast majority of applications within 10 working days. Applicants are notified by email of the decision and issued with a certificate if their clearance is confirmed. At the same time Higher Education Institutions (HEIs) are informed of decisions affecting their applicants.

8.5 The ATAS certificate is specific to both the programme of study that the student intends to undertake and the HEI.

8.6 HEIs have a fairly limited involvement in this process. They provide in their offer letters to students the relevant code for the programme of study the student is to follow, which enables the FCO to determine whether the programme of study is one which is covered by the ATAS arrangements. For those students undertaking postgraduate research the HEI also provides an agreed research proposal of what area of research is anticipated.

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8.7 Prior to the introduction of mandatory screening through ATAS, there was a voluntary screening system known as the Voluntary Vetting Scheme in place since 1994, also administered by the FCO. HEIs were invited to refer any applicants to the FCO for vetting. A recommendation was made to the HEI although they did not have to accept that advice. The scheme was voluntary, adherence to it by HEIs was patchy and it placed an undue burden on those who did participate. A lengthy review led to the introduction of the ATAS and the subsequent amendment of the Immigration Rules, which gives the scheme proper effect.

January 2008

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Annex A:

Abbreviations used in this memorandum ACDP Advisory Committee for Dangerous Pathogens ATAS Academic Technology Approval Scheme ATCSA Anti-terrorism Crime and Security Act 2001 CEPR Health Protection Agency's Centre for Emergency Preparedness and

Response CL Containment Level COSHH Control of Substances Hazardous to Health Regulations 2002 CTSA Counter-terrorism Security Advisers Defra Department for the Environment, Food and Rural Affairs EU European Union FCO Foreign and Commonwealth Office FMD Foot and Mouth Disease GMM Genetically Modified Micro-organism GMO Genetically Modified Organism GMO(CU) Genetically Modified Organisms (Contained Use) Regulations 2000 HEI Higher Education Institutions HG Hazard Group HPA Health Protection Agency HSE Health and Safety Executive IAPO The Importation of Animal Pathogens Order 1980 MoD Ministry of Defence NaCTSO National Counter-Terrorism Security Office NIBSC National Institute of Biological Standards and Control OIE Office Internationale des Epizooties RIDDOR Reporting of Injuries, Diseases and Dangerous Occurrences

Regulations 1995 SACGM Scientific Advisory Committee for Genetic Modification SAPO Specified Animal Pathogens Order 1998 VHCDGs Very High Consequence Dangerous Goods VLA Veterinary Laboratories Agency WHO World Health Organization WMD Weapons of mass destruction

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Memorandum 2

Submission from the Veterinary Laboratories Agency (VLA)

Executive Summary

The Veterinary Laboratories Agency (VLA) provides a significant component of the national laboratory and animal capability for conducting research on dangerous animal and zoonotic pathogens up to SAPO4/ACDP3. Overall we consider the national GB facility matches current and likely future requirements taking into account the current joint redevelopment plans for IAH Pirbright and VLA Virology on the single site at Pirbright, Surrey.

From an animal and zoonotic disease perspective many of the current biological containment facilities in the UK are modern and fit-for-purpose although others require significant capital investment to bring them to acceptable bio-containment standards. Before any new investment in national capability, their needs to be a UK-wide strategic review to ensure current and future capabilities, especially high containment animal facilities, are sited appropriately and used effectively to ensure optimum capacity.

Implementation of the Callaghan review will strengthen the current licensing and inspection arrangements by harmonising in the UK all the procedures for working with dangerous pathogens irrespective of their host.

Rigorous adherence to independent quality systems such as ISO 17025 and ISO 9001: 2000 provide assurance that valid audit trails and verifiable storage systems exist for all dangerous pathogens received at, and transported and held within organisations such as VLA.

At present security clearance of scientists working with dangerous pathogens is not harmonised in the UK. In particular, Public Sector Research Organisations (PSRE) such as government agencies appear to have much stricter security processes than many other organisations including research council institutes and universities. As a major employer of scientists, Universities clearly have an overseeing security clearance responsibility for research students and employees. However, experience in PSREs demonstrates the need for a sensible risk-based approach so as to ensure effective security procedures do not restrict unnecessarily the movement of students and scientists that is so vital for a vibrant scientific economy.

1. The current capacity for research on dangerous pathogenic material in the UK and the capability to conduct research on the causative agents of disease that may emerge at a future time.

1.1 VLA has extensive capability for conducting research on dangerous pathogens up to SAPO4/ACDP3, both in the laboratory and in large and small animal hosts. There is a recognised need for some new facilities in the UK to conduct research on zoonotic pathogens at SAPO4/ACDP4, since current

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facilities are very limited in number and focus solely on human disease, leaving scientific questions regarding the disease in animal hosts unanswered. Also, in the event of incursion of such a pathogen, current facilities would not be able to deal with the disease in animals. This gap has been recognised by Defra and BBSRC and a new joint veterinary virology facility planned between VLA Virology and IAH on the IAH’s Pirbright site will comprise a research and diagnostic capability for ACDP4 level pathogens including some capability to conduct experiments with small animals. The completion of the new facility is planned for 2012.

2. The state of biological containment facilities in the UK.

2.1 VLA places a high priority on maintaining its laboratories and animal accommodation in order to fully meet the requirements of national legislation and international recommendations pertaining to containment facilities. There is an active programme of replacement for older facilities in place, which includes the provision of new facilities for VLA Virology and IAH Pirbright by 2012. These new joint laboratory and animal facilities will house one of the largest group of veterinary virologists in the world and provide an expert knowledge base to ensure the UK is well placed to deliver underpinning research and a rapid diagnostic capability for future incursions of exotic diseases in animals of which many are likely to be new and emerging zoonotic viral pathogens.

3 Laboratory inspection regimes and the rationale and practicalities of the licensing system.

3.1 The current system is robust and workable. This system, which is risk-based, provides a degree of transparent flexibility, particularly in the area of diagnostics, where derogations are provided for certain classes of sample or use of specific, lower-risk laboratory strains of pathogens. The recent Callaghan Review considered the current regulatory framework for handling of animal pathogens in the UK. One of its main recommendations was to bring together under a single body the laboratory inspection regimes and licensing procedures for working with dangerous animal and human pathogens. VLA welcomes the Government’s decision to vest responsibility and authority to the HSE and we believe this will strengthen the current arrangements by harmonising in the UK all the procedures for working with dangerous pathogens irrespective of their host.

4. Biosafety training provision for staff working in containment facilities.

4.1 At VLA, a range of systems are in place which provide proof of competency of all staff, before they are permitted to work with pathogens unsupervised. These include training in entry and exit procedures, laboratory manipulations, environmental and personal risks and robust protocols for materials movement that ensure biosecurity. There is also an active promotion of a culture of continuous examination and incident/near-miss reporting, to

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ensure that potential gaps or flaws can be detected and remedial action taken, before accidents occur.

4.2 The technical challenges of such work at the highest containment level (ACDP4) are formidable and staff training is an essential component of any such capacity building. Specialist staff in the Virology Department at VLA are currently undertaking training in work on ACDP4 pathogens, along with developing collaborative research programmes with counterparts in Europe and USA, in order to ensure an active programme of work and staff with requisite skills are in place when the new facility at Pirbright comes online.

5. The maintenance and recording practices surrounding the storage and transportation of dangerous pathogens.

5.1 VLA has a robust and secure system of biological archive storage of materials containing such pathogens. However the funding of archives is an issue since maintenance of the vast majority of these archives are not met by funding bodies in the UK. VLA believes there should be funding available to support the maintenance of biological archives of national importance. This is particularly relevant to dangerous pathogens and the increased awareness of the risks associated with bioterrorism. We consider it is not really practical to similarly record day-to-day storage of research materials containing pathogens to the same level i.e. specific volume and titre, since this is often not known. Also, it would not be difficult to mis-record volumes or substitute material. We therefore additionally apply stringent security measures, both in terms of physical security and access, along with criminal record and counterterrorism checks of all scientific staff working with SAPO3/ACDP3 pathogens and above. We consider this provides sufficient assurance of security and provides a research environment that is workable. Furthermore, VLA Quality Systems (ISO 17025 and ISO (9000) provide assurance that valid audit trails and verifiable storage systems exist for all dangerous pathogens received at, and transported and held within, VLA.

5.2 The role of VLA, as a World Organisation for Animal Health (OIE) Reference Laboratory for 14 diseases, EU Community Reference Laboratory for three diseases, along with being an FAO World Reference Laboratory and WHO Collaborating Centre, requires frequent importation and export of suspect samples and pathogens. The current legislation is clear and is rigidly applied, both for materials being sent and received both nationally and internationally.

5.3 Occasionally, materials are received without prior notification and incorrectly packaged, which could constitute a risk to UK. In such a case, appropriate decontamination and containment procedures are applied and a strong reply is given to the submitter, pointing out such breach of international and national legislation.

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6. Measures implemented when pathogenic material cannot be accounted for.

6.1 Any incident where there has been potential for material to have been removed from any bio-secure unit without authorisation or unrecorded, an internal investigation is mounted, led by the Safety Manager and appropriate Head of Department with support from VLA Security. If such act has resulted in a potential breach of biosecurity, Defra would immediately be informed. If the pathogen was also an ACDP3 agent or above, HSE would also be informed, under RIDDOR.

6.2 In any event where suspicion of removal of material with malicious intent was revealed, the police would immediately be alerted.

7. The role of universities in overseeing security clearance for research students working with dangerous pathogens.

7.1 As mentioned, all scientific staff at VLA are subjected to criminal record and counterterrorism checks. It is our experience that the security clearance of staff and students attending UK universities is variable and cannot always be relied upon as compared with scientists and students employed by Public Sector Research Establishments (PSRE). For this reason we also require and perform identical checks on any students or visiting scientists, before permitting access to bio-secure areas, along with training requirements similar to core staff before permitting unsupervised working. We also seek assurances from the students’ employer that they have completed a training programme and are competent to work with dangerous pathogens.

7.2 Where, for reasons of geography or nationality, security checks cannot be completed, visiting scientists are required to be accompanied by trained VLA staff at all times.

January 2008

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Memorandum 3

Submission from Dr George McIlroy, Chief Executive, Agri-Food and Biosciences Institute for Northern Ireland

BIOSECURITY IN UK RESEARCH LABORATORIES

Summary of Evidence The Agri-Food & Biosciences Institute (AFBI) is a Non-Departmental Public Body (NDPB) sponsored by the Department of Agriculture and Rural Development for Northern Ireland (DARD). AFBI carries out work on pathogens up to HSE ACDP (Advisory Committee on Dangerous Pathogens) hazard group 3 and monitors for pathogens up to DEFRA hazard group 4 ( SAPO (Specified Animal Pathogens Order) pathogens that may cause animal or plant diseases or food-borne illness. This work is carried out in laboratories up to ACDP biocontainment level 3. I believe that the recommendations of the Callaghan Review would greatly simplify licensing and inspection arrangements, and significantly improve the effectiveness of biosecurity measures for work on human and animal pathogens. Introduction to the Agri-Food & Biosciences Institutewww.afbini.gov.uk The Agri-Food & Biosciences Institute (AFBI) was created on 1st April 2006 as an amalgamation of the Department of Agriculture and Rural Development for Northern Ireland (DARD) Science Service and the Agricultural Research Institute of Northern Ireland (ARINI). AFBI is a Non-Departmental Public Body (NDPB) sponsored by DARD. AFBI carries out high technology research and development, statutory, analytical, and diagnostic testing functions for DARD and other government departments, public bodies and commercial companies. AFBI's NDPB status enables it to be innovative and entrepreneurial in its approach to business development. AFBI is forging new partnerships with other scientific institutes and research organisations and extending the range of services it offers. This enables AFBI’s unique breadth of scientific capabilities in the areas of agriculture, animal health, food, fisheries, environment and biosciences to be offered to a wider prospective national and international customer base. AFBI has an independent Board which is also responsible for monitoring its performance. AFBI carries out surveillance and research work on food-borne pathogens and other infectious agents that pose a threat to animal and plant health. Some of these agents are of zoonotic importance. Maintaining an emergency responses capability to outbreaks of serious animal and plant disease, to food and environmental emergencies and to chemical and biological incidents affecting public safety is an important component of AFBI’s work and responsibility.

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Response to Request for Evidence

• Current capacity for research on dangerous pathogenic material in AFBI and the capability to conduct research on the causative agents of disease that may emerge at a future time

AFBI does not hold nor carry out research on SAPO (Specified Animal Pathogens Order) category 4 pathogens. At present it is unable to do so because of the absence of a SAPO level 4 biocontainment laboratory in Northern Ireland.

AFBI carries out work on several hazard group 3 level pathogens that can cause serious disease in animals and humans. The institute has a large number of skilled staff with laboratory expertise for work on a wide variety of animal, plant and food-borne pathogens. This pool of expertise is available for work on new pathogens that could emerge in the future. Surveillance for the emergence of new animal, plant and food-borne pathogens is an important component of AFBI’s work.

• The state of biological containment facilities in AFBI

A suite of modern, state-of-the art ACDP biocontainment level 3 laboratories, which will substantially supplement existing facilities, is currently in the final stages of commissioning at AFBI. It is planned that these laboratories will be occupied in spring 2008. They will replace several older laboratories which will then be de-commissioned.

AFBI is seeking funding for the construction of a biocontainment laboratory for surveillance work on DEFRA and SAPO hazard group 4 pathogens that pose a threat to the agri-food industry and may be of importance to human health e.g. avian influenza in Northern Ireland.

AFBI also has recently constructed modern animal biocontainment accommodation for work on hazard group 3 pathogens of animals.

• Laboratory inspection regimes and the rationale and practicalities of the licensing system

AFBI laboratories are subject to inspection by the Health and Safety Executive (Northern Ireland) (HSE (NI), DARD, the Department of the Environment for Northern Ireland and the Environment and Heritage Service Radiochemical Inspectorate. Several AFBI laboratories have security approval from the Police Service of Northern Ireland antiterrorism office for work on schedule 5 pathogens as listed in the Anti-Terrorism, Crime and Security Act 2001.

I support the recent recommendations of the Callaghan Review. In particular, I agree that the use of both animal and human pathogens should be governed by a single independent regulatory framework, with responsibility for

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regulation of these pathogens passing to the Health and Safety Executive. I also strongly support the Callaghan recommendation that risk assessment should be a key element of the regulatory framework for handling animal pathogens, as it is currently for human pathogens and genetically modified organisms. I agree with the recommendation that the Advisory Committee on Dangerous Pathogens is asked to draw up guidance on a single set of containment requirements for human and animal pathogens, to complement the single regulatory framework when it is introduced.

I believe that the recommendations of the Callaghan Review would simplify licensing and inspection arrangements, and improve the effectiveness of biosecurity measures for work on human and animal pathogens.

• Biosafety training provision for staff working in containment facilities

Biosafety training for staff in AFBI includes in-house and externally procured training. For example, a number of staff have received training at Porton Down and receive regular refresher training. Staff from the Health Promotion Agency, Porton Down will be coming to AFBI in Spring 2008 to provide a week-long course in biosafety to another group of AFBI staff. AFBI staff also participate in international conferences and workshops on biosafety.

All research undertaken in AFBI is accredited to ISO 9001 and, where relevant, to GLP (Good Laboratory Practice) standards of accreditation. Analytical tests in many laboratories are also accredited to the ISO17025 standard Application of the standard operating procedures required for these standards is an important element in strengthening biosafety protocols within AFBI.

• The maintenance and recording practices surrounding the storage and transportation of dangerous pathogens

Staff and contractors who are to work on the site are security vetted by DARD. Security of stored pathogens in AFBI has several levels. The sites at which hazard group 3 pathogens are held are protected by 24-hour security staff and a perimeter fence. All visitors to AFBI must report to security staff on arrival where they are issued with passes which must be displayed at all times while on-site. Visitors must be accompanied by members of AFBI staff who must display visible ID at all times. Access to areas in which hazard group 3 pathogens are held is controlled by a proximity card and/or proximity card and “PIN” number and there is a record kept of visitors/ contractors to these laboratories. Within these secure areas, hazard group 3 pathogens are held in locked containers (normally refrigerators). Written records are maintained of all stored hazard group 3 and schedule 5 pathogens. AFBI’s Veterinary Sciences Division was highly commended following a recent inspection of schedule 5 facilities by the PSNI.

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A significant number of AFBI staff have received training in packaging of samples of pathogenic material to International Air Transport Association (IATA) standards and are used for packaging and dispatching such material for transport.

• Measures implemented when pathogenic material cannot be accounted for

There have been no examples of such unaccounted loss in AFBI. In the event of an unaccounted loss, the immediate area would be restricted until evidence gathering and assessments have been made. The visitor and contractor access records would be examined. Security vetting for contractors who have worked on site since last audit of cultures would be reviewed to ensure there have been no lapses in vetting. The PSNI would be informed and forensic services sought for evidence gathering. DARD would be informed of the incident.

• The role of universities in overseeing security clearance for research students working with dangerous pathogens

While AFBI is not a university, a small number of university research students work in AFBI laboratories. Unless working in a laboratory approved by the PSNI for work on schedule 5 pathogens, there is no formal security clearance process for these students. However, the number of students who might work on hazard group 3 pathogens is very small and they are closely supervised by AFBI staff all of whom have an appropriate level of security clearance. January 2008

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Memorandum 4

Submission from the Institute of Safety in Technology and Research

Biosecurity in UK research laboratories The opportunity to participate in the discussion concerning this important topic is welcomed by the Institute of Safety in Technology and Research (ISTR).

The ISTR is a professional association of in safety professionals from the whole spectrum of public, government and commercial research and high technology organisations with similar research and technological interests. The organisation was formed in 1982.

The members, currently 250 come from across research organisations but are mostly universities and are highly qualified and have a huge body of experience.

Its aims are to further the advancement of safety skills and knowledge among its membership; the maintenance of the professional standards; the preservation and enhancement through representation to bodies of influence; the promotion of communication and exchange of information; the maintenance of dialogue with other professional bodies in areas of related interest.

With the increased activity in bioscience and biotechnology within members’ workplaces, a Bio sub-group has been established within ISTR. There are three regional groups meeting several times a year and one major symposia on a current topic.

The Institute runs skills workshops, and three open symposia each year. Recent subjects of symposia have included: Animal facilities, Benefits of improving health & safety; The GMO regulations 2000; Laboratory containment; Student placements; Off site working; Biological safety, Improving Health and Safety, Managing contractors, Legislation update, Transport safety, Laboratory design, Biosafety auditing, Novel technologies, physical agents..

In addition to the meetings there is web based information, discussion forum, award programme for outstanding performance, membership directory, twice yearly publication and a new accreditation scheme. The Institute and its members interact on a regular basis with regulators especially NATSCO and HSE. This document brings together the comments of a component of the research community comprised of professional safety practitioners working in the areas of cutting edge biological research in UK universities, government laboratories, commercial biopharm industry, hospitals and charities. There is an active UK biosafety/biosecurity community which liaises with regulators and others in the related biological areas such as animal containment and welfare, occupational diseases, gene-therapy, technology and product manufacturers. Also engaging with other countries and international GOs/NGOs to exchange and share experiences. In Europe and beyond there are a number of initiatives on improving biosafety bio-risk and biosecurity (WHO, EU, CEN, EBSA). Laboratory Standard http://www.ebsaweb.eu/EBSA+Activities/Laboratory+Standard/Background.html Review of EU Arrangements for Biosafety http://www.ebsaweb.eu/EBSA+Activities/Biosafety+Europe.html Biopreparedness

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http://www.ebsaweb.eu/ebsa_media/Downloads/EBSAActivities/com2007_0399en01BioPreparedness-view_image-1-called_by-ebsa-original_site--original_page-355.pdf

Submission

Summary

• Education; o Regulators o Specialist Biosafety Advisors o Researchers and undergraduates o Architects and engineers in containment

• Implementation of existing regulation evenly • Learning from European and World Experiences • Co-ordination of funding of containment facilities including infrastructure

Who we are; Institute of Safety in Technology and Research; has members represent professional safety practitioners in the field of high technology research in universities and other research organisations. We are the only national forum for biosafety and biosecurity in the UK and as such represent the experts in biosafety and biosecurity for the United Kingdom. In addition many of our members are active in European activities to promote better bio controls and uniformity of standards

Response

the current capacity for research on dangerous pathogenic material in the UK and the capability to conduct research on the causative agents of disease that may emerge at a future time;

The UK has a comprehensive range of university, governmental and private laboratories researching into health, medical, animal, plant and immunology and diagnosis and detection systems for dangerous pathogens. The community works closely at a scientific level and is well regarded around the world. However, source of funding is wide ranging and disparate. The lack of co-ordinated research is lacking. This leads to overlap and duplication. The capacity exists within the scientist's expertise and facilities, as long as the funding can be made available. Many funders appear to be unwilling to acknowledge that running the sorts of containment facilites which are required is an expensive business, however, and seem unwilling to contribute towards the necessary overhead costs.

Further there are organizations with little experience of pathogens and genetic modification engaging in new fields with little prior experience. The ability for regulators to respond quickly to emerging infections which the UK plays a significant part in national response is questionable as illustrated with participation in global outbreak while addressing local outbreaks.

the state of biological containment facilities in the UK;

A recent survey (HSE) of the highest containment level 4 laboratories in the UK identified ten facilities. The procedures for human pathogen-related work generally are satisfactory. The issues related to animal pathogen work are more complex The majority are old or ageing.

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There has been a lack of coherent strategy for UK contained research leading to “silo” operation and varying standards and levels of investment in infrastructure or maintenance. Grant based research often covers research and some refurbishment and thus does not address basic of secure services and ongoing costs. These laboratories have been very expensive. Note US experience of ‘explosion’ of new facilities with no confirmed on going funds or ability to provide sufficient trained staff.

The number of containment laboratories in UK has grown as interest in dangerous pathogen research has grown. The skills and training has not matched this as experience staff have drifted away. Understanding of containment construction and a caucus of engineering knowledge has added to diverse engineering standards and lack of UK based specialist containment architects and engineers.

laboratory inspection regimes and the rationale and practicalities of the licensing system;

Some institutes are frequently inspected (HSE, DEFRA, EA, CPA, MHRA) and high operational standards are expected. Other laboratories, perhaps those not normally associated with biology are less scrutinized. This has resulted in severe differences in operational standards related to biosecurity. The field of biosafety/biosecurity requires broad experience current inspectors of HSE or DEFRA do not have sufficient range of experience. The context of the work is very important. Why are diagnostic standards lower than in research, it is the nature of the risk to workers, the community and the environment.

Frequent and non risk based legislation and elevated inspection expectation discredits risk based controls.

Many parts of the world have laboratory certification. This variously involves local authority or national highly commercial schemes. Varying levels of federal regulation often sets the acceptance criteria. The burden not only to administer such schemes but also prepare for certification is highly time consuming taking researchers away from project time, adds time to project start sometimes by years and thus cost and delay. The value and benefit of any licensing should be considered in relation to risk from unregulated work and advantages of bureaucratic oversight.

The process of lab notification has worked well in the UK. Licences for working with certain most dangerous agents has to date been adequate. Additional and conflicting list of agents can dilute the emphasis on “most dangerous” c.f. Schedule 5. It may seem attractive to raise standards across the board but risk based controls and restriction that is proportionate without affecting the ‘health’ of UK science and global public health.

biosafety training provision for staff working in containment facilities;

In many parts of the world biosafety and biosecurity are included in undergraduate and masters programmes in biological subjects. This is rare in the UK. Principle investigators are required to ensure that researchers are competent including in safe working. This is difficult where their own experience/training is limited. There are few courses and mostly offered in house thus perpetuate current practice.

Disiplines outside biology and health (structural and electronic engineers) are increasingly using biological agents with no basic knowledge. Essential is ensure adequate controls are maintained is the role of the “biological safety officer” also referred to as biosafety specialist. Currently there is no regulatory description of the role or knowledge require. The ISTR has been developing an accrediation programme for training providers developing foundation and professinal level courses in biosafety/biosecurity topics. Further the scheme which is ISTR

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funded develops and recognises personal development as a specialist and will increase the number and quality of providers. The quality and standing of advice to employers on the complex range of safety and regulatory matters from enforcers and specialists needs shoring up with well desigend training programmes.

This would place biosafety specialists on a par with radiological, pharmacy and medical laboratory specialists accreditation.

the maintenance and recording practices surrounding the storage and transportation of dangerous pathogens;

Historically research laboratories accumulate collections of biological agents and the accuracy of the accounting is variable. There is a valid argument to consolidate master stocks into fewer appropriate holdings where security and inventory control is maintained.

The provenance of holdings is scientifically important and proper accountability is essential for valid result reporting. The conditions under which agents are held also vary due to diverse locations and underinvestment. Appreciation of the “value” of biological material is not well understood or well resourced.

The recently revised transport of dangerous goods regulations (IATA/ADR) including pathogens has a generally high compliance where there is understanding.

measures implemented when pathogenic material cannot be accounted for;

Key to the control of the most dangerous pathogens is proper accounting and a foil to that is a loss response system. It is therefore part of good general management of dangerous pathogens that procedures to readily identify loss, detect theft or misappropriation and to intervene and thus require education as well. ISTR is well placed to assist in developing training in biosecurity risk evaluation and controls.

the role of universities in overseeing security clearance for research students working with dangerous pathogens.

The success of research is collaboration between institutes nationally and internationally, exchange of students and research to ensure best brains and the advancement of scientific knowledge. To exclude such transit would have a profound and disproportionate impact on UK science. There is no consistent UK procedure for undertaking identity and background checks. For those individual wishing to conceal affiliation this may not be adequate. Any system must be easy, swift and at modest cost. Systems operated in US (CFR 49) have been hampering programmes, added cost and considerable delay.

Recommendations There is considerable misunderstanding and use of some of the related terminology in the fields of biosafety, and biosecurity. It is essential that common internationally applied terms are used or referenced. http://en.wikipedia.org/wiki/Biosafety The ISTR would welcome funding stream to assist in developing training for undergraduate, principle investigators and specialists in biosafety, bio security and bio containment. The ISTR would welcome interaction with policy makers and participation in developing control measures with policy makers and regulators.

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The ISTR would welcome support to participate in European initiatives to ensure UK interests are properly represented cf CEN workshops require funding matching before EU funds are available. Also participants must self fund to participate in meeting held in various locations in Europe, thus travel budgeting has to be found. ISTR is a voluntary organization and has limited funds from membership fees only. ISTR suggests development of training programmes for researchers, regulators and containment construction specialists in physical and personnel security in relation to the handling and holding dangerous pathogens. January 2008

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Memorandum 5

Submission from Merial Animal Health BIOSECURITY IN UK RESEARCH LABORATORIES

Merial is pleased to have the opportunity to provide input to the Innovation Universities and Skills Select Committee review of biosecurity in UK research laboratories. 1 Merial Animal Health 1.1 Merial is a global, innovation-driven animal health company. It provides a comprehensive range of products to enhance the health and well-being of a wide range of companion and production animals. Merial researches, manufactures and markets veterinary pharmaceuticals and vaccines; many of its products are considered the gold standard in their categories. Jointly owned by the two major human pharmaceutical companies, sanofi-aventis and Merck, Merial is the largest animal health company solely dedicated to veterinary products. 1.2 In the United Kingdom, Merial employs some 200 people. Commercial activities are headquartered at Harlow, Essex, which also has responsibility for business in the Republic of Ireland. 1.3 For the past 15 years, Merial’s Industrial Operations function has operated a foot-and-mouth disease (FMD) and, more recently, a bluetongue (BTV) vaccines centre at Pirbright, Surrey. [The Pirbright site has been the centre of UK foot and mouth disease vaccine production since 1963.] This is one of the company’s 15 manufacturing plants around the world. Pirbright has two units producing active ingredients for FMD and bluetongue virus vaccines and employs over 80 people. 1.4 Merial Pirbright has three main roles:

The manufacture of FMD viral vaccines for use in Europe, North Africa, Middle East, and Asia

The manufacture of viral antigens of BTV which are made into finished vaccines at manufacturing plants in Lyon, and

Running the world’s largest FMD (vaccine) antigen bank, which enables Merial to provide a rapid and effective response when members of the bank (typically international governments) request emergency vaccines against FMD.

1.5 Throughout its tenure of the site, Merial has rebuilt, extended and modernised the facilities it acquired. The most recent major investment was £10 million in 2005 to add the second production unit, which supports the company’s commitment to BTV vaccine manufacture.

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The following points are made in response to the issues posed in the announcement of the Committee’s inquiry: 2. The current capacity for research on dangerous pathogenic material in the UK and the capability to conduct research on the causative agents of disease that may emerge at a future time. 2.1 In the main, Merial Pirbright manufactures FMD and BTV active ingredients (or antigens) for use in the production of vaccines against these devastating animal diseases. In the case of BTV, once the active ingredients are produced they are sent to Merial’s European headquarters in Lyon for the final stage of the vaccine production process. 2.2 Whilst most of Merial’s work at the Pirbright site is predominantly focused on virus and vaccine production, a small amount of research has been carried out. This work is occasionally done to monitor and improve different aspects of the manufacturing processes and is thus more in the nature of development. 3 The state of biological containment facilities in the UK. 3.1 Merial meets, and in many areas, exceeds the biosecurity requirements of the regulations and guidelines that govern its activities. The manufacturing stages that involve live virus are contained within closed steel vessels that are themselves located within biosecure rooms protected by high efficiency particulate air (HEPA) inlet and outlet filters, and pressures negative to ambient. Access to these rooms is strictly controlled and monitored. Apart from specially-packaged small samples of virus sent to other approved laboratories from time to time, nothing leaves this area without decontamination or treatment. Where small amounts of virus need to be handled, e.g. for procedures such as quality control (QC), this occurs within Class II safety cabinets within the biosecure areas of virus production and QC. 3.2 A multi-layered approach is adopted for the safe handling of live virus so that a single equipment failure or other mishap does not lead to an environmental threat. In addition, improvements are always sought. Despite Merial’s existing biosecurity arrangements satisfying all appropriate authorities, we have recently installed facilities to heat treat waste that might contain live virus as this method is considered by some authorities to have advantages compared with chemical treatment alone. 3.3 The two thorough investigations (carried out by the Health and Safety Executive - HSE – and Professor Brian Spratt) into the 2007 FMD outbreak recognised the importance of Merial’s biosecurity processes, which were not found to have been breached. Merial viewed this as an endorsement of the high standards it both aspires to and seeks to improve. [Section 6.3 of the Spratt report (Independent Review of the safety of UK facilities handling foot-and-mouth disease virus, 31 August 2007) provides an overview of biosecurity procedures at the Merial Centre.]

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4. Laboratory inspection regimes and the rationale and practicalities of the licensing system. 4.1 Merial’s activities are inspected routinely by the Veterinary Medicines Directorate with regard to Good Manufacturing Practice (GMP) and by Defra with regard to its Specified Animal Pathogens (SAPO) licences for FMD and BTV. The HSE conducted an exhaustive inspection in connection with the 2007 FMD outbreak. From time to time, the regulatory authorities of governments for whom Merial maintains antigen banks also inspect the manufacturing facilities. Merial therefore works hard to ensure that it meets not only all UK regulatory requirements, but also those of a number of governments around the world. 4.2 Regulation is the life blood of the veterinary health business; Merial welcomes the reassurance and opportunity for improvement that the UK inspection regime offers. 5. Biosafety training provision for staff working in containment facilities. 5.1 The training Merial provides employees is driven by the joint needs of biosafety, GMP and general HSE guidelines/requirements. Standard Operating Procedures (SOPs) are the bedrock of how antigen and vaccine manufacturing activities at the site are conducted. Before staff begin working with pathogenic materials it is necessary for them to complete a personalised induction and training process which involves:

a) Formal induction on all biosecurity and HSE requirements for both the Merial site and any areas of the Institute for Animal Health site that may be applicable, b) Formal briefing by the onsite HSE officer, and c) A declaration must be signed to confirm all staff have understood and agree to comply with all regulations.

5.2 Following this introductory training, employees receive bespoke training required for their specific function or departmental responsibility. This process is under the responsibility of the departmental supervisor, and operatives do not work independently until all levels of competence required have been demonstrated. Depending on the technical aspect of their work this process can take anywhere between three and nine months. 5.3 While all this is suitable for day-to-day needs, Merial also seeks to broaden the experience and knowledge of its employees in more specialist areas by the use of ad hoc training sessions. A range of training courses has been organised in recent years including use of fire extinguishers, manual handling, principles of liquid filtration, principles of sterilisation, air filter testing, basic microbiology, and process valve maintenance. Some of these courses have been organised by companies that provide equipment used at the site. 5.4 Merial is proud of its culture of continuous improvement and is investigating with a local college the provision of additional, non-vocational qualifications in management techniques and risk assessment, to further add to its staff training. Merial would welcome the availability of some form of tertiary

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education that would further help staff put their activities into the wider microbiological context with regard to the exotic pathogens handled. 6. The maintenance and recording practices surrounding the storage and transportation of dangerous pathogens. 6.1 Maintenance and record keeping with regard to FMD and BTV vaccines/virus are covered by the regulations relevant to Merial’s vaccine manufacturing activities. These are: the Specified Animal Pathogens Order 1998 (Defra Containment Level 4) and the Veterinary Medicines Regulations 2006. Records are under the final responsibility of the Quality Operation function, the head of which is the Site Biosafety Officer. Access to records is limited by a range of controls, partly physical (e.g. swipe card access to restricted areas) and partly operational (e.g. SOPs and record sheets monitored and checked by Quality Operations, key documents protected by passwords and access rights to PCs). 7. Measures implemented when pathogenic material cannot be accounted for. 7.1 The creation, movement and storage of live virus is closely monitored and recorded; the situation that such material could not be accounted for has never arisen in Merial’s experience. In the unlikely event that a known loss occurs, there are a number of SOPs in place for any given situation. These range from protocols to deal with the spillage of pathogenic materials to defined processes for closing down the factory in the event that air pressure in the restricted areas drops, for example as a result of a power failure. All such incidents must be reported to the Site Biosecurity Officer who, as a matter of course, would inform all senior personnel and relevant officials at Defra. If theft were suspected, then the police would also be informed. 7.2 The only incident that might be considered in this regard – though Merial wishes to stress that pathogenic material was not unaccounted - was the recent failure of a valve within the restricted area. Last November, Merial voluntarily shut down its vaccine production centre at Pirbright due to the discovery of a leaking valve inside the restricted area. This situation was handled by the biosecure waste treatment facilities on site and as a result no live virus was released into the environment or was unaccounted. The extensive biosecurity measures that Merial has in place meant that the virus was contained within the closed drainage system before passing to the chemical treatment facility for deactivation. 7.3 In the immediate days following this incident, Merial replaced and tested the valve in question and put in place two additional layers of biosecurity, including a second (“policeman”) valve and additional containment systems. While clearly undesirable, this unprecedented incident underlines the need to have robust biosecurity measures in place to ensure several layers of environmental protection. January 2008

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Memorandum 6

Submission from Andrew Thompson, Biological Safety Officer, Oxford University

Biosecurity in UK research laboratories The experience at Oxford University

Summary The full implementation of required construction, security, and management standards for laboratories working with micro-organisms and appropriate training and monitoring of personnel and work being undertaken at Oxford University provides the necessary level of biosafety and biosecurity to prevent inadvertent release of bioagents into the population or environment. It would be difficult for an uninformed outsider to gain access to material from University premises. Therefore the implementation of any further security measures is extremely unlikely to prevent the misuse if biological but is likely to be extremely detrimental to ongoing research. Any desire to improve the situation is better directed at identifying insiders intent upon perverting ongoing research but such an informed individual is more likely to use material obtained more easily elsewhere.

Terminology - Biosafety and biosecurity

Biosafety is concerned with protection of the human population from accidental exposure or release whereas biosecurity is concerned with protection of the human population from deliberate and unauthorised removal of bioagents (and requiring controls over and above those of biosafety) OR accidental or deliberate release of environmental (plant or animal) pathogens. Animal or plant pathogens do not pose a threat to human health and therefore do not require “biosafety” measures but they do pose an environmental hazard and require biosecurity measures to be put in place to control them. These do however, overlap with biosafety controls.

Licensing

The use of ACDP listed Hazard Group 2 and Hazard Group 3 pathogens is notified to the Health and Safety Executive prior to work commencing. However, once notified and permission granted, the University is at liberty to continue working with the pathogens throughout its premises. The University maintains a very close liaison with the HSE with regard to working with such pathogens and further controls are enacted via the notification and fee required to undertake any genetic modification on such pathogens. Between 80% and 90% of all work with HG2 and HG3 pathogens involves genetic manipulation ensuring that almost all specific work is identified to the HSE .

Work with non-modified plant and animal pathogens and administered through DEFRA requires a specific renewable license to be granted rather than simple permission to commence work being granted via a letter as happens with modified pathogens. The process is, if anything, more vigorous and more controlled than that undertaken for human (ACDP)

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pathogens and again, there is very close monitoring of specific work. NB there is crossover between human pathogens and animal pathogens with some being subject to both DEFRA and HSE controls.

Storage of pathogens

There is a significant level of inventoried long-term storage of micro-organisms at Oxford University. Such storage tends to be very controlled with accurate maintenance of records. This enables researchers to retrieve stored samples and replenish stocks in a controlled manner allowing for continuity of the research effort and provides a contingency in the event of loss of working material. Anecdotally, the issue of stocks going missing is not perceived to be a problem although it may occur. It might be possible to circumvent inventory controls in some large scale storage facilities in order to obtain material when it would otherwise not be readily available but where detected this would not automatically result in an investigation unless it was obvious that the removal of stocks was malign.

Experimental material is subject only to the control of researchers at the bench and may not involve detailed records being held beyond a simple note in an experimental notebook. Additionally, there is a degree of fluidity between stored stocks and cultured stocks with the capacity for a small frozen vial to be rapidly expanded to litres of cultured material in very short time. Individual researchers or groups controlling their own experimental material at the lab level would not therefore necessarily identify the unaccountability of material as significant as it is easy to expand from frozen stocks and experimental material may be readily lost through contamination with adventitious agents or failure to expand. This makes the keeping of detailed and accurate records of exact quantities both difficult and meaningless.

Transport of pathogens

Regarding the transportation of pathogens, in my opinion, the enforcement of existing legislation administered by ICAO represents the best method of controlling this area of vulnerability. The legislation requires samples to be correctly identified, classified, labelled, and packed appropriately. There is sufficient information and protection to enable each package to be transported securely but not identified as containing specific pathogens and once in the transportation system the package is effectively lost until it reappears at its destination. There is an inherent degree of security in this and it would require a great deal of intelligence to intercept such a parcel with any degree of effectiveness. Having stated that, an individual at any courier agency could intercept all packages marked as UN2814 or UN2900 and divert them to be trawled for likely contents but this would probably be detected fairly quickly. Again, the appropriate co-ordinating authority should discuss this with courier agencies and ICAO/IATA to address personnel security issues to ensure rapid detection in the event of such an instance.

Pathogen and laboratory biosafety

Individuals working in containment laboratories at Oxford University are offered a series of increasing levels of training starting with basic biosafety provided at the corporate level. Due to the large number of researchers, students, and visitors it is not always possible to ensure full training is received immediately as marrying training programmes with short term visits or ad hoc start dates is not possible. However, there is an expectation that supervisors will provide the necessary and specific training required to work with the particular agents being used on a research or teaching project in addition to basic training. Supervision then becomes the key factor where initial basic training has yet to be received.

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All laboratories handling micro-organisms or cell cultures at Oxford University are built or are refurbished to a minimum Containment Level 2 standard. Enactment of the construction, security, and management standards of CL2 and CL3 ensures that the possibility of accidental exposure or release is minimised to be effectively zero irrespective of the level of training and supervision being received. These measures are audited via a series of annual spot checks and full inspections in each department to ensure standards are constantly being checked and improved where necessary. Hazard Group 3 pathogens are subject to more rigorous controls, the most effective being highly restricted access, with permission to work only being given to individuals who have been suitably trained with a period of supervision prior to being allowed to work alone. With such measures in place it is unlikely that inadvertent exposure to, or escape of,dangerous pathogens will occur.

Pathogen and laboratory biosecurity

At Oxford University we have sought to enact the requirements of the Home Office standards for laboratories holding substances and pathogens listed in Schedule 5 of the Anti Terrorism Crime and Security Act. I have some issues with those requirements in that potential targets for theft become more clearly identified by storing them in specific marked areas whereas in the normal running of a lab working at Containment Level 2 or 3 samples are stored in a fashion that's familiar to each individual researcher and often subject to a coded nomenclature. This actually makes samples far more difficult to identify to anybody else and they therefore become "lost". Storing samples in specific and identified areas makes them more vulnerable to removal by the determined illicit entrant. Additionally, live cultures are more difficult to secure in such a manner as they are held in incubators that are generally easy to gain access to.

However, by enacting the physical standards and treating the curtilage of the lab and/or the building as the secure area I feel that Oxford University labs are not particularly vulnerable to theft of samples by outside agents and whether or not samples are stored more securely becomes irrelevant if the outer security is sufficient. A determined entry would still require pathogens (or substances) to be identified from the myriad others held.

Misuse of micro-organisms

Many hazardous pathogens are widely available in the environment to somebody with a little knowledge and understanding so it would be unnecessary to attempt to obtain them illicitly from a lab. Ungulate or primate carcasses discovered in central African countries represent a likely source of many pathogens suitable for use in crude bio-terrorism weapons rendering the need to obtain pathogens from Western labs unnecessary.

The main threat from research labs, in my opinion, comes from modification of micro-organisms, or access to modified micro-organisms, by an inside agent, either as part of an approved modification experiment or illicitly. It is impossible to monitor what individuals undertake as there is no accountable product, there being no finite quantities as in radiological or chemical agents, and only a small quantity need ever be removed if facilities for propagation existed elsewhere. It would also require unattainable levels of supervision and control that would completely remove the ability of researchers to work effectively to ensure unauthorised work did not occur. The reality is that in an open research environment it would be relatively easy and entirely undetectable for an individual to obtain, wild type pathogens or notified GMMOs with increased pathogenicity, or pervert their work and produce modified pathogenic agents such as ‘flu’ virus. As the work would be it would not be undertaken at the otherwise required higher level of containment and would not therefore be subject to the scrutiny of working in those conditions. The use of biological safety cabinets and simple

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good technique could ensure an operator could work safely and undetected at Containment Level 2.

This kind of activity, in my opinion, represents the biggest threat posed by research labs. If it were deemed that such a threat does exist then one means of policing it without being unduly draconian would be to implement random sampling of experimental samples, as in dope testing sportsmen and women. The Health and Safety Executive has powers of entry and could enact this. Unannounced visits could be used to take samples for verification elsewhere. However, the cost of such an exercise and likely rate of discovering suspect samples (has it ever actually happened in the UK? Unlikely) might make it unworkable but the possibility of such a check might act as a deterrent.

Control of research activity is probably better directed elsewhere. Ensuring lab personnel are bona fide, especially where the work involves using known pathogens or adding pathogenic traits such as virulence factors to higher hazard group agents would be one area but how this can be achieved without fundamentally affecting the freedom of academic research is difficult to foresee. Ensuring references are in order should be undertaken anyway as straightforward good employment practice and screening of new and existing employees on police or other security databases could be utilized (although in my civilian life, I have issues with the use of such entities). This, of course, disregards pressure being brought to bear on otherwise bona fide individuals in the form of bribery, coercion or other pressures. The opinions of principle investigators should be sought for confirmation of my statements regarding threat source and the opinions of university administrators/human resources personnel should also be sought for discussion of the feasibility of better ensuring the integrity of personnel.

Additionally, seemingly bona fide individuals could simply be gaining experience in research laboratories to be used elsewhere beyond the control of the EU. This again would require vigilance by personnel departments but balancing academic freedom with both restrictive practices might prove unworkable without being over-authoritarian and might be perceived as institutionalised discrimination. It also ignores the fact that many individuals who might represent a threat through personal ideologies were trained long before the perceived threat from bio-terrorism became more pronounced and have the skills necessary.

Anecdotally, access to former Soviet weapons facilities in the Stani republics is not well controlled, and the inventories of pathogens may well have been lost in the turmoil of the massive political upheavals of the early 1990s (see the BBC’s ”Holidays in the Danger Zone” documentary series) and this represents probably the biggest threat from lab-based pathogens and is beyond the control of the EU.

Misuse of information

Regarding censorship of novel information, it's my opinion that there is more than sufficient information already freely available for the virulence and infectivity of pathogens to be increased sufficiently for simple but effective bioagents to be produced. Censorship would be just that and entirely undesirable from a societal viewpoint.

Plant and animal pathogens

As noted, the use of such pathogens is subject to certain controls and licences for obtaining and dispersing are required but otherwise all the points applying to human pathogens will apply to these pathogens or micro-organisms. The misuse of a plant or animal pathogens could cause enormous economic impact in both developed countries and in

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developing countries relying on subsistence farming or dependent on cash crop for export farming.

Foot and mouth disease virus represents a significant economic threat in the UK and Europe although this is an entirely fabricated situation as the use of vaccines could prevent this. Only the desire of the UK to be declared virus-free (otherwise masked by the use of whole population vaccine) to protect a now small export market creates this situation. This man-made issue should be resolved elsewhere to remove an unnecessary but significant threat, FMDV being extremely transmissible.

Essential equipment and reagents

Monitoring of purchases of essential equipment and reagents to culture pathogens may be possible as this might identify possible targets for investigation. The experiences of the UN WMD Inspectors and control of supplies to Iraq may be applicable. Microbiological safety cabinets are readily available on eBay for instance so legislation would be required to control supply of such items.

January 2008

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Memorandum 7

Submission from Robert W Osborne

Biosecurity in UK Research Laboratories

1. Summary: This paper presents a University Biological Safety Adviser’s view to 6 of the

7 criteria laid out for the above Inquiry. The precise scope of the Inquiry is open to differing

interpretations; the writer has attempted to define his contribution to specific limits. In the

author’s restricted view, the UK has many quality facilities at medium to high containment

status but there may be a need for further infrastructure at the highest level. The standards

and requirements dictated by legislation and formal guidance are world class but there is

room for improvement in various factors of the management and oversight of medium to high

hazard level activities. Some suggestions and recommendations are highlighted.

2. Introduction: This paper is submitted to the Innovation, Universities and Skills

Committee of the Parliament of the United Kingdom for consideration in their Inquiry entitled –

Biosecurity in UK Research Laboratories, published 6/12/07. It is restricted in its views as the

author, although respected in his field, can only have limited information consequential to his

role within two specific organisations. Compared to the regulators his understanding

nationally and internationally can likewise only be limited, based on visits when opportune and

professional conferences etc. However, many of the comments are shared with peer

professionals.

[2/1] Contributor’s background:

Current role: Biological Safety Adviser [BSA] University of Glasgow [UG] UK

Remit: To advise on the handling of pathogens and genetically modified organisms [GMOs]

by the University community ensuring control of the associated hazards/risks and preventing

harm to persons the institutions neighbours and the broader environment.

Expertise: A brief resume is given as an Appendix.

[2/2] Representation/the University environment: This submission is primarily based on the

writer’s engagement in a University environment. UK Universities have a very open culture

albeit the last decade has seen the imposition of greater security driven by the need to

counter terrorism. In addition, University management of all activities is extensively delegated

to Departments/Divisions and in turn to leading academics - scientists, Principal Investigators

[PIs] - as managers. The latter may cover large but often small groups and thus may not have

a corporate overview. Typically Universities operate within the legislative framework of both

European Directives, national [GB] and delegated and international regulation, [details will not

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be presented here]. In the biological context, delegation to local parliaments adds some

additional burden.

University Biological Safety Advisers and Officers: The role of BSAs is outlined in the remit

above. BSAs do not have managerial authority operating by education and persuasion. If

necessary, to take corrective action resort is made to line management structures and/or the

regulators; professionalism would preclude inaction. In contrast, University Biological Safety

Officers [BSOs] have an authoritative but directed role that will vary with institution and remit.

When addressing genetic modification responsibilities, typical BSO duties are laid out in the

formal Compendium of Guidance that accompanies legislation 1.

[2/3] Clarification: The following limiting factors for this contribution are brought to the

Committee’s attention.

[i] Biosecurity: This term has more than one meaning depending on context. Firstly, as a

means of containing an infectious agent or secondly to preclude removal of a biohazardous

agent by those with nefarious intent. The two control regimes are intimately related but not

identical; this contribution focuses on the first definition.

[ii] Dangerous Pathogenic Material [DPM]: DPM falls into various hazard classification

schemes. This text assumes that it will [/may] contain agents of [human] hazard groups [HGs]

-3 and -4 and selected microbes of HG-2, [ACDP]. For animal pathogens, infectious agents

will be exotic and cause serious economic harm [compare human infection], animal HGs -3

and -4. Containment Levels [CL] discussed correlate to equivalent HGs.

[iii] The Competent authority [CA]: The several regulatory bodies that specifically overview

this University’s activities with DPMs include the Health and Safety Executive [HSE] [human

pathogens / all GMOs], the Scottish Executive Environment and Rural Affairs

Department/Department for Environment, Food and Rural Affairs [SEERAD/DEFRA] [animal

pathogens] and the Home Office [anti-terrorism]. Such bodies may / do act collaboratively. In

this paper, the term CA will apply to any of the regulatory bodies.

[iv] The Callahan Report 2: Whilst inevitably there are shortcomings, this is an excellent

document. It re-affirms the responsibilities of senior management towards organisational

operations including biosecurity, demonstration of leadership and establishment of a strong

safety culture. Further, it recommends many approaches that the writer and colleagues have

been promoting to the SEERAD/DEFRA inspectorate for years. The principal shortcoming is

the proposal for full cost recovery; that is not seen worldwide and could further drive the

science outside of the UK.

SEERAD have not had a strong inspectional culture. This University’s experience has shown

a lack of continuity and a continuing evolution of interpretation of its own Guidance. That

Guidance lacks the application of the risk assessment process adopted for human pathogens,

at times it is excessively prescriptive and is difficult to “sell” and justify. Further, in parts it

goes beyond ACDP standards. However, the regulator has been helpful and supportive with

licensing and applications. The Reports recommendation for a single inspectional regime

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pursuing common standards for human/animal DPM is to be applauded. However, as a

single, distant regulator, HSE will need to extensively further develop its understanding of the

best of the veterinary culture.

3. The Committee’s Selected criteria

[3/1] The capacity to conduct research on DPM:- Currently the most hazardous materials

[HG-4] are not handled outside of specialist research institutions, [e.g. the Porton complex,

NIBSC, MRC-Mill Hill] none of which are in Scotland. Following the escapes of smallpox in

the 1970s, no UK Universities have suitable facilities [a confidential source indicates one

University is currently proposing such a development]. It is thought that picture is common to

Europe. In contrast, there is emergence of suitable facilities attached to American

Universities, suggesting the UK may be disadvantaged. If UK Universities are to be licensed

to work at CL-4 a significant but achievable improvement of biosafety culture and overall

management will be fundamental. It is suggested if there is an identified need for such

facilities their construction should be limited to a central strategic resource accessible to

University projects with suitable support for staff training etc. Location will be a major public

issue [e.g. USA].

For CL-3 activities the UK is well served. Many facilities exist in UK universities. Within this

University, they have been built on a piece-meal project/grant approval basis rather than as a

strategic investment. Concomitantly, typically they are small, disparate and have been

developed with extensive inefficiencies emanating from a poor understanding of the

requirements by design and construction teams, despite the writer’s deliberations, with much

“reinvention of the wheel”. Whilst meeting the required standards after extensive

development, most within this University are currently underused or non-operational due to

funding changes but could be readily returned to active status. The described scenario is not

atypical of peer Universities.

Facilities at CL-2 are also readily available. Most but not all of this institution’s biological

laboratories will be suitable for handling HG-2 agents/GMOs. Rooms for small animal

experimentation meet CL-2 standard as a minimum; limited facilities for CL-3 studies can be

returned to front-line use. There are no facilities for large animal experimentation at CL-3/4

but the organisation has links to the Moredun Research Institute.

This University cannot match the capacities of large peer organisations in the “golden

triangle”. Staffing capacity for many of the CL-3 facilities in UG would need some minor

investment, particularly refresher training.

[3/2] The state of Biological Containment facilities:- The standard demanded by formal

legislation/guidance at the various levels is as good as any in the advanced world with the UK

often leading the field. Within this University, current facilities range from excellent to poor.

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This institution has shown progressive development with much new build or refurbishment;

the latter has seen / is seeing upgrading from CL-1/2 to CL-2 as a minimum in most cases.

Subject to 3/1 above, all CL-3 facilities are good. Both CL-2/3 meet and exceed legal

requirements, however, they do not equate to the best in private industry. Limited resources

induce a need to share facilities/equipment with the inherent risk of compromising

containment; that too is not unique to this organisation.

[3/3] Laboratory Inspection regimes, rationale/practicalities of licensing:

[i] General comments:- The regime of a formal permissioning/licensing procedure authorised

by an external independent professional CA is excellent in principle. All interested parties,

active stakeholders, funding bodies, the general public, need to be confident that high

standards driven by diligent inspection within a precautionary approach are extant when

handling agents which could have a profound effect on populations, the ecological

environment or economically. The carrot and stick approach supported by an appeal

procedure for the scientific community remains fundamentally important. High hazard

activities – work with agents of HG-3 or -4 – tend to be extremely well managed but in certain

but not all disciplines, CL-2 activities, tend to have a more relaxed culture. For the latter, the

writer encourages a more disciplined approach backed up by CA action.

[ii] CL-4 facilities:- The current regime operated by the CA whereby formal approval and

authorisation following intense scrutiny precedes any handling of DPM is commended.

[iii] CL-3 facilities:- In the writer’s experience, commencement of activities at CL-3 with

human pathogens may precede complete CA inspection and scrutiny albeit that review will

follow soon thereafter. In contrast to HSE, SEERAD/DEFRA pre-inspect prior to licensing and

permissioning of “wet” work. The current HSE approach could allow poor-practice in the short

term and that is insufficiently stringent, the author recommends the same regime as applied to

HG-4 activities. A relatively recent change in legislation requires HG-3 and certain HG-2

activities to be formally notified to HSE. The regime is a little more stringent with GMOs.

[iv] CL-2 facilities:- Apart from certain Notifications to HSE, in the writer’s experience, there is

no pre-activity inspection and review when handling pathogens. There is more stringency in

the regime with GMOs whilst SEERAD/DEFRA do pre inspect before licensing “wet” work.

[v] Final points:- The SEERAD/DEFRA approach has been found wanting at the Pirbright

complex. The highest standards would have been expected from sites subject to multiple

regulatory reviews. It remains unclear why matters of evident concern were not

detected/rectified by/communicated between the regulatory bodies; further could this

shortcoming be replicated? Whilst considerable effort is made to inspect experiences of

SEERAD/DEFRA inspections indicates at times a lack of continuity and experience.

Overall, the writer would like to see more frequent and penetrative inspection and auditing of

facilities and activities particularly for higher hazard status projects. That does not need to be

externally driven but could/should be effected ‘in-house’ regularly and subsequently subject to

CA validation. Although intimated, that is not definitively laid out in legislation and guidance,

or enforced during local inspection/auditing visitations [HSE]. Unfortunately, resources and

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expertise to permit systematic and detailed inspection/auditing are often insufficient. In

addition, more frequent reviews by external bodies to CL-3 facilities, subject to adequate

safeguards, are to be encouraged.

[3/4] Biosafety training provision:- Two inter-related separate issues need to be considered –

biosafety management – facilities, staff, procedures - and practitioner attributes – skills and

practices. At CL-4, the necessary knowledge, skills and expertise can only be acquired in the

few specialist facilities. The writer is aware of one week-long training initiative at Winnipeg,

Canada which takes non-resident trainees, there is likely to be something similar in

Australasia.

At the lower levels, CL-3 and CL-2, there are limited courses. The most well-known and

successful biosafety management course has progressively evolved and is run by MRC,

[suggest the Committee approaches Drs Jackett or Mitchell via MRC HQ], designed for

managers and practitioners within departments and is open to non MRC interested parties,

the writer having contributed peripherally. However, it is understood it is likely to cease or be

franchised elsewhere shortly. At the practitioner level MRC did run a series of workshop

courses for their AIDS Directed Programme [ADP] in the late 1980s, the writer is not aware if

these have been resurrected in any form. Commercial organisations provide some specific

short courses, e.g. Transport of biological materials.

The Institute of Safety in Technology and Research [ISTR] and MRC are preparing a

curriculum for biosafety managers/practitioners at intermediate and senior professional levels,

again the writer having contributed peripherally. The Committee is further directed to Dr.

Jackett and Mrs Sheeley, [Mrs Sheeley will be contributing to the Committee]. These two

initiatives deserve active support and should be firmly encouraged and adequately funded as

a national resource.

Specific practitioner courses are limited, most training will be acquired ‘on the job’ from

shadowing experienced staff or after previous roles including Ph-D and Post-Doctoral training

and supplementary induction. There are occasional issues of insufficient supervision by

Principal Investigators [PIs]. Similarly, a major concern of the writer is the use of GM

techniques as a tool in a wide variety of biological and non-biological sciences by individuals

who sometimes show insufficient understanding of the biosafety/containment requirements for

handling infectious agents, albeit such work is generally of low hazard status. These

concerns are local management issues but again are not unique to this University.

The writer remains most concerned that UK Universities did not actively contribute to the

recent International Biosafety and Biosecurity Standard Development initiative. At that time,

funds were not available locally albeit several approaches were taken. The writer was given

short shrift on approaching the University Safety and Health Association [USHA]; he was

unable to attend any of the meetings and the University sector was not appropriately

represented by others. Universities are expected to and do operate in a global context, this

non-participation [disinterest?] was a major faux-pas.

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[3/5] Inventories of stored agents and transportation of DPM: - Quality science demands

retention and access to valuable DPM and the maintenance of detailed inventories. The

security and professionalism of such databases is being instituted/improved driven by CA

inspection and the application of electronic formats. Historically, institutions such as

Universities, have not maintained corporate permissioning regimes for acquisition/supply of

DPM. What is in place has been driven by individual scientists/managers and agent

containment requirements. Typically, for higher hazard activities such inventories are good

but there remains much wanting particularly at the lower hazard levels. Legislation [e.g.

COSHH] makes stipulations and is assisting the ongoing changes of the culture with the

introduction of approval procedures now becoming the norm. These comments do not apply

for HG-4 activities, the writer does not have recent experience.

National and international transportation of DPM between institutions tends to be via

competent couriers though not guaranteed. Within an institution, mechanisms are continually

improving to meet a professional standard although an ongoing continuous evolution requiring

routine monitoring locally and by the CAs.

[3/6] Loss of pathogenic material:- Regular checks of DPM will not be performed unless there

are good reasons [scientific need, legislation]. Losses also occur due to technical difficulties

and theft, the latter might not be immediately realised. The actions that follow losses will be

dictated by individuals, groups and regulation. Corporate responses will be at a later stage,

usually in mitigation.

[3/7] Overseeing security clearance for research students:- This section is more competently

considered by colleagues, the writer will comment very briefly at this stage. Locally Policy has

been developed with Human Resources dictated by Home Office guidance.

[4] Summary of recommendations:

[i] If there is an identified need for further CL-4 facilities, it is suggested their construction

should be limited to a central strategic resource accessible to University projects with suitable

support for staff training etc.

[ii] Encouragement of a more disciplined culture for certain disciplines operating at CL-2,

backed up by CA action.

[iii] A common permissioning regime be applied for HG-3 and -4 activities based on current

practice for the latter.

[iv] More frequent and penetrative inspection and auditing is applied (a) of facilities and

activities in general and (b) by external bodies to CL-3 facilities, subject to adequate

safeguards.

[v] Training initiatives led by MRC and ISTR deserve active support and should be firmly

encouraged and adequately funded as a national resource.

January 2008

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Footnote: The writer had approached academic colleagues for contributions but it is thought

that the short timescale following awareness of this initiative has not enabled such

submissions.

R. Osborne

[BSc, MSc, Dip2-OSH, CMIOSH, MISTR] [University Biological Safety Adviser] [25/01/08]

[SEPS, Pearce Lodge, University of Glasgow, Glasgow, G12-8QQ, Scotland, UK]

References:- 1 = Compendium of Guidance, SACGM, 2007 2 = A Review of the Regulatory Framework for Handling Animal Pathogens. Report of a

Committee chaired by Sir Bill Callaghan, Defra Publications, 2008

Appendix:

Role of a University Biological Safety Adviser: The remit described at section [2/1] translates

to taking a leading role in educating, [advising and directing] or assisting, researchers and

managers of relevant legislation, in hazard and risk recognition, risk assessment and

management and practical procedures for handling human, animal, plant or microbial

organisms or materials, their pathogens and GMOs.

Background experience: 26 years of laboratory based investigations of the diagnosis, biology,

vaccinology and epidemiology, including vector borne transmission, of certain veterinary

viruses of major economic consequence [1970-1986; Institute of Animal Health-Pirbright] and

human / feline immunodeficiency viruses including biosafety management of high

containment facilities [1987-1997; UG]. 12 years overseeing corporate biosafety

management, as a BSA [1995 – date; UG].

Professional activities: Member of HSE’s Scientific Advisory Committee for Genetic

Modification [Contained-Use] [SACGM]. Member of the following professional bodies:

Society for General Microbiology [SGM]; European Biosafety Association [EBSA] [and former

member of the Conference Committee]; Chartered Member of the Institute of Occupational

Safety and Health [CMIOSH].

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Memorandum 8

Submission from Prospect

Biosecurity in UK Research Laboratories

Introduction 1. Prospect is a trade union representing 102,000 scientific, technical, managerial and specialist staff in the Civil Service and related bodies and major companies. Our members include 4,000 scientific and technical staff in five research councils and 68,000 scientists, engineers and technologists overall. Many of our members work in sectors where biosecurity is a key part of their professional lives, for example in defence and animal research. This response is informed by the expertise of these members. The current capacity for research on dangerous pathogenic material in the UK and the capability to conduct research on the causative agents of disease that may emerge at a future time 2. Prospect members work with micro-organisms up to hazard group 4 (causing fatal and untreatable diseases). There are few such laboratories in the UK, probably amounting to less than 10 overall, but these include facilities at the Health Protection Agency and a couple of other Research Council Institutes. Most large universities with established medical microbiology departments will have a level 3 facility i.e. working with micro-organisms that cause fatal diseases in healthy hosts but with treatment available. Veterinary disease institutes, such as the Veterinary Laboratories Agency at Weybridge, also work to level 3 as will institutes involved in work on TB or HIV. The state of biological containment facilities in the uk 3. Public sector facilities include Porton Down, which are world-class. All facilities need to be of equal or greater standards than legislative requirements. Clearly there has been much publicity over the state of containment facilities at Pirbright. Laboratory inspection regimes and the rationale and practicalities of the licensing system 4. Prospect would expect facilities to be regularly inspected at senior corporate and local levels. It is important that inspection procedures do not become too regimented, as this can cause things to be missed. HSE also regularly inspects high containment facilities, though clearly the regulatory and inspection regimes are likely to change in the light of the recommendations of the Callaghan Review. Prospect would recognise the benefits of both a single inspection/enforcement authority for animal and human pathogens and the

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importance of avoiding potential conflicts of interest. With HSE taking on this responsibility we will wish to have confidence that its operational staff implement HSE instructions on making and maintaining contact with employee representatives. Biosafety training provision for staff working in containment facilities 5. It is of utmost importance that staff working with high containment facilities receive appropriate training. For example, the Defence Scientific and Technical Laboratory (DSTL) provides a hierarchy of training. These start with taught courses at level 2. Staff are then required to work at level 2 and receive hands on training for more than a year and to serve a probationary period before progressing to level 3. For level 4 the requirement is to work at level 3 and receive hands on training for more than a year as well as serving a probationary period and undertaking high level consultation with safety experts. Measures implemented when pathogenic material cannot be accounted for 6. As staff are security cleared and high containment facilities are access controlled, this is not perceived as a major problem. Records are kept as a matter of routine, though these may be of limited value due to the ease of generating more material. It is impossible to guarantee that records will never be falsified. January 2008

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Memorandum 9

Submission from the Wellcome Trust

BIOSECURITY IN UK RESEARCH LABORATORIES Introduction

The Wellcome Trust is grateful for the opportunity to respond to the Innovation, Universities and Skills Committee’s inquiry on biosecurity in UK research laboratories.

The Wellcome Trust is the largest charity in the UK. It funds innovative biomedical

research, in the UK and internationally, spending around £600 million each year to support the brightest scientists with the best ideas. The Wellcome Trust supports public debate about biomedical research and its impact on health and wellbeing.

Through our grant funding schemes, the Wellcome Trust supports a broad portfolio

of research in immunology and infectious diseases of humans and animals – providing research and career support for outstanding scientists in both the UK and in developing countries. We also support the development of key resources for the research community – for example, we have funded the Health Protection Agency’s National Collection of Pathogenic Viruses since its establishment in 1999.

In addition, we fund the Wellcome Trust Sanger Institute in Hinxton,

Cambridgeshire – one of the world’s leading genomics research centres. The Sanger Institute has sequenced the genomes of many pathogenic organisms of medical significance – including the causative agents of tuberculosis, malaria, typhoid fever and plague. It has a number of major ongoing research programmes that aim to further understanding of the genetic basis of pathogenicity, interactions with host immune systems, and anti-microbial drug resistance in a range of human and animal pathogens.

This response reflects the joint views of the Wellcome Trust and the Sanger

Institute, and was informed by limited additional consultation with members of our research community.

Balancing benefits and risks of research

We recognise that it is absolutely vital that research involving hazardous pathogens and toxins is conducted in appropriately equipped and adequately resourced facilities, with robust safety and security procedures in place that minimise risks of harm to laboratory workers, the wider public, and the environment.

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It must be emphasised, however, that research involving these agents will be absolutely crucial to combat the threat of both existing and newly-emerging infectious diseases. The UK has considerable research strength in this area, and it is vital that the resources and conditions are in place to enable responsibly conducted research to flourish. It is important therefore that the regulatory framework achieves a suitable balance – providing appropriate safeguards whilst not unduly restricting this essential research.

All research institutions funded by the Wellcome Trust are required, as a condition

of grant funding, to comply with the requirements of all relevant regulatory authorities in taking forward the funded research. The Sanger Institute has appropriate processes in place to ensure that it complies with requirements of all regulatory authorities in relation to its work involving pathogenic organisms and materials derived from them. These processes are reviewed regularly.

Responsibilities of research institutions

We accept that it is primarily the responsibility of research institutions that work with hazardous biological agents to ensure that this research is conducted safely, and that all associated risks are mitigated in line with regulatory provisions and guidelines in this area. It is crucial that institutions ensure that their staff members are fully aware of all relevant regulatory requirements to address all risks of harm associated with their research. In addition, researchers, students and technicians working with hazardous agents must receive tailored training before they begin this work and refreshers at regular intervals thereafter, including updates on regulatory developments.

The role of dedicated Biological Safety Officers (BSOs) in institutions is vital in this

regard. Their responsibilities ought to include actively tracking regulatory developments, advising their institution’s senior management team on their implications, and liaising with regulatory authorities on an ongoing basis. In addition, they need to take the lead in raising awareness of regulatory requirements among staff and in ensuring the delivery of effective training provisions.

At the Sanger Institute, for example, a dedicated BSO operates within the Health &

Safety Team. The Institute supports fully the vital importance of this role in helping to ensure that regulatory compliance and best practice in managing biological safety in research are achieved. A key contribution has been the development of a regime of training for researchers operating in Containment Level 2 and Containment Level 3 facilities, both ab initio and refresher to maintain competences.

In order to ensure best practice across the sector, it would be valuable to develop a

common understanding of what the role of the BSO should involve. This would include defining professional competence requirements and providing common, independently accredited training modules addressing biosecurity issues within a dedicated syllabus of general biological safety training, which institutions could apply in a flexible manner to their circumstances.

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To help achieve this, there might be scope to formalise the roles and responsibilities of dedicated institutional BSOs within the context of existing regulatory instruments – particularly the Control of Substances Hazardous to Health Regulations (COSHH) and the Genetically Modified Organisms (Contained Use) Regulations. We suggest that this could be considered in implementing the recommendations of the Callaghan review, as part of a new single regulatory framework for work on human and animal pathogens.

We are aware that there are concerns relating to sustainability of research on

hazardous biological agents – both in terms of the provision of adequate funding for research facilities equipped to undertake work on these agents, and also in terms of the retention of technical expertise in research institutions. It is vital that the Government ensures that sufficient long-term funding is provided to key national institutions. This must enable them to maintain, and upgrade as required, the facilities required to conduct vital research involving hazardous agents in a secure environment, and to retain core technical staff. It is also important that institutions themselves develop appropriate succession planning arrangements to ensure retention of skills within their staff.

Responsibilities of regulators

Whilst the primary responsibility for ensuring safety and security must rest with institutions, we believe that relevant regulatory agencies also have an obligation to ensure that they coordinate effectively in developing and implementing regulatory processes. In particular, they should seek to minimise duplication and overlap as far as is possible. Regulators should also ensure that they communicate requirements effectively through provision of accessible and practical guidance for research institutions, and through regular engagement activities with designated points of contact therein.

We would note that there is a considerable amount of existing regulation relating to

biosecurity. The overall picture is quite complex, with several different Government departments and agencies responsible for different elements of the overall framework. These include the Health and Safety Executive, the Home Office (through the Anti-Terrorism Crime and Security Act 2001); BERR (through Export Control regulations); the Foreign and Commonwealth Office (via the Academic Technology Approval Scheme); the Department of Health and Defra.

It is our view that these existing regulatory instruments provide a highly rigorous

framework to protect biosecurity of research conducted in UK laboratories. We would suggest that any gaps, deficiencies or inconsistencies should be addressed through the further development or enhanced implementation of these existing tools, rather than through the development of new regulations – which we feel could unnecessarily raise the existing regulatory burden on the research community. We would, however, welcome any improvement and simplification of the existing framework consistent with the principles of the Hampton review.

To this end, we welcome the recommendations of the recent Callaghan review to

create a single regulatory framework to govern work with human and animal

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pathogens, the implementation of which should streamline and enhance existing processes. It will be important that there is adequate consultation with the research community as this process moves forward. We urge regulators, particularly those identified in paragraph 16 above, to seek further opportunities both to coordinate their procedures and to undertake joint communication activities which clarify how different elements of the regulatory framework fit together.

For instance, a single focal point of contact between a research institution and the

cohort of regulators would be helpful. This function could sit within the Health and Safety Executive, and could operate regionally so that it acts as a conduit between research institutions and the relevant authorities responsible for regulatory oversight in that location. At the local level, such a system would help to build integrated arrangements between institutions and the various regulators. Strategically, at the national level, it could assist the various regulators to have a clearer picture of, and to develop enhanced responses to, biosecurity risks.

Finally, we would like to draw the Committee’s attention to the recent European

Commission Green Paper on Biopreparedness, which was published in July 2007. Whilst broadly supportive of parts of this document, we were concerned that some of the options under consideration might seek to duplicate or replace existing national processes at UK level and increase the regulatory burden on researchers. Research Councils UK and the Wellcome Trust submitted a joint response to this consultation in which we outlined these concerns. This response is appended as Annex A.

January 2008

ANNEX A European Commission – Green Paper on Bio-preparedness Joint response by Research Councils UK and the Wellcome Trust (Sept 2007) Introduction Research Councils UK and the Wellcome Trust are pleased to have the chance to respond to the European Commission on the policy options set out in its Green Paper on Bio-preparedness. 1. Research Councils UK (RCUK) is a strategic partnership that champions the

research supported by the seven UK Research Councils. The Research Councils are independent non-departmental public bodies, funded by the UK Government’s Science Budget through the Department for Innovation, Universities and Skills. They are incorporated by Royal Charter and together manage a research budget of over £2.8 billion (€4 billion) a year. Through RCUK, the Research Councils work

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together to champion the research, training and innovation they support. See: www.rcuk.ac.uk.

2. The Wellcome Trust is the largest charity in the UK. It funds innovative

biomedical research, in the UK and internationally, spending around £500 million (€715 million) each year to support the brightest scientists with the best ideas. The Wellcome Trust supports public debate about biomedical research and its impact on health and wellbeing. See: www.wellcome.ac.uk.

3. Over the last few years, our organisations have contributed actively to policy

discussions at UK and international level aimed at addressing risks that life sciences research could be misused for terrorist purposes. In September 2005, the Biotechnology and Biological Sciences Research Council (BBSRC), the Medical Research Council (MRC) and the Wellcome Trust published a joint policy statement on managing risks of misuse associated with grant funding activities. This statement identifies a series of agreed actions that the three organisations have implemented to raise awareness and to help ensure that any risks of misuse associated with research proposals are considered at the grant application stage. The full statement is appended as Annex B.

4. The Research Councils and the Wellcome Trust support a broad portfolio of

research aimed at enhancing our understanding of infectious diseases in humans and animals, and at developing improved approaches for their control. In particular:

• the BBSRC sponsors the Institute for Animal Health (IAH), which provides

world reference laboratories for the United Nations Food and Agriculture Organisation on foot-and-mouth disease, rinderpest and peste des petits ruminants, and a regional reference laboratory service to the World Organisation for Animal Health for several other diseases – including bluetongue and Marek’s disease.

• the MRC funds and sponsors work on human pathogens – for instance, the

MRC’s National Institute for Medical Research (NIMR) conducts research on influenza and through the World Health Organization (WHO), characterises newly emergent influenza viruses from across the world. It helped to detect the avian H5N1 and H9N2 strains that caused human outbreaks in 1997, 1999 and from 2003 to the present day.

• the Wellcome Trust funds basic and clinical research in the fields of infection

and immunity, pathogen and host genetics, and tropical medicine – both in the UK and internationally. It supports the Wellcome Trust Sanger Institute, a world-leading genomics research centre, which has sequenced the genomes of many key human and animal pathogens – including the agents that cause tuberculosis, typhoid and plague.

5. Our response begins with some general comments on the Green Paper. We then

provide our views in response to the specific questions highlighted in the consultation document. We have restricted our comments to those questions which fall within our remit as research funders.

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GENERAL COMMENTS ON THE GREEN PAPER 6. RCUK and the Wellcome Trust are supportive of the stated aim of the Green

Paper to stimulate debate within and between EU member states on how to reduce biological risks. We also agree with the statement in the Green Paper that whilst the risk of bioterrorist attacks has been statistically low, the consequences of any such incidents could be devastating. Public concern regarding the risk of such attacks is also significant. We recognise, therefore, that it is crucial that appropriate mechanisms exist at national and international levels to address risks that biological research could be misused for terrorist or other harmful purposes.

7. It is equally important to recognise, however, that research involving hazardous

biological agents will be essential to address the diseases that these agents cause and to enhance our ability to respond to bioterrorist threats. Indeed, such research should be seen as an integral component of overall “bio-preparedness” efforts. It is vital, therefore, that responsibly-conducted research of this type is not unduly restricted.

8. We would also emphasise that international collaboration, mobility of scientists

across borders and open exchange of research results through peer-reviewed publication are essential to the international research endeavour and scientific progress. We would be extremely concerned by the addition of any new regulatory measures which might unnecessarily limit these processes.

9. We agree fully with the statement in the Green Paper that the measures taken

should be proportionate in terms of the threat they seek to minimise and to respond to. We support the view that approaches such as awareness-raising and supportive financial programmes should be used in the first instance rather than new legislation. We also agree that if additional measures are considered appropriate, they should build on existing regulatory processes and use existing structures and expert groups wherever possible.

10. Further to this point, we consider that the UK already has a regulatory framework

in place to ensure that biological research involving hazardous agents is conducted safely and securely. Whilst any scope to further strengthen these existing instruments should be explored in a manner proportionate to the threat faced, we do not think there is a need for any additional formal regulatory mechanisms in the UK at this stage.

11. Within this existing regulatory framework, we do, however, support the need for

the scientific community to strengthen mechanisms of self-regulation to ensure that risks that research could be misused for harmful purposes are considered and addressed in an appropriate manner. It is important to acknowledge that issues of ‘dual-use’ may arise both in cases where research directly involves the use of hazardous agents and in cases where it does not. Our organisations believe that processes based on responsible self-regulation by the scientific community will ultimately provide the most sensitive and effective way of addressing these issues.

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12. We recognise that awareness-raising is crucial in underpinning effective self-regulation and we strongly support the Green Paper in promoting dialogue on European-level actions that could enhance awareness-raising efforts across EU member states.

13. Finally, we also support the Green Paper in promoting discussion on how public

and animal health surveillance and response mechanisms can be strengthened and coordinated more effectively across member states in order to enhance our ability to respond to disease threats, whether these are naturally occurring or the result of a terrorist attack. However, these issues fall outside our remits as research funders, and we will therefore leave detailed comment on the role of different national and EU-level bodies to organisations more closely involved in this area.

RESPONSES TO CONSULTATION QUESTIONS Q1 Is a comprehensive approach to European biological risk reduction and preparedness required? Q2 How could the EU bridge the perceived gap between non-proliferation and international cooperation in a dual-use field such as biology? 14. We consider that the response to biological risk reduction needs to be coordinated

globally. We are unsure how some of the proposals set out in the Green Paper would fit within existing international processes – such as the Biological and Toxin Weapons Convention and the work of the WHO and Organisation for Economic Co-operation and Development (OECD). It is also unclear how some of the proposals would relate to ongoing European activities – such as the work of the European Biosafety Association (EBSA)1. We would emphasise that it is essential that the need for any further European-level activities is considered based on a clear analysis of previous and ongoing work, and in the context of a wider global framework.

15. We agree, however, that there could be significant benefit in the development of

EU-level actions to promote cooperation and communication between member states – particularly in terms of sharing regulatory good practice and in developing training and awareness-raising activities. This could also facilitate coordinated European input into global-level discussions. It is essential, however, that any activities avoid the unnecessary creation of additional regulatory burden, where existing national processes are already fit-for-purpose.

Q5 Would peer evaluation methods be useful in addressing existing shortcomings across Europe?

16. We consider that the assessment of biosafety and biosecurity issues associated

with individual research institutions and research programmes should be regulated at national level by member states. We agree, however, that there could be value in European-level processes, involving appropriate expert “peers”, that periodically review overarching national regulatory frameworks and share best practice amongst member states. This would be provided such systems could be

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implemented without adding to the regulatory burden for states where existing processes are sufficiently robust.

Q6 What role should be played by the private sector in a public-private partnership?

17. We agree strongly that the private sector has a key role to play in discussions on reduction of biorisks. In particular, there will be considerable benefits in promoting dialogue and information sharing between public and private sector research organisations regarding best practice on biosafety and biosecurity concerns. There are already effective models for promoting networking between public and private sector on these issues – including the European Biosafety Association.

Q7 Should an EBN (European Bio-Network) be created in order to support the implementation of the results of this consultation? 18. The case for establishing the proposed “European Bio-Network” should be

explored in light of existing advisory structures and ongoing work at national, European and global level. Clearly, the role and make-up of any such body would depend on the nature of the actions required at EU-level, which we expect will be informed by the outcomes of the present consultation. If plans to establish an EBN do proceed, it will be crucial that it seeks to draw on the experiences of other similar bodies – such as the US National Science Advisory Board on Biosecurity and the WHO Scientific Working Group on Life Science Research and Global Health Security.

Q9 Should awareness among stakeholders be increased about possible risks related to biological research and commercial activities and about the rules they have to comply with? If so, how? Q10 Do you experience difficulties in following new adjustments of rules and restrictions? If so, which ones? 19. We agree that existing regulatory frameworks in this area are complex. We

support the need for improved awareness-raising both on risks associated with biological research and on regulatory requirements, and agree that there could be an important role for EU-level actions to assist member states in strengthening activities at national level.

20. In the research institutes and units operated by the UK Research Councils,

dedicated Biological Safety Officers (BSOs) have a responsibility for tracking regulatory developments; advising their senior management on their implementation; and raising awareness of these requirements more broadly within their institutions. We suggest that there might be scope to establish a common understanding at European level for the role of BSOs in research institutions and for EU-level work to support member states in training these individuals.

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21. Since 1998, the MRC has, in collaboration with the University of Sussex, provided its own course to train BSOs to a common standard of competence. In addition to training BSOs at MRC Units, this course has been provided to a wide range of delegates from universities and private sector research institutions in the UK and from overseas. As far as we are aware, this is one of few training courses of this type and might provide a useful model to assist in the identification of common training requirements. We would be happy to provide further information on this course if this would be helpful.

Q11 Should common minimum bio-standards and the exchange of best practices be developed at the EU level?

22. We believe that the EU could play an important role in promoting the exchange of regulatory good practice in biosafety and biosecurity between member states. However, it is crucial that any such work uses existing frameworks and does not add unnecessarily to the regulatory burden in member states (such as the UK) with fit-for-purpose existing systems. It is also vital that all member states are encouraged to adhere to best practice rather than simply to minimal standards, and that individual states have the freedom to “gold plate” any EU requirements as they judge appropriate.

Q12 Would you be interested in developing rules for national certification and registering of facilities and researchers which could facilitate European and international exchange of samples and expertise?

23. We expect that responsibility for the development of any such rules in the UK would fall to the UK Government and relevant regulatory authorities. The Research Councils and the Wellcome Trust would be happy to feed into these discussions and input scientific expertise as required. If a system could be developed which could facilitate the exchange of samples and expertise at EU and international level without adding unduly to the existing regulatory burden in the UK, then we would of course be supportive of this.

Q13 What should be included in national registers – agents, facilities, activities – ensuring that there are no loopholes and that the security and oversight requirements avoid damaging health, safety, research or industrial activities?

24. We would note that such registers are already in place in the UK as the result of existing regulatory requirements.

Q14 Should a limited number of bio-researchers possess security clearance? If so, on what basis would you identify them?

25. We agree that appropriate levels of security screening for researchers working with potentially hazardous agents should be undertaken. However, we do not feel that the number of researchers possessing “clearance” to conduct such research should be “limited” to any arbitrary number (which might be one interpretation of the question). We also strongly disagree with the suggestion that access to “sensitive” research results should be limited to researchers with such clearance –

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this threatens the principle of open communication in science and could be detrimental to the research enterprise (please refer to our response to Q22 below).

26. We welcome the statement in the Green Paper regarding the importance of

international exchange of scientific personnel to the research enterprise, and the need to ensure that, whilst appropriate security checks are undertaken, these do not unduly restrict the ability of talented scientists and students from overseas to work in laboratories in EU member states.

Q15 Should a specific and limited number of laboratories, health institutions, production establishments, pharmaceutical and food-processing plants be accredited on the basis of compliance with minimum security standards?

27. We consider that the UK already has a system in place which ensures that only laboratories with appropriate safety and security standards can conduct work on specified hazardous agents. Hence an “accreditation” process essentially already exists at the national level. As noted in our response to Q11, there could be benefit in work to share regulatory best practice at EU-level, but we would emphasise once again that where existing national systems are fit for purpose they should not be duplicated nor replaced by new processes.

28. Whilst we agree that only those laboratories meeting required standards should be

licensed at national level to conduct work involving hazardous agents (and that in reality only a small number of specified laboratories will be equipped to work with the most dangerous organisms), we would again question why an accreditation system would be restricted to a “specific and limited” arbitrary number of laboratories.

Q17 Should there be EU funding for joint training and awareness raising?

29. We agree that the EU should provide funding for training and awareness-raising activities for those member states that require this support.

Q18 Should EU-level lists of biological agents of special security concern be developed jointly by the Member States and the Commission? Q19 If you believe that each Member State should have its own pathogen lists, do you agree that interaction with other Member States on this topic could be beneficial for your organisation?

30. We agree that a single list of biological agents of special security concern which

was developed and coordinated effectively at international level would be very helpful if this could be achieved. Ideally, we feel such a list should be maintained at a global, rather than a European, level (for example, via the World Health Organization).

31. Either way, we believe that member states should have the freedom to add

additional agents to any such list as they feel appropriate at national level. We

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agree that mechanisms to facilitate dialogue between member states on this issue should be encouraged.

Q21 Should public and private funding for research on bio-substances be made conditional on the compliance of bio-standards? 32. Yes, we agree fully that research funders should make their funding conditional on

compliance with national biosafety and biosecurity regulations. Institutions funded by the UK Research Councils and the Wellcome Trust are already required, as a specific condition of grant funding, to comply with the requirements of all relevant regulatory authorities in taking forward their funded research.

33. Our organisations also have additional processes in place to ensure that the

research we fund complies with the highest ethical, as well as scientific, standards. In particular, the Research Councils and the Wellcome Trust have ethical advisory procedures through which we can obtain expert advice on research proposals that raise concerns that would not be addressed through standard licensing or local ethical review processes. In addition, our organisations actively promote best practice in the conduct of our funded research. We provide guidelines on good research practice, which set out minimal standards with which we expect researchers and institutions in receipt of our funding to comply, and have explicit policies on research misconduct.

34. As highlighted above, the BBSRC, the MRC and the Wellcome Trust also have a

common approach in place to help ensure that possible risks of research misuse associated with research proposals are considered by both grant applicants and reviewers (see the policy statement at Annex B). We have introduced a standard question on application forms and ask both our expert referees and our Funding Committees to consider any risks of misuse associated with the proposals they review. We hope that our policy provides a useful model for other funding agencies, and we would be more than happy to provide further information on this as required.

35. Whilst we accept that funding agencies have an important role in addressing risks

of research misuse, we are slightly concerned by some of the language in the Green Paper – particularly the suggestion that research grants should be assessed on the “ability of the given applicant to comply with bio-standards, as well as possible future security guidelines”. We believe that this type of assessment is the role of the relevant national regulatory authorities and employers, and not funding agencies. It is also unclear how either funding bodies or the majority of scientists who peer review our grant applications could be in a position to judge the nature of “possible future security guidelines”.

36. It is also important to emphasise that it is not the role of funding agencies to

monitor compliance with biostandards once a research grant has been awarded. This is the responsibility of research institutions in receipt of the funding, with oversight by relevant national regulatory authorities. We agree, however, that funding bodies should have appropriate sanctions in place for researchers or institutions where breaches of accepted regulatory practice have been proved.

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Q22 Do you agree that a publication procedure should be applied where sensitive biological dual-use research should be published in two versions: a public version with no publishing restrictions (without sensitive content); and a restricted version containing the sensitive parts of the research with access only for relevant bio-stakeholders?

37. No, we believe that the results of research, incorporating the full content of peer reviewed scientific publications, should be available in the public domain, unless there is a specific reason why they should be withheld in an individual case (such circumstances being very exceptional).

38. We would therefore be extremely concerned by the introduction of any system

which imposed limits to the principle of open communication in science. We believe that the dissemination of research results through publication in peer reviewed journals should be subject to voluntary self-regulation by the scientific community, and not formal regulation by governments or the EU. It is important to acknowledge that the scientific publishing community has been proactive in recognising and promoting discussion on this issue – for example, through the “Statement of Journal Editors and Authors Group on Scientific Publishing and Security”, which was published in February 20032.

39. In terms of the specific process proposed in the Green Paper, we believe that it

would be infeasible to define “sensitive” research in any meaningful way that would enable the identification of the small subset of publications that might be of concern. We would also question how such a system would identify “relevant bio-stakeholders” or control how they assessed and disseminated information contained in research papers. Furthermore, it would surely be impossible to regulate scientific publication – which is an international activity – at European level. In short, we feel such a system would be at best unworkable, and could potentially seriously hinder the scientific enterprise.

Q23 Could the EBN assist in the development of bio-security and bio-safety guidelines for publicly funded research?

40. Any such activity would need to be carefully coordinated with other relevant

organisations, and avoid duplicating other work. For example, the European Biosafety Association is already engaged in a process to develop international standards for the laboratory management of biorisks3, which we understand to be covering similar ground to the guidance envisaged by the Green Paper.

Q24 Should mandatory academic courses on bio-standards and best practices become part of the university curriculum in the field relevant to life sciences?

41. The Research Councils and the Wellcome Trust do not fund undergraduate education. At post-graduate level, we would support in principle the inclusion of standard content in courses which informed students of relevant regulatory requirements in this area and encouraged them to think about the wider implications of their research. We believe there could be value in the development of EU-level actions to assist member states in introducing such

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training at national level, as a component of wider awareness-raising activities. We suggest that this could best be incorporated through the development of modules that could be incorporated into existing courses, rather than through the development of new dedicated courses.

42. We would emphasise that scientists, technicians and students working in high risk

areas should receive relevant tailored training from their research institutions on formal regulatory requirements and best practice before initiating such work. Appropriate refreshers (which include updates on any new regulatory requirements) should also be provided to such staff at regular intervals. As noted above, we believe dedicated institutional Biological Safety Officers would have a key role to play in provision of this training.

43. It is important that training requirements are introduced in a flexible way that does

not disadvantage visiting scientists from overseas or researchers who move into biological science disciplines later in their careers. For example, it may be possible to build any new training into standard health and safety induction programmes in institutions.

Q25 Should researchers in life sciences be obliged to adopt a professional code of conduct? Q26 Should the above-mentioned professional code of conduct be developed at EU level? If so, by whom?

44. We believe that codes of conduct have an important role in awareness-raising and encouraging responsible self-regulation within the scientific community, and their development and dissemination by appropriate national and international bodies should be encouraged. We consider, however, that codes of conduct do not provide the appropriate tool through which to enforce compliance with biosecurity standards, and feel, therefore, that a mandatory code that was enforced top-down at EU-level would not be appropriate. As has been highlighted in previous discussions of this topic, the extent to which biological researchers form a single, defined “profession” is open to debate, and so an overarching professional code might not be applicable in this area4.

45. We agree that there could be a role for EU-level activities to assist member states

in developing codes of conduct, as part of their awareness-raising efforts, and promoting their adoption at institutional level. The Research Councils and the Wellcome Trust are supportive of the UK Chief Scientific Adviser’s Universal Ethical Code for Scientists5, which we suggest represents an excellent model. It is also important to acknowledge that there is existing international work on which member states and other organisations could draw in developing suitable codes – such as the InterAcademy Panel Statement on Biosecurity6.

Q30 Should the EU look into the possibility of developing a capacity for test detection tools on live and dangerous substances?

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46. Yes, we agree that the EU should investigate this possibility. The EU might find the UK Government’s Foresight initiative work on Detection and Identification of Infectious Diseases helpful in informing its work in this area7.

References

1. For more information on the European Biosafety Association (EBSA), see: www.ebsaweb.eu 2. The Statement of Journal Editors and Authors Group on Scientific Publishing and Security

(February 2003) may be accessed at: www.asm.org/Policy/index.asp?bid=20507 3. Further information on the EBSA’a International Laboratory Biorisk Management Standard

project can be found at: www.ebsaweb.eu/EBSA+Activities/Laboratory+Standard.html 4. See, for example, the report of the joint Royal Society-Wellcome Trust workshop “Do no harm:

reducing the potential for the misuse of life science research” in October 2004, available at: www.royalsoc.ac.uk/document.asp?id=2830

5. The UK Chief Scientific Adviser’s Universal Ethical Code for Scientists can be accessed at: www.berr.gov.uk/science/science-and-society/public_engagement/code/page28029.html

6. The InterAcademy Panel Statement on Biosecurity (published December 2005) can be accessed at: www.royalsoc.ac.uk/document.asp?id=3948

7. The report of the Foresight project on the detection and identification of infectious diseases was launched in April 2006 and is available at: www.foresight.gov.uk/Previous_Projects/Detection_and_Identification_of_Infectious_Diseases/

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ANNEX B

MANAGING RISKS OF MISUSE ASSOCIATED WITH GRANT FUNDING ACTIVITIES A joint Biotechnology and Biological Sciences Research Council (BBSRC), Medical Research Council (MRC) and Wellcome Trust policy statement The BBSRC, the MRC and the Wellcome Trust have each issued position statements on bioterrorism and biomedical research. These cover issues such as: balancing benefit and risk; funding decisions; dissemination of research; international collaboration and training; and promoting research best practice and ensuring public trust. The position statements are available on the organisations' websites.

The position statements propose that a system based upon self-governance by the scientific community will ultimately provide the most effective means of managing risks of misuse. We suggest that the community should take active steps to further develop mechanisms of self-governance, and that through doing so the community can ensure that responsibly conducted research is not unnecessarily obstructed. The BBSRC, the MRC and the Wellcome Trust already have rigorous processes in place for ensuring that the research we support is of the highest scientific quality and conforms to all relevant ethical and regulatory requirements. In light of concerns over research misuse, we have been working in partnership to examine how these existing procedures could be strengthened to help ensure that risks of misuse associated with research projects are identified and assessed at the grant application stage, where it is possible to do so. We have consulted members of funding and advisory committees across the three organisations, on the basis of a discussion document. The outcome of this has led the BBSRC, the MRC and the Wellcome Trust to agree changes to our policy statements, guidance and procedures in four areas:

• introduction of a question on application forms asking applicants to consider risks of misuse associated with their proposal

• explicit mention of risks of misuse in guidance to referees as an issue to consider • development of clear guidance for funding committees on this issue and the

process for assessing cases where concerns have been raised • modification of organisational guidelines on good practice in research to include

specific reference to risks of misuse. The misuse of research for terrorist purposes may be only one of a number of possible ways in which the outcomes of research could conceivably result in harm. Therefore, these changes refer to all kinds of research misuse. These changes have been introduced to heighten awareness, and as a means of identifying possible risks of misuse at an early stage. Ultimately what matters most is people's motives. The changes we are implementing to our processes will not be sufficient on their own to prevent misuse by somebody with that primary intent. Other processes within the research environment are therefore also important; these

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include effective research governance at the local (institutional) level, appropriate levels of caution in making appointments, and compliance with existing health and safety regulations. September 2005

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Memorandum 10

Submission from Research Councils UK (RCUK) Biosecurity in UK Laboratories Research Councils UK is a strategic partnership set up to champion the research supported by the seven UK Research Councils. RCUK was established in 2002 to enable the Councils to work together more effectively to enhance the overall impact and effectiveness of their research, training and innovation activities, contributing to the delivery of the Government’s objectives for science and innovation. Further details are available at www.rcuk.ac.uk The Research Councils welcome the opportunity to respond to the House of Commons Committee’s Call. This evidence is submitted by RCUK on behalf of the following Councils:

Biotechnology and Biological Sciences Research Council (BBSRC) Medical Research Council (MRC) Natural Environment Research Council (NERC)

It represents their independent views. It does not include or necessarily reflect the views of the Science and Innovation Group in the Department for Innovation, Universities and Skills. In addition to this response, the BBSRC is submitting separate information to this Inquiry. The BBSRC response deals more specifically with its sponsored institutes and, in particular, the Institute for Animal Health at Pirbright. 1. Introduction Clarification of terms i) Biosecurity and biosafety The title of this Inquiry refers to ‘Biosecurity’ without defining the term. One definition is in the guidance issued for the Anti Crime and Terrorism Act 2001 (ACTA), where it is used in a very precise way. The ACTA treats biosecurity and biosafety as two complementary but distinct concepts, and deals specifically with biosecurity for a limited number of both animal and human pathogens and toxins. Definitions of the two concepts, which are in accord with the ACTA, can be found in the document “Biorisk Management – Laboratory Biosecurity”, published by the World Health Organisation in 20068. In this: 8 www.who.int/csr/resources/publications/biosafety/WHO_CDS_EPR_2006_6/en/

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• Laboratory biosafety describes the containment principles, technologies and practices that are implemented to prevent the unintentional exposure to pathogens and toxins or their accidental release.

• Laboratory biosecurity describes the protection control and accountability for valuable biological materials (including pathogens and toxins) within laboratories in order to prevent their unauthorised access, loss, theft, misuse, diversion or intentional release.

[In addition, the term biorisk management has been used for risk management relating to failures in either biosafety or biosecurity]. This response refers to both biosafety and biosecurity (as defined above). ii) Dangerous Pathogen The term dangerous pathogen means different things in different pieces of legislation and may or may not include all or part of a pathogen’s genome or genetically-modified organisms (GMOs) containing parts of the genome. For the purposes of this Inquiry, we have taken dangerous pathogens to mean any human or animal pathogens including genetically-modified forms, identified by formal risk assessment or through mandatory regulation to require handling in containment level 3 or 4 laboratories. It also includes, when specified in the same legislation, any DNA sequence from that pathogen which is potentially infectious or pathogenic, or any genetically-modified organism containing such material. This is a ‘catch-all’ definition which reflects the diverse work of the Research Councils and the complexity of the regulations. iii) Containment level For the purpose of this Inquiry, we have defined containment level 3 and 4 laboratories as laboratories that meet the requirements in the guidance from ACDP, SACGM or DEFRA (see below) for levels of containment required that are appropriate to the work being done. This reflects the fact that Research Council containment laboratories may work with animal or human pathogens or both, and that pathogens vary in terms of modes of transmission/ infection, and susceptibility to disinfection/inactivation. Regulatory Climate Scientists using containment laboratories work in a very complex regulatory climate outlined below. Working with dangerous pathogens therefore has to be very carefully managed by well-informed staff. The ACDP SACGM and others have made great efforts to simplify this by producing excellent guidance documents which aim to integrate the requirements of all of the regulations. Even so it would be extremely beneficial for scientists if this regulatory climate could be simplified further. Regulation and guidance concerning the safe handling, storage and disposal of human pathogens and genetically-modified human and animal pathogens is provided by the Health and Safety Executive on the advice of the Advisory Committee on Dangerous Pathogens (ACDP) and the Scientific Advisory Committee on Genetic Modification (SACGM). These advisory bodies have produced excellent practical guidance

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bringing together all of the relevant legislation. Transportation regulations, such as those of the International Air Transport Association (IATA), are extremely complex and only small sections apply to dangerous pathogens. Until the ACDP incorporated the relevant sections into their guidance, they were not well understood. Staff managing transport regulations require specialist mandatory training. Guidance on transportation, safe handling, storage and disposal of economically important animal pathogens, identified by the Specified Animal Pathogens Order 1998’ (SAPO) is provided by DEFRA. DEFRA also regulates the importation of all other animal pathogens from outside the UK. The requirements of this legislation for containment laboratories are clear, but are not well linked to the similar health and safety legislation. It would be helpful to create such a linkage. Finally, requirements concerning the biosecurity of a subset of these human and animal pathogens which could be used for terrorist purposes are contained in the “Security Standards for Laboratories (in accordance with Part 7 of the Anti Terrorism Crime and Security Act 2001 - ACTSA)”. This guidance is generally clear and straightforward, but adds a new set of elements to both containment laboratory design and management. If these are not incorporated when the laboratory is built, they can be difficult to fit subsequently. This guidance is not safety oriented, and so is not concerned with containment. It introduces the concept of critical areas where the pathogens listed may be used, stored, transported or destroyed, and these may be outwith the containment laboratory itself. Although this is a simple concept, it is not an obvious one to scientific staff used to the concept of containment levels and so requires training. The guidance also introduces management procedures which are purely security related, and which therefore may be outside the experience of many scientists and laboratory managers. 2. Research Council work on Dangerous Pathogens The MRC and BBSRC support research into infections and microorganisms both through grants/ fellowships to Universities and to their own Units and Institutes. NERC’s work in this area is done mostly by its Centre for Ecology and Hydrology (CEH). Scientists need to be able to work with dangerous pathogens to help advance knowledge, and to develop novel vaccines, therapeutics and diagnostics. Regulation to protect human health and the environment is of course essential, but control measures need to be proportionate and risk-based. Where the research is undertaken through grants to Universities, the University is responsible for biosecurity and biosafety. Where the research is undertaken in a Research Council Unit or Institute, then the particular Research Council is responsible. The remainder of this submission refers mainly to the latter. BBSRC-sponsored Institutes are currently separate legal entities to BBSRC, and therefore biosecurity and biosafety are the responsibility of the Institute Director. The policy is based on the legal requirements. Adherence to the statutory requirements is also the responsibility of the Director on the advice of the local Health and Safety Officer.

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Where there is a joint (MRC/University) use of a facility, the MRC always ensures that a single organisation has overall responsibility. In all facilities managed by the MRC, there are excellent relationships with the host institution (where there is one). For MRC establishments, policy on biosecurity and biosafety is the responsibility of Head Office, in particular the Head of Health, Safety and Security. The policy is based on the legal requirements. In the establishments themselves, adherence to the statutory requirements is the responsibility of the Director on the advice of the local Health and Safety Officer, who in turn is advised by the MRC Head of Health, Safety and Security. In 2005/06, the MRC spent £8.0m on such research in total, £6.6m of which was in our own establishments. In its response (7 September 2007) to the publication of reports into Foot and Mouth outbreak in Surrey, the Government indicated that it had commissioned a Regulatory Review, under the chairmanship of Sir Bill Callaghan, of the current regulatory framework. The report9 was published on 13 December 2007. This included comparison of regulation of animal and human pathogens and considered whether the differences were justified and what improvements might be made. The Report recommended, inter alia, that DEFRA, DH, HSE and other interested parties work together to develop a single regulatory framework to govern work with human and animal pathogens; and that the ACDP be tasked with formulating a common set of containment measures to apply to both animal and human pathogens. The report also recommended that the HSE become the single regulatory body for both animal and human pathogens. BBSRC, MRC and NERC support this recommendation, but caution against adding to the regulatory burden if it leads to added costs or discourages continued research on important pathogens. Any proposed changes should be risk-based, and accompanied by an impact assessment and a consultation with the research community. The MRC is leading the ISTR (Institute of Safety in Technology and Research) Working Group developing standards for biosafety professionals. This will include entry qualifications and requirements for continuous professional development. This approach is supported by the HSE. (The Callaghan Report also refers to this – paragraph 4.4.6.1). The Health Protection Agency is shortly to undertake a strategic review of high-level (ACDP and SAPO level 4) containment facilities in the UK. This is expected to report in the first half of 2008. This will be chaired by Professor George Griffin (St George’s Hospital Medical School, London). It will review existing capability, and advise on future national requirements, including the organisation of such facilities and the degree of centralisation. 3. The current capacity for research on dangerous pathogenic material in the UK and the capability to conduct research on the causative agents of disease that may emerge at a future time. 9 www.DEFRA/SEERAD.gov.uk/animalh/diseases/fmd/investigations/bill-callaghan.htm

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This section should be read in association with the separate submission from BBSRC. At present, the MRC establishments that undertake research on dangerous pathogens (as defined above) are:

• National Institute for Medical Research (NIMR), Mill Hill • Laboratory of Molecular Biology, Cambridge • Virology Unit, Glasgow • Prion Unit, London • Human Immunology Unit, Oxford • Molecular Haematology Unit, Oxford • MRC/UVRI Uganda Research Unit on AIDS, Entebbe • MRC Gambia Unit, Fajara

All have CL3 facilities, except NIMR which has both CL3 and CL4. Institute/Unit Containment

level No of labs

Pathogens held, and under what regulations

HSE/ACDP SAPO ATCSA NIMR 4 – SAPO

and HSE 1 Avian

Influenza Virus.

3 - HSE 9 HIV Mycobacterium tuberculosis Plasmodium falciparum

LMB 3 - HSE 1 HepB Virology 3 – SAPO

and HSE 4 HIV

HepB HepC

Prion Human Immunology

3 - HSE 2 HIV-1 HIV-2 SIV Dengue virus

Molecular Haematology

3 - HSE 1 Recombinant lentiviruses

Uganda 3 (HSE) 1 HIV Gambia 3 (HSE) 1 HIV

Tuberculosis

From the MRC’s perspective, the current capacity is adequate. However, the HPA Review referred to above may come to a different conclusion concerning overall UK capacity. Most of the UK’s capability to work in high containment on animal and plant pathogens resides in BBSRC institutes. In particular:

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Animal Pathogens

• Institute for Animal Health (IAH) – Compton site: endemic disease, (e.g. TB, Salmonella); unique resources for immunology in cattle (MHC herd) and chicken (for avian flu work).

• IAH – Pirbright site: exotic viral diseases (e.g. foot and mouth, bluetongue). • Roslin - Neuropathogenesis Unit : prion diseases (scrapie and BSE). • Institute for Food Research: food-borne zoonoses (including food poisoning)

Plant Pathogens

• Rothamsted Research:

IAH, Roslin (including Neuropathogenesis Unit), and IFR all have CL3 facilities, except IAH – Pirbright site, which has CL4. NERC’s Centre for Ecology and Hydrology has two category 3 facilities, at CEH Lancaster and Oxford. The Oxford laboratory has the most comprehensive facilities, and has equipment in place to sterilise liquid effluent and solid waste. Using these facilities, CEH has conducted extensive research into the molecular biology of human pathogens and their modes of action. It is now focussing more on the environmental distribution and transport of certain pathogens, the ecology of selected invertebrate vectors and the distribution and role of pathogens in the population biology of natural (non-human, non-livestock) hosts in the environment. Surveillance of the presence of (potential) disease-causing organisms in (potential) vector populations, and the prevalence of the (potential) vectors themselves, is an area which could sensibly be developed to provide greater advance warning of the transport of pathogens and the likelihood of disease outbreaks, especially in view of the implications of climate change for vector movement. A routine screen of many wildlife species could yield important data on environmental disease reservoirs, alerting us to the presence in the UK of certain disease-causing organisms (some viruses for example) that might suddenly become a problem even though they are not a problem at the moment. 4. The state of biological containment facilities in the UK. This section should be read in association with the separate submission from BBSRC. The Containment Level 3 facilities for which the MRC is responsible all meet HSE requirements, and the CL 4 facility for which the MRC is responsible meets DEFRA and HSE requirements. The MRC is advised by the National Counter-Terrorism Security Office (NaCTSO) on the physical security standards of its containment facilities. Local counter-terrorism advisors advise the MRC on the interpretation of the national guidelines for individual facilities. NERC’s CEH adheres to all the proscribed procedures for category 3 work.

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5. Laboratory inspection regimes and the rationale and practicalities of the licensing system. This section should be read in association with the separate submission from BBSRC. Laboratory inspection regimes are currently the responsibility of HSE and DEFRA, but this may change if the recommendations of the Callaghan Report are implemented. [In addition, the MRC is currently updating its audit process for its own CL 3 and 4 facilities. MRC inspections of these are planned to be undertaken every year for CL 4, and every three years for CL 3]. (In terms of the rationale and practicalities of the licensing system, the MRC has nothing to add to the recommendations of the Callaghan Report). 6. Biosafety training provision for staff working in containment facilities. Training is key to the safe operation and management of containment labs. There are three groups of staff who require training: i) biological safety officers who have responsibilities for all aspects of biological safety but may have limited practical experience of CL3 and CL4; ii) containment laboratory managers or supervisors who should ideally be both practically trained and have a comprehensive understanding of the regulations and be able to train and assess other staff; and iii) users who need practical training to work in the laboratory, but who only need to have a limited knowledge of the regulations. The MRC provides the only training course in the UK for biological safety officers (though the MRC and other organisations provide training for other staff working in Containment 3 laboratories). Other institutions (public and private) send their staff on these courses. In the public sector, it is difficult to recruit such officers; currently there are a small number of competent practitioners in the market place. The containment managers and supervisors, who have day to day management responsibilities, are key as they usually train the much larger user population and so set the work standards. Again, they are difficult to recruit and retain, and training courses would help secure the supply of such staff. The training of managers and supervisors clearly has to translate into very thorough training of the laboratory staff. It is good practice to maintain records of training in order to demonstrate competence. 7. The maintenance and recording practices surrounding the storage and transportation of dangerous pathogens. The maintenance and recording practices required by the legislation vary depending on the pathogen worked with and the legislation. Health and safety legislation is primarily concerned with safety and does not dictate maintenance (other than that storage should be safe), or recording procedures or labelling of material. Good laboratory practice, however, does require keeping detailed inventories of material and monitoring storage facilities, but it is not a legal requirement. The GM regulations are more concerned with control of material and preventing release into the environment, and so require all material to be accounted for but do not specify how.

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Transport legislation requires clear identification of pathogens being transported, the quantities, appropriate packaging and safety labelling. A single nationally accepted system for logging information on the storage of dangerous pathogens could be advantageous, provided it were inexpensive and simple to operate. Such a system could be used to log details of all pathogens, even those of accepted low virulence, and would allow easy exchange of data when samples are moved between laboratories. SAPO licences are specific to the work and require storage details to be held of locations, quantities of material and records of disposal. DEFRA prefers SAPO material to be stored separately from other material as they are particularly concerned about accidental transmission of infection through physical contact with other materials. Disposal has to be recorded. Transportation is also closely controlled. DEFRA does not specify labelling requirements. ATCSA has introduced a new level of storage and inventory security for a limited list of pathogens. It specifies labelling which must be unidentifiable to unauthorised persons a detailed inventory and an audit system which allows tracking of all material from cradle to grave. It also requires completely secure storage. BBSRC, MRC and NERC abide by the requirements for storage laid down by HSE and DEFRA, and by the transportation requirements laid down for example by IATA, and by the European Agreement concerning the International Carriage of Dangerous Goods by Road (‘ADR’). The implementation of the ATCSA requirements is in progress at a local level following advice from local counter terrorism security advisors. Consideration should be given to introducing a coding system for all dangerous pathogens similar to that used for chemicals or dangerous goods. This would facilitate the identification of dangerous pathogens and assist in management and inventory control. It would also assist in the recovery of any missing material and assist in the response to finding material outside the appropriate containment facility. More detail is given in the next section. 8. Measures implemented when pathogenic material cannot be accounted for. All MRC units and BBSRC and NERC Institutes handling pathogens have Standard Operating Procedures for storage, record keeping, receipting incoming samples and audit/procedure for missing samples. There is no formal requirement, as for example for radioactive material, to account for missing pathogens In HSE legislation, though, if there were thought to be health/safety implications in an MRC establishment, the Head of Health, Safety and Security would be alerted and appropriate investigations pursued. For BBSRC Institutes, the Institutes Health and Safety Officer is responsible in liaison with the Biological Safety Advisor. If the recommendation of the Callaghan Report is implemented to transfer responsibility for inspection and enforcement functions in respect of animal pathogens to the HSE, the HSE would be well placed to provide guidance covering both human and animal pathogens.

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A standard labelling system would greatly facilitate management of material and could help prevent accidental loss and assist the response to missing material and improve the chances of recovery. Such a system would need to be simple as label surfaces are often small. This could involve use of a specific colour vial or vial insert or label which signifies the material is a hazard group 3 or 4 pathogen. The system could also use a code letter indicating the same information. This could be linked to a series of standard instructions to be followed by emergency service or other trained personnel, on finding material in an inappropriate context. For example this material requires inactivation by autoclaving. It could also indicate, for example, whether exposure to contents requires medical attention. A second letter or number code could identify the source laboratory. Such a system would not specifically identify the material and so would meet the ATCSA requirement. 9. The role of universities in overseeing security clearance for research students working with dangerous pathogens. The process of security clearance for foreign research students who propose working with dangerous pathogens is undertaken by the Foreign and Commonwealth Office. The scheme, ‘The Academic Technology Approval Scheme’ replaced the ‘The Voluntary Vetting Scheme’ on 1 November 2007. Potential students (if non-EU/EEA (including Switzerland) nationals and proposing to work in certain designated disciplines) are referred to the FCO by the University to which the student has applied. None of the three Councils referred to here is aware of any cases where this process has not appeared effective for its students. At present all overseas staff and students who are successful applicants for posts in all BBSRC Institutes are subject to vetting by the institute HR department. All successful applicants for posts or visiting research workers are vetted before they are allowed to work at Babraham Institute or IAH. A similar approach is taken at NERC’s CEH. The MRC has introduced the Government’s recruitment Baseline Security Standard, which applies to all staff. January 2008

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Memorandum 11

Submission from the Advisory Committee on Dangerous Pathogens Biosecurity in UK Research laboratories 1 As the Select Committee on Innovation, Universities and Skills is conducting a new inquiry into biosecurity in UK Research laboratories, I would like to alert it, to work the Advisory Committee on Dangerous Pathogens (ACDP) are set to currently undertake. I am the Chair of the ACDP. 2 ACDP is a non-statutory advisory non-Departmental Public Body. The Committee comprises a Chairman and presently 13 members. The membership is tripartite, with scientific experts, employer and employee representatives. 3 The terms of reference for ACDP are: “ To advise the Health and Safety Commission, the Health and Safety Executive, Health and Agriculture Ministers and their counterparts under devolution in Scotland, Wales and Northern Ireland, as required, on all aspects of hazards and risks to workers and others from exposure to pathogens” 4 Following the accidental release of the FMD virus from Pirbright, Sir Bill Callaghan was asked by the Government to urgently review the regulatory framework for animal pathogens. The Government has accepted all the recommendations set out in Sir Bill Callaghan’s report. One of his recommendations was to develop a single regulatory framework to govern work with human and animal pathogens. To support this he also recommended that ACDP be tasked with formulating a common set of containment measures to apply to both animal and human pathogens. 5 ACDP is due to meet on 5 February and will discuss how we are going to take this recommendation forward, which is likely to involve the setting up of a Working Group. 6 You should also be aware that I shall be chairing a review (although not in my capacity as Chair of the ACDP) that the Medical Research Council has asked the Health Protection Agency (HPA) to undertake on containment level 4 laboratory facilities. The review is due to report to the HPA in June 2008. The Review will look at issues such as capacity, training requirement/needs, and regulations covering these facilities. January 2008

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Memorandum 12

Submission from PFIZER Ltd The information in this response has been collated following discussions with a range of key colleagues at Pfizer’s Global Research and Development (PGRD) facility in Sandwich, Kent. The information provided focuses primarily on issues relating to the relatively limited use of ACDP group 3 pathogens, and of schedule 5 toxins, the biosecurity arrangements for which are anticipated to be of most interest to your study. Pfizer is the world’s leading pharmaceutical company and the world’s largest investor in R&D, and our Sandwich site is a key part of our company’s efforts to discover and develop new medicines. Excellent scientists and world class facilities to support biochemical and clinical research are critical to our organisation, and we take very seriously our responsibilities to operate safely and securely. Sandwich has an enviable record of productivity and a long history of generating important new treatments for a range of conditions from cardiovascular to infectious disease. The most recent medicine to be discovered and developed at Sandwich is maraviroc - the first in a new class of therapies for HIV. To summarise our response, PGRD biology facilities and operations are designed and operated with biosecurity as a key factor alongside traditional Environmental Health and Safety (EHS) considerations. We operate to very high standards. Arrangements on site and the commitment of our staff have ensured that no ACDP group 3 pathogens or any schedule 5 toxins10 have ever been misplaced or lost at Sandwich. Physical and procedural controls, risk assessments, staff training and awareness – together with physical inspections and active follow up – are all in place to ensure that activities relating to biosecurity are rigorously controlled and any risks minimised. 10 Sch. 5 of the Anti-Terrorism, Crime and Security Act 2001

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The current capacity for research on dangerous pathogenic material in the UK and the capability to conduct research on the causative agents of disease that may emerge at a future time.

Reference the use of ACDP Group 3 pathogens.

Within the Pfizer Ltd UK Research and Development Laboratories based in Sandwich, Kent there are two facilities which routinely operate at Containment Level 3 (CL3).

Both facilities operate at small volume, ‘research’ scale only. Thus at any one time the maximum quantity by volume will be approx. 40 litres.

The larger of the 2 CL3 facilities has 4 laboratories housing 4 class 1/3 (hybrid) microbiological safety cabinets (MSC). All are routinely operated as class 1. A robotic facility for high throughput screening is also operated, under containment conditions, within this facility.

The 2nd CL3 facility comprises 2 laboratories each with 2 class 1 MSCs, 4 in total. The group 3 pathogens handled to date have been HIV and Hepatitis-C virus. Approximately 75% in practice being HIV.

An in-vivo CL3 unit has been designed and constructed within our Comparative Medicine Department. Tested at commissioning (yr 2000) to ensure it meets the standards required for CL3 animal research the unit has in practice only been used for level 2 work. There currently no plans to conduce CL3 animal research in the unit.

We make limited use (by quantity) of Schedule 5 toxins. Our total stored quantity is typically 5 – 10mgs of these materials. We are therefore registered with and regularly inspected by the Home Office. We have two storage locations (-20oc and +4oc). Security of these toxins is maintained by procedural and physical containment measures in accordance with Home Office requirements. There are currently no plans to significantly increase our usage.

The state of biological containment facilities in the UK. Our CL3 facilities are designed, built and operated to very high standards. Our facilities are highly technically engineered, and maintaining them to such high standards requires a significant commitment in terms of time, money and expertise.

Laboratory inspection regimes and the rationale and practicalities of the licensing system. Internal Inspections:- Local inspections are performed by trained users on a monthly basis and are made and recorded by reference to agreed checklists. Management led inspections are performed on a six monthly basis. EHS Audits

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are undertaken periodically by the EHS Department. In all cases actions are derived to address any issues raised during the inspections and tracked to completion.

Inspections consider physical conditions; procedural compliance and staff knowledge.

External Inspections:- In 2007 a Health and Safety Executive Specialist Biosafety inspection team undertook an inspection of our biologics areas (CL2, CL3 and Genetic Modification activities). The inspectors were clearly knowledgeable their interactions with our scientists and EHS professionals were constructive.

In recent years we have had annual inspections by the Home Office with regard to the security of Schedule 5 toxins. In all cases we have met and in some areas exceeded the expectations as well as the requirements.

During 2007 Pfizer’s Global EHS Audit Team and an external / independent EHS Management Systems audit team have also audited our Biosafety programmes.

In our experience the licensing of our facilities and, where appropriate, of the activities undertaken therein have been conducted professionally and in a constructive manner. The Home Office inspections in relation to our Schedule 5 toxins are not in themselves problematic. However, as a general observation the frequency and time taken over these inspections (our time and that of the inspectors) is arguably disproportionate to the risk posed by our very limited use. We have notified the Home Office on the basis that we exceed the 5mg maximum quantity that we could hold without notifying. In practice we hold approx 5-10 mg. This has prompted annual inspections for the last three years. Our security standards are very high when considered from the perspective of general security (the Sandwich site – like all major pharmaceutical research centres – is a highly secure location) and also when reviewed specifically by reference to security of any toxins.

In order to maximise the overall benefit of these inspections, further consideration of details relating to the actual quantity of toxin(s) held/used and past inspection reports for a notified location should be taken account of when scheduling future inspections.

Biosafety training provision for staff working in containment facilities; Research biologists are trained internally on the EHS aspects of their jobs. Some of this training is ‘generic’ whilst some focuses specifically on a given activity. Staff who are not scientists but whose job requires that they access biology laboratories (e.g. cleaners, engineers) also receive awareness training focussed on their EHS considerations whilst they undertake their activities. Engineers, cleaners etc. do not have access to CL3 units except during routine closures (post fumigation) or in exceptional circumstances based on a specific

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risk assessment and under close supervision.

For staff working in our CL3 facilities a purpose written Code of Practice (COP) is maintained. Familiarisation with the COP is a core part of the training for all colleagues who work in the CL3 facilities. The COP also details specific training requirements for all CL3 users. The training requirements include practical supervisory oversight and are only signed off by a supervisor once appropriate experience is gained and skills demonstrated.

Colleagues who handle Schedule 5 toxins are experienced biologists with the general training referred to above. They are additionally trained in the exacting security arrangements in place for the storage and use of schedule 5 toxins and in the risk assessments that are maintained for their tasks.

The maintenance and recording practices surrounding the storage and transportation of dangerous pathogens. Pfizer has an in-house Dangerous Goods Safety Adviser (DGSA) at Sandwich and make use of this expertise to ensure that we import, export, package and generally transport biologics in accordance with regulatory requirements both with regards to the sender and recipient locations.

Measures implemented when pathogenic material cannot be accounted for. We have not encountered this problem with either CL3 or Schedule 5 toxins. However, internal investigation processes are in place and would be actioned in the event that any pathogenic material could not be accounted for. These processes are designed to identify both direct and indirect causes of any incidents that result in unaccounted material.

The role of universities in overseeing security clearance for research students working with dangerous pathogens. Security clearances are included in our own screening programmes and thus we do not rely on University or Contractor screening programmes. January 2008

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Memorandum 13

Submission from the Biosciences Federation and the Institute of Biology

Biosecurity in UK Research Laboratories

Summary

1. IOB and BSF welcome this inquiry by the IUS Committee. We recognise not only the serious potential threat posed by deliberate exploitation or accidental escape of many laboratory collections but also the essential and beneficial contribution to society of research involving such material. We hope that this consultation process will lead to improved practices and increased peace of mind for researchers and the public.

2. The current capacity for work on dangerous pathogens is limited and may not

be sufficient to allow the desired level of Category 4 research both in terms of facilities and of fully trained personnel.

3. There is concern that, despite Full Economic Costing for universities, the

pressure to generate measurable output and income causes infrastructure funding to be shifted towards short term projects to the detriment of routine maintenance. Licensing and monitoring should require full costing of, and budgeting for, maintenance as well as provision for decommissioning at the end of each licensing period to accommodate the possibility of non-renewal.

4. The role of Safety Officer should be responsible, visible, highly trained and

senior. While moves to avoid negative effects of health and safety regulations may be appropriate in some areas, biosafety must always be paramount in the handling of pathogens. Moreover, biosecurity should be given priority over other matters such as trade agreements etc.

5. Routine and unannounced inspections are infrequent in the absence of reported

incidents. Transport of dangerous agents between facilities needs to be examined, particularly with regard to planning for critical incidents and communication of these strategies. Training advice from the Advisory Committee on Dangerous Pathogens (ACDP) is well regarded, however, actual training is heavily dependent upon internal procedures at each facility.

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Appendix 1 Q1. The current capacity for research on dangerous pathogenic material in the UK and the capability to conduct research on the causative agents of disease that may emerge at a future time A1. The current capacity for such work is limited11 and may be inadequate to allow the desired level of Category 4 Pathogen research both in terms of facilities and of sufficiently trained personnel. Research on Category 4 and 3 agents is necessary to allow recognition of new variants, to identify and trace contacts of potentially exposed travellers and animals, and to compare outbreaks from different areas. It is important for researchers and regulators to recognise that release of notifiable animal, bird and plant pathogens can hamper trade and transport within a country and have a detrimental effect on the economy, and that security against theft should therefore be as high in these cases as for agents of dangerous human and zoonotic diseases. Q2. The state of biological containment facilities in the UK A2. Category 3 pathogens pose a very serious risk and how and where to do research on agents and infected animals needs to be considered very carefully. Any facility dealing with microorganisms dangerous to man or commercially important animals and plants should have modern well maintained systems that are guaranteed to inactivate the agents before disposal of the residue of experiments. All systems should be visible to inspection, and old-fashioned hidden pipes or inaccessible filtration units cannot be allowed. There is considerable concern that economic pressure shifts focus towards short term budgeting at the expense of routine maintenance and replacement. It is essential that the need for excellent biosecurity is considered in reviewing budgetary requests to funding bodies. Applicants should be encouraged to apply for the full cost of maintaining top class systems in the knowledge that the need for the research will be the deciding factor and not the cost of the biosecurity. Q3. Laboratory inspection regimes and the rationale and practicalities of the licensing system A3. The rationale of the licensing system is well thought out and implemented. However, there are a number of potential areas of concern; old facilities are difficult to inspect and there are areas where identification of poor internal processes might be unlikely. There is an impression that once licences have been issued routine and spot inspections are rare, unless an incident is notified, and that even change of organism does not necessarily trigger a site inspection. 11 The Callaghan Report (p10) notes that there are 10 Category 4 held licences in England.

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We note that Category 4 inspection in particular, and indeed Category 2 and 3 facilities are under the care of very few inspectors. The granting of licences to new facilities at new locations needs to be carefully considered to ensure that qualified and experienced personnel are available to establish mature, expert and responsible practices. Q4. Biosafety training provision for staff working in containment facilities A4. The need for exemplary practice is obvious and within the limited facilities in the UK standards appear to be good. The advice which we have received from experienced managers is that biosafety rules should be simple and adhered to totally. Moreover, in order to aid this, the safety officer should be highly trained and have an important and responsible position in the organisation allowing good communication with all levels. Requirement for routine, recorded and frequent (weekly) timetabled internal reporting from Safety Officers to Heads of Department or Directors of Research should be recommended. In addition facility for communication directly with the licensing authority to raise concerns and seek external advice should be considered. The ACDP has a series of useful booklets and guidelines but does not specifically govern training. Training is left very much to local conditions. These are generally good but collaboration between sites and indeed international collaboration requires a high degree of trust between licensees. Training records are reviewed but review is reactive rather than proactive. Q5&6. The maintenance and recording practices surrounding the storage and transportation of dangerous pathogens and measures implemented when pathogenic material cannot be accounted for A5&6. Maintenance and storage are generally covered by internal training but transport (and international transport) of dangerous agents needs careful consideration. The OECD has recently considered this in relation to Biological Resource Centres.12 Moreover, there are cultured organisms not listed as Category 3 or 4 which pose a threat to agriculture and thus to productivity (yield) and quality (producing toxins and damaging stored product) and we would urge improved practice and rigour in the handling and distribution of these organisms also. Considerable attention is given to receipt of specimens and dangerous material within facilities and to labelling of items for transport but there does not appear to be good knowledge of contingency plans for loss of, or damage to, items in transit. 12 OECD Best Practice Guidelines for Biological Resource Centres. Available at http://www.oecd.org/dataoecd/7/13/38777417.pdf

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Q7. The role of universities in overseeing security clearance for research students working with dangerous pathogens A7. There is little enthusiasm for an increased role for Universities in monitoring and vetting potential staff. The Security Services are experienced and resourced for this and the establishment and expansion of good communications between the two sectors should suffice. There should never be unauthorised personnel in secure laboratories and employment procedures should afford an opportunity for security checks. January 2008

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Appendix 2 Member Societies of the Biosciences Federation Association for the Study of Animal Behaviour Association of the British Pharmaceutical Industry AstraZeneca Biochemical Society Bioscience Network British Andrology Society British Association for Psychopharmacology British Biophysical Society British Ecological Society British Lichen Society British Mycological Society British Neuroscience Association British Pharmacological Society British Phycological Society British Society of Animal Science British Society for Developmental Biology British Society for Immunology British Society for Matrix Biology British Society for Medical Mycology British Society for Neuroendocrinology British Society for Plant Pathology British Society for Proteome Research British Toxicology Society

Experimental Psychology Society Genetics Society Heads of University Biological Sciences Heads of University Centres for Biomedical Science Institute of Animal Technology Institute of Biology Institute of Horticulture Laboratory Animal Science Association Linnean Society Nutrition Society Physiological Society Royal Microscopical Society Royal Society of Chemistry Society for Applied Microbiology Society for Endocrinology Society for Experimental Biology Society for General Microbiology Society for Reproduction and Fertility Universities Bioscience Managers Association UK Environmental Mutagen Society UK Federation for Culture Collections Zoological Society of London

Associate Member Societies BioIndustry Association Royal Society Wellcome Trust

Medical Research Council Merck, Sharpe and Dohme Biotechnology & Biological Sciences Research Council

Additional Societies represented by the Institute of Biology Anatomical Society of Great Britain & Ireland Association for Radiation Research Association of Applied Biologists Association of Clinical Embryologists Association of Clinical Microbiologists Association of Veterinary Teaching and Research Work British Association for Cancer Research British Association for Lung Research British Association for Tissue Banking British Crop Production Council British Inflammation Research Association British Marine Life Study Society British Microcirculation Society British Society for Ecological Medicine British Society for Research on Ageing British Society of Soil Science Fisheries Society of the British Isles Freshwater Biological Association Galton Institute Institute of Trichologists

International Association for Plant Tissue Culture & Biotechnology International Biodeterioration and Biodegradation Society International Biometric Society International Society for Applied Ethology Marine Biological Association of the UK Primate Society of Great Britain PSI - Statisticians in the Pharmaceutical Industry Royal Entomological Society Royal Zoological Society of Scotland Scottish Association for Marine Science Society for Anaerobic Microbiology Society for Low Temperature Biology Society for the Study of Human Biology Society of Academic & Research Surgery Society of Cosmetic Scientists Society of Pharmaceutical Medicine Universities Federation for Animal Welfare

Additional Societies represented by the Linnean Society Botanical Society of the British Isles Systematics Association

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Openness The Biosciences Federation and the Institute of Biology are pleased for this response to be publicly available and will be placing a version on www.bsf.org and on www.iob.org once the committee's permission to do so has been granted. For any queries regarding this response, please contact Dr Laura Bellingan, Institute of Biology, 9 Red Lion Court, London, EC4A 3EF, email: l.bellingan@iob.org or Dr Caroline Wallace, Biosciences Federation, email: cwallace.bsf@physoc.org The Biosciences Federation (BSF) is a single authority representing the UK’s biological expertise, providing independent opinion to inform public policy and promoting the advancement of the biosciences. The Federation brings together the strengths of Member Organisations and Associate Members (Appendix 2), including the Institute of Biology. The Institute of Biology (IOB) is an independent and charitable body charged by Royal Charter to further the study and application of the UK’s biology and allied biosciences. IOB has 14,000 individual members and many specialist learned Affiliated Societies (Appendix 2). Together, BSF and IOB represent a cumulative membership of over 65,000 individuals, covering the full spectrum of biosciences from physiology and neuroscience, biochemistry and microbiology, to ecology, taxonomy and environmental science.

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Memorandum 14

Submission from the Institute for Animal Health

The Institute for Animal Health is pleased to contribute to the information-gathering for the IUSSC Inquiry on biosecurity and offers the following views on the points to be considered. To ensure the UK base for studying epizootic and/or zoonotic diseases in livestock is ensured for the future, three key areas need increased attention:

• Sustainable long term funding of key facilities, that ensures these facilities are not compromised by short term volatility of grant funding.

• A predictable regulatory framework that is proportionate and risk based administered by a competent regulatory authority that is resourced to maintain a supportive and constructive dialogue with the duty holders.

• Capability and regulatory gaps be closed in the area of human hazard group 4 organisms affecting large animals, including livestock species.

THE CURRENT CAPACITY FOR RESEARCH ON DANGEROUS PATHOGENIC MATERIAL IN THE UK AND THE CAPABILITY TO CONDUCT RESEARCH ON THE CAUSATIVE AGENTS OF DISEASE THAT MAY EMERGE AT A FUTURE TIME The capability and capacity of UK facilities has to be measured against the challenge that dangerous pathogens pose to the UK. Population growth and population densities, together with other globalisation issues, increase the threat from newly emerging and existing pathogens. On average every 18 months, a new hazard group 3 or 4 pathogen is identified. The economic damage inflicted by infectious diseases has the potential to be enormous and the benefits to be gained by studying infectious diseases exceed the current spend on infectious disease research by orders of magnitude. High hazard pathogens exotic to the UK pose a particular threat as there is no herd immunity and each incursion results in significant damages. Long distance travel and food miles increase the likelihood of introducing such diseases to the UK. Countries that are the most likely source for these pathogens are predominantly in the developing world and tend to be preoccupied with other priorities and may not be not adequately resourced to address the challenges. The first world is today more vulnerable to accidental or malicious introduction of new disease agents, even though many are potentially relatively easy to control by vaccination. 8.8 Human versus animal and plant pathogen facilities Different high containment facilities need to be distinguished based on the pathogens, the host species, and the activities they can accommodate (e.g. small-scale in vitro lab work, in vivo facilities for work in laboratory or natural host species, and industrial-scale production facilities). Veterinary high containment facilities for large animal in vivo work are concentrated at the Veterinary Laboratories Agency, Weybridge and IAH, with some facilities at

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the Moredun Research Institute. In number and capacity, the largest facilities are maintained at the IAH for a globally leading research programme on exotic animal diseases. In capacity and capability these facilities are adequate for the UK requirements. The UK has currently no facilities capable of handling large animals infected with human hazard group 4 viruses and uncharacterised human hazard group 3 viruses. This is a capability gap in the UK portfolio but is needed to interrogate the role of a livestock reservoir for serious human pathogens for existing and emerging pathogens. During the SARS epidemic rapid progress was hampered by a lack of facilities that could handle in vivo a poorly or uncharacterised pathogen, with a brief track record of high mortality. On a precautionary principle such work would require access to a large animal Containment level 4 facility.

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Gap Analysis of UK Capability work on human hazard group 3+/4 pathogens.

A B C D E F

Facility requirements to meet preventative and contingency research needs on hazard group3/4 agents affecting livestock species

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11.1 Development of diagnostic assays: including the validation and

generation of reference reagents for nucleic acid based and serological assays for humans and animals (incl. farm animals)

1.1.1 - for lab animal species 1.1.2 - for primates 1.1.3 - for companion animal species and wildlife 1.1.4 - for farm animal species1.2 Application of diagnostic assays 22.1 vaccine development 2.2 vaccine efficacy testing33.1 in vitro efficacy testing of antivirals3.2 in vivo efficacy testing of antivirals +4

Epidemiological Risk Assessments (incl. reservoir competency studies, vector competency studies, identification of transmission routes, infectious dose assessments, meat and food safety studies)

4.1 viruses affecting only humans, rodents and dogs and cats4.2 viruses affecting farm animals ( incl. horses) and wildlife species55.1 disinfectant suspension tests 5.2 determination of physical inactivation properties 5.3 inactivation in contaminated animal products and carcasses66.1 veterinary teams trained to work with large animals under maximum

containment conditions

current UK facilities X X X X

facilities proposed for Pirbright Redev X X X X

facility essential to carry out this activityno facility currently capable of delivering activityfacility partially capable of activitiescurrent facilities capable of delivering activity

ACDP4 facilities

Capability for Virus inactivation studies

Veterinary Capability to deal with disease outbreaks in large animals

Antivirals Development Capabilities

Vaccine Development Capabilities (incl. farm animals)

Disease Diagnosis Capabilities

Too small facilities with extremely high overheads and little or no economy of scale High containment facilities are always expensive to build and to maintain. Due to the standard barrier facilities required, the cost for small facilities is disproportionately more expensive per unit of contained space. The provision of suitable resilience for all necessary systems makes them even less viable financially as a national facility,

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especially for in vivo work. The provision of greater capacity in very few large facilities enables the best use of the facility space over time and allows scheduled down times to have the smallest possible effect on the research programmes. The administrative burden for such facilities is a significant factor and there is no economy of scale in smaller facilities. The net cost per 1m2 can be more than triple in small facilities, which translates into very high costs for full economic costing. In state-of-the art SAPO4 facilities, the net cost per 1m2 of animal room may be between £30k and 90k and translates into significant costs for capital and depreciation under rules of full economic costing. There are no facilities in the UK for work on human hazard group 3+ and 4 pathogens in livestock species The UK capability for high containment work was discussed at a workshop convened by the former government chief scientist, Sir David King, in March 2005 (the report from this workshop is available from the HSE). In brief, there are no in vivo facilities capable of accommodating a national research effort on a newly emerging hazard group 4 pathogen that infects humans through contact with infected livestock species, (e.g. horses, cattle, sheep and pigs). Synergies between Diagnostic and Research Facilities are underutilised Facilities essential for a national emergency response to human and animal disease outbreaks are able to draw on a competent workforce working in a complementary manner (e.g. BBSRC-funded fundamental research at IAH Pirbright Laboratory complements the Defra-funded surveillance work in times of trouble and maintain this work force to further scientific progress in “peace” times. In the interest of specialisation, the activities of fundamental research and diagnostics have been separated completely in many Laboratories. In low-containment facilities with lower overheads, this concept may work, while in high containment facilities a capacity for suitable skills cannot be maintained with only diagnostic work. The risk is a shortage of skills in times of a national emergency if the numbers of science workers with the necessary competency are too low. Science Hotel Concept The high costs of high-containment facilities naturally limit the number and size of these facilities in the UK. Rather than having a (large number) of facilities scattered in the UK for in vivo work, better value for money is achieved by maintaining a small number of larger, very well equipped facilities, and to make these more accessible to the academic community. There are many benefits in a science hotel concept, but these have to be balanced against other issues like security, health and safety obligations and liabilities. THE STATE OF BIOLOGICAL CONTAINMENT FACILITIES IN THE UK UK investment into biocontainment facilities has been very restricted for some years and the UK has, as a result, fallen behind many international competitors as measured in scientific output on high hazard pathogens. Recent introduction of full economic costing was not matched with an increase in government funding. This has left government funded research facilities under resourced.

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Laboratory inspection regimes and the rationale and practicalities of the licensing system The Callaghan Review used prosecutions as a measure of the effectiveness of the regulatory framework. Prosecutions are expensive and often compromise the effective working relationship between the regulator and the duty holder. The interface between duty holder and regulator should be suitable to identify problems before they require prosecution. However, this situation requires suitable competence and resource within the regulatory authority in order to advise the duty holders in good time. At least in the past the regulators (HSE and DEFRA) have not been resourced to inspect in any detail the infrastructure underpinning containment laboratories.

Licensing System Any licensing system can only be as good as it is resourced and competent for the task. The principle of a licensing system is good in that it means shared responsibility between the regulator and the licensee. Thus the requirements for the operation have to be clearly defined by the regulator and, in turn, the licensee has clear performance targets. A notification and consent system gives full responsibility to the dutyholder. However, unlike a licensing system which by definition is restrictive, it gives the dutyholder control over their facilities and site, encouraging scientific development and flexibility. But it requires a good relationship with a well resourced regulator to work well. Where the regulatory requirements for facilities change, it is important that new rules are introduced with a sufficient lead time to be implemented.

BIOSAFETY TRAINING PROVISION FOR STAFF WORKING IN CONTAINMENT FACILITIES Training staff in biosafety is an essential element for the safe operation of any high containment facility. Biosafety training is not currently available as a UK approved standard, resulting in inconsistency across institutes especially at higher containment. This means that such training is unfortunately not always transferrable from/to other facilities and retraining in local arrangements is generally required. The cost benefit struggle IAH believes that good safety training is an essential complement to good facilities and is even more important in poorer facilities and the institutional culture has to reward good safety culture and competence at least equally high to scientific achievements.

DANGEROUS PATHOGEN STORAGE AND TRANSPORTATION During the past few years much attention has been paid to the security of pathogen storage and transportation. Because pathogens can replicate and the mechanisms for quantifying infectivity are only approximations, absolute quantities of pathogens cannot be recorded in a meaningful way. Laboratory biosecurity ( as defined by WHO and RCUK) has to become a new regulatory requirement for dangerous pathogens. It is important that the requirements for laboratory biosecurity are not conflicting with HSE requirements and the regulatory expectations are clearly communicated and

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proportionate to the risk. The risk is reduced by either reducing the likelihood and/or the severity of this risk. The severity can only be reduced by preventing the removal from the facility, while the likelihood will depend on a number of factors, such as the trustworthiness of the staff with access to the pathogens – not just the pathogen storage facilities and the layers of intruder protection around the pathogen storage facilities that prevent forced entry and removal. The key issue is the trustworthiness of the staff with access to the pathogens and how this can be maintained and assured. A competitive salary that draws in the best talents, a vetting procedure that identifies high risk candidates and a secure system for assuring protection to those put under pressure from outside to source material from a containment facility are necessary requirements. The effort that is put into protecting access to the critical pathogen storage is not much different from that for the pathogen handling laboratories, where the pathogen is cultured. This effort has to be evaluated against the difficulty of accessing such infectious material in the field: For many diseases it is very difficult to source the infectious material in the field because they are rare and/or highly lethal without appropriate safety precautions and equipment. Cost of Transportation Transportation of Dangerous Pathogens is now very expensive and restricts the beneficial exchange of clinical samples between developing countries and the UK. 8.9 The security of pathogens kept in the laboratory has to be balanced against

the availability of pathogens in the field. Any risk mitigation measures must be considered in light of the reduction in risks that they achieve. If a dangerous pathogen is abundant and available outside of the laboratory (i.e. in the field), security measures within the laboratory may not reduce substantially the overall risk, regardless of the extent and cost of the measures taken. For example, some veterinary high-risk pathogens are common in many countries and can be recovered easily from field with only limited scientific and technical expertise and, if the pathogen is not a zoonotic, with no risk to the individual. In contrast, many high-risk pathogens of humans are very difficult to obtain in the field without substantial risk to the individual.

MEASURES IMPLEMENTED WHEN PATHOGENIC MATERIAL CANNOT BE ACCOUNTED FOR The requirements for inventories have to ensure that they are easily complied with to prevent costly investigations into data recording errors. THE ROLE OF UNIVERSITIES IN OVERSEEING SECURITY CLEARANCE FOR RESEARCH STUDENTS WORKING WITH DANGEROUS PATHOGENS" ATAS - Academic Technology Approval Scheme (ATAS) There is a need to balance the accessibility of UK facilities for the essential training of diagnosticians from developing countries against the possibility of malicious staff/visitors/students A central security clearance of people with access to high containment facilities is

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desirable as the means of an individual university or institute are limited and cannot match government intelligence. It is important that this effort does not create an insurmountable impediment (in terms of time and cost) that could compromise the benefits gained from academic exchange. Reference laboratories for infectious diseases are also important training centres for diagnosticians and researchers from other countries that do not have the critical mass to maintain a cohort of competent staff from their own resources. While scientists and technical staff from other countries may pose a small risk, this is counterbalanced by their contributions to tackling key diseases at source in developing countries. The risk of natural introductions would be increased greatly without training centres overseas being maintained and populated with skilled persons. January 2008

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Memorandum 15

Submission from the Biotechnology and Biological Sciences Research Council (BBSRC)

INQUIRY INTO BIOSECURITY IN UK LABORATORIES Background 1. BBSRC13 is the UK’s principal funder of basic and strategic bioscience. To deliver

our mission, we support research and postgraduate training in universities and research centres throughout the UK, including seven BBSRC-sponsored institutes. We also promote knowledge transfer from basic research to applications in business, industry and policy, and foster public engagement in the biosciences.

2. As a major public funder of bioscience, BBSRC invests over £40M per annum in

research and training on a wide range of pathogens of plants, animals and humans. We work with sister research councils such as MRC and NERC where our research interests are complementary. Over half of BBSRC’s funding for research on plant and animal pathogens is deployed through key BBSRC-sponsored institutes (see below), with the remainder going to leading University departments.

In summary BBSRC wishes to make the following main points to the Committee:

• Excellent basic bioscience research is essential to combat the threat of dangerous pathogens and to minimise their economic and social impact. It is not only human and livestock pathogens that present a risk but also those of key crops upon which the farming economy and food production depends.

• Most of the UK’s capacity to work on dangerous pathogens of livestock and plants rests in BBSRC-sponsored institutes. This is particularly the case with animal disease where the Institute for Animal Health (IAH) is a major international centre of excellence.

• The BBSRC institutes are a vital national resource and provide the Government with crucial expertise and unique facilities not available in universities.

• It is essential that institutes such as IAH are financially sustainable to maintain investment in skills and modern well equipped facilities, are able to work with dangerous pathogens and are well governed.

• The ongoing redevelopment of IAH-Pirbright as a national centre for surveillance, diagnosis and research on exotic viral pathogens of animals must continue with all partners (BBSRC and Defra) committed and sharing the full costs.

3. In making this submission we focus on the first three points raised by the IUS

Committee (current capacity, state of biosecurity facilities and 13 BBSRC, a non-departmental public body, is one of seven Research Councils supported through the Science and Innovation Group of the Department for Innovation, Universities and Skills (DIUS). BBSRC works with partner Research Councils through RCUK.

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inspection/licensing). The remaining points are covered in the joint response from BBSRC, MRC and NERC via RCUK.

Dangerous pathogens14 pose a significant economic and social threat 4. Infectious pathogenic organisms pose a major risk of disease to plants (crops),

animals and people, where the health, economic and social impacts are potentially huge – for example, the 2001 foot and mouth disease (FMD) outbreak was estimated to have cost the UK economy around £8 billion15.

5. The threat posed by dangerous pathogens is increasing with growing

international movement of people, livestock and agricultural products. This is compounded by the effects of climate change that expose the UK to emergent diseases – e.g., the first cases of bluetongue virus in the UK were recorded in summer 2007. Zoonotic infections16, including major foodborne pathogens, also continue to pose risks to public health. These include transmissible spongiform encephalopathies (e.g. BSE/vCJD), avian influenza, SARS, Salmonella and E.coli O157.

6. Plant pathogens (fungi, bacteria, viruses and invertebrates), although not directly

a human health issue, nevertheless have the potential to cause significant economic and amenity loss. In the 1970s the introduction of Dutch elm disease changed the face of the UK countryside with the destruction of millions of trees. Recently Sudden Oak Death has arrived, prompting concerns that further losses of native trees may occur. It is only the availability of modern fungicides and other agrochemicals that prevent significant yield losses of many priority crops due to pathogens.

7. Despite the UK’s phytosanitary regulations and practices (administered by Defra)

several significant plant diseases pose a threat to the UK. Warmer summers could result in the emergence of diseases that have not previously thrived under UK conditions. One example is black stem rust; an aggressive disease of wheat. In 2007, a particularly virulent strain of this disease (Ug99) spread to Yemen from East Africa, following the first discovery in Uganda in 1999. There are now concerns that it could spread both to Europe and Asia. UK wheat cultivars have not been bred to resist this disease, and its arrival could result in significant increases in fungicide use and associated cost increases to the industry. A precedent for such pandemic expansion has already occurred with the spread of soybean rust out of Africa into South America in 2001 (and subsequently the southern USA), resulting in the need for fungicide treatment on the soybean crop for the first time.

Science is vital to combat the threat of dangerous pathogens 8. High quality basic and strategic bioscience is essential to prevent or treat disease

outbreaks. Research provides an understanding of the infectious organism and its interaction with the host. This knowledge underpins the development of rapid and reliable diagnostic tests, and effective vaccines, therapies or other control strategies. With the support of mathematical modelling and epidemiological data,

14 We take dangerous pathogens to mean those included in: The Advisory Committee on Dangerous Pathogens (ACDP) Approved List of biological agents, for the purposes of the COSHH Regulations 2002 (particularly the Group 3 and Group 4 biological agents); Specified animal pathogens listed in Part I of the Schedule to the Specified Animal Pathogens Order 1998 ; Human and animal pathogens covered by the Home Office ‘Pathogens and Toxins Guidance’ (ATCSA 2001 Schedule 5 Order 2007 Notes; and The Plant Health (England) Order 2005 as amended, and equivalent regulations 15 Economic costs of the foot and mouth disease outbreak in the United Kingdom in 2001. D. Thompson et al (2002). Rev. sci. tech. Off. int. Epiz., 21 (3), 675-687 16 Zoonotic infections are those that can pass from animals/livestock to people

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scientific research determines our ability to implement an effective response to dangerous pathogens and to minimise their impact.

9. Examples of where science has been instrumental in responding to outbreaks

include the recent cases of bluetongue in the East of England (see Annex 1 for the bluetongue story) and in the 2007 FMD outbreak, where state-of-the-art genome sequencing promptly identified the order in which farms became infected (techniques developed from fundamental genetic research at IAH), and where rapid diagnosis was provided through the development of a lateral flow device for the detection of FMD virus particles. Results were delivered to Defra within one hour of the samples being received at Pirbright.

Overarching responsibility for biosecurity 10. Where research is undertaken through BBSRC grants to universities, the

university is responsible for biosecurity. Where the research is undertaken in a BBSRC institute then health and safety and biosecurity are the responsibility of the institute Director, who is accountable to Council though the BBSRC Chief Executive and is responsible to the Chair of the respective governing body. The Director cannot delegate or devolve this accountability but may delegate duties and authority to senior members of the management team. The remainder of this submission refers mainly to the institutes.

Points raised by the IUS Committee a) The current capacity for research on dangerous pathogenic material in the UK and the capability to conduct research on the causative agents of disease that may emerge at a future time. Animal pathogens 11. Capacity for research on dangerous pathogens of animals is concentrated mainly

in the BBSRC-sponsored Institute for Animal Health and the Veterinary Laboratories Agency. There is further capacity, though small in comparison to IAH and VLA, at the Roslin Insititute (work on transmissible spongiform encephalopathies), Moredun Research Institute (Scottish Government-sponsored) and a few universities, typically in vet schools.

12. The IAH is a world leading centre17 of excellence for research on diseases of

farm animals and has disease containment and other facilities that are unique in the UK. IAH hosts world, EU and regional reference laboratories for a number of diseases and its work provides vital support to Defra through independent scientific and policy advice, disease surveillance, diagnosis and response to disease outbreaks. The journal Nature in an editorial in its 20 September 2007 edition stated:

“The IAH is central to Britain’s ability to protect itself against future outbreaks of animal disease, whether unleashed by natural causes, human error or enemy action. It also has a vital role in these issues internationally. To fulfil these roles the institute requires (and indeed has) a world-class research base that lets it address key scientific questions and at the same time maintain and develop the techniques needed to identify and deal with diseases.”

17 Research within IAH is split over two sites: IAH-Compton - endemic disease, (e.g. TB, Salmonella); unique resources for immunology in cattle (MHC herd) and chicken (for avian flu work). IAH-Pirbright - exotic viral diseases (e.g. foot and mouth, bluetongue), world reference laboratories. Unique facilities in the UK for working with disease agents in large animals.

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13. The ability of IAH-Pirbright to work with pathogens such as foot and mouth disease virus in large animal hosts in bio-containment facilities is a major asset and is lacking in the university sector.

Foodborne zoonoses 14. UK capacity to conduct research on pathogens responsible for foodborne

zoonoses is located mainly in the BBSRC Institute of Food Research (IFR), IAH and strong university groups e.g. Cambridge and Birmingham. IFR currently has the capacity to conduct research across the full range of foodborne and gut pathogens and associated toxins, working with organisms at ACDP Hazard Group 1, 2 and 3. IFR has one of the very few facilities within the UK able to deal with Clostridium botulinum (the causative agent of botulism) and any associated major outbreak.

Plant pathogens 15. Defra Plant Health Division administers and issues licences to import, move or

keep prohibited plant pathogens (and invertebrates). Capacity to work on quarantined or licensed plant pathogens is concentrated in BBSRC institutes such as Rothamsted Research and the John Innes Centre, or in other PSREs such as the Scottish Crop Research Institute, Central Science Laboratory (Defra) and Forest Research. Some universities, especially those linked to former research institutes, such as Warwick HRI, also have some capability. The UK commercial sector has limited capability with the shift of the agrochemical and biotech industries to mainland Europe and the USA. Syngenta (Jealott’s Hill) is the only large industry research facility remaining.

Future capability? 16. It is not possible to predict the full range of pathogens that will threaten the UK in

the future; e.g. avian flu hardly featured in disease strategies a few years ago. It is clear, however, that climate change and increased mobility of people, livestock and food products will increase the disease threats at our borders. The UK must therefore maintain sufficient flexible research capability to work not only on the pathogens that we can see pose a potential threat but also on those that will surprise us.

17. In the field of animal disease research, IAH is clearly a national centre but its

facilities and infrastructure are in need of replacement (see below on ‘state of UK facilities’ for more details). The planned redevelopment of IAH-Pirbright by BBSRC and Defra will result in state-of-the-art containment facilities due to be commissioned in 2012. But the cost has risen and it is vital that all partners make the necessary funding commitments to see the project through.

18. The future capacity for research on dangerous pathogens of animals needs to be

considered more widely than just BBSRC Institutes. There are benefits to maintaining the strong linkages between basic and strategic research and wider diagnostics. We are therefore of the view that there needs to be an overarching national strategy, involving all associated public funding bodies (e.g. Defra, MOD, HEIs and devolved governments), and considering resources at Veterinary Laboratories Agency (VLA), Porton Down and the veterinary schools together with those of BBSRC institutes.

19. The UK’s current capacity to work on zoonotic organisms and emergent plant

pathogens is probably adequate. Facilities for work on insect-transmitted plan diseases, such as those caused by viruses and phytoplasmas, which are likely to increase in importance with climate change, are currently limited to a few

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Institutes (e.g. BBSRC-sponsored Rothamsted Research) that have containment facilities for both insect vectors and microbial pathogens, and hence are well placed for future eventualities. There are now concerns however that UK expertise in practical crop pathology is eroded to the extent that we do not have sufficient expert capability in place to quickly indentify and deal with all of the potential plant disease problems that could emerge. We accept that this is a side issue to containment facilities, but it is highly relevant to future capability.

b) The state of biological containment facilities in the UK. 20. We are aware of no specific issues with the containment facilities necessary to

conduct research on foodborne zoonotic organisms or plant pathogens for which BBSRC is the funder. In fact BBSRC institutes have some of the best facilities nationally. The remainder of this section of the submission therefore deals with the state of biological containment facilities for work on animal pathogens.

The IAH estate 21. Over the past decade, BBSRC has been actively restructuring its institutes to

maintain crucial capabilities and secure national facilities to support their long-term sustainability.

22. Given the nature of the work at IAH, modern facilities and high-level biosecurity

must be of the utmost importance. BBSRC has already recognised the need to modernise the IAH estate and has set in train a multi-million pound investment as follows:

Pirbright 23. In 2002 BBSRC Council commissioned a review18 (chaired by Professor Keith

Gull) on IAH-Pirbright. The report found the condition of much of the Pirbright site infrastructure was unsatisfactory and identified a clear need for urgent investment in new laboratories and facilities. BBSRC Council quickly took forward the recommendations from the report, leading to the ongoing major redevelopment of the Pirbright site in partnership with Defra following a further review of UK facilities Dr by Richard Cawthorne, the then Deputy Chief Veterinary Officer.

24. The redevelopment includes the relocation of the virology work at the VLA from

its current location at Weybridge to the Pirbright site, joining IAH virology research in a new state-of-the-art laboratory complex. Once the new development is operational (scheduled for 2012) it will be one of the foremost facilities in Europe and probably the World.

25. The cost of the project was estimated in 2003 at £121M to be jointly funded by

BBSRC, the DIUS Large Facilities Capital Fund and Defra. But the cost now looks certain to rise to accommodate regulatory changes, market conditions and high inflation for building work. It is vital that the partners in this ambitious development continue to invest and meet fully their share of the revised cost of £165m.

26. Following the foot and mouth outbreak in summer 2007 the Government

commissioned two reports to investigate any possible link between the outbreak and the Pirbright site, which is shared by the IAH and Merial Animal Health Ltd.

18 Review of the Institute for Animal Health - Pirbright Laboratory:

http://www.bbsrc.ac.uk/organisation/policies/reviews/operational/0207_iah_pirbright.html

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The HSE was asked to investigate potential breaches of biosecurity and Professor Brian Spratt was asked to examine more broadly the safety of UK facilities handling FMD virus.

27. Whilst the CL4 facilities at IAH-Pirbright met Defra licensing requirements, the

HSE report concluded that it was highly likely that the FMD virus originated from the Merial or IAH sites at Pirbright, most likely through a drain that was no longer in good repair, and that the virus was carried off site by a contractor’s vehicles. If this is correct then it is an unfortunate irony that the presence of contractors on site was part of the construction of the new high containment laboratories.

28. Professor Spratt in his report underlined that the redevelopment at IAH-Pirbright

should continue as a matter of urgency – a point clearly endorsed by the Government in its formal response19. Professor Spratt made two recommendations that are particularly relevant to the UK’s future capability:

• Recommendation 10 urges a re-examination of the Pirbright development plans to ensure that all safety critical issues have been addressed.

• Recommendation 12 proposes that given biosecurity is of utmost importance then there should be a review of funding, governance and risk management at IAH-Pirbright to ensure an appropriate focus on biosafety and biosecurity in the future

29. BBSRC is pursuing both of these recommendations with due urgency. The latter

review (recommendation 12) is being chaired by Professor Sir John Beringer (ex ProVC of the University of Bristol and current member of the Government’s Council for Science and Technology). BBSRC Council has asked Sir John’s review to look at the future of IAH as a whole (not just the Pirbright site) and he will report in April 2008 on the most appropriate future governance, funding and risk management arrangements for this key institute. The IUS Committee may wish to invite Sir John to give oral evidence in its current inquiry.

Compton 30. The IAH-Compton site, with its focus on research on endemic diseases of

livestock, also requires major work to bring it to modern standards; some of the buildings are no longer usable. An estates strategy is being developed to modernise or replace the Compton research facilities and meet regulatory needs. Options include redevelopment at Compton or moving to another site, possibly co-location with Pirbright.

31. Pending the outcome of Sir John Beringer’s review, and if Compton is to be

replaced in full, then the necessary investment could be as high as £220M over the next 6-7 years. BBSRC would meet 50% of the costs and would be looking for a substantial contribution from the DIUS Large Facilities Capital Fund.

c) Laboratory inspection regimes and the rationale and practicalities of the licensing system. 32. We agree with the recommendations made recently in the report by Sir Bill

Callaghan on the regulatory framework for animal pathogens20. In BBSRC’s view the new single regulatory framework, which is to be in place by the end of 2008, must address the following:

19 http://www.defra.gov.uk/animalh/diseases/fmd/investigations/pdf/govstatement_fmd2007.pdf 20 http://www.defra.gov.uk/animalh/diseases/fmd/investigations/bill-callaghan.htm

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• There should be a single, independent regulator for all aspects of work involving animal pathogens. The regulator needs to be independent of, and separate from any funder, customer or governor. We endorse the proposal that HSE takes on this role.

• There should be a single regulatory framework that is applied consistently and transparently. It emerged from the Spratt and HSE reports into the first phase of the 2007 FMD outbreak that the conditions of IAH and Merial’s SAPO 4 licences issued by Defra were different, even though the two organisations were on the same site, sharing infrastructure and working with the same viruses, albeit in vastly different quantities – IAH in millilitre volumes and Merial in thousands of litres.

The crucial inconsistency was that Merial’s SAPO 4 licence allowed the company to discharge live virus material into a drainage system whereas the IAH licence did not. The drain was neither designed for live virus nor operated on the basis that live virus would be entering the system; furthermore the lease from IAH to Merial prohibited the release of such substances in to the drain.

There was a lack of transparency because neither Defra nor Merial informed IAH of the Company’s licensing conditions. Defra took the view that all licensing matters are confidential between Defra and the licensee, even when there were two parties operating on the same site and using shared infrastructure. Our view, reinforced by events subsequent to the FMD outbreak, is that all aspects of regulation must be transparent and any changes to a licence for one operator on a site where there are multiple operations must be consulted upon with all those occupying the site.

• There must be an expert regulator that understands the risk and cost benefit balance of its regulatory impacts and has the capacity and expertise, potentially international, in biocontainment infrastructure to audit to an appropriate level containment facilities such as those at IAH. Again, we would have confidence in HSE being such a regulator.

January 2008

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Annex 1

The Science behind Bluetongue Bluetongue virus (BTV) causes a severe disease in some ruminants such as sheep and cattle. Biting midges spread the virus between animals, and sheep are particularly prone where symptoms include fever, lameness, rapid loss of condition and muscle wastage. Bluetongue is historically rare in Europe but over the past eight years it has killed over 1.5 million sheep, across twelve EU countries. Major outbreaks in the Mediterranean Basin and Balkans in 1998 were followed by the first cases in northern Europe in 2006 and the first in the UK in 2007. Researchers at the IAH-Pirbright laboratory have long been tracking the progress of bluetongue northwards and advising that it would eventually reach the UK. Institute scientists were the first to show that the bluetongue virus could swap hosts to other species of midge and that infected insects could be carried long distances on the wind. In collaboration with the Universities of Cambridge and Liverpool, IAH scientists developed new mathematical models that showed the critical role of temperature in the infection process. Too cold and the virus will not build-up sufficiently in the midge for effective infection; too hot and the midges might die before they are able to transmit the virus. Crucially the work predicted that the UK would be suitable for the establishment and spread of bluetongue. The UK farming community was bracing itself for a bluetongue outbreak in 2007 after IAH scientists in collaboration with the Met Office used meteorological analysis of the northern European outbreak in 2006 to show that the temperatures were ideal for rapid multiplication of the virus in the midges, and easterly winds in 2007 could easily carry the biting insects to south eastern England. IAH is the Bluetongue Reference Laboratory on behalf of the European Union and the World Organisation for Animal Health (OIE). As a world centre for bluetongue research IAH has helped to provide detailed knowledge of the virus and its molecular structure; knowledge that is essential for rapid and accurate diagnosis. On the same day in 2007 that IAH confirmed the presence of bluetongue virus in Suffolk, tests showed that the virus was of the same serotype as was in Belgium and neighbouring countries, thus confirming earlier predictions about the spread of the disease. During the 2007 bluetongue outbreak, IAH has been able to make a diagnosis within 2 hours for the antibody test, and within 6 hours for the test that detects the bluetongue virus’ genetic material (RNA) on blood samples received from a farm where bluetongue is suspected. This service is provided 7 days a week. The testing of blood samples taken from animals in the control zone (in which infected animals have been confirmed) and in the surrounding protection zone helps to identify whether the disease is spreading further, and the limits to which it has spread. The institute scientists and collaborators are currently investigating many aspects of bluetongue transmission and risk in several ongoing projects, using techniques from field collections and laboratory experiments to computer modelling and satellite imagery. Recent work has described a novel mechanism for the virus to conceal itself within host immune cells, which may offer some insight into the puzzling ability of the virus to reappear in areas after long periods of absence and without any apparent reintroduction event.

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Memorandum 16

Submission from Universities UK

Biosecurity Universities UK is pleased to submit written evidence to the Innovation, Universities, Skills and Science Select Committee on the issue of biosecurity. This note makes some general points about the current regulatory regime and how universities fit into this, and some of the issues that arise. Introduction The need to secure substances or technologies that could have the potential to be misused or harm the public is taken very seriously by universities. There are already a number of pre-existing frameworks that either directly or indirectly regulate this area, covering universities and other research labs. It is also an area of regulation that is not static, with revised or additional requirements encouraging more advanced procedures. The former Science and Technology Committee visited this issue in 2003 and since then there have been a number of new developments. Regulation in this area is often not a straightforward issue. Any controls that prevent misuse or spread of substances or technologies can also potentially impact upon legitimate scientific activity. In many cases the substances, knowledge and technologies in this area are termed ‘dual use’. The ‘dual use’ dilemma faced by policy makers is that compared to hostile applications there are a large number of peaceful purposes. Universities are also large diverse organisations, which have a significant number of regulatory requirements placed on them, and it is important to bear in mind the burden this creates. Getting the regulatory balance right can therefore be difficult. Current regulatory landscape Health and Safety at Work Act 1974, whilst primarily designed to enhance safety in the workplace does, for example, give detailed guidance on handling dangerous pathogens, and therefore has benefits for security purposes. The Health and Safety Executive (HSE) regulate the condition of containment facilities and university labs are required to meet definitive standards. The HSE will undertake inspection on application of a license, or every 3-4 years. Recording of materials is covered under the H&S Act, though there may be some merit in exploring how this can be improved upon. The processes for logging materials under the Human Tissues Act may provide an example of good practice. Biosecurity training is currently limited within the sector, though there is currently a course run by the University of Sussex, jointly with the Medical Research Council (MRC). Universities UK would support the expansion of such training schemes within the sector, both for academic and relevant non-academic staff.

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2001 Anti-Terrorism Crime and Security Act The aim of this legislation is to provide oversight of the possession and transfers of technology, so as to stop its application for illicit purposes. The 2001 Anti-Terrorism Crime and Security Act amended the Biological Weapons Act 1974, and placed new legal obligations on the scientific community to ensure that technologies are not misused or misappropriated. The Act is enforced through the police force. The police from a local constabulary will check security measures in universities. A recent study undertaken by the Science Policy Research Unit (SPRU), at University of Sussex, shows that legislation in this area has been well implemented and has not had any significant negative impact on research activity21. BTWC (Biological and Toxic Weapons Convention) The Foreign and Commonwealth Office (FCO) leads for the UK on the Biological and Toxic Weapons Convention (BTWC) 1972, which is implemented in UK law by the Biological Weapons Act 1974. There are regular international meetings that explore how the Convention can be strengthened. There is currently no verification mechanism for countries signed up to BTWC, unlike the Chemical Weapons Convention, which has validation and enforcement through the Organisation for the Prohibition of Chemical Weapons (OPCW). OPCW do regular inspections and compile returns. Universities have to submit reports to BERR, which it then submits to OPCW. There is an inventory of classified chemicals, and usually, communication with BERR lies with university safety officers. Guidance from MRC, Wellcome Trust and BBSRC In September 2005 the UK’s three leading bioscience research funding agencies published a joint policy statement on reducing the risk of the research they fund being misused for harmful purposes by terrorists, or others. The Medical Research Council (MRC), the Wellcome Trust and the Biotechnology and Biological Sciences Research Council (BBSRC) issued the statement in light of public concerns that bioscience research could be misused in the development of bioweapons. Following consultation across the organisations’ funding and advisory committees the MRC, Wellcome Trust and BBSRC examined how existing procedures might be strengthened to heighten awareness amongst the scientific community and identify and assess risks of misuse at the initial grant application stage. This process has led to a series of common changes to each organisation’s policy statements, guidance and procedures. These include changes to funding application forms, the development of clear guidance for funding committees and modifications of organisational guidelines on good practice in research. Export control regulations The Export of Goods, Transfer of Technology and Provision of Technical Assistance (Control) Order 2003, implemented under the Export Control Act 2002, contains controls on biological weapons and regulates the transfer of intangible technologies. The new controls (and indeed the old ones) have significant implications for scientists working in HEIs. 21 Ref

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Universities UK worked with the DTI as the regulations developed to help to ensure that the rules were effectively communicated and understood within the academic scientific community. However, there remains some uncertainty about the extent to which the academic community is fully aware of the new regulations and obligations. The then DTI developed an explanation note for scientists (with input from Universities UK, Royal Society and Medical Research Council). This was circulated to all members of Universities UK. Universities UK are currently in discussion with the BERR on how the regulations and requirements can be promoted further. Academic Technology Approval Scheme (ATAS) The former Voluntary Vetting Scheme (VVS) focusing on postgraduate research students in specific subject areas from specific countries was reviewed by the FCO and Cabinet Office from 2004-07. The review was initiated following concerns about the effectiveness of the scheme as a counter-proliferation measure raised both by HEIs and the Foreign Affairs Select Committee. A new scheme, the Academic Technology Approval Scheme (ATAS), has been developed and the FCO began formal operation of the new scheme in November 2007 following a two-month trial period. Ahead of its implementation there was considerable dialogue between the higher education sector and the FCO to try to ensure the new scheme operated appropriately. It is also Universities UK’s understanding that the timescales outlined for the scheme are shorter than those in operation in a number of competitor countries including the USA. As at January 2008 Universities UK has not received any significant concerns from HEIs about the new scheme. The view from the sector appears to be that the scheme is a proportionate response to an important national security issue. HEIs welcome the fact that the scheme applies equally to all HEIs and all relevant students. It is also appropriate that the UK Government controls this vetting process rather than the situation that operated under VVS where HEIs had to decide whether to refer applicants to the Government or not. Universities UK do not believe that further vetting schemes would be required at lab level. This would prove difficult and burdensome for institutions to manage and would largely duplicate vetting schemes already in place at a national level. However, it must be recognised that the scheme has not yet operated during the peak period for student recruitment and admissions. If the ATAS scheme is not able to process applications within expected timescales in June, July, August and September it could lead to delays in students entering the visa system and also lead to delays in the visa system. Delays in the visa system may mean that students miss the expected start of their programmes. Key features

• The new scheme applies to all international (non-EEA) postgraduate research students in specific subject areas (identified by the Joint Academic Coding

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System (JACS)) and a small number of Masters programmes in specific subject areas.

• It requires students who fall into the above category to seek and obtain ‘clearance’ before they can apply for a visa or entry clearance to come to the UK or to renew a visa if they are already in the UK.

• ‘Clearance’ is sought through a free, online application process to the FCO. • The student is asked to provide information on their proposed research area in

the application. • The FCO aim to decide on most applications within 5-10 working days and all

applications within three weeks. • Participation in ATAS has been mandatory from 1 November 2007. • Once ‘clearance’ has been obtained a student is able to enter the visa process

and as part of the visa process students are required to provide evidence of the ‘clearance’ in the form of a ‘clearance certificate’.

Issues There remain some issues to consider around the new scheme.

There could be difficulties for students who are renewing visas and require ‘clearance’ as length of leave does not always correspond to course length so there could be students who have progressed onto research programmes using existing visas but then seek ‘clearance’ and are refused. The FCO has said that this scenario is very unlikely but Universities UK has already been alerted to at least one case of an ATAS refusal involving a student who was already part way through their research programme. This scenario can cause significant difficulties for the student involved, the HEI involved and obviously does not reflect well on the UK. It is still a comparatively new scheme. Work needs to continue to ensure information about the scheme is communicated both overseas and in the UK. The new system does not link directly into the existing visa system and will not link into the new points-based immigration system. If the turnaround time for the processing of applications becomes longer it could present difficulties for the recruitment and admission of international postgraduate students. Subject areas covered by the scheme The scheme primarily focuses on postgraduate research students but a small number of taught Masters in certain subject areas are included. If the exit qualification will be a Doctorate or Masters by Research (MRes, MPhil etc but not MEng, MPharm, MSci) the following subject areas are included:

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Subjects allied to Medicine: JACS codes beginning:

• B1 – Anatomy, Physiology and Pathology • B2 – Pharmacology, Toxicology and Pharmacy • B9 – Others in Subjects allied to Medicine

Biological Sciences: JACS codes beginning:

• C1 – Biology • C2 – Botany • C4 – Genetics • C5 – Microbiology • C7 – Molecular Biology, Biophysics and Biochemistry • C9 – Others in Biological Sciences

Veterinary Sciences, Agriculture and related subjects: JACS codes beginning:

• D3 – Animal Science • D9 – Others in Veterinary Sciences, Agriculture and related subjects

Physical Sciences JACS codes beginning:

• F1 – Chemistry • F2 – Materials Science • F3 – Physics • F5 – Astronomy • F8 – Physical and Terrestrial Geographical and Environmental Sciences • F9 – Others in Physical Sciences

Mathematical and Computer Sciences JACS codes beginning:

• G1 – Mathematics • G2 – Operational Research • G4 – Computer Science • G7 – Artificial Intelligence

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• G9 – Others in Mathematical and Computing Sciences

Engineering JACS codes beginning:

• H1 – General Engineering • H2 – Civil Engineering • H3 – Mechanical Engineering • H4 – Aerospace Engineering • H5 – Naval Architecture • H6 – Electronic and Electrical Engineering • H7 – Production and Manufacturing Engineering • H8 – Chemical, Process and Energy Engineering • H9 – Others in Engineering

Technologies JACS codes beginning:

• J2 – Metallurgy • J4 – Polymers and Textiles • J5 – Materials Technology not otherwise specified • J7 – Industrial Biotechnology • J9 – Others in Technology

1. Subjects included for Taught Masters as well as Doctorate and Masters degrees by research (but not MEng, MPharm, MSci):

• F2 – Materials Science • F3 – Physics (including Nuclear Physics) • H3 – Mechanical Engineering • H4 – Aerospace Engineering • J5 – Materials Technology not otherwise specified

Conclusion Universities take their responsibilities for biosecurity very seriously. As has been outlined in this note there are a number of legal and regulatory requirements covering the condition and maintenance, and security of university labs. There are also wider requirements on the exchange of knowledge and technologies, processes to vet students, and conditions and requirements outlined by funders of research. Universities UK believe that the current framework of regulation, which has developed over time, provides a high level of reassurance. Any further regulation or

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requirements could have the potential to duplicate what is already there, damage legitimate scientific activity, or create significant burden for universities. Further requirements, must also; of course be proportionate to the risk. Any further proposals in this area must therefore be considered very carefully. We are mindful that processes can always be improved and have indicated some areas where we feel this could be the case e.g. more widespread biosafety training. January 2008

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Memorandum 17

Submission from the Academy of Medical Science

1. The Academy welcomes the opportunity to respond to the Innovation,

Universities and Skills Committee inquiry regarding ‘Biosecurity in UK Research Laboratories’. The Academy of Medical Sciences promotes advances in medical science and campaigns to ensure these are translated as quickly as possible into benefits for society.

2. Overall, the Academy considers that existing regulations and standards of

security and safety in UK laboratories are good. We emphasise that it is essential for the UK to maintain its excellent reputation for highly competitive research into dangerous pathogens and to attract the best researchers from around the world. The Academy also stresses that high quality research into dangerous infectious agents is essential to equip the UK to deal with public health emergencies and any bioterrorist threats; the risks associated with this research are low and far outweighed by the benefits. However, we are aware that the consequences of accidental release of a hazardous pathogen may be severe, thus, measures must be taken to ensure that all high category facilities are adequately monitored, managed and well maintained.

3. The current capacity for research on dangerous pathogenic material in

the UK and the capability to conduct research on the causative agents of disease that may emerge at a future time

The UK maintains a competitive edge in fields of research concerning dangerous pathogenic material. However, whilst the current capacity of category 2 and 3 labs in the UK is sufficient, the Academy considers that capacity in category 4 labs should be improved for continued prominence in these research fields. At present, the majority of category 4 facilities are focused in the South of England and provision of a greater number of such facilities in the North of England would be beneficial. We consider that these facilities should be fully integrated with reference and research laboratories.

4. The uncertain nature of future threats and continuing risk of emerging zoonotic diseases also underscores the need for adequate infrastructure in the UK that can support a broad range of human and veterinary research, despite the considerable cost of building and maintaining category 4 units. A system of upgrading category 3 facilities to category 3+ could be considered in line with an assessment of the need to develop a greater number of category 4 facilities. We also note that a balance must be maintained between capacity for both hazardous bacterial pathogens and pathogenic viruses.

5. UK expertise was mobilised rapidly during the outbreak of Severe Acute

Respiratory Syndrome (SARS) in 2002-3, particularly by HPA, but this would not necessarily have been possible for other pathogens. Additionally, in this case, funds for SARS research were mainly mobilised from University sources. The time required to fulfil containment regulations would have made it difficult to initiate a SARS primate study rapidly in the UK, if it had been necessary. Thus, the use of a generic Home Office project licence for the UK could be considered in order that imperative research may proceed, should the public health need arise.22 The emergence of SARS in 2002, combined with the

22 Academy of Medical Sciences, 2003. Severe Acute Respiratory Syndrome (SARS). Accessed January 2008 at: http://www.acmedsci.ac.uk/p99puid21.html

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recent outbreak of Foot-and-Mouth Disease virus (FMDV), demonstrate the need to mobilise expertise with speed. Thus, in addition to developing sufficient infrastructure to capitalise on the expertise currently available, the need to prepare the next generation of expertise and to maintain a cadre of appropriately trained staff must be considered.

6. The state of biological containment facilities in the UK

Overall, the safety record of UK laboratories is good and inspections carried out by the Health and Safety Executive (HSE) ensure that bio-containment facilities are functioning appropriately. However, the accidental release of FMDV at the Pirbright laboratories in August 2007,23 demonstrates the need for effective governance, clear ownership of research sites and allocation of adequate funds for the maintenance of high category sites. Maintaining negative pressure required in a category 3 research laboratory is more challenging in older buildings and new designs of negative pressure laboratories within existing rooms may need to be considered, despite the costs entailed. Inspections should include appropriate checks that infrastructure is safe and well maintained.

7. Laboratory inspection regimes and the rationale and practicalities of

the licensing system

The Academy welcomes the proposal to develop a single regulatory framework for the regulation of laboratories covering the handling of human and animal pathogens.24 Use of a single independent regulatory body will improve the clarity of messages delivered and will unify approaches to research on human and animal pathogens.

8. The Academy is aware that there is rigorous attention to compliance with HSE

regulations by safety officers and high safety levels will be assured by good working relationships between safety officers and HSE representatives. However, we also note that whilst inspections are a necessary component of ensuring laboratory safety, a multiplicity of inspections can unduly affect continuity of research, owing to the need to fumigate and clear laboratories. Nevertheless, inspection regimes for high containment laboratories must continue to ensure that access is secure, movements are recorded and that equipment is functioning appropriately.

9. We are concerned that there is a tendency for the rationale used by the HSE and

relevant bodies regarding regulations for high containment laboratories to be based on the concept of preventing aerosol or droplet dissemination. Yet, a number of hazardous pathogens, such as HIV, are not airborne thus regulations must take account of other methods of dissemination.

10. Biosafety training provision for staff working in containment facilities

The Academy considers that biosafety training provision for staff is generally of a good standard across the board and supports HSE requirements to ensure

23 Professor Brian Spratt CBE FRS (August 2007). Independent review of the safety of UK facilities handling Foot-and-Mouth Disease Virus. Accessed January 2008 at: http://www.defra.gov.uk/animalh/diseases/fmd/investigations/pdf/spratt_final.pdf 24 http://www.defra.gov.uk/corporate/ministers/statements/hb071213.htm

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adequate standards of training and record keeping. The majority of training is likely to take place at the research site, thus standards may vary markedly between institutions. Nevertheless, laboratory inspections would ensure that training is appropriate by quickly identifying poor safety standards.

11. The maintenance and recording practices surrounding the storage and transportation of dangerous pathogens

Overall, we believe these practices to be adequate but highlight that responsibility for good practice remains with the University or research institute. Adequate recording procedures are assured by logging of samples both prior to entrance into containment 4 facilities and within containment 4 facilities. Monitoring of such practice would present significant logistical issues. Despite this, effective recording of the use and storage of pathogens could be improved by using currently available monitoring software. Additionally, both national and international rules for transport of dangerous pathogens and material assure that samples can only be shipped if they are properly packed and accompanied by appropriate documentation. One caveat is that it has become progressively more difficult and more expensive to transport dangerous pathogens and improvements could be made to address this. Further barriers to efficient transport of pathogens would unduly affect collaboration and the progression of scientific research.

12.Measures implemented when pathogenic material cannot be

accounted for

Samples stored in category 4 facilities are routinely audited on a monthly and quarterly basis, which would highlight whether any pathogenic material cannot be accounted for. Further investigation by the Safety Officer and reporting to the Home Office and Police would ensure that any discrepancies are reported and appropriately managed.

13. Continuing dialogue between the HSE and researchers and/or Safety Officers is important for ensuring that all pathogenic material is accounted for and appropriate laboratory practice and waste disposal maintained. Requirements for appropriate sealing and detailed labelling of transported material prevents any hazard from being presented in the event of material being lost during transit.

14.The role of universities in overseeing security clearance for research

students working with dangerous pathogens

The Academy is concerned by the ability of universities to refer certain applicants, suspected of attempting to further knowledge that could threaten national security, to the UK Government’s Foreign and Commonwealth Office (FCO) for security checks through the Voluntary Vetting Scheme. Between 1998 and 2004, 2419 individuals were volunteered under this system and the FCO advised that 260 individuals be declined admission between 2000 and 2004.25 We stress that international researchers make an immensely valuable contribution to the enhancement of scientific knowledge and emphasise the importance of attracting talented researchers from around the world to UK research universities. Thus, we consider it essential that security clearance does not unduly exclude or delay

25 http://www.fco.gov.uk/Files/KFile/VVS.doc

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applications from students or post-doctoral scientists with a particular nationality. We stress that free international movement of scientists is critical to scientific collaboration and activity. We also note that the voluntary nature of referral to this FCO scheme inevitably creates wide variation between institutions in the extent to which further security checks are performed.

15.The Academy also wishes to highlight that free exchange and sharing of scientific

findings through peer-reviewed journals are central to scientific discovery and must not be limited by further regulation. We stress that the benefits of enhanced and applied knowledge through the sharing of research findings far outweigh any risks.

January 2008

The Academy is particularly grateful to Sir John Skehel FRS FMedSci, Professor Geoffrey Smith FRS FMedSci, Professor Malcolm Malim FRS FMedSci and Professor Robin Weiss FRS FMedsci for their helpful contributions to this response.

The Academy of Medical Sciences The Academy of Medical Sciences promotes advances in medical science and campaigns to ensure these are converted into healthcare benefits for society. Our Fellows are the UK’s leading medical scientists from hospitals and general practice, academia, industry and the public service. The Academy seeks to play a pivotal role in determining the future of medical science in the UK, and the benefits that society will enjoy in years to come. We champion the UK’s strengths in medical science, promote careers and capacity building, encourage the implementation of new ideas and solutions – often through novel partnerships – and help to remove barriers to progress.

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Memorandum 18

Submission from the Health Protection Agency

BIOSECURITY FOR THE HANDLING AND STORAGE OF HUMAN PATHOGENS IN THE HEALTH PROTECTION AGENCY EXECUTIVE SUMMARY 1. The Health Protection Agency is responsible for most of the ACDP Category IV laboratories in the UK, along with a large number of ACDP Category III laboratories. These laboratories, the National Collection of Type Cultures and the National Collection of Pathogenic Viruses contain all the microorganisms (with the exception of variola) listed in Schedule 5 of the Anti-terrorism, Crime and Security Act 2001 Part 7 - Security of Pathogens and Toxins (ATCSA 2001). Work with these organisms contribute to the Agency’s remit in public health, including its role in counter-terrorism and its contributions to global public health. All of the laboratories in its major research centres have been recently audited by the National Counter Terrorism Security Office (NaCTSO) and no substantially issues have been identified. In addition, most of the regional laboratories which house Schedule 5 microorganisms have been audited by NaCTSO and there is an active dialogue about future registration between the remaining laboratories and NaCTSO. All staff which work in high containment laboratories receive extensive training and those which work in ACDP Category IV laboratories undergo security screening.

BACKGROUND INFORMATION 2. The Health Protection Agency is an independent expert organisation established by Parliament in 2003 to protect people from hazards to health, including infections, chemicals or radiation. From 2009 the HPA will also incorporate the standards and biological control functions of the National Biological Standards Board. The Agency develops science into sound evidence and advice and provides leadership to ensure that our advice is turned into practice. It also provides a full range of medical, scientific and technical services in support of our health protection role. The Agency aims to:

• provide independent evidence-based expert advice without bias or prejudice • Act on sound evidence and translate science into new ways of protecting the

population – being measured by our impact on public health • Widen the public health base by working with and training others • Provide a trusted effective interface with Government, other health

organisations and the public - including vulnerable disadvantaged groups thus helping to reduce inequalities.

• Set health protection standards for ourselves and others to employ FACILITIES FOR HANDLING AND STORING PATHOGENIC MICROORGANISMS

3. The Agency has two major research centres which handle and store microorganisms which are pathogenic for humans. The Centre for Emergency Preparedness and Response (CEPR) is located on Porton Down, near Salisbury in

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Wiltshire and the Centre for Infections (CfI) is in Colindale on the North Western outskirts of London. The Agency’s third research centre, the Centre for Radiation, Chemicals and the Environment (CRCE) at Chilton in Oxfordshire does not handle any microorganisms. In addition the Agency provides Local and Regional microbiology services (LARS) organised into 30 Health Protection Units (HPUs) and a Regional Microbiology Network (RMN) of 8 laboratories and 37 collaborating laboratories. The roles of LARS and RMN are summarized in Annex A. 4. The Centre for Emergency Preparedness and Response CEPR has 35 ACDP Category III laboratories covering almost 850- square meters. These laboratories enable work with pathogenic organisms in culture and also small experimental animals, including non-human primates. It also has two ACDP Category IV laboratories covering an area of almost 60 square metres, for working with pathogens in culture using sealed “cabinet lines”, and 6 ACDP Category IV laboratories covering about 150 square metres for work with small experimental animals, including non-human primates. The ACDP category IV laboratories and many of the ACDP Category III laboratories were built over 50 years ago and refurbishment and upgrading work is becoming increasing difficult. Consequently the HPA has begun discussions with DH about the long term strategic redevelopment of the Porton site which will involve the construction of new high containment laboratories. In addition, the Agency has commenced, in conjunction with the MRC, a national review of ACDP category IV and SAPO category IV laboratory facilities within the UK. 5. The Centre for Infections CfI houses 14 ACDP Category III laboratories covering over 450 square metres and one ACDP Category IV laboratory covering almost 65 square metres. These laboratories are suitable for working with cultured microorganisms only. 6. Regional Microbiology Network There are eight Regional microbiology laboratories, some of which handle and/or store schedule 5 organisms. Details of the work of these laboratories can be found in Annex A. HAZARDOUS ORGANISMS HANDLED AND STORED IN HPA LABORATORIES

7. CEPR, CFI and the NaCTSO-compliant regional laboratories handle and store a wide variety of Schedule 5 organisms and further details can be supplied if the Committee wishes. Several, but not all RMN and LARS laboratories handle or store Schedule 5 pathogens and further details can also be supplied if the Committee wishes. 8. National Collection of Type Cultures The National Collection of Type Cultures (NCTC) supplies reference bacterial cultures of medical, scientific and veterinary importance world-wide to support academic, health, food and veterinary institutions. The collection (which is certified to BS EN ISO 9001:2000) comprises over 5000 bacterial cultures, together with over 100 mycoplasmas and more than 500 plasmids, host strains, bacteriophages and transposons.

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Situated at the Health Protection Agency's Centre for Infections at Colindale (formerly Central Public Health Laboratory), NCTC has ready access to the wide-ranging expertise of an internationally-renowned body of specialists in clinical and environmental microbiology. These experts check each new batch produced by NCTC, ensuring quality control second to none.

Whilst the collection is maintained and supplied in traditional glass ampoules, some cultures are available as more user-friendly LENTICULE discs, in both qualitative and quantitative formats.

In addition to the supply of bacterial cultures, NCTC also provides a range of associated services, which include:

1. Freeze-drying of customers' own strains. 2. International Depository Authority (IDA) patent depository for bacterial

cultures. 3. Production of cultures and samples for use in EQA schemes. 4. Provision of cultures in LENTICULE disc format.

Founded in 1920, NCTC is the longest-established collection in the world offering a bacterial culture supply service. It is recognised internationally, serving as a European Resource Centre for Plasmids and a United Nations Educational, Scientific and Cultural Organization (UNESCO) Microbial Resource Centre (MIRCEN). It also holds and supplies some of the more popular cultures of the National Collection of Pathogenic Fungi (NCPF).

9. National Collection of Pathogenic Viruses

The National Collection of Pathogenic Viruses (NCPV) preserves well-characterised, authenticated human pathogenic viruses in a secure facility. The agents or nucleic acids derived from these viruses are supplied to the scientific community according to national and international guidelines. The Collection is primarily comprised of human pathogenic viruses requiring handling at biosafety levels 3 or 4, but has expanded to encompass hazard group 2 pathogens. Most of the material is in the form of cell-cultured virus stocks, but provision has also been made (where desirable or necessary) for selected clinical material and uncultivable viruses to be archived as serum, tissue or other biological samples, or in the form of cloned material. The Collection contains materials which are not readily available to the wider scientific community, particularly in the area of emerging virus diseases. We expect the Collection to be of benefit in the future development and testing of vaccines and antiviral compounds, in the development and validation of diagnostic test systems, and in the conservation of biodiversity.

AUDIT BY NACTSO. 10. Both CFI and CEPR, including NCTC and NCPV, have been audited by NaCTSO and no significant issues were identified on either site. Three RMN laboratories are already registered with NaCTSO. Where registered, RMN laboratories are in ongoing dialogue with local Counter Terrorist Security Advisors (CTSAs) in order to ensure compliance with the 2001 act and subsequent

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guidance. Most other RMN laboratories do not have to register with the Home Office due to the ‘diagnostic specimen’ exclusion (para 2 (3)(c)(i+ii)2002 SI No.1281). Although not Home Office registered, many HPA RMN labs still have regular CTSA visits as a proactive initiative by NaCTSO and local CTSAs. These have proved beneficial with positive feedback from the laboratory managers on advice they have received. RMN laboratories regularly review any schedule 5 organisms kept for legal reasons to ensure we are registered appropriately for these. Some food, water and environment laboratories have to retain stocks of organisms such as E.coli 0157 and C.perfringens until any prosecutions by local authorities have taken place. Steps are being taken to register these laboratories where appropriate. Some RMN laboratories have historical stocks of schedule 5 organisms retained for research purposes (e.g.: C.perfringens stored at the Cambridge-based HPA laboratory). Discussions, based on scientific value, are taking place on whether to destroy or register stocks. The CfI Mycology Reference Unit (MRU) embedded in the RMN Bristol laboratory has stocks of the fungi Cladophialophora bantiana and Cryptococcus neoformans. CTSAs already regularly visit and advise the MRU which has resulted in various upgrades to security. Steps are underway to register this laboratory with the Home Office. TRAINING AND SCREENING OF STAFF 11. All staff working in any laboratory handling or storing human pathogens receive extensive training at the appropriate level. In addition, the HPA trains staff from other organizations in the handling and storage of human pathogens. Details of these training programmes can be provided if requested. All staff working in ACDP category IV laboratories undergo security checks at SC level. The backgrounds of staff in other laboratories are checked as for all government employees, upon appointment. TRANSPORT OF HAZARDOUS MICROORGANISMS 12. In April 2005, the Health Protection Agency Executive Group mandated an HPA stakeholder group to alert the HPA and HPA Collaborating Laboratories to changes in the transport regulations for infectious substances, and to draft best practice guidance. A guidance document. 'Interim Guidelines on infectious substance transfers at HPA and HPA Collaborating Laboratories, 2005', was distributed by HPA Local and Regional Services. (Copies can be provided if required). This was produced in conjunction with Dr. Tony Phillips, a former senior member of staff at the Dstl laboratories at Porton Down. These regulations, The Carriage of Dangerous Goods and Use of Transportable Equipment (Amendment) Regulations 2005, entered into force on 22 July 2005, but the Department of Health obtained a derogation for mycobacterium tuberculosis, E. coli 0157 and Shigella dysenteriae to be transported as Schedule B organisms within the UK. Dr. Robert Spencer from the HPA sits on the UN Sub Committee of Experts on the Transport of Dangerous Goods and on the Globally Harmonised System of Classification and Labelling of Chemicals. January 2008

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ANNEX A

LOCAL AND REGIONAL SERVICES (LARS)

The Role of LARS The LARS Division of HPA was created in 2003 by bringing together the PHLS Regional Laboratories and approximately 100 local and nine regional NHS communicable disease control teams, many with single handed senior members of staff. During the first two years the Division moved towards the provision of an integrated, coherent and consistent national health protection service delivered through front line services in partnership with the NHS, Local Authorities and other agencies across the range of HPA responsibilities and not just communicable disease control. In order to ensure resilience, to provide critical mass for the wider range of health protection threats dealt with by the HPA, and to enable a balanced mix of skills in teams, some 100 small local teams were amalgamated into 30 (as of October 2006) larger Health Protection Units (HPUs). In 2005, the HPA Board agreed a series of proposals to further strengthen its frontline services. The “Strengthening the Frontline” policy recognised that the core functions are to be provided by expert multidisciplinary teams, local enough to be sensitive to the needs of communities, but large enough to sustain the expertise and capacity to respond to the full range of health protection threats. The policy required a shift of resource to front line Health Protection Units. and that the LARS division is divided into “LARS laboratories” and “LARS Health Protection Units”, each with an Executive Director. The creation of two new front line divisions took place in 2006. HPU Heads report to Regional Directors who in turn report to the Director of LARS. The management of the Health Protection Units is now through an executive made up of the regional directors and the LARS director. A common approach is being implemented within regions with each having an executive team made up of the Regional Director and heads of HPUs who will take responsibility for deployment of all regional resources. 1.2 Mapping HPU functions In parallel with “Strengthening the Front Line” in 2005, the Health Protection Agency developed a project to map the activities of its local health protection units. To do this a categorisation of health protection was devised: Communicable Disease threats

• Health care acquired infection and antibiotic resistance • Vaccine preventable diseases • Gastrointestinal including food and waterborne • Respiratory and other systemic infections including tuberculosis • Zoonoses and other emerging infections • Sexually transmitted and blood borne infections

Allergens including chemicals, moulds, plant and food allergens, house dust mites. Chemicals and Poisons

• Chemicals in products • Poisons • Pesticides • Chemical incidents • Chemicals in waste, water, air, food • Contaminated land

Radiation

• Low and high dose ionising radiation • Non ionising radiation

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• Noise Extreme Events

• Weather (e.g. winter and summer mortality) • Global warming • Disasters (e.g. flooding, bombings etc)

Psychological threats (e.g. psychogenic incidents, terror and the fear of health effects from exposures). Wider Public Health Issues

• Built environment • Neighbourhoods and incivilities • Transportation

A hierarchy of activity was described, moving from the science base through surveillance, risk assessment to advisory leadership and management. In 2006, Health Protection Units assessed their activity within these sub-domains. There was considerable variation between units, explained partly by epidemiology such as higher rates of Tuberculosis in inner cities or distribution of chemical hazards from industrial sites around the country, but mainly it was explained by the way in which the local units were created at the inception of the HPA. In some parts of the country infection control staff came into the HPA bringing their work, and in other parts this did not happen to the same extent. In order to develop a specification for the functions and outputs of Health Protection Units, not only the sub domains but the roles, responsibilities and functions and outputs of Health Protection Units needed to be spelled out in relation to the work of other parts of the HPA and other partners in Health protection. To do this, a number of scenarios were developed. The scenario work has exposed the facts that there are areas of activity where clear governance and assurance systems need strengthening. A particular issue was how the HPA Centres were linked to LARS in managing incidents, and what are the lines of accountability. This has been addressed in the new HPA Incident Plan. Moving on from the review of current HPU functions, this business plan includes objectives to define the HPU of the future and the processes and systems that must be developed.

REGIONAL MICROBIOLOGY NETWORKS (RMN)

The Regional Microbiology Network (RMN) was established as a Division of the Health Protection Agency in April 2006. The RMN is composed of eight Regional Microbiology Laboratories and thirty seven Collaborating Laboratories. These Laboratories provide frontline diagnostic and public health microbiology services to NHS Trusts and HPA Health Protection Units. There are twenty six Food, Water and Environmental (FW&E) Laboratories of which nine are directly managed by the HPA and seventeen are located in Collaborating Laboratories in NHS Trusts. The vision for the RMN is “To create an effective and efficient modernised HPA Microbiology Laboratory Network capable of addressing present and future challenges”. This will address the main health protection functions outlined in the Chief Medical Officers strategy for combating infectious diseases “Getting ahead of the curve”. The Network needs to be robust with strong links to the wider microbiology community to share expertise, capability and capacity. Such a network partnership will enable the HPA

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to be proactive, flexible, resilient and responsive to future needs and developments in health protection in the UK. A key relationship for the RMN is to continue to work seamlessly with the Local and Regional Services Division to produce the essential data to support frontline health protection activities locally, regionally and nationally. Working in partnership with the Centre for Infections (CfI) will provide the RMN and the HPA with opportunities to improve the responsiveness of diagnostic services to local public health and clinical needs. An example of this is the H

5N

1, regional capability for not only a rapid

local diagnostic service but also the ability to affect rapid public health interventions. There are several challenges facing the RMN not least the recent changes in the NHS and in particular the Department of Health “Modernisation of Pathology” programme. The HPA is committed to supporting the programme but must ensure in so doing it secures the outputs needed to deliver its functions. The Carter Report of the Review of NHS Pathology Services is likely to have far-reaching effects on the way in which pathology services in England are configured and delivered. The report identifies changes which will have implications relating to surveillance and not least laboratories. The main risk for future health protection laboratories is that the recommendation of increased plurality of providers, including the private sector, could affect the current flow of information, isolates and samples. However, the RMN together with the CfI has developed service specifications and commissioning arrangements. In addition, the HPA is actively involved in influencing the development of future services and ensuring that health protection functions are a core component of pathology services. A major task for 2007/08 for the new RMN Division is developing all the relevant frameworks essential to underpin the necessary activities to deliver a well managed and coordinated Division. These include corporate and clinical governance, frameworks for health and safety, risk management, business support, finance and human resources.

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Memorandum 19

Submission from AstraZeneca

Biosecurity in UK Research Laboratories

AstraZeneca is a major international healthcare business engaged in the research, development, manufacture and marketing of prescription pharmaceuticals and the supply of healthcare services. It is one of the world's leading pharmaceutical companies with healthcare sales of $26.47 billion and leading positions in sales of gastrointestinal, cardiovascular, neuroscience, respiratory, oncology and infection products. AstraZeneca is listed in the Dow Jones Sustainability Index (Global) as well as the FTSE4 Good Index. 1. AstraZeneca is actively engaged in research programmes to develop prophylactic

and therapeutic pharmaceuticals to prevent and treat infectious disease and is pleased to make a contribution to this important inquiry.

2. Our research in this area requires us to work with relevant biological agents

including naturally occurring human and animal pathogens, genetically-modified micro-organisms and a number of toxins of biological origin. We are committed to ensuring high standards of biosafety and biosecurity apply to all relevant activities in the UK and elsewhere.

3. We recognise that successful management of risks associated with such work must

address both biosafety and biosecurity issues26.

4. On the specific issues raised by the Committee we offer the following comments.

The current capacity for research on dangerous pathogenic material in the UK . 5. Infectious diseases continue to cause high numbers of cases of morbidity and

mortality around the world. Among these are relatively new diseases such as HIV AIDS and Severe Acute Respiratory Syndrome (SARS) and more recently, limited cases of human infection with highly pathogenic avian influenza strains.

6. Recent years have also seen a resurgence of some infectious diseases including Tuberculosis where there is particular concern about the emergence of multi- and extensively drug-resistant strains of the causative organism.

7. Resistance to existing antibiotic therapies is also a serious concern in other diseases including infections caused by MRSA which in the UK and elsewhere continues to be major problem in hospital-acquired infections.

26 “Biosafety” is used here to describe the containment principles, technologies and practices that are implemented to prevent the unintentional exposure to biological agents and toxins, or their accidental release while “Biosecurity” is used to describe measures for access control and accountability for use of biological agents and toxins within laboratories, in order to prevent their loss, theft, misuse, diversion of, unauthorized access or intentional unauthorized release.

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8. While appropriate prescribing by physicians and encouragement of better patient compliance will help to mitigate the spread of drug resistance, the underlying phenomenon is an inherent feature of microbial evolution.

9. Against this background there is a clear and demonstrable need for continuing basic research to better understand the mechanisms of pathogenicity and drug resistance and for application of this understanding in research to discover and develop new therapies.

10. The emergence of HIV had a positive impact on virology research capability but some of the facilities developed at the time are now aging and grant funding appears to be declining.

11. The cost of education and training in this research area is high and in a number of academic centres, departments of microbiology and virology have been subsumed into more general biological science departments. Overall this means that resources are increasingly being concentrated into a small number of departments.

The capability to conduct research on the causative agents of disease that may emerge at a future time. 12. The emergence of new infectious diseases is likely to be a continuing problem.

13. In the specific field of animal virology, cut backs in funding occurred some years

ago so that without specific impetus for strengthening this area, resources to deal with future demand may be insufficient.

14. There is also a risk of research into other parasitic diseases declining. The state of biological containment facilities in the UK 15. We note that UK law27,28 and associated guidance provides standards for the

design and operation of microbiological containment laboratories. These standards have been developed to ensure that appropriate safeguards can be provided according to the hazards posed by pathogens and the associated risk attached to relevant work activities. While there are restrictions on access even at Containment Level 2, these have traditionally been prescribed to afford an adequate standard of safety for those working in the facility and to guard against accidental escape into the wider community rather than the risks of deliberate misappropriation, theft, subversion and misuse.

16. We also note that the Anti-terrorism, Crime and Security Act 2001 provides for notification to the Home Office of possession of relevant materials and also for the establishment of appropriate physical, procedural and personnel screening measures. The Act also provides for inspection by the relevant authority that may also require implementation of specified measures to improve existing arrangements where this is deemed to be necessary. AstraZeneca supports the

27 The Control of Substances Hazardous to Health Regulations 2002 28 Specified Animal Pathogens Order 1998

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need to ensure that proportionate biosecurity measures are taken with respect to work with relevant materials.

17. Laboratories where pathogens are handled in the UK should be designed,

constructed, operated and maintained to comply with the relevant standards of containment provided for in UK legislation and account taken of associated guidance. AstraZeneca complies with these standards and has also adopted local procedures to ensure that biosecurity issues are suitably addressed. In addition, a global procedure is being developed to ensure that appropriate biosecurity measures are implemented at all relevant sites even where there is no specific national legal requirement.

Laboratory inspection regimes and the rationale and practicalities of the licensing system. 18. We believe that it is important for organisations to implement appropriate self-

inspection and auditing regimes as part of their biosafety and biosecurity management procedures.

19. We recognise the additional assurance provided for through inspections and/or

audits by regulators and we support a proportionate, scientific and risk-based approach to the regulation of work activities involving the use of hazardous biological materials.

20. We support the recommendations made in the Callaghan Review29 to merge the regulatory regimes governing work with human and animal pathogens and for enforcement to be the responsibility of the Health and Safety Executive.

Biosafety training provision for staff working in containment facilities. 21. Staff working in containment facilities must have demonstrable competence not

only to work to high scientific standards but also to work safely. Identification of biosafety training needs and providing for these to be met is critical in ensuring this, and we believe that this issue should be addressed in any biosafety and/or biosecurity management programme. A range of training processes may be used but “hands-on” training, under an appropriate level of supervision is an essential element in any training programme.

22. We encourage academic institutions to ensure that relevant programmes in relevant disciplines include appropriate provision for the development of an understanding of microbiological risk assessment, associated safety control measures and their application.

29A Review Of The Regulatory Framework For Handling Animal Pathogens Chaired by Sir Bill Callaghan. Presented to the Secretary of State for Environment, Food and Rural Affairs 13 December 2007

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The maintenance and recording practices surrounding the storage and transportation of dangerous pathogens. 23. National and international regulations are in force governing the transport of

dangerous substance including hazardous biological materials. These include provisions for appropriate packaging and labelling and there are also specific requirements for security plans in connection with the transport of high consequence agents. We believe that strict adherence to the requirements of the current regulations provides an appropriate level of safeguard in terms of safety and security.

24. Inventories should be maintained for all relevant materials but the level of detail recorded may vary according to the risk associated with the material in question. Safe and secure storage should be provided and used with specific measures being determined and applied in accordance with risk assessment and the requirements of national legislation.

Measures implemented when pathogenic material cannot be accounted for. 25. RIDDOR 30 specifies requirements to report accidental releases of biological

agents likely to cause severe human illness and the COSHH regulations require employees to report to their employee or the employer’s nominated representative any accident or incident which has or may have resulted in the release of a biological agent which could cause severe human disease. It is not clear from this wording whether or not this requires reporting where inventories indicate that relevant material is unaccounted for and we believe that guidance from the authorities would be helpful on this matter.

26. We believe that irrespective of any legal requirements, failure to account for pathogenic material should as a minimum, be reported through the management line. Appropriate emergency procedures taking account of this type of incident should be in place and should be implemented if an incident occurs. Depending on the specific circumstances, those measures may need to include reporting to the relevant authorities.

27. Irrespective of any reporting to and investigation by those authorities,

organisations should carry out their own investigation and act on any findings and recommendations that arise out of the investigation.

The role of universities in overseeing security clearance for research students working with dangerous pathogens. 28. We believe that it is essential for continued progress in this area for there to be a

strong UK academic base in the areas of microbiology, virology and molecular biology.

30 Reporting of Injuries, Diseases and Dangerous Occurrences Regulations 1995

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29. Research students typically are involved in research studies on projects of 1 – 3 years duration. The relatively short duration of projects, the associated high turnover, the significant numbers engaged in such studies, and the costs of carrying out security clearance checks mean that there are particular difficulties for universities in ensuring that all students are suitably screened in this respect.

30. It is essential that highly competent and suitably trained individuals are available

to carry out relevant work activities in countries where there are relatively high levels of endemic and newly emerging infectious diseases. These conditions are often associated with developing nations. Attracting research students to UK academic institutions for part or all of their formal training is not only an important issue for those institutions but also serves to help ensure that students who subsequently return to their home countries or other developing nations will be able to draw on their experience in the UK to the benefit of their homeland. While we recognise and accept the need for appropriate screening we also believe that it is important that unnecessary obstacles are not put in the way of international academic interchange.

January 2008

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Memorandum 20

Submission from the British Embassy, Warsaw By what mechanism(s) are microorganisms classified with regards to their potential danger and their need to be contained? The mechanisms are defined by Annex 1 to Health Minister’s Decree from 22nd April 2005. There are four containment groups: 1. Agents with little probability of causing human diseases 2. Agents that may cause human diseases and be harmful to laboratory staff, but the probability of their spread among the population is low. There are efficient methods of healing and preventing them. 3. Agents that cause serious diseases, are dangerous to laboratory staff, and their spread among the population is highly probable. Efficient methods of healing and prevention usually do exist. 4. Agents that cause serious diseases, are dangerous to laboratory staff, and their spread among the population is highly probable. Efficient methods of healing and prevention usually do not exist. The above-mentioned decree implements the rules of Directive 2000/54/EC of the European Parliament and the Council from 18th September 2000. What are the categories of biological containment in use? Like other countries covered by ISO norms, Poland uses the division into four classes of biological containment. How are licenses to use dangerous pathogens in research awarded? Project approval and funds assignment procedure consists of opinions of 3 reviewers and of the bio-ethics commission. The ultimate decision is taken by a commission in the Science & Higher Education Ministry. However it is not a license to use dangerous pathogens in research, since current rules do not envisage such licenses. What is the inspection regime for laboratories licensed to use dangerous pathogens? The intention of using pathogens above 2nd class of biological containment needs to be submitted to the laboratory of the local Sanitary Inspectorate:

• At least 30 days prior to the first use of a dangerous biological factor

qualified into classes 2-4 of biological containment

• In each case when changes crucial to safety & health of staff in the

workplace occur

• Within 30 days after finishing such activity

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• Immediately, in each case of accident or failure that might have caused

release of harmful biological agents belonging to classes 2-4 of biological

containment

Such information should include:

• Name and address of unit and what activities it undertakes

• Section where exposure to dangerous agents occurred

• Name, function, address and tel. no. of person responsible for health & safety in

the workplace

• Result of risk assessment undertaken, name of dangerous agent, containment

class, exposure time, type of work carried out

• Preventive measures envisaged

• Number of staff exposed

What training is mandatory / recommended for staff working in containment facilities? According to the Labour Code and the above-mentioned Health Minister’s Decree,

employers are bound to carry out training for staff. Such training must include issues

regarding:

• Potential threat to employees’ life & health caused by exposure to dangerous

biological agents

• Measures that need to be implemented in order to prevent threats caused by

dangerous biological agents

• Sanitary & hygiene requirements

• Means of group and individual protection

• Activities undertaken in case of failure or accident, and to prevent such things from

happening

What are the regulations regarding the storage and transportation of dangerous pathogens? • Bill on foreign traffic of goods, technologies and services of strategic importance

to national security, and to maintain international safety and peace, 29th November 2000

• European Parliament and Council’s Directive 2000/54/EC on the protection of workers related to biological agents at work, 18th September 2000

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• European Parliament and Council’s Directive 2001/83/EC on the community code relating to medicinal products of human use

• International Health Regulations (IHR) • Bill on carriage of dangerous goods by road, 28th October 2002 • European Agreement concerning the International Carriage of Dangerous Goods

by Road (ADR) What measures are in place to be implemented when pathogenic material cannot be accounted for? Each unit possessing or working with dangerous material has its own procedures. It is obvious that the police and relevant authorities responsible for citizen protection are informed in case of unaccounted pathogenic material. Who is responsible for overseeing security clearance for research students working with dangerous pathogens – what is the role of universities in this process?

University Rectors and Directors of R&D centres take responsibility for

security clearance. Decisions are taken on the basis of information gathered about a

person with access to pathogens, opinion got from this person’s supervisors, members

of the bioethics committee etc.

January 2008

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Memorandum 21

Submission from the Science and Innovation Section, British Embassy, Seoul

Biosecurity in UK research Laboratories

Biosafety has been institutionalised in the Republic of Korea since 1997. The first steps were taken in order to ensure the reliability of recombinant DNA technology. The Ministry of Health and Welfare (MOHW) published its ‘Guidelines for Research Involving Recombinant DNA Molecules’. The MOHW established the Division of Biosafety Evaluation and Control under the Korean Centre for Disease Control (KCDC). The division is responsible for setting national biosafety guidelines, certifying Biosafety Level (BSL) 3 and 4 facilities, overseeing the national framework of biosafety management and reviewing and coordinating all activities relating to living modified organisms (LMOs) derived from modern biotechnology, highly dangerous pathogens and toxins. The Division is responsible for enacting mandatory regulations relation to LMOs and high dangerous pathogens, establishing criteria for the installation and operation of the four biosafety level facilities, evaluating research plans which require national permissions and the monitoring of notifications on acquisition and transfer of highly dangerous pathogens and toxins. It also pursues the strengthening of laboratory biosafety through the development of human risk assessment techniques and related legislation, including laboratory biosafety. By what mechanism(s) are micro-organisms classified with regards to their potential danger and their need to be contained? What are the categories of biological containment in use? Micro-organisms are classified by: a) pathogenicity of the micro-organisms; b) mode of transmission and host range; c) availability of effective preventive measures (e.g. vaccines) d) availability of effective treatment (e.g. antibiotics). Like many countries, including the UK, there are four biosafety levels (BSL) for facilities: BSL-1 : organisms/toxins pose low risk to personnel and the environment. BSL-2 : pose moderate risk to personnel and environment. BSL-3 : usually cause serious disease BSL-4 : produce very serious disease that is often untreatable. There is currently no BSL-4 facility in Korea. The MOHW revised ‘The Guidelines for Research Involving Recombinant DNA Molecules’ in 2007 and it now includes categories of biological containment made on the basis of international biological containment levels. How are licenses to use dangerous pathogens in research awarded? According to the Prevention of Contagious Diseases Act, every researcher who uses and keeps dangerous pathogens should notify the KCDC. The KCDC issues licences. In case of non-dangerous pathogenic micro-organisms, each laboratory should operate its own lab biosafety management system.

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What is the inspection regime for laboratories licensed to use dangerous pathogens? According to the Prevention of Contagious Disease Act, all laboratories using any of the 32 kinds of dangerous pathogens designated by the government should report the status of the pathogens’ storage to the KCDC twice a year. The KCDC inspects licensed laboratories once a year. What training is mandatory / recommended for staff working in containment facilities? The KCDC operates a 21-hour training course for laboratory biosafety managers every year. The managers are obliged to arrange mandatory biosafety training to all staff in each lab once a year. What are the regulations regarding the storage and transportation of dangerous pathogens? Under the Prevention of Contagious Disease Act it is compulsory to notify the KCDC of the possession and transport of any of the specific 32 pathogens. Most of the associated regulations follow those of the WHO. If researchers use unknown pathogenic material they should request a pre-assessment to KCDC. The KCDC has 13 safety regulations to deal with unknown pathogenic material. What measures are in place to be implemented when pathogenic material cannot be accounted for? There are guidelines for preventing pathogenic material from going missing e.g. reporting, marking, designating of special storage facilities, checking consumption every six months and reporting consumption to the KCDC etc. If material goes missing, the case must be reported immediately to the KCDC who will investigate it. There has been no case of missing material so far. Who is responsible for overseeing security clearance for research students working with dangerous pathogens – what is the role of universities in this process? Universities need to get permission from the KCDC in order to build BSL-3 or 4 facilities,. The university is required to appoint an Institutional Biosafety Committee (IBC) within the university to oversee the security clearance of research students. In the case of building BSL1 or 2 facilities, universities need on report the facility to the Ministry of Science and Technology. In these cases forming an IBC in the university is recommended, but not mandatory. The KCDC encourages universities to manage their own facilities through the biosaftey training. 28 January 2008

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Memorandum 22

Submission from the British Embassy, Berlin 1. By what mechanisms are micro-organisms classified with regard to their potential danger and their need to be contained? The classification of micro-organisms with regard to their danger are subject to a range of Council Directives and reflected in the German Genetic Engineering Act (implementing EU regulations into national law), the Genetic Engineering Safety Ordinance and the Biological Agents Ordinance (which draws on the former). Extract from Biological Agents Ordinance on the classification into risk groups: "Classification of biological agents into risk groups (1) For the classification of biological agents into risk groups 2 to 4 Annex III of Council

Directive 90/679/EEC of 26 November 1990 (OJ EC No. L 374 p.1), as amended by Council Directive 93/88/EEC of 12 October 1993 (OJ EC No. L 268 p. 71), last amended by Commission Directive 97/65/EC of 26 November 1997 (OJ EC No. L 335 p.17) shall apply. In the case that Annex III of Directive 90/679/EEC is amended in the light of technical progress pursuant to the procedure laid down in its Article 19, the Annex shall apply in its amended version after expiry of the deadlines for transposition laid down in the amended directive. The amended version may be applied already as from the entry into force of the amended directive.

(2) Where biological agents are not covered by para. 1, the employer shall classify them in

respect of specific activities into risk groups according to the state of the art in science and technology. In addition the notifications pursuant to section 17 para. 4 shall be observed.

(3) Where a classification into several risk groups is possible in respect of specific activities

the agent shall be classified in the highest risk group." The risk assessment of research using pathogens is carried out prior to the research work and has to be repeated if substantial changes in working conditions occur. 2. What categories of biological containment in use? The categories of biological containment in use are set out in Annex II and Annex III of the Biological Agents Ordinance (http://www.baua.de/nn_12422/de/Themen-von-A-Z/Biologische-Arbeitsstoffe/Rechtstexte/pdf/biological-agents-ordinance.pdf see p. 22-25) 3. How are licenses to use dangerous pathogens in research awarded? The licensing of laboratories and research involving dangerous pathogens usually fall under the Genetic Engineering Act (GenTG, Sections 8 - 11), as most involve some type of genetic modification. Where animal pathogens or human pathogens are involved, the Animal Disease Act (TierSG) and Animal Pathogen Ordinance (TierSErrV) and/or the Infectious Diseases Protection Act (IfSG) also play a role. Licenses to use dangerous pathogens in research are awarded by the competent Länder authorities. Scientists need to obtain a license for each individual research stage and usually provide their own assessment of the individual security levels. The responsible authority at Länder level will consult the Central Committee for Biological Safety (ZKBS) on GM-related research and laboratories. It checks the applications and makes a recommendation to the Länder authorities on whether to go with the scientist's assessment or propose an even higher safety level. The competent Länder authority then issues a license stating the safety

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level and any other safety requirements to be met by the applicant. The ZKBS regularly publishes reports and postions on biological risks. The award of licenses to use dangerous pathogens in research are regulated in the Biological Safety Ordinance (BioStoffVerordung - BioSV) and - in case of genetically modified pathogens the Genetic Engineering Safety Ordinance (GenTechnikSicherheitsVerordnung - GenTSV). Research license for human pathogens is granted in line with the Infectious Diseases Protection Act (Infektionsschutzgesetz - IfSG, Chapter 9, Sections 44 to 53 on work with human pathogens). Since 2004, the Federal Office of Consumer Protection and Food Safety (BVL) has been the leading federal authority responsible for the field of genetic engineering in Germany. It is national competent authority in line with the Genetic Engineering Act (Gentechnikgesetz GenTG) and Ordinances. The BVL assesses notifications for the experimental use of genetically modified organisms (GMO). It is involved in the approval of GMOs in connection with food and feed. The BVL gives advice to the Federal and Länder Governments and the competent authorities responsible for biological safety in genetic engineering. The BVL evaluates the safety of genetically modified organisms that are used in contained systems for research and industrial production. Beyond that, the BVL issues authorisations in Germany with the measures required for the safe use of GMOs in temporally and spatially limited experimental releases into the environment. In the EU-wide notification procedures for the commercial use of GMOs (placing on the market), the BVL issues the German position and coordinates the national and international obligations of Germany for enabling co-existence, i.e. the separation of GMOs and non-GMOs. Furthermore, the BVL coordinates environmental monitoring of GMOs by collecting and evaluating the monitoring reports received from notifiers including public institutions and promotes the exchange of information between applicants, governmental agencies and the public. 4. What is the inspection regime for laboratories licensed to use dangerous pathogens? The competent authorities at Länder level are entitled to carry out ad-hoc inspections without prior warnings. The frequency of inspections depends on the safety level of the individual laboratories. Safety level 3 and 4 laboratories licensed for GM research are inspected at least once a year (see Genetic Engineering Act GenTG, Section 25). If an inspection reveals any inadequacies and safety gaps, those labs will be be inspected more frequently. (There are only two level 4 GM labs licensed in Germany.) The safety of non-GM laboratories used for research on human or animal pathogens are subject to the Biological Agents Ordinance (BioStoffV), the Animal Disease Act (TierSG) and Animal Pathogen Ordinance (TierSErrV) and Infectious Diseases Protection Act (IfSG). These labs are inspected by the authorities responsible for health & safety, occupational health, animals and food safety. Anecdotal evidence suggests that research labs work very closely with the competent authorities at a very early stage - including the planning or estension of new laboratories. There is consensus that this avoids misunderstandings and unnecessary cost for inadequate safety measures. It also provides an opportunity for the competent authority to verify that the operator of a research lab is competent, well equipped and able to handle sensitive material. There is anecdotal evidence, that ad hoc inspections are seen as impractical as the members of staff authorised to take inspectors to the sensitive areas of research institutes may not be available. 5. What training is mandatory / recommended for staff working in containment facilities? Staff responsible for work in containment facilities are required to have a suitable level of qualifications plus additional mandatory training. This is set out in Section 15 and Section 12

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of the Genetic Engineering Safety Ordinance (GenTSV) Staff responsible for containment facilities are usually experienced Postdoc-researchers who have to undergo mandatory training that covers legal requirements, safety regulations, interaction with the competent authorities, and the specific tasks they have as project leaders with responsibility for a containment facility. Mandatory training is provided by or in close cooperation with the authority responsible for licensing and monitoring biological / GM safety - usually in the form of a 2-3 day course. All staff working in safety level 3 labs, have to undergo special training in and practice the use of protective clothes before they are allowed to work in such facilities. All training is documented and monitored at inspections. For non-GM laboratories similar regulations apply which are set out in the Infectious Diseases Protection Act (IfSG) 6. What are the regulations regarding the storage and transportation of dangerous pathogens? The storage and transport of GM organisms is regulated in the Genetic Engineering Act GenTG (Section 3). Similar regulations apply under the Infections Diseases Protection Act IfSG. The packaging of microorganisms for transport is set out in the form of German Industry Standards (DIN) by the German DIN Institute. Information on packaging and labelling for transport of dangerous pathogens are also available from Deutsche Post AG. For transport of dangerous pathogens by air, the ICAO Technical Instructions Document Technical and Dangerous Goods Regulations (DGR) of the International Air Transport Association (IATA) apply. IATA Technical Instructions for the Safe Transport of Dangerous Goods by Air apply (see http://www.iata.org/workgroups/dgb.htm. 7. What measures are in place to be implemented when pathogenic material cannot be accounted for? Staff working on dangerous pathogens are required to document all research steps, including resulting products, physical transfer or destruction of pathogenic material. This documentation has to be kept for a minimum period of five years. Medium and high risk pathogenic material is usually handled under the supervision of others. Organisms only allowed to be handled in safety level 3 labs may only be handled in the presence of at least two witnesses, who have to certify this with their signature. Access to such substances is limited. Additionally, the amount of pathogens currently stored is registered and monitored regularly. The use, transport and destruction of pathogens is also documented. In case pathogenic material is missing and cannot be accounted for, the research lab alerts the authority with the relevant supervisory competence and the police. The Genetic Engineering Act GenTG (Sections 14-16 and 17) and Sections 6, 9. 21, 32-36) set out the obligations to report if pathogenic material is missing. The Genetic Engineering Safety Ordinance regulates the wastewater and waste treatment in laboratories handling GM organisms. As far as my contacts recall, there has not been a serious incident of unaccounted GM or pathogenic material in Germany. 8. Who is responsible for overseeing security clearance for research students working with dangerous pathogens / what is the role of universities in this process? There is no agreed approach to security clearance for research students working with dangerous pathogens. At non-university research facilities some checks are being made to find out whether students are kosher - but this will only be sample checks, no comprehensive

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checks. Given the growing number of students and researchers with faked references; research institutes and the German Academic Exchange Service scrutinise these more closely, which migh indirrectly benefit research labs. The respnsibility for security clearance of students and researchers rests with the individual directors of research labs and does not seem to be done at university level. 9. Further information Biological Agents Ordinance - 2004 Update (English) http://www.baua.de/nn_12422/de/Themen-von-A-Z/Biologische-Arbeitsstoffe/Rechtstexte/pdf/biological-agents-ordinance.pdf Federal Institute for Occupational Safety and Health - laws and ordinances on biological safety: http://www.baua.de/de/Themen-von-A-Z/Biologische-Arbeitsstoffe/Rechtstexte/Rechtstexte.html__nnn=true Guests our Regelung der Gentechnik (GenTG) (German only) http://www.gesetze-im-internet.de/bundesrecht/gentg/gesamt.pdf Verordnung über die Sicherheitsstufen und Sicherheitsmaßnahmen bei gentechnischen Arbeiten in gentechnischen Anlagen (Gentechnik-Sicherheitsverordnung - GenTSV) (German only) http://www.gesetze-im-internet.de/bundesrecht/gentsv/gesamt.pdf List of Federal Acts and Ordinances on genetic engineering and related areas http://www.rp.baden-wuerttemberg.de/servlet/PB/menu/1158799/index.html January 2008

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Memorandum 23

Submission from the British Consulate in Italy

B. Level of Containment A. Containment measures

2 3 4 1.Isolation of laboratory (environmental and functional isolation from general traffic)

No recommended Yes

2. Inward airflow and outward airflow must be filtered through a HEPA filter or similar

No Yes just on outward airflow

Yes

3. Access must be limited to authorised personnel

recommended Yes Yes, through a compensation chamber

4. Room sealable for decontamination

No recommended Yes

5. Specific disinfection procedures

Yes Yes Yes

6.The working area must be kept under negative pressure

No recommended Yes

7. Effective control of vectors, e.g. rodents and insects

recommended Yes Yes

8. Water-repellent surfaces, easy to clean

yes, for benches

yes, for benches and floor

Yes for benches, furniture, walls floor and ceiling

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9. Surfaces resistant to acids, alkali, solvents, disinfectants

recommended Yes Yes

10. Safe storage for biological agents

Yes Yes Yes, biological safety cabinets

11.Personnel safety monitoring capability e.g.window, CCTV

recommended recommended Yes

12. Laboratories need to contain all the necessary equipment

No recommended Yes

13. Infected materials, including animals, need to be handled in safety booths, insulators or other appropriate containers

Where appropriate

Yes, in case of airborne infections

Yes

14. Animal carcass incinerator

recommended Yes (available)

Yes, on site

15. Equipment and procedures for waste treatment

Yes Yes Yes, with sterilisation

16. Effluent treatment No Optional Optional January 2008

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Memorandum 24

Submission from the British Embassy, The Hague

Biosecurity in UK research Laboratories

1) By what mechanism(s) are micro-organisms classified with regards to their potential danger and their need to be contained?

• Human pathogens are classified according to the national legislation

(Dutch Safety and Health Act) based on EU/2000/54, which are the guidelines the Dutch Society for Microbiology adhere to.

• No EU or national legislation available for animal pathogens.

Classification on potential danger and need of containment are based on own classification list of the National Reference Laboratory (Central Veterinary Institute of Wageningen UR, Lelystad) in accordance with Ministry of Agriculture. This is the only institute in the Netherlands with High Containment Unit for working with animal pathogens.

2) What are the categories of biological containment in use?

• Biosafety levels of 1-4 are in place for human pathogens. • Also for animal pathogens a 1-4 level range is in place according to the

recommendations of OIE for agricultural facilities. 3) How are licenses to use dangerous pathogens in research awarded?

• Licences to use dangerous pathogens in research are awarded according to

the Environmental Management Act and Establishments and Permits Decree.In the Environmental Management Act and the Establishments and Permits Decree, the need for a permit for laboratories, animal housing facilities, growth chambers, greenhouses and production facilities is laid down in case these buildings are used for the contained use of dangerous pathogens and GMOs. This permit is issued by the local authorities (council, province) or in exceptional cases by central government.

Dangerous Substances Act: Decree on Genetically Modified Organisms The basic rules for permits for introduction into the environment and contained use (permit regarding working rules) are laid down in this Act. The Environmentally Hazardous Substances Act: Decree on Genetically Modified Organisms (GMO Decree). Passed in 1990, this decree regulates the use of genetically modified organisms under Dutch law. The decree requires anyone who wishes to work with GMOs in the Netherlands to obtain a permit.

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VROM acts as the competent authority, in line with the statutory role of the Minister of VROM. The decree deals with several issues. For example:

• it defines a GMO; • it describes which techniques result in the creation of a GMO; • it describes which techniques result in the creation of a GMO but are

exempted from the regulation; • it specifies which techniques do not result in a GMO.

Furthermore, the decree lays down rules for administrative procedures that must be followed when a permit is issued. The Ministerial Regulation on GMOs is linked to the GMO Decree and lays down more detailed (technical) rules which apply primarily to the contained use of GMOs. The most important rules are:

• the need for a Biological Safety Officer (contained use) or Environmental Safety Officer (introduction into the environment) at each institution or company working with GMOs for internal implementation and inspection;

• the technical rules for each facility for contained use and the working rules in these facilities which are specified for 25 different types of facilities;

• the risk assessment rules for contained use; • the rules for transport and storage of GMOs and the storage of waste

containing GMOs. Other legislation relevant to GMOs In the Netherlands, in addition to the legislation on environmental risk assessment of GMOs, activities involving GMOs are also governed by other legislation. This other legislation can be divided into two types of legislation. 1. Legislation specifically designed to cover certain aspects of the making of

or the use of GMOs. The scope of this legislation is restricted to GMOs. • Decree on biotechnology with animals which governs the ethical

evaluation of genetically modifying animals • Integration in the Dutch Food law of the Food/feed regulation (EC)

1829/2003 • Implementation of the Biosafety Protocol (BSP) as implemented in

European Directive Error! Hyperlink reference not valid.. In the Netherlands these aspects are governed by the GMO Decree.

2. General legislation that was not originally specifically intended to include GMOs, but which also applies to GMOs. Only the legislation for which this is most often relevant is listed here.

• The Working Conditions Decree protects workers against microbiological hazards.

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• The Transportation of Dangerous Goods Act sets out the requirements for the transportation of GM materials or GM-contaminated materials.

• The Animal Welfare Act governs assessment of the need for animal testing

• The Disclosure of Information on Disasters and Serious Accidents (Disclosure of Information) Decree (Biro). Under the Biro, a permit holder must provide the local authorities with information about anything that could lead to a disaster or serious accident. The decree also requires the permit holder to draw up a contingency plan for implementation under such circumstances.

Special arrangements for working with Foot-and-mouth disease: The only institute that is allowed to work with FMD in The Netherlands is the Central Veterinary Institute of Wageningen UR as appointed by the Ministry of Agriculture based on EU2003/85: the laboratory and its facilities meet the reuirements as laid down in EU2003/85 and the ‘Minimum standards for Laboratories working with foot and-mouth virus in vitro and in vivo’ established by the European Commission for the control of foot-and-mouth disease, 26th session, Rome, April 1985, as modified in 1993.

4) What is the inspection regime for laboratories licensed to use dangerous

pathogens?

Various inspections are in place. • Inspection by the local authorities once a year (Environmental

Management Act) • Inspections by the Dutch labor inspectorate (Dutch Safety and Health Act) • Inspections by the EU Commission (according to EU 2003/35) • External evaluation by international experts (initiated by the National

Reference laboratory itself) 5) What training is mandatory / recommended for staff working in containment

facilities?

A special training program at the Central Veterinary Institute of Wageningen UR, Lelystad

6) What are the regulations regarding the storage and transportation of dangerous pathogens?

National guidelines regarding the storage and transportation of dangerous pathogens are based on:

1) World wide: According to recommendations by the UN committee of Experts on

the Transport of Dangerous Goods”.

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2) Europe: The binding recommendations of the UN committee have been documented in the European agreement concerning the international carriage of dangerous goods by road. By a European guideline (94/55/EG) this European agreement has been made compulsory also for national transport.

3) National: The European guidelines are recorded in the “Regulations on transport

of dangerous goods by road”, which is based on the law for transportation of dangerous goods.

4) Transport of animal material: The European regulation containing health

directions concerning animal products not mend for Human consumption (nr. 1774/2002/EG).

7) What measures are in place to be implemented when pathogenic material

cannot be accounted for?

Various measures are in place, a warning can be issued or licences can be revoked based on breaching of the Health and safety act or Environmental act.

8) Who is responsible for overseeing security clearance for research students working

with dangerous pathogens – what is the role of universities in this process?

Institutes themselves are responsible for overseeing security clearance for research students working with dangerous pathogens. January 2008

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Memorandum 25

Submission from the British High Commission, Canada Executive Summary: The Public Health Agency of Canada classifies pathogens using a risk system based on pathogenicity and mode of transmission. Recently there has been a shift towards classification using minimal containment levels required to provide safe manipulation of pathogens. (Paragraphs 1-2) The agencies responsible for overseeing bio-security in research facilities in Canada are the Public Health Agency of Canada (PHAC) and the Canadian Food Inspection Agency (CFIA), while transportation of pathogens into Canada falls under the jurisdiction of Transport Canada. Dangerous pathogens require permits from the Public Health Agency of Canada, Transport Canada and the Canadian Food Inspection Agency for their use in research facilities. In addition, laboratory facilities handling dangerous pathogens require prior certification from PHAC and where applicable, CFIA. (Paragraphs 3-9 and 15) The Public Health Agency of Canada publishes a manual with guidelines to follow for the design, construction, maintenance and protocols to be used in containment laboratories. This provides a set of general recommendations for facilities to follow when developing their own protocols and procedures. In the case of university laboratories, a bio-safety committee is appointed by the university to deal with all matters related to laboratory bio-safety and bio-security. (Paragraphs 10 and 19)

All facilities dealing with dangerous pathogens are required to have inventory controls and emergency plans in place as part of their operational protocols, however there is no universal or standard procedure available to account for missing pathogenic material. Facilities are responsible for devising their own methods for inventory control and emergency preparedness. These activities are strongly encouraged by the Public Health Agency of Canada as well as public funding agencies. (Paragraphs 16-19)

Innovation, Universities and Skills Committee

Inquiry into Biosecurity in Research Laboratories, Canada By what mechanism(s) are micro-organisms classified with regards to their potential danger and their need to be contained? (1) The Public Health Agency of Canada classifies micro-organisms based on a risk level system that depends on pathogenicity, mode of transmission, availability of preventive measures and treatments, and severity of economic or health consequences brought about by a potential wide-spread infection. Recently there has been a shift towards classification of pathogens based on their handling requirements using four biological containment levels.

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What are the categories of biological containment in use? (2) There are four progressively stringent containment levels in use, depending on the type of agents handled and based on the minimum containment level required for safe manipulation of pathogens. These containment levels indicate the operational, physical, engineering and technical constraints required for safe handling of pathogens. These procedures are in turn based on the pathogenicity, potential for serious health and economic consequences, and preventive measures and treatments available for particular pathogens. http://www.phac-aspc.gc.ca/ols-bsl/containment/index.html How are licenses to use dangerous pathogens in research awarded? (3) Dangerous pathogens require importation permits depending on their source and the containment level required for their manipulation. The import and use of human pathogens is regulated by the Human Pathogens Importation Regulations and requires a permit issued by the Office of Laboratory Security at the Public Health Agency of Canada.

(4) Human pathogens requiring containment levels 2, 3 and 4 require a valid permit. These permits allow for the import, use and storage of dangerous pathogens. Before issuing a permit, the Public Health Agency of Canada will inspect the research laboratory to ensure that criteria for containment level is adequate and that operational, mechanical and physical bio-safety and bio-security attributes are in place to handle pathogens at the specified containment level. After evaluation of the permit application and inspection of laboratory facilities, a permit is issued for single or multiple entries of the pathogen into Canada, on a case by case basis.

http://www.phac-aspc.gc.ca/ols-bsl/pathogen/index.html

(5) Permits for animal and plant pathogens are awarded by the Canadian Food Inspection- Agency. In the case of zoonotic pathogens which can be transmitted from animals to humans, two separate permits are required, one from the Public Health Agency of Canada and another one from Canadian Food Inspection Agency. Both agencies will be involved in the inspection and certification of the laboratory facilities in this case.

What is the inspection regime for laboratories licensed to use dangerous pathogens? (6) Facilities for containment levels 3 and 4 require certification from the Public Health Agency of Canada for handling dangerous pathogens. There are approximately 90 containment level-3 laboratories and a single level-4 facility in Canada (7) In order to initially certify containment level 3 and 4 facilities, the Public Health Agency of Canada will inspect the research laboratories to ensure that criteria for containment level is adequate and that operational, mechanical and physical attributes are in place for handling the pathogenic material. Guidelines to prepare for these inspections are provided by the Public Health Agency of Canada. (8) Furthermore, level-4 facilities undergo a yearly inspection to ensure that bio-safety attributes are maintained and updated. Level-3 facilities do not undergo further inspection after the initial certification, however in order to maintain their certification

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they are required to submit a form documenting any changes undergone in the facility after the initial certification on a yearly basis. (9) Finally, if zoonotic pathogens are concerned, the Canadian Food Inspection Agency is also involved in the initial inspection for certification of level-3 facilities. http://www.inspection.gc.ca/english/sci/bio/anima/inspect/certqueste.shtml What training is mandatory / recommended for staff working in containment facilities? (10) Guidelines for training staff in all containment facilities is provided by the document Laboratory Bio-safety Guidelines published by the Public Health Agency of Canada. This document is sent to facilities upon request or can be accessed through the agency’s web-site. (11) Training is mandatory for certification of level-3 and 4 facilities, as it is evaluated as part of the Standard Operating Procedures for certification of these facilities. Training on potential hazards, reducing infection risks, operational procedures, decontamination and emergency protocols are recommended for containment level 2 to 4 laboratories. In addition, requirements for training staff in the physical operation and design of the facility are required for containment levels 3 and 4. (12) There are no standard training programmes outlined, however the Public Health Agency of Canada requires evidence that the training undertook is specific to the pathogens handled and that staff have completed and understood the training programme. (13) An instructional DVD on operational procedures for containment level-3 laboratories is available at a moderate cost from the Public Health Agency of Canada. (14) The Public Health Agency of Canada will be holding its second annual Canadian Bio-safety Symposium on June 1-3 this year. http://www.phac-aspc.gc.ca/ols-bsl/l3-n3-2003/index.html What are the regulations regarding the storage and transportation of dangerous pathogens? (15) Regulations for storage and transportation of dangerous pathogens are under the authority of Transport Canada. Transport Canada regulations require an additional permit for transport and storage of dangerous pathogens under the category of Infectious Substances and Biological Products in the Transportation of Dangerous Goods Act. Compliance with these regulations involves following containment specifications and providing Transport Canada with information on staff training and storage or disposal procedures. http://www.tc.gc.ca/acts-regulations/general/t/tdg/regulations/tdg001/part_1.htm

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What measures are in place to be implemented when pathogenic material cannot be accounted for? (16) Measures to account for missing pathogenic material fall under the responsibility of the facility. However, as part of the certification criteria for level-3 and 4 laboratories, a plan to control accidents involving dangerous pathogenic material and an inventory of the pathogens in the facility must be included in the Standard Operating Procedures submitted to the Public Health Agency of Canada. However currently there is no standard protocol in place for maintenance of inventories or emergency preparedness plans for laboratories to follow. Facilities are encouraged to report incidents to the local law authorities. (17) However, in case of highly infectious substances belonging to risk groups 3 and 431 the Public Health Agency of Canada must be informed if shipments of pathogens go missing or are delayed during their importation into Canada or while they are being transported from one facility to another within Canada. (18) Further control and compliance over incidents involving pathogenic material is indirectly exerted by funding agencies and provincial governments, which require that facilities be compliant with the guidelines indicated in the Guidelines for Laboratory Bio-safety produced by the Public Health Agency of Canada to authorise funding. Who is responsible for overseeing security clearance for research students working with dangerous pathogens – what is the role of universities in this process? (19) Each university designates a bio-safety committee, which is responsible for overseeing security clearance requirements for students working with dangerous pathogens. All containment level-3 laboratories require all staff, from support to research staff working within the facility to undergo security clearances. January 2008 31 Reference is made to the risk groups in Appendix 3 of the Toxic and Biological Substances classification under the Transportation of Dangerous Goods Act, Transport Canada.

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Memorandum 26

Submission from the British Embassy, Tokyo

Inquiry into Biosecurity in UK research Laboratories This report was prepared in response to inquiry into biosecurity at laboratories in relevant countries by the Innovation, University and Skills Committee. The report is based on hearings from the Ministry of Health, Labour and Welfare (MHLW) and the National Institute of Infectious Diseases (NIID) in Japan. By what mechanism(s) are micro-organisms classified with regards to their potential danger and their need to be contained? What are the categories of biological containment in use? In 1999, Japan enacted the law concerning prevention of infectious diseases and medical treatment for patients with infectious diseases, replacing the 100-year-old “infectious disease prevention law.” The new law was then revised in 2006 and became effective in June 2007 so that specific pathogens, including toxins, became categorised into the Groups 1-4. These categories were created by MHLW, which partly used guidelines of the US Centre for Disease Control and Prevention as a reference. MHLW is responsible for pathogens at any laboratories, not the Ministry of Education, Sports, Culture, Science and Technology. Before the revised law was introduced, the Japanese government had no regulations about how to deal with dangerous pathogens. Researchers used to handle them at their discretion, while voluntarily following the biosafety level (BSL) guidelines of NIID. Behind the revision was the 11 Sept terrorist attacks, which raised concerns about biological terrorism, as well as the rapidly changing environment about infectious diseases. MHLW allows research institutes to take a maximum 5 years until can fully follow the new law. Group1: Possession is prohibited in principle, but would be allowed for research institutes designated by the government. (6 kinds of pathogens i.e. ebolavirus, Crimean-Congo hemorrhagic fever, pox). MHLW says there is no pathogens of Group 1 in Japan at present. Group 2: Possession is allowed upon MHLW’s permission (6 kinds, i.e. SARS corona virus, Bacillus anthracis, pest, botullinus bacillus) Group 3: Possession is allowed by filing for registration to MHLW. (23 kinds, i.e. coccidioidomycosis, monkeypox virus)

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Group 4: Possession is allowed without registration or permission as long as researchers follow the law. (16 kinds, i.e. influenza virus H2N2, H5N1, H7N7, yellow fever virus, cholera bacillus, tubercle bacillus) Sometimes pathogens in Group 4 require more stringent standards for a facility than other Groups. How are licenses to use dangerous pathogens in research awarded? • Pathogens in Group 1 requires the health ministry’s permission (there are none in

Japan) • Pathogens in Group 2 require permission from MHLW upon application • Pathogens in Group 3 require registration to MHLW (researchers don’t need to

wait for permission). • Pathogens in Group 4 are handled under self-imposed management by individual

research institutes (but will have to follow provisions stipulated in the law, such as ‘botullinus bacillus has to be dealt at a laboratory with a lock.’ But researchers need neither file for registration nor application for permission).

For all the Groups, researchers will have to follow a certain standard stipulated in the law, such as 1) restriction to the entry into the laboratory, 2) establishment of locked equipment and surveillance equipment to prevent robbery, 3) equipment to kill pathogens and 4) safety cabinets to prevent the occurrence and spread of infectious diseases. What is the inspection regime for laboratories licensed to use dangerous pathogens? Inspections are conducted under the revised law. The law allows the government to conduct spot inspection, check paper documents, ask questions to people concerned, obtain pathogens or materials contaminated with the pathogens from laboratories. What training is mandatory / recommended for staff working in containment facilities? Researchers who deal with pathogens in Groups 1 and 2 are obliged to take educational training at least once a year, such as to review the law’s provisions, and take original training made by individual institutes. MHLW doesn’t have manuals of educational training. What are the regulations regarding the storage and transportation of dangerous pathogens? The law stipulates rules on the storage, usage and transportation of pathogens in Groups 1-4. For example, research institutes have to register those who are allowed to enter the controlled area, lock the storage and meet conditions of packages/containers to transport pathogens. Transportation of pathogens in Groups 1-3 requires report to the police (before and after the transportation. Delay of transportation also has to be reported. This is one of the issues that researchers complain a lot.) Transportation by aircraft has to follow regulations of the International Civil Aviation Organisation.

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What measures are in place to be implemented when pathogenic material cannot be accounted for? When the pathogenic material is missing, it is handled as an “accident.” For pathogens in Groups 1 and 2, the law requires research institutes/laboratories to create their own “guideline to prevent infectious diseases” in a written form, in which they have to stipulates instructions to follow in the event of such accidents. The guideline is subjected to submission to MHLW. For pathogens in Groups 3 and 4, research institutes/laboratories also have to create instructions, but do not have obligation to submit. For all the group categories, they have to report the accident to the police. Who is responsible for overseeing security clearance for research students working with dangerous pathogens – what is the role of universities in this process? For Groups 1 and 2, research institutes have to appoint a person responsible for the security clearance. The person should have one of the following qualifications 1) medical doctor, 2) veterinarian, 3) dentist, 4) pharmacist, 5) clinical technologist or 6) university degree holder of biology, agriculture or relevant research fields. January 2008

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Memorandum 27

Submission from the British Embassy, Copenhagen

General comment: There is presently no Danish legislation which specifically address biosecurity issues. However, such legislation is in the process of being enacted (see http://borger.dk/forside/lovgivning/hoeringsportalen/faktaside?p_back_url=http://borger.dk/forside/lovgivning/hoeringsportalen?p_myndighed=971&p_hoeringid=1344000079). Furthermore, some aspects of biosecurity are covered by other Danish laws such as biosafety legislation .

1. By what mechanism(s) are micro-organisms classified with

regards to their potential danger and their need to be contained?

Denmark participates in international working groups (such as the Australian Group). These groups seek to identify micro-organisms with dual use potential (i.e. organisms and technology with beneficial as well as harmful potential). The potential is estimated by evaluating characteristics of the micro-organism such as pathogenicity, whether it is contagious, whether the disease can be treated, if it can be weaponized, stability, and how easily it is grown. In short a microorganism is added to the list if it is anticipated that the microorganism holds a certain potential to pose a threat to national security. This list is used to control import/export and the list is therefore more a cross-border control than a laboratory security control. Border control in Denmark is under the authority of the Danish Enterprise and Construction Agency. 2. What are the categories of biological containment in use?

For the time being there are no biosecurity categories. However many agents on the dual use list are also listed on the biosafety list. Agents on the biosafety list are classified on basis of their biosafety implications (biosafety classes 1-4. please confer with http://www.at.dk/sw12854.asp). The above mentioned draft biosecurity law does not specify if more biosecurity categories should be established and if so how each category should be defined. Furthermore it remains to be determined how the proposed law will be implemented in the lab (e.g. to which standards the agents should be guarded). 3. How are licenses to use dangerous pathogens in research

awarded?

To be determined. However, it is anticipated that there will be a legitimate need to handle dual use agents and that supervisors may need national security clearance (not yet clear to which degree) 4. What is the inspection regime for laboratories licensed to use

dangerous pathogens?

Again presently inspections are only biosafety focused. The Danish Working Environment Authority enforces the biosafety law and is doing this by inspections. There is no entity for enforcing biosecurity - but the proposed law suggests establishing one. 5. What training is mandatory / recommended for staff working in

containment facilities?

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Employees are hired only if basic requirements are met (e.g. previous lab employment). In most cases neighbor training is initiated shortly after employment. Every year an individual education/development plan is agreed for each employee. Finally, some labs hold exercises. It is anticipated that the implementing and maintenance of biosecurity will add new requirements for training. 6. What are the regulations regarding the storage and

transportation of dangerous pathogens?

The Environment Law (Miljøloven) and the IATA regulations - no security specific legislation/regulation. 7. What measures are in place to be implemented when

pathogenic material cannot be accounted for?

There are presently no measures. 8. Who is responsible for overseeing security clearance for

research students working with dangerous pathogens - what is the role of universities in this process?

To be determined. One anticipated model could be that a new entity (e.g. the one mentioned in question 4) could oversee security clearances nationally. At the facility level a new position responsible for local biosecurity could be established.

January 2008

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Memorandum 28

Submission from the British Embassy, Washington

US Biosecurity Introduction Biosecurity regulation in the US is complex and involves the participation of many different US federal agencies. In addition, individual states and local governments may impose their own restrictions on the types of research that can be conducted or classes of micro-organisms entering that community. In general, the level of regulation logically increases with the perceived level of danger associated with a given micro-organism. The US divides threats in terms of those posing risks to human health and risks to animal/plant health. Human health issues are regulated by the US Department of Health and Human Services (HHS) and animal/plant issues are managed by the US Department of Agriculture (USDA). In the case of HHS, most regulatory authority has been delegated to its constituent agencies, the Centers for Disease Control (CDC) and the National Institutes for Health (NIH). USDA utilises its Animal and Plant Health Inspection Service (APHIS) to manage the plant/animal dimension. The discussion in this paper will speak generally to human, animal and plant health; however there is a human health bias. Some variations exist for the animal and plant health regulations. Biosafety Guidelines and Categories Inquiry Questions: By what mechanisms are micro-organisms classified with regards to their potential danger and their need to be contained? What are the categories of biological containment in use? Published by HHS, NIH and CDC, the Biosafety in Microbiological and Biomedical Laboratories Handbook (BMBL)32 has become the cornerstone of biosafety practice in the US. It is a key document and would be recommended for anyone wanting an understanding of US biosafety practice. The 5th edition was last produced in 2007 and available in pdf format. The US uses a system of 4 biosafety levels (BSLs) to describe the danger and the corresponding practices, equipment and facilities. The BSL levels thus serve a similar purpose to the UK’s microbiological containment levels (CLs). BSL4 represents the most dangerous pathogens while BSL1 represents microbes that are not known to cause disease. A table summarising the levels, equipment and practices is attached. Following from the BSL level, equipment and facilities are further described. In the US there are three main classes of biological safety cabinet that are used in combination with particular types of facilities. For example, BSL4 microbes could be used with a Class III cabinet or Class I/II if in combination with a positive pressure personnel suit. 32 BMBL Handbook - http://www.cdc.gov/od/ohs/biosfty/bmbl5/bmbl5toc.htm

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Select Agents Inquiry Question: By what mechanisms are micro-organisms classified with regards to their potential danger and their need to be contained? In addition to BSL category, the US has established a list of pathogens and toxins that it believes pose a severe threat to public health and safety (including humans, animals and plants). Referred to as “Select Agents33,” these biological agents and toxins are given special treatment under US law. The current list of select agents is attached to this note. Following from this, specific agents have been identified as having the possibility of being efficiently used for bioterrorism. Categories of A through C help public health agencies prepare appropriate responses34. For determining select agents related to human health, HHS considered the following:

• the effect on human health of exposure to the agent or toxin • the degree of contagiousness of the agent or toxin and the methods by

which the agent or toxin is transferred to humans • the availability and effectiveness of pharmacotherapies and

immunisations to treat and prevent any illness resulting from infection by the agent or toxin

• any other criteria, including the needs of children and other vulnerable populations, that HHS considers appropriate

Policy History and Federal Regulations Following the Oklahoma City bombing in 1995, the US Congress passed the Anti-terrorism and Effective Death Penalty Act of 199635. In this act, HHS was given authority to register and track dangerous pathogens. This was soon followed by the terrorist events of September and October 2001 with anthrax spores mailed to prominent politicians and media personalities. In response, Congress passed three new pieces of legislation that further strengthened oversight of dangerous microbes and toxins. The legislation included: the Uniting and Strengthening America by Providing Appropriate Tools Required to Intercept and Obstruct Terrorism Act of 2001 (PATRIOT Act)36, the Public Health Security and Bioterrorism Preparedness and Response Act of 200237 and the Agricultural Bioterrorism Protection Act of 2002. The provisions of these Acts were implemented through the issuance of federal rule 42 CFR Parts 72 and 7338, 7 CFR 331 and 9 CFR Part 12139. These rules regulate the possession, use and transfer of dangerous pathogens and toxins defined as “select agents.” They also established a national database for groups licensed to work with the select agents and set criminal penalties for individuals and groups that fail to 33 US Select Agents - http://www.cdc.gov/od/sap/docs/salist.pdf 34 Bioterrorism Agent Classification - http://www.bt.cdc.gov/agent/agentlist-category.asp 35 Anti-terrorism and Effective Death Penalty Act of 1996 - http://thomas.loc.gov/cgi-bin/query/z?c104:S.735.ENR: 36 PATRIOT Act - http://www.selectagents.gov/resources/USApatriotAct.pdf 37 Public Health Security and Bioterrorism Preparedness and Response Act of 2002 - http://www.selectagents.gov/resources/PL107-188.pdf 38 HHS Select Agent Final Rule - http://www.cdc.gov/od/sap/42_cfr_73_final_rule.pdf 39 USDA Select Agent Final Rules - http://www.cdc.gov/od/sap/42_cfr_73_final_rule.pdf

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comply with the rules. Under the rules, certain US agencies have been delegated the following authorities:

• Department of Health and Human Services (authority delegated to US Centers for Disease Control (CDC) – Responsible for oversight of select agents effecting human health and licensing groups to possess, use or transfer said agents

• Department of Agriculture (authority delegated to Animal and Plant Health

Inspection Service (APHIS) – Responsible for oversight of select agents effecting animal/plant health and licensing groups to possess, use or transfer said agents

• Department of Justice (authority delegated Federal Bureau of

Investigation, Criminal Justice Information Services Division (FBI) - responsibility to conduct electronic checks (i.e. security risk assessments) on groups that apply to possess, use, or transfer select agents as well as personnel that require access to select agents and toxins.

The regulations also contain requirements that ensure select agents are handled safely and secured against unauthorised access, theft, loss or release. For example, research groups and their personnel must undergo a security risk assessment by the FBI as part of the licensing process; groups must limit access to select agents and implement biosafety, security and incident response plans. In addition, all select agents must be transferred in accordance with the regulations with any theft, loss or release of the select agent reported to the CDC or APHIS. To assist with the process of licensing and processing research requests, CDC and APHIS have established the National Select Agent Registry (NSAR). Full details of this registry can be found at: http://www.selectagents.gov/index.html Licensing Inquiry Question: How are licenses to use dangerous pathogens in research awarded? Who is responsible for overseeing security clearance for research students working with dangerous pathogens – what is the role of the universities in this process? Under the select agent regulations, a research group must register (or be licensed) to work with or have contact with any select agent. The registration is only valid for the specific agents, activities and location as indicated on registration. This process is initiated by the interested entity submitting an application to the appropriate agency (CDC or APHIS)40. An entity can be a government agency, academic institution, corporation, company, partnership, society, association, firm or any other legal entity recognised in the US. If the entity represents many individuals, the entity must designate a responsible officer to act on behalf of the entity. In the application, the entity must list every individual that will have access to the select agent. After the application is made, the FBI will conduct a security risk assessment. This assessment 40 NSAR Select Agent Application - http://www.selectagents.gov/resources/APHIS-CDC%20Form%201Pt1.pdf

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includes fingerprinting all staff listed on the application and background checks. The assessment must be renewed and can only be issued for a period not to exceed five years. Only individuals with a security risk assessment for the application can be allowed access to the select agent. Inspection Inquiry Question: What is the inspection regime for laboratories licenses to use dangerous pathogens? Inspections are co-ordinated by CDC and APHIS. The federal rules authorise inspections without notification to any licensed site. Inspections are typically done prior to issuing a license to evaluate the premises and records to ensure compliance with rules. This includes inspection or copying any records associated with select agent activities. A set of inspection videos can be seen at: http://www.selectagents.gov/FacilityInspectionDVD.htm Training Inquiry Question: What training is mandatory/recommended for staff working in containment facilities? As stated in the CFR rules (42 CFR 73.15),

“(a) An individual or entity … must provide information and training on biosafety and security to each individual with access approval from the HHS Secretary or Administrator before he/she has such access. In addition, an individual or entity must provide information and training on biosafety and security to each individual not approved for access from the HHS Secretary or Administrator before he/she works in or visits areas where select agents or toxins are handled or stored (e.g. laboratories, growth chambers, animal rooms, greenhouses, storage areas, etc.). The training must address the particular needs of the individual, the work they will do, and the risks posed by the select agent or toxins. (b) Refresher training must be provided annually. (c) A record of the training provided to each individual must be maintained. The record must include the name of the individual, the date of the training, a description of the training provided, and the means used to verify the employee understood the training.”

Containment Inquiry Question: What are the regulations regarding the storage and transportation of dangerous pathogens? The federal regulations require that the registered entity develop a biosafety plan that is commensurate with the risk of the agent or toxin. This plan must provide

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procedures sufficient to contain the select agent or toxin and consider in the BMBL41. The plan must also be reviewed annually. Security Inquiry Questions: What are the regulations regarding the storage and transportation of dangerous pathogens? What measures are in place to be implemented when pathogenic material cannot be accounted for? US federal regulations require (42 CFR 73.11):

“(a) An individual or entity required to register under this part must develop and implement a written security plan. The security plan must be sufficient to safeguard the select agent or toxin against unauthorised access, theft, loss, or release. (b) The security plan must be designed according to a site-specific risk assessment and must provide graded protection in accordance with the risk of the select agent or toxin, given its intended use. The security plan must be submitted upon request. (c) The security plan must: (1) Describe procedures for physical security, inventory control, and information systems control,(2) Contain provisions for the control of access to select agents and toxins,(3) Contain provisions for routine cleaning, maintenance, and repairs,(4) Establish procedures for removing unauthorised or suspicious persons, (5) Describe procedures for addressing loss or compromise of keys, passwords, combinations, etc. and protocols for changing access numbers or locks following staff changes,(6) Contain procedures for reporting unauthorised or suspicious persons or activities, loss or theft of select agents or toxins, release of select agents or toxins, or alteration of inventory records, and (7) Contain provisions for ensuring that all individuals with access approval from the HHS Secretary or Administrator understand and comply with the security procedures.(d) An individual or entity must adhere to the following security requirements or implement measures to achieve an equivalent or greater level of security:(1) Allow access only to individuals with access approval from the HHS Secretary or Administrator, (2) Allow individuals not approved for access from the HHS Secretary or Administrator to conduct routine cleaning, maintenance, repairs, or other activities not related to select agents or toxins only when continuously escorted by an approved individual,(3) Provide for the control of select agents and toxins by requiring freezers, refrigerators, cabinets, and other containers where select agents or toxins are stored to be secured against unauthorised access (e.g., card access system, lock boxes),(4) Inspect all suspicious packages before they are brought into or removed from the area where select agents or toxins are used or stored,(5) Establish a protocol for intra-entity transfers under the supervision of an individual with access approval from the HHS Secretary or Administrator, including chain-of-custody documents(6) Require that individuals with access approval from the HHS Secretary or Administrator

41 BMBL Handbook - http://www.cdc.gov/od/ohs/biosfty/bmbl5/bmbl5toc.htm

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refrain from sharing with any other person their unique means of accessing a select agent or toxin (e.g., keycards or passwords),(7) Require that individuals with access approval from the HHS Secretary or Administrator immediately report any of the following to the Responsible Official:(i) Any loss or compromise of keys, passwords, combination, etc.,(ii) Any suspicious persons or activities,(iii) Any loss or theft of select agents or toxins,(iv) Any release of a select agent or toxin, and(v) Any sign that inventory or use records for select agents or toxins have been altered or otherwise compromised, and(8) Separate areas where select agents and toxins are stored or used from the public areas of the building.(e) In developing a security plan, an entity or individual should consider, the document entitled ‘‘Laboratory Security and Emergency Response Guidance for Laboratories Working with Select Agents. Morbidity and Mortality Weekly Report December 6, 2002; 51:RR–19:1–6.’’ The document is available on the Internet at: http://www.cdc.gov/mmwr.(f) The plan must be reviewed annually and revised as necessary. Drills or exercises must be conducted at least annually to test and evaluate the effectiveness of the plan. The plan must be reviewed and revised, as necessary, after any drill or exercise and after any incident.

Role of the University and NIH Guidelines for Research Involving Recombinant DNA Molecules A final point when considering US regulation in regard to biosafety is NIH regulation on experimentation utilising DNA recombinant molecules. With the advent of genetic engineering, the public became concerned with the insertion of genetic material into organisms with possibly unknown outcomes. As a result, special guidelines were put in place to ensure that genetic manipulation was carried out responsibly42. This is particularly the case when using DNA recombinant methods on select agents. The NIH guidelines call for the establishment of Institutional Biosafety Committees (IBCs) that approve and monitor recombinant research that could result in dangerous results. The IBCs function in a manner very similar to Institutional Review Boards (IRBs) that are established to monitor human clinical trials. With the advent of IBCs, many institutions have started to use the IBC to monitor both recombinant DNA work as well as any research done with select agents. For example Boston University discusses the function of its IBC at: http://www.bumc.bu.edu/Dept/Content.aspx?DepartmentID=357&PageID=5570 The use of IBCs is very important to universities as federal regulations place the legal liability on the entity licensed to conduct experimentation. The university is responsible for all of the requirements under the regulations and also the consequences of any failures. Thus the research institution would need to apply for a license to APHIS/CDC for any research students working with dangerous pathogens and those students would need to have an FBI background check. A recent example in Texas by Texas A&M University showed that a lab employee lacked the clearance to work with a dangerous agent. The CDC has halted research in the lab as a result. 42 NIH Guidelines - http://www4.od.nih.gov/oba/rac/guidelines/guidelines.html

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An article relating to this incident can be found at: http://www.aaas.org/news/releases/2007/1121biosafety.shtml Federal Agency Links – National Select Agent Program - http://www.selectagents.gov/ Centers for Disease Control (CDC) - http://www.cdc.gov/od/sap/ Animal and Plant Health Inspection Service (APHIS) - http://www.aphis.usda.gov/programs/ag_selectagent/index.html National Institutes of Health (NIH) Recombinant DNA Advisory Committee (RAC) - http://www4.od.nih.gov/oba/rac/guidelines/guidelines.html Federal Bureau of Investigation - http://www.fbi.gov/hq/cjisd/cjis.htm January 2008

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Memorandum 29

Submission from the British High Commission, Wellington

UK SELECT COMMITTEE INQUIRY INTO BIOSECURITY IN UK RESEARCH LABORATORIES

Executive Summary

The regulation of the importation and propagation of hazardous organisms in New Zealand is governed by the Hazardous Substances and New Organisms Act 1996 and the Biosecurity Act 1993 and by standards, policies and methodologies developed by the New Zealand Environmental Risk Management Authority and the Ministry of Agriculture and Forestry Biosecurity New Zealand.

Criteria for the classification of micro-organisms into risk groups and the requirements of laboratories designed to contain hazardous organisms are laid out in the Australian/New Zealand Standard AS/NZS 2243.3:2002, Safety in Microbiological laboratories.

Submission

1. The importation and handling of hazardous organisms in New Zealand is governed by the Hazardous Substances and New Organisms Act 1996 and the Biosecurity Act 1993 and by standards, policies and methodologies developed by the New Zealand Environmental Risk Management Authority (ERMA) and the Ministry of Agriculture and Forestry Biosecurity New Zealand (MAFBNZ).

2. New Zealand laboratories are classified as physical containment (PC) level 1, 2 or 3 in accordance with Australian/New Zealand Standard Safety in laboratories, Part 3: Microbiological aspects and containment facilities, (AS/NZS 2243.3:2002). Facilities handling hazardous organisms are subject to audit against this standard. Audits are undertaken by the facilities approval group of MAFBNZ. MAFBNZ’s own PC3 containment facility is subject to external audit by an independent third party. There are no PC4 laboratories in New Zealand.

3. MAF/ERMA New Zealand Standard 154.03.02 Facilities for Microorganisms and Cell Cultures: 2007 covers the handling of organisms that have been identified as risk goods under the Biosecurity Act 1993. Work with these organisms, which include genetically modified organisms, unwanted organisms, risk species and restricted organisms, is subject to compliance with statutory regulations specified in the Biosecurity Act 1993 and the Hazardous Substances and New Organisms (HSNO) Act 1996. This standard sets specifications for holding micro-organisms and animal cell cultures, that are new to New

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Zealand and includes the minimum requirements that must be met for the containment of unwanted or restricted micro organisms.

4. Micro-organisms that are considered by a MAF Chief Technical Officer (CTO), appointed under section 101 of the Biosecurity Act, to be risk goods are required to be held in transitional facilities. Risk goods are those for which it is reasonable to suspect constitute, contain or harbour an organism that may cause unwanted harm to natural and physical resources or human health in New Zealand or interfere with the diagnosis, management, or treatment, in New Zealand, of pests or unwanted organisms.

5. If these organisms are new to New Zealand, approval for these organisms to be imported into containment facilities is given subject to containment controls specified by ERMA. Once approved by ERMA, permission to import such organisms is given through a permit to import and an import health standard and may be subject to conditions specified by MAF.

6. In addition to approval to import exotic organisms by ERMA and MAF, propagation of organisms declared unwanted under the Biosecurity Act requires approval of a CTO.

7. The containment facility operator is responsible for ensuring mechanisms are in place for resourcing the facility to operate to the MAF/ERMA standard and ensuring that the requirements of a Quality Management System can be met.

8. An Operator must be approved by the Director-General of MAF in accordance with section 40 of the Biosecurity Act 1993, if the Director-General is satisfied that the applicant:

• is a fit and proper person to operate the facility • has the authority to resource and operate the facility • has the technical and financial resourcing mechanisms in place to

maintain that facility

9. The Operator must document and implement a Quality Management System (QMS) for the facility based on the principles of, but not requiring accreditation to, AS/NZS ISO 9001: 2000, NZS/ISO/IEC 17025: 2005, or similar recognised quality management system. The QMS should be documented as a “containment manual” or in an alternative format that clearly documents requirements and enables ready access for practical use and inspection..

10. All people working in the facility must have appropriate working knowledge commensurate with their responsibilities. The QMS must include a training programme that describes how people working in the facility will be made aware of, and understand:

• the purpose of the facility • the statutory and regulatory requirements which relate to work with

microorganisms being held in containment • the principles and practices of containment, as established in

AS/NZS 2243.3: 2002,

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• the procedures used in the facility to maintain containment and fulfill the purpose of the type of facility

• the purpose of, and controls specified by, any HSNO Act Approval for import of new microorganisms contained in the facility

• the conditions specified by MAF in any permit(s) to import, import health standard(s) and/or CTO permission(s) relating to any unwanted microorganism

11. The QMS must also specify how the training programme is to be implemented, evaluated and improved and must stipulate the frequency of refresher courses. Records of training must be documented for all people working in the facility.

12. Access to the facility should be limited to trained personnel authorised to work in the facility. However, visitors may be permitted entry provided they are accompanied by such personnel. Visits must be recorded in a visitors log book for security purposes, and visitors must adhere to access procedures. Entry and exit procedures must be made available at the entrance to the facility, specifying essential requirements such as laboratory coats and protective clothing, signing access log books, and hand washing.

13. Staff and students and contractors working in MABNZ’s containment facility are required to have a security clearance. The security clearance process is overseen by MAF Human Resources staff.

14. Transport of microorganisms must comply with the International Air Transport Association (IATA) Dangerous Goods Regulations, according to the level of risk.. Although the IATA Dangerous Goods Regulations are written specifically for air transport, the packaging and labeling requirements must be applied to all transport to final facility destinations in New Zealand. Operators must ensure, to the best of their ability, that goods being imported into, and within, New Zealand are packaged as per the IATA Dangerous Goods Regulations. The minimum requirement is for micro-organisms s to be packaged according to Packing Instruction No. 650 of the IATA Dangerous Goods Regulations. All products that are infectious or potentially infectious for humans or animals must be packaged according to Packaging Instruction No. 602 of the IATA Dangerous Goods Regulations.

15. Facilities approved to the MAF/ERMA standard are audited every 6 months by a MAF Inspector or Enforcement Officer. The audit is a compliance audit, where the facilities' defined systems are compared against those required by the standard. It will necessarily include a process audit, which will validate the processes and procedures in place. The Operator must provide Inspectors access to the facility, records and documents for inspection and audit or to investigate non-compliances with this standard.

16. The Operator must ensure that an internal audit programme is carried out to assess the effectiveness of containment policies, risk management, and operational procedures. During the internal audit, particular emphasis must be placed on verifying that the registers of micro-organisms are accurate and up to date, the training programme is

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being implemented and is effective, and any corrective actions have been resolved in a timely manner.

17. New Zealand has a limited number of laboratories designed to handle hazardous micro-organisms. The highest level of containment is at the MAF owned facility at the National Centre for Biosecurity and Infectious Disease, Wallaceville, Upper Hutt. This facility is designed to meet the requirements of AS/NZS physical containment level 3 and also incorporates the additional features of OIE containment level 4. It is shared by MAF BNZ’s Investigation and Diagnostic Centre and Environmental Science and Research, New Zealand’s medical diagnostic reference laboratory. For the purposes of the remainder of this submission only organisms causing significant animal disease will be considered.

18. Organisms handled in New Zealand’s veterinary laboratories are classified into Risk Groups 1,2,3 and 4 according to criteria contained in the AS/NZS 2243.3:2002, Part section 3, Degree of hazard from micro-organisms. The classification has been drawn up by modification of the WHO guidelines and is based on the pathogenicity of the agent, the mode of transmission and host range of the agent, the availability of effective preventative measures and the availability of effective treatment. For organisms of veterinary significance, the criteria in the OIE Terrestrial Animal Health Code (2007) Chapter 1.4.5 which include whether an organism is exotic, endemic or subject to official control as well as host range, transmission and availability of prophylactic or therapeutic treatments are also considered.

19. In May 2006, ERMA considered an application by MAFBNZ to import any micro-organisms that may cause disease of significance to animals that have the biological characteristics of Risk Groups1, 2 or 3 into containment for diagnostic purposes. ERMA considered the risks, costs and benefits of the proposed importation. After consultation with the public and industry bodies, consultation with other Government Departments and a public hearing, ERMA approved the application with controls. The controls included limitation of use to MAFBNZ’s Investigation and Diagnostic Centre Physical Containment level 3 laboratory which is on the National Centre for Biosecurity and Infectious Disease campus at Wallaceville, Upper Hutt. The approval was for importation of any micro-organisms that may cause disease of significance to animals that have the biological characteristics of Risk Group1, 2 or 3 as defined in AS/NZS 2243.3:2002 and therefore capable of being contained within a PC3 level containment facility. Viruses that cause vesicular diseases of animals such as foot and mouth disease and organisms that fall with in Risk Group 4 were not included in the application and were specifically exclude from the ERMA approval.

20. Controls covered Laboratory registration requirements, sources of organisms, identification of organisms, sources, transport packaging and labelling, operating procedures, storage, exclusion of unauthorised people from the facility, control of the effects of accidental release or escape, inspection and monitoring requirements, and qualifications required of persons responsible for implementing the controls. The

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approval also specifically excluded using the organisms to deliberately infect live animal hosts.

21. Research on organisms in Risk Group 4 or organisms causing vesicular disease of livestock is not carried out in New Zealand although diagnostic tests that do not require access to the living organisms are available for many of these diseases.

22. Most hazardous organisms affecting animal health, including organisms causing zoonotic human disease, are exotic to New Zealand thus all work undertaken with these organisms is carried out under MAF’s control in its physical containment level 3 laboratory. The ERMA approval excludes infection of animals thus research work with these organisms is confined to in vitro studies.

January 2008

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Memorandum 30

Submission from the Czech Republic

Inquiry into Biosecurity in UK research Laboratories

Introduction The inquiry has shown that overall competencies over Biosecurity issues in the Czech Republic are fragmented between the following institutions of public administration:

Ministry of Health (protection of public health, health of employees at the workplace and general hygiene, health and safety)

Ministry of Agriculture (protection of animals and plants) Ministry of Environment (GMO) State Office for Nuclear Safety (supervision of the ban on biological weapons)

Terminology of the legal documents is not harmonised. It usually does not provide clear definitions and used terms are rather vague. Most of the legal issues are limited to biosafety. The Czech Republic does not have any Acts specifically dealing with biosecurity, or prevention of serious accidents caused by dangerous biological agents. Answers to submitted questions: 1. By what mechanism(s) are micro-organisms classified with regards to their potential danger and their need to be contained? Micro-organisms including various biological agents are classified according to the Act of the Czech Government 361/2007. In the Czech Republic, this Act implements the Directive 2000/54/EC of the European Parliament and of the Council on the protection of workers from risks related to exposure to biological agents at work. The Act 361/2007 divides biological agents into 4 categories depending on the risks of infections. Category 1 should not cause any human disease. Category 2 can cause a disease and can be dangerous to employees, it is improbable that the biological agent would escape from the workplace, and an effective prevention and cure are usually available. Category 3 can cause a disease and be dangerous to employees, there is a potential that the biological agent can escape out of the workplace, and an effective prevention and cure are usually available. Category 4 can cause a disease and be dangerous to employees, there is a potential that the biological agent can escape out of the workplace, and an effective prevention and cure are unavailable. The list of biological agents with the classification into one of the above categories is included as an attachment to the Act 361/2007 (click on the icon below to see the attachment).

Adobe Acrobat Document The document is in Czech, but names of biological agents are in Latin and an

expert will easily understand them. The category of potential danger is the digit in second column. Letters in the third column can contain the following notes: A - possible allergic effects; D - a list of employees exposed to these biological agents has to be stored for 10 years after the last known exposition to the biological agent; T - creates toxins; V - effective vaccine is available; H - currently does not exist any proof of human infection caused by other retroviruses of monkey origin. Category 3 is recommended as prevention for working with such biological agents.

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Adobe Acrobat Document This list of highly dangerous and dangerous biological micro-organisms and

toxins (pages 9406-9410), unfortunately in Czech only (same latin terminology as in the previous document), is a part of the Regulation 474/2002 enforced by the State Office for Nuclear Safety, which is monitoring a ban on bacteriology and toxin weapons, as stated in the Czech Act 281/2002. State Office for Nuclear Safety leads the evidence of all licences for work with highly dangerous and dangerous biological agents and toxins in individual laboratories. The evidence lists include names of responsible representatives, types and amounts of biological agents, aims of the research etc. 2. What are the categories of biological containment in use? There are no formal categories of biological containment as such. The levels of containment and required security depend on the category (from 1 to 4), into which the biological agent or toxin is allocated (see previous answer). Each category of dangerous micro-organisms has it's own requirements given by the Act of the Czech Government 361/2007. The requirements are similar to the technical categories BL2, BL3 and BL4 WHO. Currently, there is only one laboratory for the highest security (Category 4) in the Czech Republic. There are 10 laboratories with a clearance for the Category 3, many microbiological labs for Category 2 and many school laboratories satisfying criteria for Category 1. 3. How are licenses to use dangerous pathogens in research awarded? Licences to work with dangerous pathogens and toxins are awarded by the State Office for Nuclear Safety. The applicant has to be a legal or physical person with a permanent address in the Czech Republic. Representatives of a legal person or a physical person have to be at least 21 years old, with clear criminal and offences records. The applicant has to appoint a scientific representative responsible for dealing with dangerous pathogens. He also has to satisfy many other criteria such as a technical documentation of the laboratory, accreditation, purpose of the use, research, and work with the dangerous pathogens, list of all pathogens with amounts that the applicant will need for research and a length of research period. The State Office for Nuclear Safety has 60 days to make a decision about the licence request. 4. What is the inspection regime for laboratories licensed to use dangerous pathogens? Institutions protecting public health carry out inspections at all places of work regardless of the type of work. In addition to that the State Office for Nuclear Safety carries out inspections in laboratories, which use dangerous pathogens. Licence holder has an obligation to allow inspection of his facilities. He has to instruct inspectors about the scope and type of current work, and about the safety measures necessary for the inspection work. The licence holder has to enable a location of monitoring devices to detect the levels of dangerous pathogens and toxins in the inspected laboratory. Inspectors have the right to take samples for analysis. 5. What training is mandatory / recommended for staff working in containment facilities? Employers in the Czech Republic are generally responsible for appropriate training for all staff including health and safety. International ISO norms and national CSN

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norms, in particular the CSN EN 12741, govern everyday operations of laboratories. Regular training is a part of such process. 6. What are the regulations regarding the storage and transportation of dangerous pathogens? General methodologies related to the storage of dangerous pathogens are not available. It is the responsibility of a director of individual institution to put down and enforce local rules (physical protection and rights to access). Protection of the biological agents during transport follows the European Agreement concerning the International Carriage of Dangerous Goods by Road (ADR), Multilateral Special Agreement on Carriage of Dangerous Goods (RID), and a Czech legislation reflecting these international agreements. 7. What measures are in place to be implemented when pathogenic material cannot be accounted for? Everybody, who finds out about a loss of pathogenic material, is bound by law to report the theft immediately to authorities (police, State Office for Nuclear Safety). The follow-up situation depends on the category of biological agents, on the amount of it, environment etc. The most dangerous cases would be treated according to a special Act 240/2000, also called The Crisis law, which stipulates how to manage critical situations. Less dangerous cases would be dealt according to the Act 258/2000 on protection of public health, or according to the Act 166/1999 on veterinary services in case of animal pathogens. An offender could be prosecuted according to the Czech Penal Code 140/1961 for spreading an infectious disease and also for theft. 8. Who is responsible for overseeing security clearance for research students working with dangerous pathogens – what is the role of universities in this process? The responsibility for overseeing security clearance is ultimately on director of institution/university. The responsibility might be designated to a head of a research laboratory. Universities usually use only Category 1 laboratories. If postgraduate students work at Category 2, or very rarely at Category 3 laboratories, the director of the institution (e.g. Microbiological Institute) is responsible for a security clearance. January 2008

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Memorandum 31

Submission From The British Embassy Berne, Switzerland

Biosecurity at Switzerland’s high-risk research laboratories

(CAT III & IV security levels) Preamble In comparison with neighbouring countries and despite her small size, Switzerland has a dense network of accredited high-level category (CAT) III and category IV biosecurity labs. This is due to Switzerland’s substantial industry and research base in biotechnology, pharmaceuticals and biomedicine. It may also be due, at least in part, to Switzerland’s historical problem with repeated incidence of mad cow disease, BSE, as in the UK. In the above context, the Swiss tend to talk about biosafety rather than biosecurity. This report uses both words interchangeably and in the same context. The Swiss Ordinance on Contained Use of Organisms (ESV, see 4. below) stipulates that laboratory research at Swiss CAT I and II biosecurity labs (with nil to minimal security risk) is subject to notification/registration and that laboratory research at Swiss CAT III and IV (moderate to high security risk) is subject to issue of a specific licence. At the highest danger level, the government maintains two CAT IV and one CAT III national reference laboratories • The Central Virological Lab (LCV), CAT IV, since February 2007, within the

Central Bacteriological Lab at the University Hospital of Geneva, for dangerous human pathogenic material (www.hug-ge.ch/maladiesinfectieuses , English pages also). A new dedicated website is under construction. This falls under the Swiss Federal Office of Public Health (FOPH / BAG).

• The Institute for Animal Viral Disease and Immuneprophylaxis (IVI), CAT IV, since 1992, for diagnosis, monitoring and control of highly contagious animal pests at the Mittelhäusern animal facility near Berne (www.bvet.admin.ch/ivi). This falls under the Swiss Federal Office for Veterinary Affairs, BVET, and, in turn, under the Swiss Federal Office for the Environment (FOEN / BAFU).

• The National Reference Lab for Anthrax (NANT), CAT III, at the Institute for Veterinary Bacteriology at the University of Berne (www.vbi.vetsuisse.unibe.ch/ ).

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New Spiez High Containment Laboratory (CATs IV, III) In November 2007 construction started on a second human CAT IV pathogenic reference laboratory at the existing Spiez nuclear biological chemical (NBC) lab facility near Berne. This for an approved price tag of 28 million Swiss Francs (UK £ 12.5 million) and after 10 years of deliberation and planning. Covering 4 floors over an area of 2300 m2, the new facility is slated for commissioning in 2010 (www.labor-spiez.ch/old/e/ ) . A six page technical briefing brochure in English can be downloaded at www.ar.admin.ch/internet/armasuisse/en/home/themen/immo//projekte.html Biosecurity at Swiss laboratories falls under the jurisdiction of several Swiss Federal Agencies or Offices, as well as local cantonal authorities. The governing Federal Offices are • Federal Office for Public Health, FOPH / BAG

www.bag.admin.ch - dedicated Section on Biological Security

• Federal Office for the Environment, FOEN / BAFU

www.bafu.admin.ch - dedicated Section on Biotechnology and flows of matter • Swiss Expert Committee on Biosafety, SECB / EFBS www.efbs.ch/buwal/eng/ RESPONSES TO SPECIFIC QUESTIONS FROM THE COMMITTEE 1. By what mechanisms are micro-organisms classified wrt their potential

danger and their need to be contained? By European norms. Please see EU Council Directive 2000/54/EC under www.eur-lex.europe.eu. The Swiss govt also has separate general classification schemes (see Containment Ordinance under 6.) and specific ones for parasites (2003, 40p), bacteria (2003, 176p), fungi (2004, 115p, English) viruses (2004, English, 32p) and cell lines (2007, English). All can be accessed electronically under www.bafu.admin.ch/biotechnologie/01744/01753/index.html?lang=en Unless explicitly stated above, documents are available only in German, French and Italian.

2. What are the categories of biological containment in use? Categories I-IV. By European norms. Please see EU Council Directive 2000/54/EC under www.eur-lex.europe.eu.

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Specifically, Swiss bio labs are subdivided into biosecurity categories 1, 1D, 2, 2D, 3, 3D and 4D. The three CAT IV biosecurity labs have been listed above.

At the CAT III level, there are more than 40 accredited public and private sector labs. Accreditation is issued on the basis of individual disease / pathogen indications, so the number of dedicated individual labs breaks down to 32. Most are specialist University or hospital labs and cantonal labs. All can be referenced and called up by multiparameter searches (eg region, year of registration etc.) on the public register database of the Swiss Federal Office for the Environment FOEN/BAFU at www.bafu.admin.ch/biotechnologie/verzeichnis/index.html?lang=en None of Switzerland’s large biopharma corporations eg Novartis, Roche maintain CAT III or CAT IV labs in Switzerland, but do so abroad. This may relate to the strictness of legislation pertaining to such labs in Switzerland. Some other private sector CAT III labs in Switzerland are • Nestlé Research Labs at Vers-chez-les-Blanc / Lausanne

www.research.nestle.com (though currently operating only at CAT II level)

• Crucell-Berna Biotech AG, Berne. www.crucell.com

• Institut Viollier AG at Allschwil/Basel – a Swiss network of commercial analytical labs www.viollier.ch/index.cfm?&o_lang_id=2

• Prionics AG, in Zurich – Swiss SME focused on animal diagnostics, esp. BSE www.prionics.com

• Alicon AG, in Zürich – Swiss SME founded in 2004, focused on food diagnostics & CJD. www.alicon.ch

• Institute for Res in Biomedicine, IRB, in Bellinzona, canton of Ticino www.irb.unisi.ch

At the national level, the Swiss national conference of health directors commissioned the establishment of a network of regional high security government reference laboratories in 2006. This involved subdivision of Switzerland into 6 regions to more effectively manage potential crises brought about by human or animal epidemics or pandemics. The advantages of this network of high security government biolabs are cited as being flexibility, geographic coverage and a healthy measure of redundancy between respective laboratories. These regional government CAT III reference labs are listed in Appendix 1.

3. How are licenses to use dangerous pathogens in research awarded? Licenses are awarded by Swiss Federal Office for the Environment, FOEN / BAFU on the basis of

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• guidance – see www.bafu.admin.ch/biotechnologie/01744/01749/index.html?lang=en

• formal electronic application procedures - see

www.bafu.admin.ch/biotechnologie/01744/03225/index.html?lang=en

• implementation guides - see www.bafu.admin.ch/biotechnologie/01744/01752/index.html?lang=en At FOEN, the entry and exit point for all notifications and licence applications under the Swiss Containment Ordinance (see 4. below) is the Federal Coordination Centre for Biotechnology. See www.contactbiotech.ch .

4. What is the inspection regime for laboratories licensed to use dangerous pathogens? Switzerland has ratified the Cartagena Protocol on Biosafety. Please refer www.bafu.admin.ch/biotechnologie/02618/index.html?lang=en . The Federal Government has devolved inspections to the regions that are known locally as cantons (see article 20 of Swiss Ordinance on Contained Use of Organisms, ESV; section 6.) There are 26 cantons and every canton has its own laboratory. However, only a few cantons have CAT III or CAT IV laboratories. Please refer in particular to Cantonal inspections: practical aspects, p 51-53 in Biosafety Officer Manual 2006 www.bafu.admin.ch/biotechnologie/01744/02964/index.html?lang=en Cantonal authorities also determine the frequency of inspections. However, inspections can also be ordered immediately or ad hoc on consensus between federal and cantonal authorities in instances where non-compliance with Swiss Ordinance on Contained Use of Organisms, ESV, is suspected. Training and further education of cantonal inspectors is handled by the cantonal authorities and by means of periodic courses that are convened by Federal agencies. Insofar as possible, inspections are standardised at the national level and according to international norms. For example, a normed checklist is used, see www.bmgfj.gv.at/cms/site/detail.htm?thema=CH0254&doc=CMS1150109483398 In general an inspection is made after a licence has been granted by the appropriate authority (FOEN or FOPH), i.e. while an activity is carried out. During the construction of a new lab inspections are carried out during the commissioning process.

Example: Institute for Animal Viral Infections, IVI, near Berne (FOEN / BAFU)

IVI’s security measures are audited by independent experts. This includes assessment of risk management measures.

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The maximum-security area of IVI is situated in a separate building about 100 metres away from the office and administration building. It has an electronically secured and monitored fence and gate. The main entrance door to the building opens only with a valid badge. If the gate or the door are not closed again within a certain time, or if someone climbs the fence, the monitoring system automatically alerts both an internal 24-hour-stand-by for emergency duties and the police. This serves to prevent unauthorised access and theft of animal pathogens. Such an incident has thus far not happened. Inside the maximum-security area several security measures must be followed to gain access to the laboratory. First, there is a single person decontamination area which is accessible only by badge, after that there is an outer change room, where everyone has to get completely undressed (including jewellery, etc.) before entering an air-tight shower. After this shower there is an inner personnel clothing room where special clothing is provided by the laboratory. In this area there is already a negative pressure to ensure that airborne pathogens cannot escape. The next door leads to the sanctum which – considering the time-consuming procedure to get here – looks quite normal and does give the impression of being a category 4 maximum security lab. Staff do not wear protective clothing but the same green and white clothes as the visitors. The security category 4 applies only with respect to the outside world. Inside the lab no special precaution is necessary because the pathogens that are analysed usually are nonhazardous for human beings. Only when work is done with rabies- or bird-flu H5N1-viruses additional security measures are applied.

To minimise risk, there is a significant difference to a normal lab: What comes in, stays in or gets out only after it has been sterilised and decontaminated.

Exhaust air is piped through two aerosol filters that retain even the smallest particles including viruses and bacteria. All sewage from the lab, shower, toilet and from the maximum-security animal wing is heat-treated to kill pathogens before leaving the site. Every apparatus or device that has to leave the lab (e.g. for repair) is disinfected with formaldehyde or ethylene oxide. Animals that were infected with pathogens for testing purposes are slaughtered in a separate room, dissected and heated-treated an autoclave. Although the facility was built 15 years ago it has been continuously upgraded and remains state-of-the-art. Security measures are maintained at a consistently high level and are described as above-average. Other laboratories raise or lower their security levels at different times – depending on the danger level of work being carried out. Or other labs define different areas with different security levels. At IVI, the maximum risk rules are applied at any time and anywhere without exception. So the green and white clothing stays within the maximum security area and is washed and dried there. It is forbidden to take notes or print-outs to the administration building, everything has to be sent by e-mail or fax. Finally the employees have to take a shower (and to use the shower gel twice) that lasts at least three and a half minutes every time they leave the lab. For reasons of time-efficiency, the lunch break is held within the cat 4 facility - a cook in a fully equipped kitchen within the cat 4 area prepares meals for the 30 to 35 persons working inside.

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Every employee is placed on a three-day quarantine after having left the lab. Contact with “epidemic susceptible animals”, i.e. cattle, pigs, goats, sheep and other cloven-hoofed animals is strictly forbidden. In particular, visits to zoos, farms and circuses are forbidden.

5. What training is mandatory / recommended for staff working in containment facilities?

Currently, there is no mandatory training scheme. The Swiss Federal Office of Public Health FOPH/BAG, the Swiss Federal Office for the Environment FOEN/BAFU and the Swiss Expert Committee for Biosafety EFBS all run one basic one day course for Biosafety Officers once a year. This is recommended for all biosafety officers (BSOs). See www.bafu.admin.ch/biotechnologie/01744/02964/index.html?lang=en Beyond this, half day thematic seminars are offered. Staff training is offered by a Swiss virtual Institute based in Berne. It is called the Biosafety Institute, b-safe GmbH (www.b-safe.ch ). B-safe was founded in 2003 with the role of providing specialist training and knowledge transfer. It is a non-profit organisation. Swiss Federal Offices are preparing a formal curriculum for training of Biosafety Officers for CAT I – CAT III labs. The curriculum is made up of 39 thematic areas for BSOs and this training will take 3-7 full days spread over several months, depending on the lab safety level addressed. Once approved, this training will become mandatory and will include a formal examination. These courses are slated for launch from or after 2009. The two cat 4 labs train / coach their staff themselves according to their needs. Inspections by the Cantons and of federal offices (FOEN, FOPH, Swiss National Accident Insurance Agency - SUVA) as well as international reviews ensure that the training is up-to-date.

6. What are the regulations regarding the storage & transportation of dangerous pathogens?

Storage

Governed by Swiss Ordinances on Contained Use of Organisms (ESV) , and European Agreement on International Carriage of Dangerous Goods by Road (ADR). Swiss Ordinance on Contained Use of Organisms, CO of 26 August 1999 (36 sides). SR 814.912. Non-binding English translation available under www.bafu.admin.ch/biotechnologie/01744/index.html?lang=en

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Transportation subject to detailed regulations Transport is a very complicated issue. Fact sheet memoranda are in preparation by Swiss Expert Committee for Biosafety, EFBS. Will be available in public domain once completed. Governed by international ordinances from IATA (International Air Transport Association) and IMO (International Maritime Organisation). See also Transport regulations in Biosafety Officer (BSO) manual 2006, Nov 2006, p 36-50, at www.bafu.admin.ch/biotechnologie/01744/02964/index.html?lang=en Link J. (23 Nov 2006). Transport of infectious substances and GMO. Swiss Expert Committee for Biosafety. English slide presentation, 21 slides, pdf. Available at www.bafu.admin.ch/biotechnologie/01744/02964/index.html?lang=en • Transport of infectious biological reagents and organisms, Aug 2006,

Berne/Zurich, 36 sides, valid until 30 June 2007. Authors Küng & AWEL.

Bureau for waste,water,energy and atmosphere, AWEL Department for waste and operations Biosafety Section Construction Directorate of the Canton of Zurich Nb This document is available only in German.

• World Health Organisation home page www.who.int

o WHO: Transport of infectious substances o WHO: Transport of samples containing avian influenza

Other regulations/laws/ordinances for environment, employees, food, animal protection, etc. Please see www.bafu.admin.ch/biotechnologie/02618/index.html?lang=en . Potential relevance (text available in German, French, Italian only) • Federal law on epidemics (1974, 14p) • Federal law on epizooties (1967, 22p)

7. What measures are in place to be implemented when pathogenic material

cannot be accounted for? Measures are governed by the Swiss Ordinance on Major Accidents, OMA (German: Störfallverordnung, StFV) of April 1991, Swiss Law document SR 814.012.

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The document can be downloaded as 30p pdf file in German, French, Italian only, from www.admin.ch/ch/d/sr/c814_012.html Regional, ie. Cantonal authorities are responsible for executing inspections. As a rule, every lab operator is charged with putting in place an emergency plan. The lab operator is also fully responsible for this emergency plan.

8. Who is responsible for overseeing security clearance for research students

working with dangerous pathogens – what is the role of universities in this process? According to the Containment Ordinance the applicant (project leader, head of lab etc.) and / or the BSO are responsible for observing the general and the supplemental safety rules. See also FOEN guideline “Biosafety Officers (BSO). Status, duties and responsibilities. 2005.“ www.bafu.admin.ch/publikationen/index.html?lang=en&action=show_publ&id_thema=6&series=VU&nr_publ=4404 The Ordinance on occupational safety in biotechnology (SAMV) states that the employer is responsible for safety. Particularly inexperienced employees have to be trained and invigilated with the utmost care. Universities themselves play no particular role.

9. Further information on Switzerland www.efbs.ch/buwal/eng/ Swiss Expert Committee for Biosafety Elected for 4 year terms of office Current President Prof med. Pascal Meylan, Clinical Virologist, Inst for Microbiology, University of Lausanne www.bag.admin.ch/themen/medizin/00708/index.html?lang=en

Biological Safety Section Swiss Federal Office for Public Health, FOPH www.bafu.admin.ch/biotechnologie/01744/01745/index.html?lang=en

Swiss Federal Coordination Centre for Biotechnology Within Swiss Federal Office for the Environment, FOEN, Berne www.erfa-bio.ch Swiss intercantonal knowledge exchange portal for expert groups in biotechnology and genetics (German only) www.bats.ch Portal of Swiss Centre for Biosafety and Sustainability, Zurich and Basel Chapters on Biosafety, Medicine, Agriculture Concerned with assessment of new technologies in biosafety area.

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www.ecogen.ch Portal of Swiss Federal Coordination Centre for Biotechnology for notifications and licence applications for authorisation under the Ordinance on the Contained Use of Organisms (SR 814.912 – see 6.1)

University Risk Institutes concerned with Biosafety issues www.crn.ethz.ch Crisis and Risk Network, CRN, at Swiss Federal Institute of Technology at Zurich, ETHZ www.risiko.unibe.ch Expert Centre on Risk Management, University of Berne (website in German only)

We can furnish names and contact details of experts at Swiss CAT IV (and CAT III) biosecurity labs on request.

10. Useful literature

FOPH / BAG Bulletin (14 Aug 2006). Bulletin 33, p 668-672

Diagnostics in the domain of biological agents – state of the art and perspectives on the regional network of (high security) laboratories in Switzerland. (hard copies in German, French, Italian only) Biosafety Officer (BSO) manual (23 Nov 2006). 65 p. English. Available as pdf file at www.bafu.admin.ch/biotechnologie/01744/02964/index.html?lang=en Gschwind, M. (23 Nov 2006), Swiss Accident Insurance Agency SUVA. English presentation Biosafety Regulations in Switzerland, 117 slides, pdf. Available at www.bafu.admin.ch/biotechnologie/01744/02964/index.html?lang=en

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APPENDIX 1

The six regional high-level CAT III biosecurity labs maintained by the Swiss Federal government

Region Location Name / Institute www North Basel-Stadt

Cantonal Laboratory of the City of Basel

kantonslabor-bs.ch (English pages available)

South Bellinzona Cantonal Institute for Microbiology

ti.ch/laboratorio (Italian)

East Zurich Institute for Medical Microbiology lab, IMM Inst for Medical Virology lab, IMV also National Centre for Retro-viruses, Univ of Zurich

imm.uzh.ch/he.html imv.uzh.ch (English)

West Geneva, Lausanne

Central Laboratories for Virology and Bacteriology, University Hospitals of Geneva; Institute for Microbiology, University Hospital of Vaud

hug-ge.ch/ maladiesinfectieuses chuv.ch/imul (English)

Central-East

Lucerne Institute for Medical Microbiology, Cantonal Hospital of Lucerne

ksl.ch/standorte/Luzern/kliniken/zentrum-fuer-labormedizin/institut-fuer-medizinische-mikrobiologie.html (German)

Central-West

Spiez near Berne

Spiez NBC Laboratory labor-spiez.ch (German, English pages available)

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Memorandum 32

Submission from the Association of the British Pharmaceutical Industry (ABPI)

BIOSECURITY OF UK RESEARCH LABORATORIES

1. The UK pharmaceutical industry is actively engaged in research programmes to develop prophylactic and therapeutic pharmaceuticals to prevent and treat infectious disease. The Association of the British Pharmaceutical Industry (ABPI) is the leading organisation that represents pharmaceutical and biopharmaceutical companies, including contract research organisations, who develop and manufacture innovative medicines.

2. Research in this area requires work with relevant biological agents including

naturally occurring human and animal pathogens, genetically-modified micro-organisms and a number of toxins of biological origin. Companies are committed to ensuring high standards of biosafety and biosecurity apply to all relevant activities in the UK and elsewhere.

3. It is recognised that successful management of risks associated with such work

must address both biosafety and biosecurity issues43. 4. On the specific issues raised by the Committee we offer the following comments.

The current capacity for research on dangerous pathogenic material in the UK . 5. Infectious diseases continue to cause high numbers of cases of morbidity and

mortality around the world. Among these are relatively new diseases such as HIV AIDS and Severe Acute Respiratory Syndrome (SARS) and more recently, limited cases of human infection with highly pathogenic avian influenza strains.

6. Recent years have also seen a resurgence of some infectious diseases including Tuberculosis where there is particular concern about the emergence of multi- and extensively drug-resistant strains of the causative organism.

7. Resistance to existing antibiotic therapies is also a serious concern in other diseases including infections caused by MRSA which in the UK and elsewhere continues to be major problem in hospital-acquired infections.

8. Against this background there is a clear and demonstrable need for continuing basic research to better understand the mechanisms of pathogenicity and drug resistance and for application of this understanding in research to discover and develop new therapies.

43 “Biosafety” is used here to describe the containment principles, technologies and practices that are implemented to prevent the unintentional exposure to biological agents and toxins, or their accidental release while “Biosecurity” is used to describe measures for access control and accountability for use of biological agents and toxins within laboratories, in order to prevent their loss, theft, misuse, diversion of, unauthorized access or intentional unauthorized release.

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The capability to conduct research on the causative agents of disease that may emerge at a future time. 9. The emergence of new infectious diseases is likely to be a continuing problem.

While appropriate prescribing by physicians and encouragement of better patient compliance will help to mitigate the spread of drug resistance, the underlying phenomenon is an inherent feature of microbial evolution.

The state of biological containment facilities in the UK 10. We note that UK law44,45 and associated guidance provides standards for the

design and operation of microbiological containment laboratories. These standards have been developed to ensure that appropriate safeguards can be provided according to the hazards posed by pathogens and the associated risk attached to relevant work activities. While there are restrictions on access even at Containment Level 2, these have traditionally been prescribed to afford an adequate standard of safety for those working in the facility and to guard against accidental escape into the wider community rather than the risks of deliberate misappropriation, theft, subversion and misuse.

11. We also note that the Anti-terrorism, Crime and Security Act 2001 provides for notification to the Home Office of possession of relevant materials and also for the establishment of appropriate physical, procedural and personnel screening measures. The Act also provides for inspection by the relevant authority that may also require implementation of specified measures to improve existing arrangements where this is deemed to be necessary. We support the need to ensure that proportionate biosecurity measures are taken with respect to work with relevant materials.

12. Laboratories where pathogens are handled in the UK should be and are designed,

constructed, operated and maintained to comply with the relevant standards of containment provided for in UK legislation and account taken of associated guidance.

Laboratory inspection regimes and the rationale and practicalities of the licensing system. 13. We believe that it is important for organisations to implement appropriate self-

inspection and auditing regimes as part of their biosafety and biosecurity management procedures.

14. We recognise the additional assurance provided for through inspections and/or

audits by regulators and we support a proportionate, scientific and risk-based approach to the regulation of work activities involving the use of hazardous

44 The Control of Substances Hazardous to Health Regulations 2002 45 Specified Animal Pathogens Order 1998

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biological materials.

15. We support the recommendations made in the Callaghan Review46 to merge the regulatory regimes governing work with human and animal pathogens and for enforcement to be the responsibility of the Health and Safety Executive.

Biosafety training provision for staff working in containment facilities. 16. Staff working in containment facilities must have demonstrable competence not

only to work to high scientific standards but also to work safely. Identification of biosafety training needs and providing for these to be met is critical in ensuring this, and this issue should be addressed in any biosafety and/or biosecurity management programme. A range of training processes may be used but hands-on training, under an appropriate level of supervision is an essential element in any training programme.

17. We encourage academic institutions to ensure that relevant programmes in relevant disciplines include appropriate provision for the development of an understanding of microbiological risk assessment, associated safety control measures and their application.

The maintenance and recording practices surrounding the storage and transportation of dangerous pathogens. 18. National and international regulations are in force governing the transport of

dangerous substance including hazardous biological materials. These include provisions for appropriate packaging and labelling and there are also specific requirements for security plans in connection with the transport of high consequence agents. We believe that strict adherence to the requirements of the current regulations provides an appropriate level of safeguard in terms of safety and security.

19. Inventories should be maintained for all relevant materials. Safe and secure storage should be provided and used with specific measures being determined and applied in accordance with risk assessment and the requirements of national legislation.

Measures implemented when pathogenic material cannot be accounted for. 20. RIDDOR 47 specifies requirements to report accidental releases of biological

agents likely to cause severe human illness and the COSHH regulations require employees to report to their employee or the employer’s nominated representative any accident or incident which has or may have resulted in the release of a biological agent which could cause severe human disease. It is not clear from this wording whether or not this requires reporting where inventories indicate that relevant material is unaccounted for and we believe that guidance from the

46A Review Of The Regulatory Framework For Handling Animal Pathogens Chaired by Sir Bill Callaghan. Presented to the Secretary of State for Environment, Food and Rural Affairs 13 December 2007 47 Reporting of Injuries, Diseases and Dangerous Occurrences Regulations 1995

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authorities would be helpful. Depending on the interpretation placed on the existing law, the authorities may also wish to consider the need for amending legislation.

21. We believe that irrespective of any legal requirements, failure to account for pathogenic material should as a minimum, be reported through the management line. Appropriate emergency procedures taking account of this type of incident should be in place and should be implemented if an incident occurs. Depending on the specific circumstances, those measures should involve reporting to the relevant authorities.

22. Irrespective of any reporting to and investigation by those authorities,

organisations should carry out their own investigation and act on any findings and recommendations that arise out of the investigation.

The role of universities in overseeing security clearance for research students working with dangerous pathogens. 23. We believe that it is essential for continued progress in this area for there to be a

strong UK academic base in the areas of microbiology, virology and molecular biology.

24. Research students typically are involved in research studies on projects of 1 – 3 years duration. The relatively short duration of projects, the associated high turnover, the significant numbers engaged in such studies, and the costs of carrying out security clearance checks mean that there are particular difficulties for universities in ensuring that all students are suitably screened in this respect.

25. It is essential that highly competent and suitably trained individuals are available

to carry out relevant work activities in countries where there are relatively high levels of endemic and newly emerging infectious diseases. These conditions are often associated with developing nations. Attracting research students to UK academic institutions for part or all of their formal training is not only an important issue for those institutions but also serves to help ensure that students who subsequently return to their home countries or other developing nations will be able to draw on their experience in the UK to the benefit of their homeland. While we recognise and accept the need for appropriate screening we also believe that it is important that unnecessary obstacles are not put in the way of international academic interchange.

We hope that this brief response is helpful to you in your consideration of these issues. January 2008

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Memorandum 33

Submission from the British Embassy, Paris Inquiry into Biosecurity in UK Research Laboratories Question 1: By what mechanism(s) are micro-organisms classified with regards to their potential danger and their need to be contained? The classification of micro-organisms follows the EU directive from 1990 by which they are classified in 4 categories of biosecurity. The directive was transposed into French law in 1994. In 1996 and 1998, the law was modified to increase the classification of certain micro-organisms which could constitute a bioterrorism threat. Question 2: What are the categories of biological containment in use? The categories of containment are also those derived from the 1990 EU directive i.e. L1, 2, 3 & 4. However, on 16 July 2007, the French law was changed to list five different types of containment in separate annexes to the law, according to their context (see http://droit.org/jo/20070804/MTST0756429A.html):

‐ Medical analysis and medical biology laboratories

‐ Pathology laboratories

‐ Laboratories undertaking autopsies or dissection on humans or animals

‐ Research laboratories working with identified strains of pathogens

‐ Industrial and agricultural laboratories working with and identified strains of

pathogen

It was felt that the previous containment categories were too vague and did not take into consideration the specificities of these different professional contexts. The annexes list, item by item, the obligatory measures relating to the design, internal organisation, technical procedures, individual protection and hygiene in each type of laboratory and for each level of biosecurity within these different types of laboratory. Question 3: How are licenses to use dangerous pathogens in research awarded? A licence is necessary for anyone working on or handling any pathogen which features on a published list of pathogens considered to be dangerous (see http://admi.net/jo/20040807/SANP0422322A.html). This list includes all level 4 and some level 3 micro-organisms but also some level 2 pathogens (such as polio) which are considered to be a significant threat in terms of bioterrorism because of their rapid oral transmission. The licences are given by the French Agency for Health Safety and Medical Products (AFSSAPS - http://agmed.sante.gouv.fr/) and are mandatory for any manipulation of the pathogens on this list. The AFSSAPS is under the control of the Ministries of Health and of Research. The licence is awarded for one or micro-organisms for one or more specified activities and always to a named person. Before issuing the licence, the AFSSAPS asks for evidence of the named person’s competence in safely manipulating the pathogen, details of the place where the activity will take place and the authorisation of the director of the laboratory where the activity takes place as well as the director of the

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establishment if this is not the same person. The director has a legal obligation to provide the appropriate containment facilities for the pathogen featuring on the licence application. For level 4 laboratories (there is one in France, in Lyon), the Ministry of the Environment (MEDAD) must also give its approval as these laboratories are considered “classified installations”. The MEDAD must also give its authorisation to all industrial laboratories handling listed pathogens. AFSSAPS responsibility is limited to the protection of personnel and of public health whereas the MEDAD is responsible for territorial protection and thus of the laboratory installation itself. Question 4: What is the inspection regime for laboratories licensed to use dangerous pathogens? Before a licence is awarded, the laboratory where the work is to be undertaken is inspected by the AFSSAPS to ensure that all the evidence provided in the application form is in order. The inspectors provide an opinion to the AFSSAPS evaluation department which then issues the licence if its decision is positive. Once a licence has been issued, the AFSSAPS undertakes additional routine inspections once every three years. The laboratories are informed of the inspectors’ visit three weeks in advance in writing. However, if an inquiry is underway into the biosecurity in the laboratory then an inspection may take place with no prior warning. During the routine inspections all documents detailing the qualifications and training of the personnel must be provided to the inspectors. For industrial laboratories, a GMP inspection takes place at the same time as the routine inspection, both done by AFSSAPS inspectors. For Level 4 laboratories, MEDAD‘s environmental inspectors may also join the other inspectors so that only one joint inspection is done. Any anomalies discovered during inspections are categorised as ‘critical’, ‘major’ or ‘other’. If the anomaly is considered ‘critical’, the licence is taken away immediately and the licence holder has 15 days in which to reply with a list of the actions s/he will take to conform to the conditions of the licence and when these will be implemented. A second inspection will take place 6 months or one year later in any laboratory where anomalies have been noted. Question 5: What training is mandatory / recommended for staff working in containment facilities? Training of staff comes under the general work code (Code du Travail) which states that all workers exposed to a biological hazard must have specific training and medical surveillance. Training is mandatory in hygiene and security, in manipulation of hazardous materials and in microbiology, plus other training specific to the material being handled. Each laboratory must undergo a risk assessment and training is adapted to the particular risks presented in each laboratory. Other mandatory training is adapted to the particular task that the laboratory worker is asked to undertake. The content of the training sessions is subject to inspection during the routine inspections referred to in Q4.

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Question 6: What are the regulations regarding the storage and transportation of dangerous pathogens? The storage, conservation and transportation of dangerous pathogens are subject to the same legislation regarding licences referred to in Q3, if the pathogens are on the published list of dangerous pathogens. Otherwise the transport of micro-organisms is subject to international transport legislation. Question 7: What measures are in place to be implemented when pathogenic material cannot be accounted for? When pathogenic material cannot be accounted for, the director of the laboratory or the licence holder is required by law to make a declaration of loss to the regional authorities (Prefecture), to the police and to AFSSAPS. However, it has recently been decided that a more rigorous system should be put in place so that all anomalies and accidents are systematically registered even when there is no loss of material. This system would be analysed by a quality commission and an annual evaluation made of all laboratories with AFSSAPS licences to ensure better traceability. In industrial laboratories, the application of GMP ensures that this is already the case. Test laboratories and level 4 laboratories have been obliged to apply GLP since 2004. Any laboratory which discovers a dangerous (listed) pathogen strain in a sample must report this to one of the National Reference Centres for the pathogen in question within one month or must apply for a licence to work on it. Question 8: Who is responsible for overseeing security clearance for research students working with dangerous pathogens – what is the role of universities in this process? The licence holder is responsible for including the names of all those who will be working with the pathogen in the licence application, including technicians and research students. The application is systematically passed to the “Senior Civil Servant for Defence and Security” (Haut fonctionnaire de défense et de sécurité) in the Ministry of Health who can decide whether or not to authorise particular named students. For overseas students, the names are also passed to the appropriate secret and security services (Direction de la Surveillance du Territoire - DST). January 2008

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Memorandum 34

Submission from the Society for General Microbiology (SGM) Introduction The Society for General Microbiology, founded in 1945, is an independent professional scientific body dedicated to promoting the ‘art and science’ of microbiology. It has now established itself as one of the two major societies in the world in its field, with some 5,500 members in the UK and abroad. General Comments The Society for General Microbiology (SGM) welcomes the Select Committee's inquiry into Biosecurity in UK research laboratories. Specific Comments

• the current capacity for research on dangerous pathogenic material in the UK and the capability to conduct research on the causative agents of disease that may emerge at a future time;

Research involving these hazardous agents is absolutely essential in order to combat the threat of existing and emerging infectious diseases. Any regulatory framework must achieve a suitable balance - providing appropriate safeguards whilst not unduly restricting crucial research. It is compulsory that research involving hazardous pathogens or toxins is conducted in appropriately equipped and resourced facilities. Associated requirements are robust safety and security procedures that ensure minimal risks of harm to laboratory workers, the wider public and the environment. With the exception of some MoD establishments, the UK capacity is lacking in training and facilities. The area of infectious diseases, which underpins much of this work, has been identified as needing strategic boosts for example by studentship programmes funded by MRC. The SGM is concerned that the UK should maintain and indeed strengthen the capacity for research into dangerous pathogens that may emerge or re-emerge through natural processes and through malicious release.

• the state of biological containment facilities in the UK; Modern, well maintained facilities are required for research on dangerous pathogens and biosecurity should be considered when allocating budgets. Several Universities are building level 3 containment suites in order to increase the capacity to work with higher level pathogens and respond to emerging disease threats meaningfully. However, the state of central large animal facilities is deplorable. These need to be provided centrally as few or no Universities would have a sufficient volume of work to sustain these on a full economic costs basis.

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The UK needs to continue to invest in this area so as to set up facilities at the Institute for Animal Health or elsewhere. The state of the highest category containment laboratories (BSL 4) in the civil sector, such as at the Health Protection Agency and at the National Institute of Medical Research, has been deteriorating over time and will probably require significant capital investment in order to maintain state-of-the-art capacity.

• laboratory inspection regimes and the rationale and practicalities of the licensing system;

Old facilities can be difficult to inspect, so regimes would benefit from an overall updating of facilities. In general, there are few inspectors and inspections of licensed facilities are rare. Laboratory inspection regimes conducted by the Health & Safety Executive are good, but there appears to be over-emphasis on a spurious rationale for respiratory safety containment even for pathogens that do not spread by this route; therefore some rethinking about practicalities concerning true dangers and possibly false security would be advisable. Any licensing system needs to be confined to category 3 pathogens and above and should not be bureaucratic. A very considerable amount of time is spent on dealing with the bureaucratic implications of some work, including research on animals using genetically modified micro-organisms. It is difficult to say what should be jettisoned but the cumulative effect of the bureaucracy is stifling. Having said this, licences for new facilities should be considered carefully.

• biosafety training provision for staff working in containment facilities; It is the responsibility of research institutions working with hazardous biological agents to ensure that this research is safely conducted. All clinical and academic researchers, students and technicians working with hazardous agents should receive correct and specific training before they begin this work. Training programmes must include refreshers at regular intervals thereafter, including updates on regulatory developments. Dedicated Biological Safety Officers (BSOs) in institutions must take the leading roles in responsibility for organizing and delivering effective staff training, tracking developments, and advising institutions' senior management. Government must ensure sufficient long-term funding is provided to key national institutions for provision of research facilities equipped to undertake work on these agents, and for retention of technical expertise in research institutions. This also includes maintenance of culture collections. Institutions themselves should develop appropriate succession planning arrangements to ensure continuity of skills within their staff. While biosafety training provision for staff at universities and research institutions appears to be rigorous, there is a danger that the UK is gradually losing expertise to investigate and handle certain dangerous pathogens through previous lack of interest and lack of adequate funding, both in the

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medical and in the veterinary fields. Greater emphasis on training is needed; as the UK is a signatory to the Biological and Toxic Weapons Convention, it needs to take its responsibility in this area more seriously. Reviews of training (which is controlled by individual facilities) should be more proactive.

• the maintenance and recording practices surrounding the storage and transportation of dangerous pathogens;

The maintenance and strict recording practices of the storage and transportation of dangerous pathogens is an area that needs to be continually monitored in order to improve security and to introduce better recording practices afforded by computerised methods. If any changes are envisaged they should be applicable only to the highest categories of pathogens. The term dangerous pathogens as defined in UK legislation covers too wide a range of organisms. The primary responsibility for ensuring safety and security must rest with institutions. However, relevant regulatory agencies also have an obligation to coordinate effectively in developing and implementing regulatory processes. There seems to be lack of consistent guidelines and regulations on the transport of potentially hazardous biological materials between different countries.

• measures implemented when pathogenic material cannot be accounted for;

It is of crucial importance to ensure appropriate measures to follow up investigations into the provenance and destiny of dangerous pathogens, without triggering unnecessary panic if an audit of the pathogens appears faulty. It should be made applicable only to category 3 organisms or above. Better contingency plans are needed for loss and damage during transportation.

• the role of universities in overseeing security clearance for research students working with dangerous pathogens.

The role of the universities is to educate and train students and research fellows in the proper practice of safe microbiology. Students and fellows should be selected on merit without prejudice as to the country of origin. However, security clearance should be sought for access to those pathogens that represent a threat to public health if released. A role for the Universities in overseeing security clearance is opposed. Universities already need to identify projects and get these approved for the issuing of visas to foreign students. A role for Universities in overseeing clearance of UK or EU individuals could be considered a breach of trust between the organization and its students. Universities are not particularly well equipped to make the proper security investigations and more clarity of guidance would be welcome in this regard. The Security Service is well equipped to carry out such clearances and improved communication between

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the Services and Universities working with dangerous pathogens would be advantageous. It should be borne in mind that there are several dangerous pathogens which are dangerous only to those who handle them and not to the community at large. Care should be taken that security clearance is not so risk averse as to become over-zealous because the UK could lose its microbiological experts. For example, the President of this Society understands that he would not pass positive vetting at the Department of Defence yet his advice in civilian biosecurity is frequently sought to the benefit of the UK. Additional Comments The SGM is also concerned about which microbes are classified as "dangerous". Like its sister organisation, the American Society for Microbiology, it notes that certain US microbiologists have been arraigned for handling or distributing microbes which for the past 50 years have been safely handled in undergraduate microbiology practical classes. While it is always wise to reappraise the classification of microbes (which themselves can change in virulence from strain to strain), conventional use of microbes should not lead authorities to regard professional microbiologists as traitors or terrorists. There is complex existing regulation relating to biosecurity with at least several Government departments and agencies involved at different levels within the biosecurity framework. The regulatory framework could be improved through simplification, clarification and co-ordination of procedures to protect biosecurity of research conducted in UK laboratories. However, development of new sets of regulations would unnecessarily raise the existing administrative burden on the research community. The Royal Dutch Academy has developed a document inspired by the fact that many countries have ratified the biological and toxin weapons convention (BTWC) in which they commit themselves to stopping the development, production or storage of biological weapons. A number of high level rules for behaviour have been identified in the document: Awareness

• Ensure that in the education and postgraduate education of life sciences researchers there is a specific and explicit part of the programme that indicates awareness and the risks of misuse of biological, biomedical and biotechnological research and ensure that people understand the limitations of the BTWC.

• Disseminate concerns in professional journals on a regular basis. Research and publication policy

• The application and evaluation procedure for research proposals includes consideration of potential dual use.

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• If there is a dual use, make a potential risk benefit analysis of the to-be-expected result of the research.

• Limit, as far as possible, the risk that scientific publication of results of potential dual use research could make an unintentional contribution to the misuse of the knowledge.

Whistle-blowing

• Ensure that every potential view of misuse of dual use technology is reported to the appropriate authorities.

• Take whistleblowers seriously. Ensure there is no detrimental effect to their career from their activities.

Internal and External Communication

• Ensure there is extra security in relation to internal and external email, mail and telephone and data security in relation to information on potential dual use research and material.

Accessibility

• Ensure there is extra security for personnel and visitors in places and companies where potential dual use research is being carried out and where material is stored.

Transport and Transfer

• Ensure that extra security screening and interest in biosecurity is developed in those people who are transporting, as well as in the recipients of potential dual use biological material.

8.10 Sources This evidence has been prepared on behalf of SGM by Professor Robin Weiss (University College, London), Professor Bert Rima (Queen’s University, Belfast), Professor Howard Jenkinson (University of Bristol) and Dr Michael Tully (Leicester School of Pharmacy)

8.11 About the SGM Society membership is largely from universities, research institutions, health and veterinary services, government bodies and industry. The Society has a strong international following, with 25% of membership coming from outside the UK from some 60 countries. The Society is a ‘broad church’; its members are active in a wide range of aspects of microbiology, including medical and veterinary fields, environmental, agricultural and plant microbiology, food, water and industrial microbiology. Many members have specialized expertise in fields allied to microbiology, including biochemistry, molecular biology and genetics. The

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Society’s membership includes distinguished, internationally-recognised experts in almost all fields of microbiology. Among its activities the Society publishes four high quality, widely-read research journals (Microbiology, Journal of Medical Microbiology, Journal of General Virology and International Journal of Systematic and Evolutionary Microbiology). It also publishes a highly respected quarterly magazine, Microbiology Today, of considerable general educational value. Each year the Society holds two major scientific meetings attended by up to 1500 microbiologists and covering a wide range of aspects of microbiology and virology research. The governing Council of the SGM has a strong commitment to improving awareness of the critically important role of microbiology in many aspects of human health, wealth and welfare. It has in this connection recently initiated a ‘Microbiology Awareness Campaign’ aimed at providing information to the government, decision makers, education authorities, media and the public of the major contribution of microbiology to society. An issue of major concern to the Society is the national shortage of experienced microbiologists, particularly in the field of clinical microbiology and in industry. To attempt to improve this situation long-term, the Society runs an active educational programme focused on encouraging the teaching of microbiology in university and college courses and in the school curriculum, including primary schools. Some 400 schools are corporate members of SGM. January 2008

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Memorandum 35

Submission from the Science & Education Department, Ministry of Health

1. The state implements classified management of the pathogenic

microorganisms on the basis of Regulations on Biosafety Management in

Pathogenic Microorganism Laboratories. The pathogenic

microorganisms are divided into four categories according to their

infectivity and their damage to individuals or groups after infection.

The first category includes microorganisms that can cause very

serious disease to humans or animals as well as to those that haven’t

been found in China or have been declared extinct.

The second category includes the microorganisms that can cause

serious disease to humans or animals and which spread

comparatively easily from human to human, animal to human, and

animal to animal.

The third category includes the microorganisms that can cause

disease to humans or animals but in general won’t result in serious

damage to humans, animals or the environment, have limited risk of

spreading, will not cause serious disease after laboratory infection

and can be controlled through effective treatments and precautions.

The fourth category includes the microorganisms that can’t in

general cause disease to humans or animals.

2. The current List of Human Infectious Pathogenic Microorganisms issued

by Ministry of Health in 2006 includes three types of category tables.

Table 1 lists 160 viruses followed by a Prion appendix. Table 2 lists 155

bacteria, actinomycete�chlamydiae, mycoplasmas, rickettsiae and

spirochetes. Table 3 is a category list of 59 eumycetes.

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All pathogenic microorganisms are classified according to the level of

harm they can do, their transportation needs and storage requirements.

The biosafety laboratory levels required by different experiments are also

stipulated. Comparatively detailed notes and instructions are attached to

each table.

3. The state implements graded management of pathogenic microorganism

laboratories. Measures on the Administration of the Examination and

Approval of Human Infectious Highly Pathogenic Microorganism

Laboratories and Biosafety of such Laboratory’s Activities (No. 50 Order

issued by Ministry of Health) applies to the examination and approval of

highly pathogenic microorganism experiments related to human health as

well as highly or suspected highly pathogenic microorganism

experiments for G3 and G4 biosafety laboratories. The Measures

stipulate that G3 and G4 biosafety laboratories engaging in highly

pathogenic microorganism experiments should obtain a Qualification

Certificate of Highly Pathogenic Microorganism Laboratories issued by

Ministry of Health. If engaging in certain highly or suspected highly

pathogenic microorganism experiments, the laboratories should obtain

approval from health administrative departments at above provincial

level.

4. The laboratory and its parent organization should strengthen biosafety

protection and the management of laboratory activities according to

relevant provisions of Regulations on Biosafety Management in

Pathogenic Microorganism Laboratories, such as to formulate scientific

and strict managerial system, to regularly inspect the implementation of

relevant biosafety regulations, and to regularly examine, maintain and

upgrade laboratory facilities, equipment and materials etc. to ensure they

measure up to the national standard. The health administrative

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departments at all levels should supervise and inspect the highly

pathogenic microorganism laboratories and such laboratory activities

based on Regulations on Biosafety Management in Pathogenic

Microorganism Laboratories.

5. The laboratory or its parent organization should regularly provide

training for the staff each year based on Regulations on Biosafety

Management in Pathogenic Microorganism Laboratories and conduct

examinations to ensure staff have mastered laboratory technical

specifications, operating rules, biosafety protection knowledge and

practical operating skills. Qualified staff passing the examination are

permitted to work in the laboratory.

6. The Regulations on Transportation of Human Infectious Highly

Pathogenic Bacterium (Virus) or Its Specimen (No. 45 Order issued by

Ministry of Health) has taken effect since February 1st, 2006. The Rules

on Managing the Storage of Human Infectious Pathogenic Bacterium

(Virus) is in the process of formulation.

7. Corresponding protective measures should be taken for suspected highly

pathogenic microorganisms according to its biosafety category.

8. The laboratory staff (including students conducting research work)

engaging in experiments related to highly pathogenic microorganisms

should pass an examination and gain approval from the laboratory

principal, who is the first person responsible for laboratory biosafety and

should supervise the safety of laboratory staff (including students

conducting research work) engaging in experiments related to highly

pathogenic microorganisms.

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The university should provide training for the students on biosafety

education and relevant knowledge about pathogenic microorganism

laboratories.

January 2008

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MEMORANDUM 36

Supplementary Memorandum from the Health and Safety Executive FURTHER INFORMATION ON HSE-REGULATED CONTAINMENT LABORATORIES You requested further clarification from HSE on the information submitted to the Committee in my letter dated 17 December 2007. I provide this below under the different headings you used:

1. What collation of information occurs as a matter of course so that the HSE and/or DEFRA and other Government departments (e.g. the Home Office) and agencies (e.g. HPA) know who is working with which pathogens at which site?

1.1. HSE collates information on wild-type human pathogens (under Control of Substances Hazardous to Health Regulations 2002 - COSHH) and on genetically modified pathogens (under the Genetically Modified Organisms (Contained Use) Regulations 2000 – GMO(CU))

COSHH

1.2. Since 2002, all new work with wild-type human pathogens has had to be notified to HSE under the COSHH regulations. These regulations require that an employer shall not use premises for the first time, unless he has notified HSE, of the use of one or more pathogens in Hazard Group 2, 3 or 4. Subsequently the use of any other Hazard Group 3 or 4 pathogen (and three named hazard group 2 pathogens - Bordetella pertussis, Corynebacterium diptheriae, and Neisseria meningitidis) at these premises, must be notified to HSE in advance.

1.3. However, these requirements were not retrospective, and some employers

using these organisms prior to 2002 were not required to formally notify HSE. That said, through surveys and information obtained during inspections, HSE has built up a comprehensive list of premises where work with dangerous pathogens is carried out, and details of the organisms being used.

1.4. The term ‘premises’ is not clearly defined in COSHH and there is flexibility

in its interpretation. Whilst the majority of notifications tend to be made at the site48 level for Hazard Group 2 & 3 agents and at the individual laboratory49 level for Hazard Group 4 agents, some organisations50 notify Hazard Group 2

48 Site: departments/locations/campuses 49 Laboratory: individual room meeting all/the majority of containment measures for that particular level e.g. CL3 50 Organisation: at the employer level e.g. University of X

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& 3 agents at the organisation level and do not link this to specific sites or individual laboratories. For HG 4 agents it is much more likely that the information will tightly linked to both site and individual laboratories.

GMO(CU)

1.5. The GMO(CU) regulations require that all premises are notified before they are used for the first time. Again there is flexibility available within the law in how dutyholders choose to define ‘premises’ but in practice HSE holds a list of all separate sites that an organisation will use to work on GMOs. The regulations require that all work with class 2, 3 and 4 GM microorganisms (GMMs) is notified in advance to the Competent Authority, and clearance/consent is obtained before work commences. Subsequently, individual activities with class 2, 3 or 4 GMMs must be notified in advance. For class 3 and 4 activities, written consent of the Competent Authority is required every time before the activity commences.

1.6. Defra and the Scottish Government act jointly with HSE as the Competent

Authority for GMO(CU) and receive copies of notifications for comment and/or consent. HSE acts as the lead within the Competent Authority, and administers the notification system. Consequently, details of all premises and the nature of the class 3 or 4 GM microorganisms being used are held by HSE, Defra and the Scottish Government.

1.7. The notifications provide information on the organisation (e.g. XX

University) and frequently individual sites (e.g. the Department of ZZ) where work is to be undertaken, but not necessarily on the individual laboratory. When work at Class 3 is notified at a new site, HSE will normally inspect the site before consent is given. Where additional work at Class 3 is notified at a previously consented site, HSE will not normally inspect prior to giving additional consent. However, the site will be inspected in the normal course of HSE’s inspection programme. All new Class 4 projects will be inspected prior to starting, irrespective as to whether the laboratory has been inspected previously.

1.8. The information held by HSE under GMO(CU) and COSHH is not routinely

shared with other agencies such as Home Office or the HPA, although may be provided in specific cases.

1.9. Where work under GMO(CU) and COSHH involves pathogens that are listed

on Schedule 5 to the Anti-Terrorism, Crime and Security Act (ATCSA), must also be notified to the Home Office. Much of the research work being carried out at containment level 3 and 4 is covered by Schedule 5. The main exceptions to this involve work with the hazard group 3 blood-borne viruses - HIV and Hepatitis B and C, and work with parasites. Where work under GMO(CU) involves pathogens listed in the Specified Animal Pathogens Order then this must also be licensed by Defra or SEERAD.

1.10. The Callaghan review (published in December 2007) recommended

that the COSHH, GMO(CU) and SAPO regulations are replaced by a single

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regulatory framework. The initial policy work to implement this recommendation is currently being undertaken by Defra and HSE.

2. The details provided to the Committee refer to both ‘sites’ and ‘organisations’. Where organisations are licensed to work with dangerous pathogens at multiple sites, what level of detail is known about the exact number and location of the sites? What are the requirements for an organisation wishing to use a pathogen at a new site where they already use this pathogen at another site? What determines whether a record is held of sites or organisations handling pathogens?

2.1. As a minimum HSE holds information on: • what organisations are working with biological agents • the number and location of the different sites of that organisation where work with

biological agents is undertaken • the different work activities involving biological agents which that organisation

can undertake.

2.2. Due to the flexible nature in which the law permits notifications to be made under both COSHH and GMO(CU) it can be difficult to capture intelligence on what particular work is being undertaken at a particular site. For example some employers choose to notify at the organisational level: once HSE have given permission for the work to proceed they are permitted to move this work between different sites (so long as those sites have been previously registered and meet the required standards) without notifying HSE. Other employers choose to notify at the site level: once HSE have given permission for the work to proceed these are not permitted to move this work between different sites without each new site notifying the work. This can apply to work at CL2 and CL3 but not CL4

2.3. HSE’s information systems capture the minimum level of information which is required by law as outlined above. This was used to prepare the information submitted in December 2007. In practice for all larger organisations with multiple sites HSE’s systems can be interrogated to give a fuller picture of what work is going on where but this is a resource intensive process. This is used by inspectors in preparing for inspection visits or assessing notifications.

3. Do the HSE and DEFRA have a systematic approach as to whether they deal with organisations or directly with sites?

3.1. The overall responsibility for health and safety rests with the employer at the organisational level. It is up to the employer to determine how they wish to interface with HSE. Most employers interact with HSE at the organisational level, nominating a central contact point (e.g. the biological safety officer in the safety department) who has an appreciation of the all the sites used for work with biological agents and the work going on there. Some employers

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choose to interact with HSE at the site level, nominating a contact point for that site only. For the larger organisations with multiple sites (e.g. Universities or Research Institutes), HSE has developed ‘intervention plans’. These involve a lead HSE inspector working with the organisation to develop a plan to improve safety over a defined time period. This results in a centralised approach, with contacts between HSE and the organisation being made through the safety office, via the biological safety officer and the HSE lead inspector.

4. In relation to organisations working with dangerous pathogens, at containment level 4 and level 3, the Committee would be grateful for more details of the locations, capacity and capabilities of these laboratories and the pathogens they currently handle.

Containment level 4 4.1. There are 10 Containment level 4 sites within the UK, all located in the South

of England. These include 7 owned by ‘government’ sponsored research institutes; 2 by private commercial animal vaccine manufacturers and 1 ‘government’ clinical diagnostic/research site. There are only a small number (9) of class 4 GM activities currently undertaken at 7 of these sites.

4.2. Of the eight government run sites, five are designed to operate at HSE

containment level 4 (although only four actually operate at this level), and three at SAPO level 4.

4.3. Seven of the sites have the facilities to work with infected animals. All the

SAPO level 4 sites can currently only work with SAPO infected animals, however 2 of these also have the capability to work with large animals. There is currently no UK facility designed for work with large animals infected with COSHH (ACDP) hazard group 4 pathogens.

4.4. The size of the facilities varies. They range from single rooms through to sites

with more than one suite of level 4 laboratories.

4.5. Of the two commercial vaccine companies, only one currently manufactures in the UK. The other only stores virus for use elsewhere in Europe. The UK manufacturer has the capacity to work at large scale – 1000s of litres per production run - with both SAPO level 3 and level 4 agents.

4.6. In addition, there are two High Security Disease Isolation Units (HSDUs)

where patients with suspected Viral Haemorrhagic Fevers are transferred for medical care. These two units are designed to allow staff to care for patients infected with viruses such as Ebola and Lassa in a safe manner. One is located in the South of England and the other in the North East of England. Both sites are due to move in the next couple of years but will stay in the same geographical areas.

Containment level 3

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4.7. Containment level 3 laboratories are widely spread throughout the UK. Our latest figures show that there are around 600 individual laboratories in GB that were designed and built to operate at containment level 351. However, many are routinely used for work at lower containment levels.

4.8. The organisation with the largest number of CL3 laboratories is the NHS,

which has approximately 170 laboratories, most of which are used for diagnostic purposes, although some research is carried out in the larger Trusts and teaching hospitals.

4.9. The academic/research institute sector has approximately 350 CL3

laboratories, which vary considerably in size and capacity. Of these approximately 150 are in research institutes, and approx 200 in universities. Private companies account for around 75 laboratories. Differentiating between university and research institute ownership is often difficult; for example, the some research organisations have laboratories in many universities and medical schools.

4.10. A large amount of CL3 capacity is held by a small number of

universities and research institutes. For example, one institute has 60 CL3 laboratories, and two universities have 84 CL3 laboratories between them.

4.11. The Russell Group of universities owns most of the academic CL3

capacity.

4.12. Many of the larger organisations have the capacity to work with animals at containment level 3. Information and data on the location of animal facilities is carefully controlled due to the risk from animal rights extremists.

4.13. A small number of research institutes and universities have the

capacity to work with large animals at CL3. A number of factors including space, cost, and access to an on-site incinerator determine the location and capacity.

March 2008 51 HSE are currently in the process of undertaking further intelligence on this issue. This figure reflects responses up to an including 7 March 2008. Further updates will be provided before 17 March 2008

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Memorandum 37

Supplementary memorandum from the Health and Safety Executive You requested further clarification on my letter dated 10 March 2008 (Memorandum 36) Paragraph 1.2: Notifications made under COSHH Legal position: Schedule 3, Part I of COSHH Para 5(1): 'an employer shall not use for the first time one or more biological agents in Group 2, 3 or 4 at particular premises ..... unless he has notified the Executive of his intention..... at least 20 working days in advance for any of the activities' Para 5(4): 'upon receipt of notification.....HSE shall, within 20 working days...send acknowledgement of receipt or request further information; within 10 working days of receipt of further information send acknowledgement of receipt' Process in Practice: There is no explicit clearance/consent required by law. In practice HSE send an acknowledgement of receipt with statement that they 'will receive a further letter in due course to confirm that you may begin work with the agent(s)' (Annex 1). Once HSE are satisfied they will send a second letter (Annex 2) to approve the work. Paragraph 2.2: movement between CL4 sites Legal position: Schedule 3, Part I of COSHH Para 6(1): 'an employer shall not consign a Group 4 biological agent or anything containing, or suspected of containing, such an agent to any other premises, whether or not those premises are under his ownership or control unless he has notified HSE of his intention to do so at least 30 days in advance' Depending on how the employer chooses to notify their premises (under both COSHH and GMO(CU) there may be the potential for work at CL4 to be moved between different sites without being legally required to notify HSE. Process in practice: All CL4 sites and laboratories have been established for some time and are well known to the HSE with a long history of interaction at the organisation, site and laboratory level. The size of a CL4 site tends to be restricted to a small number of laboratories/animal house facilities. If new agents are worked with they tend to be in these facilities which are well known to HSE with a regular inspection history. In the (very rare) event of Group 4 agents moving between different sites of the same organisation, the custom and practice is that the safety officer lead for that site will contact their lead HSE inspector to make them aware and seek assurance that this is acceptable. March 2008

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Annex 1

CONTROL OF SUBSTANCES HAZARDOUS TO HEALTH REGULATIONS 2002 (as amended) On behalf of the Executive, I acknowledge receipt of your notification for the subsequent use of biological agents in Hazard Group 3. You will receive a further letter in due course to confirm that you may begin work with the agent(s). Yours sincerely

Annex 2

CONTROL OF SUBSTANCES HAZARDOUS TO HEALTH REGULATIONS 2002 (as amended) On behalf of the Executive, I have no objections to you undertaking work with the Hazard Group 3 agent. On receipt of this letter you may begin work with the agent, namely Mycobacterium tuberculosis. There are no specific conditions attached to this letter. However, should any of the details given in your notification change substantially, you should notify us in writing of the changes. You should also keep us informed of any administrative changes e.g. change of named contact, e-mail address. This letter does not imply HSE’s endorsement of the containment and control measures taken at your premises or that these measures comply with COSHH or other health and safety legislation. HSE Inspectors may make additional observations and requirements when carrying out site inspections.