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Medicines and Healthcare productsRegulatory Agency: A Hampton Implementation Review Report

A review supported by theBetter Regulation Executiveand National Audit Office

Medicines and Healthcare products Regulatory Agency: A Hampton Implementation Review Report2

3Medicines and Healthcare products Regulatory Agency: A Hampton Implementation Review Report

Foreword

Philip Hampton’s report: Reducing administrative burdens: effective inspection and enforcement,published in 2005, is one of the cornerstones of the government’s better regulation agenda. Theprinciples of effective inspection and enforcement set out in the report, putting risk assessment atthe heart of regulatory activity, are designed to encourage a modern regulatory system which properlybalances protection and prosperity. Since 2005, the Government has established an expectation thatregulators will embed these principles in their approach to regulation.

In November 2006, the Chancellor of the Exchequer invited the National Audit Office and the BetterRegulation Executive to develop a process of external review to assess how much progressregulators had made in implementing the principles of Hampton.

“Hampton Implementation Reports” covering the work of five major regulators were published inMarch 2008. The review process is continuing. At this point in the cycle we are publishing the resultsof reviews of three regulators, each of which has a significant impact on their specific economicsectors. Together, the Gambling Commission, the Medicines and Healthcare products RegulatoryAgency, and the Animal Health agency cover a wide range of economic activity, and work to protectour interests. How they carry out their regulatory activities matters.

Full implementation of Philip Hampton’s recommendations is a journey that could take several years.This review is a ‘snapshot’ in time of the progress of each regulator towards his vision.

Each of the reviews found examples of innovation and initiative by regulators who continue to movethe regulatory agenda forward, as well as areas for further improvement.

The assessments were carried out by teams of reviewers with wide ranging experience and expertisein the field of regulation. Talking to a wide range of stakeholders, to staff at all levels within theregulator’s organisation, through visits to business sites and analysis of data and papers, the reviewteams have reached the findings and conclusions set out in this report. The reports reflect thejudgement of these review teams on the basis of the evidence put before them.

We would like to thank all of those who have continued to make these reviews a success. Inparticular, we are grateful to the regulators and their staff for providing support and making evidenceavailable to the review teams, and to all the organisations that generously gave their time to offerevidence to the reviews. Finally, we are extremely grateful to all our reviewers, and their employers,for their involvement, enthusiasm and commitment to this project.

Jitinder KohliChief ExecutiveBetter Regulation Executive

Ed HumphersonAssistant Auditor GeneralNational Audit Office


remains a target for the organisation. We wereimpressed by the MHRA’s achievements,direction of travel and its plans for improving its regulatory performance still further. We feel that the MHRA is a confident,transparent, and risk-aware organisation thathas an outcome framework that is wellunderstood across the organisation. Areas todevelop include: its internal capacity forquantifying regulatory costs; formalising its risk-based approach; being more aware of the riskof ‘gold plating’ the implementation of EUregulation; the need to communicate reasonsfor its decisions; and fine-tuning its use of ITsystems.

• The MHRA has a cadre of highlyprofessional staff who understand thesector and its risks well. Better regulationappears to be an aim from the top-down aswell as from the bottom-up of theorganisation.

• The MHRA is very effective at negotiatingat the European level – and is a thoughtleader in European negotiations.

• The MHRA operates as a joined-uporganisation. The extent of interactionacross the MHRA is impressive, and thelarge number of potential ‘silos’ that couldexist are apparently avoided. A good exampleof this is the way in which Europeannegotiations are conducted by the Agency.MHRA brings a strong grasp ofimplementation issues to its discussion ofpolicy with European counterparts.

• The MHRA generally understands itsregulated sector and the economic impactof its regulation – although its capacity forassessing and quantifying the costs ofregulation could be improved.

Summary and conclusions

This review is one of a series of reviews ofregulatory bodies undertaken at the invitation ofHM Treasury and focusing on the assessmentof regulatory performance against the Hamptonprinciples and Macrory characteristics ofeffective inspection and enforcement. It wascarried out by a team drawn from the BetterRegulation Executive (BRE), the National AuditOffice (NAO), the Human Fertilisation andEmbryology Authority (HFEA) and the NationalConsumer Council supported by staff from theBRE (see Appendix 1 for Review Teammembership).

The Hampton report1, published in 2005, is oneof the cornerstones of the government's betterregulation agenda and regulators have beenworking since then to embed his principles intheir approach to regulation. This reviewprocess is designed to identify where aregulator is on the road to full implementationand the issues each needs to address tobecome Hampton-compliant.

The Review Team is grateful to the Medicinesand Healthcare products Regulatory Agency(MHRA) for its support during the Review period;staff working at every level in the MHRA werevery open to the Review process and weregenerous with their time, experience andexpertise. We are also grateful for thecontribution of the Agency’s stakeholders fortheir helpful insights into the nature of theindustries and the wider contexts within whichthe MHRA operates.

What we found

The Review Team concluded that in most of theareas under review, the behaviours and theinstincts of the MHRA are highly Hamptoncompliant. Whilst the overall culture is‘Hampton-like’, full Hampton compliance

1 Reducing administrative burdens: effective inspection and enforcement, Philip Hampton, HM Treasury, March 2005


• The MHRA is highly focused on itsobjective of protecting public health – andthis is understood throughout theorganisation, as well as by stakeholders

• The MHRA generally consults extensivelywith external stakeholders – however onsome occasions it could consult andcommunicate more fully. This would, ifnothing else, clarify the Agency’s position

• The MHRA is developing a risk-basedapproach to inspection – and this will buildon the already strong understanding of riskwithin the organisation

• The MHRA is self-aware and we saw goodevidence of a learning organisation. It hasbuilt on lessons learned from major projectssuch as Sentinel and sunset clauses. Wewould encourage this to continue.

• The MHRA is developing strongapproaches to simplifying medicinesregulation in some areas. The BetterRegulation of Medicines Initiative (BROMI)has won an international award as a modelof better regulation policy making, althoughthe Review Team believes it could go further.


fully, measured against some of thesymptoms2 we were looking for to provideevidence of Hampton compliance.

Issues for follow-up

The following table sets out the key issues thatthe Review Team believes the MHRA needs toaddress to meet the Hampton criteria more

Issue to be addressed Hampton symptom

Improving the MHRA’s understanding of theeconomic implications of its activities.

Whilst the MHRA has developed some good examplesof impact assessments, it currently relies upon theDepartment of Health’s economists to provide specificinput into its cost-benefit analyses.

We believe that the MHRA should strengthen therobustness of its impact assessments, and look toensure that the importance of cost-benefit analysis isembedded throughout the organisation.

More widely, we believe that there is scope for theMHRA to develop greater awareness of the economicimplications of its decision making, and to streamlineprocesses for business. We comment in this report onsome relatively low risk cases where the MHRA coulddo more to take account of the sector’s practicalbusiness needs.

• The regulator undertakes robust cost-benefit analysis and impactassessments.

Gold plating

The Review Team heard some stakeholders’ views thatthere had been cases where there had been ‘goldplating’ going beyond the minimum legal requirementswhen implementing EU regulation.

The Review Team found that these had somesubstance. This is particularly clear on the ‘labellingand package leaflet regulations’ where the MHRA choseto implement the requirement early and with additionalretrospective application.

While we do not question the rationale behind theAgency’s decision in this case, we think it should bemore aware of the impact that additional nationallegislative barriers can have over and above an agreedEuropean approach. In these cases it should considerthe need for an enhanced level of communication,particularly in order to make the reasons for itsapproach clear to industry.

• Regulation has a clearly-definedpurpose, is considered to be welldesigned, proportionate, effective atachieving outcomes and understoodby business and enforcers.

2 From Hampton Implementation Reviews: Guidance for Review Teams, National Audit Office and Better Regulation Executive, July 2008


Issue to be addressed Hampton symptom

Improving the credibility and usage of the SentinelIT system

The MHRA’s cross-Agency IT system (Sentinel) is now inplace and working, but questions remain about thecredibility of the system amongst industry - part of thisrelates to ensuring that the historical data stored onthe system is accurate.

The MHRA also needs to communicate and work withthe industry to ensure that use of the system isincreased. The Review Team sees this as a two-wayprocess: listening to businesses about their needs aswell as helping them improve their understanding of thesystem and its requirements.

• The regulator makes good use of ITsolutions in data collection andprovides alternatives to paper forms

Formulation and systematisation of the Agency’sawareness and understanding of risk in relation to inspection.

We recognise that the MHRA is constrained indeveloping a fully risk-based inspection approach.

Some inspection cycles are prescribed by Europeanlegislation. Within these constraints we would stronglyencourage and support the development of a more risk-based approach to inspection.

• The regulator focuses its greatestinspection effort on businesses wherean explicit risk assessment showsthat both:

– There is a likelihood of non-compliance by business; and

– The potential impact of non-compliance is high.


Contents

Page no

Foreword 3

Summary and conclusions 4

Issues for follow up 6

Introduction 9

The Hampton vision 11

Design of regulations 14

Advice and guidance 19

Data requests 22

Inspections 25

Sanctions 29

Focus on outcomes 32

Appendix 1

Review Team membership 35

Appendix 2

Conclusions of the Hampton and Macrory reviews 36

Appendix 3

Review scope and methodology 38


(NICE) has this responsibility. Equally, it isnot responsible for regulating the marketsfor pharmaceuticals and medical devices.This rests with the Department of Healthwhich governs the price that the NHS paysfor the drugs that it uses through thePharmaceutical Price Regulation Scheme(PPRS).

5 The MHRA was established as a tradingfund. As such, it receives no central fundingfor its medicines-based activities. It mustcover its costs through the fees that itcharges for its services, such as assessingapplications for licenses to marketmedicines or approvals for clinical trials.This means it operates along broadlycommercial lines. Devices-based activitiesare funded centrally, through theDepartment of Health. In 2007-08, its totalcosts were £89.6 million and its income£93.5 million. The average number of staffemployed by the MHRA in 2007-08 was875 (full-time equivalent).

6 The pharmaceutical industry is of greateconomic significance in the UK.Expenditure on medicines accounted for0.85% of UK GDP in 2007, with exportstotalling £14.5 billion and a trade surplus of£4.3 billion. It is the biggest investor inresearch and development – £4.2 billion in2007 – and 15 of the leading 75 medicinesinternationally were developed in the UK,more than any other country except the US.It employs 73,000 people, 28,000 of whomare in Research & Development andgenerates another 250,000 jobs in relatedindustries6.

7 The medical devices sector is also highlyimportant: in 2006 the UK devices sectorincluded around 1,500 enterprisesmanufacturing medical and surgical

Introduction1 This review of the Medicines and

Healthcare products Regulatory Agency(MHRA) aims to provide a structured checkon performance against the principles3 andcharacteristics set out in the Hampton andMacrory reports (see Appendix 2).4 Theteam reviewed the MHRA against aperformance framework5 developed by theBRE and the NAO which provided a guidefor reviewers on the kind of evidence tolook for and questions to consider.However, the process is not the same inscope or depth as a full value for moneyaudit of economy, efficiency andeffectiveness and the Review Team’sconclusions are based on a combination ofevidence and judgement. A brief descriptionof the scope of the review and methodsemployed is at Appendix 3.

2 The MHRA was established on 01 April2003, following the merger of theMedicines Control Agency and MedicalDevices Agency. It is an Executive Agencyof the Department of Health and theSecretary of State for Health has overallresponsibility for the MHRA but is notinvolved in the day-to-day running of theAgency.

3 The MHRA’s mission is to enhance andsafeguard public health by ensuring thatmedicines and medical devices work andare acceptably safe. The MHRA alsoregulates tissue engineered products andblood products.

4 The MHRA is responsible solely for thequality and safety of medicines andmedical devices. It does not makedecisions on the cost effectiveness ofproducts and consequently whether theyare used by the NHS – the NationalInstitute for Health and Clinical Excellence

3 Reducing administrative burdens: effective inspection and enforcement, Philip Hampton, HM Treasury, March 20054 Regulatory Justice: making sanctions effective, Final report, Professor Richard B Macrory, November 20065 Hampton Implementation Reviews: Guidance for Review Teams, National Audit Office and Better Regulation Executive, July 20086 Source: Association of the British Pharmaceutical Industry and BERR websites


equipment and orthopaedic appliances, ofwhich approximately 70% were small ormedium sized enterprises. Manufacturersin the sector employed around 33,000people in 2006 (excluding single operators)

and overall turnover was in the region of£4.3 billion. The overall size of the UKmarket for medical devices (excluding invitro diagnostic devices) is valued in excessof £7.2 billion.


based approach. A key point here is for theMHRA to articulate its thinking about riskmore coherently and communicate this toindustry more effectively.

12 We believe that more rigorous use ofimpact assessment would enable theMHRA to test its assumptions withstakeholders more fully and thereby ensurethey achieve greater credibility for itsproposals. Highlighting the costs andbenefits of a proposed course of regulatoryaction in this way can provide robustjustification to industry.

13 We believe that the MHRA is going in theright direction, for example graduating itsapproach in relation to risk in the area ofmedicines regulation with its BetterRegulation of Medicines Initiative (BROMI).However, there are issues for the futurewhere stakeholders will rightly expect aproportionate approach to implementationof new requirements such as Braillelabelling on medicines.

14 The MHRA is currently developing a newrisk-based system for inspection, and isconducting pilots with industry to informthis work. This is building on a strongunderstanding within the MHRA of the riskpresented by specific businesses and theiroperations. This process is being takenforward thoughtfully and transparently.Inspections of devices manufacturersalready follow a risk-based approach.

15 We welcome the systematisation of theMHRA’s approach to risk in relation toinspection. However, we recognise thatMHRA is constrained in some areas byinspection frequencies set by Europeanlegislation.

16 We also found that risk-based thinking wasput to good use in areas other thaninspections. For example, the MHRA used a

The Hampton vision8 Both the Hampton and Macrory reports

are concerned with effective regulation –achieving regulatory outcomes in a way that minimises the burdens imposed onbusiness. Key to this is the notion thatregulators should be risk-based andproportionate in their decision-making,transparent and accountable for theiractions and should recognise their role in encouraging economic progress.

Risk-based

9 The Review Team found that the MHRA hasa strong spontaneous understanding of riskamongst its staff and this has been builtinto relatively new areas of regulatoryresponsibility such as Phamacovigilanceand Clinical Trials, especially in relation toinspection planning. On the medicaldevices side, all EU medical devicesDirectives are inherently risk-based in termsof the required assessment process.

10 Corporately, the MHRA appears to beprepared to take managed risks thatsupport its focus on public healthoutcomes. For example it has taken a riskin allowing self-certification of low-riskmedicines licence variations (such aspackaging changes) and also on itsapproach to new herbal medicinesregulation. However the Review Team foundthat this could perhaps go further, and hadbeen let down by failures of administration,which had been seen in some cases tohave made the process more, rather thanless, burdensome.

11 Stakeholders have on occasion accusedthe MHRA of being risk-averse in itsdecision making, for example in relation torestricting the supply of over-the-countermedicines containing pseudoephedrine.The MHRA can, at times, appear to becloser to a precautionary than a truly risk-


formal risk-assessment framework inprioritising and deciding the level of itsformal enforcement action.

We found:

• A strong, spontaneous understanding ofrisk amongst staff.

• A good direction of travel on developinga risk-based approach to inspection.

Transparency and Accountability

17 Generally, we consider the MHRA to be atransparent organisation in terms of theinformation it publishes.

18 The main issue for the MHRA in improvingtransparency is to be clearer and moreopen about its rationale for decisions madeand the communication of these to industryand the public. A good example here wouldbe regarding the communication of its workon user-testing, where there was aperception of ‘gold plating’.

19 There is also a need for more transparencyin some specific areas such as theenforcement strategy, and we welcomeproposals to work up and publish this.

20 There are some industry concerns regardingthe transparency of the Agency’s MarketingAuthorisation approvals system, with noredress for lengthy delays in processingapplications and a perceived lack ofawareness of the impact of this onbusiness planning cycles. In addition,aspects of its website layout andfunctionality can hinder efficient access by stakeholders and the public to theinformation they seek.

We concluded that, on the whole, theMHRA is transparent and accountable –however it could improve the transparencyof its approvals system.

Economic progress

21 Regulators can have a significant impact on the economic conditions under whichregulated businesses operate. This isrecognised by the statutory Code ofPractice for Regulators (the “Regulators’Compliance Code”) which states that“Regulators should recognise that a keyelement of their activity will be to allow, oreven encourage, economic progress andonly to intervene where there is a case forprotection”7. This requires regulations andtheir enforcement to be proportionate tothe potential for harm and that regulatorsshould be aware of their influence oneconomic progress.

22 The MHRA has a strong understanding ofan industry with many different sectors andwith different business models, particularlyamongst front-line staff such as inspectors.We were impressed with the understandingof SMEs, for instance, in the devicessector; the MHRA was responsive to theirneeds for guidance on specific issues. Inone case the industry identified the needfor more guidance on the regulationsapplying to first aid kits, and the MHRAworked with them to fill this gap.

23 The MHRA has also clearly taken seriouslyits role in supporting the industry withregard to the new Herbal MedicinesDirective. This is discussed more fully in the Design of Regulations section.

24 However, we found that the MHRA can onoccasion:

7 Regulators’ Compliance Code: Statutory Code of Practice for Regulators, BERR, 2007, p11


• take insufficient account of costs where it believes there is an important publichealth issue at stake;

• neglect deadlines for processing licencesthat have an impact on companies’commercial interests.

25 The MHRA should try and communicatereasons for its actions, and show that itunderstands the particular sector orregulated bodies it is dealing with.

We found that the MHRA recognises itsrole as a regulator in encouragingeconomic progress although this has beenoverridden from time to time on publichealth grounds. We recognise that thiscan be the right course of action; theMHRA should not be afraid to be explicitabout its reasons on these occasions.


Design of regulations

Key findings

• The MHRA shows outstanding leadership in Europe and European negotiation.

• The MHRA’s capacity for modelling the economic impact of its regulatory actions should be improved.

• The MHRA should be aware that it has on occasion ‘gold-plated’ European regulation.

• The MHRA generally consults well with external stakeholders regarding legislation, however it should ensure that it consults equally well when developing guidance.

• The MHRA tries to take account of the impact of new regulation on business, however in the caseof herbal medicines we would encourage the MHRA to undertake post-implementation review

Hampton principles

“All regulations should be written so that they are easily understood, easily implemented,and easily enforced, and all parties should be consulted when they are being drafted”

“When new policies are being developed, explicit consideration should be given to howthey can be enforced using existing systems and data to minimise the administrativeburden imposed”

Background

26 The regulatory regime for pharmaceuticalsis largely based on the Medicines Act1968, which brought most previouslegislation on medicines together and alsointroduced a number of other legalprovisions for the control of medicines.

27 Medicines regulation today is largely basedon European legislation and, subsequently,the Medicines Act has been amended tobring it into line with revisions to the EUregulatory regime. The current relevantlegislation is given in Directive2001/83/EC relating to medicinal productsfor human use, amended by Directives2002/98/EC, 2003/63/EC, 2004/24/ECand 2004/27/EC.

28 Additionally, the MHRA has responsibilityfor implementing and ensuring compliancewith other stand-alone pieces of EU

legislation. Recent examples have includedlegislation in clinical trials, advance therapymedicinal products and paediatricmedicines.

Medicines29 EU rules set out the respective

competences of national regulators and theEuropean Medicines Agency (EMEA) inrelation to the regulatory framework formedicinal products. There are four possiblemethods of obtaining a marketingauthorisation for a pharmaceutical product:

1 Centralised authorisation procedure: theEuropean Medicines Agency (EMEA) isresponsible for this, and it is valid acrossthe EU. It is mandatory for medicines that are:

– derived from biological processes, suchas genetic engineering;

– intended for the treatment of HIV/AIDS,


cancer, diabetes, neurodegenerative disorders or auto-immune diseases andother immune dysfunctions;

– officially designated “orphan medicines” (i.e. medicines used forrare diseases – there is specific EUregulation to encourage the develop-ment of more orphan medicines, whichare expensive to develop, but forwhich the market is limited).

Medicines outside these categories may be submitted to the EMEA forapproval, providing the medicineconcerned is a significant therapeutic,scientific or technical innovation, or if its authorisation would be in the interest of public health.

2 National authorisation procedures: Thatis, seeking authorisation for otherproducts not covered by the centralisedprocedure through only one NationalCompetent Authority (such as the MHRAor the equivalent bodies in other EUmember states).

3 Decentralised procedure: Companiesmay apply for simultaneous authorisationin more than one EU country of medicinalproducts that have not yet beenauthorised anywhere in the EU and thatdo not fall within the centralisedprocedure by appointing one MemberState as the Reference Member State.

4 Mutual recognition procedure: Gainingapproval for a medicinal product in oneMember State, then subsequentlyapplying for marketing authorisations inother Member States, whereby thecountries concerned agree to recognisethe validity of the original nationalauthorisation.

30 The respective roles of the EMEA andnational regulators vary in other areas.National regulators are responsible forimplementation and enforcement of clinical

trials8 and medical devices regulation,while the EMEA is responsible for approvingPaediatric Investigation Plans. The MHRAgranted around 4,000 marketingauthorisations in 2007-08.

Medical Devices31 Regulation of medical devices is similarly

based on EU legislation. The original EUMedical Devices Directive dates from 1994and has been revised on a number ofoccasions subsequently. Devices are alsoregulated by UK legislation implementingthe General Product Safety Directive. TheUK regulations implementing the EUDirectives are made under the ConsumerProtection Act.

32 The regulatory regime for the medicaldevices sector is more ‘light touch’ than isthe case for medicines. Many low riskproducts – e.g. hospital beds – can beplaced on the market once themanufacturer has self-certified compliancewith the regulatory requirements andnotified the MHRA.

Review Findings

The MHRA shows outstandingleadership in Europe and Europeannegotiation

33 The MHRA is focused on the outcomes itwants to achieve and is a ‘thought leader’in European negotiations. Its work isthought of highly and it ensures that ittakes a lead and drives activity across theEU in relation to both medicines anddevices regulation.

34 Stakeholder comments on the work of theMHRA in Europe were extremely positive.The MHRA was cited as one of the twobest regulatory bodies in thepharmaceutical sector in the world, andone stakeholder group recognised that theMHRA ‘bats for UK plc’ when securing theright outcomes for business.

8 Although the EMEA is responsible for maintaining a database of clinical trials conducted


The MHRA’s capacity for modelling the economic impact ofits regulatory actions should beimproved

35 The MHRA’s work in assessing the costsand benefits of its activity on the regulatedcommunity, particularly around the ImpactAssessment process, is an area we haveidentified for development. The ReviewTeam saw some very good examples ofImpact Assessments that had beenconducted, such as the Traditional HerbalMedicines Directive Impact Assessmentwhich received good feedback from theNational Audit Office in its 2006-07Evaluation of Regulatory ImpactAssessments.

36 However, a robust approach to ImpactAssessment did not always appear to betaken as a matter of course. The MHRAuses Department of Health economists forspecific economic expertise and input, andthe Review Team considers that a lack ofin-house economic expertise may be aweakness for the MHRA, and we wouldencourage moves to recruit an economistto help with its assessments.

The MHRA should be aware that it has on occasion ‘gold-plated’European regulation

37 Industry stakeholders that we interviewedwere concerned that the MHRA hasinterpreted new EU rules on “user testing”of patient information leaflets more strictlythan other member states. Whilst therelevant Directive did not require it, theMHRA decided to make this requirementretrospective and industry has had to testall existing patient information leaflets, notjust new ones. Additionally, the MHRA hasasked companies to provide detailedinformation on how they have gone aboutuser testing. Industry argued that thissignificantly increased the administrativeburden of the regulations.

38 This example is a clear instance of ‘goldplating’, where implementation of EU rulesnationally goes beyond the minimumrequirements agreed in Europe. The UKrules were implemented early and maderetrospective, two elements that wentabove and beyond minimum Europeanrequirements.

39 Whilst we understand the MHRA’s rationalefor this action – to improve public healthoutcomes – the Review Team believes thatthe MHRA could have better communicatedits rationale for its action in this case toindustry. The MHRA consulted on thisissue, but we believe that it could havedone more to communicate the impact ofits decision: in particular, by working muchmore closely with industry to understandthe cost and economic impact of thedecision.

The MHRA generally consults well with external stakeholdersregarding legislation, however itshould ensure that it consultsequally well when developingguidance

40 The MHRA generally consults well with awide range of stakeholders, for examplethrough its Regulatory Forum (see boxbelow). It also consulted on the implement-ation of the last review of EU medicineslegislation (Directive 2001/83) through anetwork of industry representatives.

41 However, we found some examples offailing to consult on the substantive body of new guidance, for example the newpharmacovigilance ‘purple guide’ will bepublished by the MHRA with little or nostakeholder input to the substantivecontent. Whilst the MHRA argues that thisis a best practice guide, they should beaware that from an industry perspectivethis can have the same impact asadditional regulation.


The MHRA tries to take account ofthe impact of new regulation onbusiness, however in the case ofherbal medicines we wouldencourage the MHRA to undertakepost-implementation review

42 The MHRA was responsible during 2002-05for negotiating and implementing an EUDirective on Traditional Herbal MedicinalProducts. Prior to this, although there hadbeen some licensed herbal medicines, theUK market was dominated by theunlicensed sector. There was evidence thatconsumers were at risk from harmfulproducts, reflecting the erratic and

sometimes low standards in parts of theunlicensed sector. The Directive requiredeach EU Member State to introduce asimplified registration scheme in whichover-the-counter traditional herbalmedicines must meet standards of safety,quality and patient information and arepermitted to make agreed minor claims onthe basis of evidence of traditional use.The MHRA developed an approach aimedat ensuring a ‘light-touch’ regulatory regimefor registered products which aredemonstrably safe and have plausibleefficacy, whilst enabling the MHRA to keeppotentially unsafe products off the market.

Good Practice – BROMI The Medicines and Healthcare productsRegulatory Agency’s Better Regulation ofMedicines Initiative (BROMI) has won aninternational award as a model of betterregulation policy making.

The Agency has introduced a system ofself-certification by the pharmaceuticalindustry for simple changes to product

labelling and information. It is intendedto allow a transition to self- and thirdparty certification in low risk areas ofmedicines regulation. This savesunnecessary bureaucracy as companiesno longer have to apply for formalapproval from the Agency and can placeproducts on the market more quickly.

This has been achieved without the needto amend legislation.

3

2

1

Self certification

3rd party approval

Full assessment

Adminburdenreduced

Delivering without need to amend legislation


43 The MHRA approach to applying theregulatory standards required by theDirective was tempered with pragmatismwhere this was possible. Additionally, giventhe inexperience of the sector withregulation, the MHRA instigated anextensive programme of help and advice,free of charge, including meetings at theAgency.

44 We understand that the MHRA is trying toregulate in a previously unregulated areaand we commend the Agency’s approach inmany ways – in particular its concern toassist industry through this new legislativeprocess. The MHRA has taken a decisivestep forward in this area.

45 We had questioned whether the MHRA hadgone slightly too far in regulatory support ofthe herbal industry in this specific instance.The MHRA provided us with furtherevidence on this point and we agree thatthey are investing support upfront for theherbal industry given that this is a majorstep-change for them moving into asystematic regulatory regime.

46 However, we believe that this level ofsupport should not last and the industryhas a responsibility to organise itselfbetter. The MHRA needs to plan for atransition to a more formal regulatoryrelationship as the implementation date of2011 approaches. MHRA recognises theneed to keep the amount of help offered toindustry under review, and in particular theextent to which regulatory meetings on thetraditional herbal registration scheme areoffered free of charge to companies.

47 We would welcome the MHRA analysing theimpact of the herbal medicines legislationfollowing implementation and ensuring itadequately meets its goal of publicprotection. As noted later in this report(paragraph 114), we recognise the difficultyin identifying and measuring outcomes forthe Agency. The MHRA has successfullyidentified proxy measures for otherworkstreams however, and we wouldencourage a similar approach in this case.

Good Practice – Regulatory ForumThe MHRA has established a RegulatoryForum, drawn from the pharmaceuticalindustry, healthcare professionals,patients’ representatives and lay people.This body meets regularly to advise theAgency on the development of newpolicies and strategies in relation tomedicines, particularly in terms ofresponding to new technologies. TheMHRA has recently adopted the sameapproach in relation to medical devices.


Advice and guidance

Key findings

• The MHRA has a good range of contact channels, which it supplements with externalengagement events.

• The MHRA is developing systems to facilitate better sharing of information across the Agency.

• The potential of the MHRA website is currently not being maximised as a communicationstool in terms of layout and usability.

• MHRA guidance is, on the whole, extensive and issued in good time although it could be ‘roadtested’ better in some cases.

• The perception and credibility of the MHRA’s approach towards better regulation can behampered by occasional miscommunication.

Hampton principle

“Regulators should provide authoritative, accessible advice easily and cheaply.”

Background

48 The MHRA has a number of well-established mechanisms for cascadingregulatory guidance and advice to itsstakeholders. These include GuidanceNotes and Directives Bulletins whichadvise industry on how to comply withregulation (e.g. changes to EU regulation,how to apply for a marketingauthorisation or approval to conduct aclinical trial).

49 Likewise there are arrangements in placeto ensure that healthcare professionalsare made aware of safety issues which arereported to the Agency, such as drug alertsor “Dear Healthcare Professional” letters.These are sent electronically using anestablished distribution list and thencascaded by recipients. There is also amonthly electronic bulletin for healthcareprofessionals, “Drug Safety Update” whichcontains latest advice from the MHRA andthe Committee on Human Medicines onsafety issues.

50 The MHRA publishes new regulatory andsafety guidance without charge on a fairlyregular basis. Guidance can be either of atechnical nature, or for use by patients,such as leaflets on how to report concernson the safety of medicines or devices.Some of the MHRA’s communicationmaterial has been approved by the PlainEnglish Campaign. The MHRA does notcharge for such written guidance.

51 The MHRA publishes a large amount ofinformation on its website and it also hastelephone and email central enquiry points,which receive around 1,000 enquiries eachweek. The nature of enquiries varies widely,from healthcare professionals requiringscientific data, through to patients seekingreassurance about medicines they havebeen prescribed.

52 The MHRA organises regular conferencesand other events around the country aimedat industry and healthcare professionals onvarious topics related to the regulation ofmedicines and medical devices.


Review Findings

MHRA has a good range of contactchannels, which it supplementswith external engagement events

53 The MHRA has a number of contactchannels. It has a general enquirieshelpline, and an extensive website. Itsupplements its general advice line withspecific regulatory contact points by bothphone and email. These regulatory contactpoints give specific and tailored advice andguidance to business on interpretingaspects of the regulatory regime.

54 In addition, we observed that MHRAinspectors provide valuable advice andguidance to industry. We were generallyimpressed with the consultative manner ofthe inspector visits we observed, and theway in which advice was used as a tool bythe inspector to try to bring the regulatedbody into compliance. MHRA inspectorsthat we saw were both helpful andknowledgeable.

55 The Review Team found evidence of a gooduse of all modes of consultation by theMHRA and a move towards greater use ofelectronic means of communication withstakeholders. In addition to these morereactive channels of communication, theMHRA holds regular conferences andevents on specific areas of regulation ofmedicines and devices to furthersupplement its normal consultationprocedures.

MHRA is developing systems tofacilitate better sharing ofinformation across the Agency

56 The Review Team was impressed with the moves the MHRA was taking to poolintelligence across the Agency, through its IT system Sentinel. The Review Teamconsiders that having one common ITsystem across the MHRA to capture allregulatory data of interactions with

businesses will be invaluable in helping toensure that the correct information isaccessed by all levels of the MHRA toinform its regulatory interactions. However,we recognise that this is work in progressand the Sentinel system will be discussed in more detail under ‘Data Requests’.

The potential of the MHRA websiteis currently not being maximised asa communications tool in terms oflayout and usability

57 The MHRA website was criticised by anumber of stakeholders. It was seen as apotentially valuable tool with a large amountof excellent material available on it.However, there was a strong feeling that itwas not currently being maximised as acommunication tool in terms of its structurewhich is not always obvious to navigate froman external perspective.

58 This problem is compounded by the poorsearch facility which currently exists on thesite. MHRA is aware of this issue and iscurrently planning to upgrade the searchfacility which will help stakeholders to findinformation more easily. However, werecommend that some more thought shouldbe given by the MHRA to the structure andlayout of its website to make it easier tonavigate. MHRA is already planning toestablish user communities, and to groupinformation on this basis.

MHRA guidance is, on the whole,extensive and issued in good timealthough it could be ‘road tested’better in some cases

59 The Review Team saw some very goodexamples of advice and guidance from theMHRA. For example, guidance on medicaldevices was cited by stakeholders as aquality product that clarified an area ofvague law without gold plating.

60 The MHRA publishes guidance tostakeholders sometimes well in advance of


the suggested 12 week limit prior to newregulations coming into force. For therecent user-testing requirements, the MHRApublished guidance to industry some 18months before the implementation date.

61 The MHRA also provides guidance toNotified Bodies, which conduct inspectionsand audit under the legislative regime forMedical Devices. Notified Bodyrepresentatives that we spoke to statedthat the guidance they received from MHRA was “as good as it gets”.

62 However, the MHRA can at times fail toadequately consult on aspects of itsguidance – an example of this is the recent‘purple guide’ on Pharmacovigilance whichwas published by the MHRA with limitedconsultation with stakeholders on thesubstantive content. Although the MHRAargues that this is a best practice tool, theMHRA should be aware that guidance itissues such as this can have the effect ofacting like additional regulation – and itshould ensure that all of its stakeholdersare fully consulted when it is planning tointroduce new guidance.

The perception and credibility ofthe MHRA’s approach towardsbetter regulation can be hamperedby occasional miscommunication

63 The Agency’s Better Regulation ofMedicines Initiative (BROMI) has won aninternational award as a model of betterregulation policy making. This model isintended to allow a transition to self- andthird- party certification in low risk areas ofmedicines regulation. However,

stakeholders said that that there had beensome issues in the way that BROMI hadbeen put into practice. For example, therewas a lack of clear communication withinthe MHRA regarding the validity ofapplications to a pilot scheme run as partof BROMI. This led to some applicationsbeing rejected erroneously by MHRA staff.

64 The MHRA has moved towards a lessextensive system of scrutiny for low-riskcases. This means that, for instance, self-certification is approved by administratorswho may have little expertise in the morecomplex regulatory problems posed byriskier applications. One of the prices ofthis more streamlined process forbusinesses is that they need to be morecareful in the quality of their applications;IT-based systems that are not individuallyprocessed by more qualified staff do nowallow room for error. Some stakeholdersfelt that the MHRA was being unnecessarilystrict in turning down faulty applications;some indeed argued that they had stoppedacting in a flexible and Hampton-compliantway in these cases. We thought that morecould be done to educate the industry intheir responsibilities here. Stakeholdersalso feel that BROMI could go further, andwe would support MHRA expanding theapproach into other regulatory areas thatare appropriate.

65 However, in general the BROMI is animportant initiative with a good directionof travel that we fully support and wewould encourage the MHRA to do more in this area.


Data requests

Key findings

• The MHRA has developed e-enabled systems to help improve efficiencies in the regulatoryapprovals system; however take-up of the full e-enabled system has been slow.

• The MHRA works well to join up with internationally equivalent bodies.

• The MHRA’s main cross-Agency IT system is now functioning as intended, but there remainissues of data cleansing and communication.

Hampton principle

“Businesses should not have to give unnecessary information or give the same piece ofinformation twice.”

Background

66 The MHRA’s regulatory activities includemaking decisions on applications fromcompanies for licences to undertakeclinical trials, market new products, deal inwholesale, import or manufacture ofmedicines and devices. As such, theMHRA must request sufficient informationto satisfy itself that at the end of the day,products used by patients are safe and willhave therapeutic benefits.

67 The MHRA has developed an informationmanagement system, Sentinel, which isdesigned to facilitate electronicsubmission through a portal for the varioustypes of medicines marketingauthorisations. Sentinel contains allhistorical scientific data submitted to theMHRA – some 30 million pages ofdocumentation. The portal uses “smart”application forms which allow companiesto check the data, at the point of enteringit into the form, which removes thepotential for errors which would otherwiserequire the form to be returned. There are

plans to extend this to other types ofapplications, as the system currently doesnot apply to clinical trials 9.

68 Training on how to use the MHRA portal isavailable free of charge, as is access tothe database for up to 7 designatedindividuals at each company.

69 The fees charged for assessingapplications vary, depending on theamount of work the MHRA needs toundertake analysing the scientific datasupplied by companies in support of theirapplications. This ranges from about£100,000 for an application for amarketing authorisation for a completelynew substance, to £2,000 - £4,000 for aclinical trial application.

70 The MHRA does not make formal datarequests to either healthcare professionalsor patients. However, it has arrangementsin place for reporting adverse incidents. Onthe medicines side, the “Yellow CardScheme” is a long established method ofreporting suspected adverse drug

9 Applications in relation to clinical trials are done through forms available on the EMEA website


reactions. The Scheme has beenprogressively extended to a wide range ofhealthcare professionals and to patientand their carers. There is also an on-lineform available for reporting adversereactions to medicines.

71 Similar arrangements are in place formedical devices. Manufacturers are legallyobliged under EU law to report adverseincidents to the MHRA and a voluntaryprocess is in place for healthcareprofessionals and patients. The MHRAinvestigated 8,000 devices-related adverseincidents in 2007-08, leading to 100devices alerts.

Review Findings

The MHRA has developed e-enabled systems to help improveefficiencies in the regulatoryapprovals system; however take-up of the full e-enabled system has been slow

72 The MHRA has been moving towards e-enabled systems and self-certification overa number of years. However, currently only2-3% of electronic applications submittedby industry through the portal are in theElectronic Common Technical Document(eCTD) format – which the MHRA arguesgives the biggest regulatory efficiencies forindustry. We find it puzzling thatbusinesses are not utilising the fullfunctionality of this system, especially aseCTD is a system that is alreadyextensively used by the pharmaceuticalindustry.

73 We believe that messages about thebenefits of fully engaging with the Sentinelsystem may have not been fully explainedto industry. Again, industry perceptions mayhave been affected by frequent rejectionsof applications that are not compatible with

the demands of the system. More could bedone to work with them to improve take-up.

The MHRA works well to join upwith internationally equivalentbodies

74 The MHRA works closely with theequivalent bodies in other EU memberstates, the EMEA and other internationalcounterparts, such as the Food and DrugAdministration in the US to harmoniseapplication forms and other data requests.In the past year it has also signed abilateral agreement with the Chinese StateFood and Drug Administration for co-operation on combating counterfeitmedicines and exchange of information onherbal medicines.

The MHRA’s main cross-Agency ITsystem is now functioning asintended, but there remain issuesof data cleansing andcommunication

75 The MHRA has developed the Sentinelsystem to act as a cross-Agency IT systemfor regulatory matters. One of its intendedbenefits is to help streamline themedicines marketing authorisation process.This has been a number of years indevelopment and has required considerableresource and effort on behalf of the MHRAto put in place a system that can not onlydeal with future workload, but also thehistorical authorisations data that hasalready been approved. This has involvedthe scanning of some 30 million pages ofdata onto the system.

76 However, as a result of the transition,issues have come to light regarding theaccuracy of some of the historical data heldby the MHRA. This has on occasion led todelays with the authorisation of newproducts. We believe that the ‘cleansing’ ofhistoric Sentinel data is an important taskfor the MHRA in terms of establishing and


maintaining system credibility amongststakeholders. The importance ofmaintaining accurate data going forward isequally crucial and in this respect ensuringthe appropriate accountability for dataquality within the MHRA is paramount. TheMHRA is aware of these issues and hasestablished a team to undertake the datacleansing process.

77 The Review Team believes that there is akey issue of communication with regards toSentinel. For example, the MHRA generateda large number of stakeholdercommunications regarding user-testingbased upon data that was drawn from theSentinel system in June 2008. However

these letters were not sent until September2008, by which time some of the data wasout of date. This, compounded by theinaccuracy problems with some of thehistorical data, led to stakeholdersreceiving warning letters threateningsuspension of marketing authorisation forissues that had already been dealt with.

78 This issue has been interpreted by industryas a consequence of systems failure in theAgency, which has had an impact on itscredibility amongst stakeholders. TheMHRA needs to be aware that Sentinel’scredibility depends not only on the data itholds, but also on the uses to which thatdata is put.


Inspections

Key findings

• MHRA inspections are lengthy and rigorous, but stakeholders derive real value from theexperience.

• We would encourage the MHRA to continue to develop a more outcome-focused approach toinspection within its current operational constraints.

• We would encourage the MHRA to work in the international arena to develop Memoranda ofUnderstanding with non-EU countries so that international Good Manufacturing Practiceinspections of business can be minimised.

• The MHRA’s inspector selection and training is rigorous and we would encourage moves toimprove continuous professional development.

Hampton principle

“No inspection should take place without a reason.”

Background

Medicines 79 Inspection of research, development and

quality control laboratories, clinical trials,manufacturers, wholesalers andpharmacovigilance systems is carried outby the Inspectorate Group of theInspection, Enforcement and StandardsDivision in the MHRA. There are 5 maininspectorates within the MHRA:

1 Good Clinical Practice (GCP) – GCPinspectors assess compliance with therequirements of GCP guidelines andapplicable regulation. GCP guidelines andregulations provide a standard for theconduct of clinical trial research;

2 Good Manufacturing and (3) DistributionPractice (GMP/GDP) – GMP inspectorsassess manufacturers’ compliance withthe provisions of their manufacturingauthorisation and the principles andguidelines for GMP as detailed in the

appropriate European Directives. GDPinspectors assess Wholesale Dealers'compliance with the provisions of theirlicence and the principles and guidelinesfor GDP;

4 Good Laboratory Practice (GLP) – GLPinspectors verify that test facilities whichconduct non-clinical safety studies onpharmaceuticals, agrochemicals,industrial chemicals, food and cosmeticsmeet GLP requirements to the standardsnecessary for regulatory purposes;

5 Good Pharmacovigilance Practice(GPvP) – Pharmacovigilance inspectorsassesses pharmaceutical companies'compliance with UK and EU legislationrelating to the monitoring of the safety ofmedicines given to patients.

80 Inspections are undertaken by MHRA staff.There were over 1,400 inspections in2007-08. Broadly there are three sorts ofinspections:


• Routine national inspections: these arescheduled inspections that UK MarketAuthorisation Holders (MAHs) undergo ona periodic basis. MAHs are notified ofthese inspections in advance and aregenerally systems-based, meaning thatinspectors examine the systems andprocedures used by a MAH to complywith existing EU and national regulationsand guidance;

• “For cause” national inspections: theseare ad hoc inspections that are triggeredas a result of, for example, safety issues,suspected violations of legislation relatingto the monitoring of the safety ofmedicines, or referrals by other MemberStates. In rare circumstances MAHs maynot be notified of these inspections inadvance;

• The Committee on Human MedicinalProducts (CHMP) requested inspections:the CHMP may request inspections ofMAHs in association with specificcentrally authorised products which caneither be routine or triggered.

81 The MHRA produces a report of its findingswithin 30 days of the end of the inspectionand the MAH then has a further 30 days torespond. Deficiencies are graded as“critical”, “major” or “other” depending ontheir seriousness. Critical findings arereferred to an expert group within the MHRAto decide on what enforcement action maybe necessary to safeguard public health.

Medical devices82 The MHRA inspects manufacturers once

their products have been placed on themarket. Pre-market inspections are carriedout by designated certification bodiesknown as Notified Bodies, such as AmtacCertification Services Ltd and BSI ProductCertification, which have been designatedas competent in the relevant fields by theMHRA. The broad process of the MHRAconducted inspections is as follows:

• Manufacturers will normally be informed14 days before the date of the proposedvisit. One of the aims of the visit is toconfirm that the essential requirements –contained in the Medical Devices andGeneral Product Safety Directives – arebeing complied with in practice.

• An authorised inspector supported, asnecessary by MHRA's product specialiststaff will undertake the inspection.

• Compliance inspectors have the right atany reasonable hour to:– Enter premises and inspect goods, other than premises occupied only as a person’s residence.

– Examine manufacturing procedures andtesting arrangements.

– Require the production of any records for examination and to take copies of,or copies of any entry in, the records.

– Seize or detain suspect records or goods which may be required asevidence in proceedings for an offencein respect of a contravention.

• Visits will normally last for no more thana day.


Review Findings

MHRA inspections are lengthy andrigorous, but stakeholders derivereal value from the experience

83 MHRA inspections (particularly those on theGMP side) can last between 2-5 days. Thecumulative burden on the regulated inpreparing for and hosting an inspection visitwas estimated by the regulated body of alarge site inspection we visited to be atleast an additional 50 staff days perinspection.

84 However, stakeholders we spoke to aboutthe process were clear that they deriveddefinite benefits from inspection. As anindustry stakeholder stated, the MHRAinspection process provided a usefulexternal validation of the company’s internalquality control procedures and ensured thatthey remained ”compliant not complacent”.Indeed, industry representatives that wespoke to stated that the monetary costs ofinspection were worthwhile given thebreadth of knowledge and experiencedemonstrated by MHRA inspectors.

85 One area that is at odds with the generallyimpressive feedback we had regardingMHRA inspection was from the NotifiedBodies. MHRA audit these bodies to ensurethat their work regulating the devices sectoris sound. However, Notified Bodyrepresentatives informed us that they feelthat the approach of some MHRAinspectors, in one area, is not Hampton-likein that issues are raised in the final auditreport that had not been raised by theinspector during the visit. We have beentold by the MHRA that this is contrary totheir standard practice of giving the NotifiedBody both an oral and written summary ofits findings at the end of the audit and onlyto include in its final audit report thoseitems so disclosed.

We would encourage the MHRAto continue to develop a moreoutcome-focused approach toinspection within the constraintsthat it currently operates

86 The Review Team recognises that in someareas, European legislation can limit theMHRA’s options as it prescribes certaininspection cycles. However, within theseconstraints, we encourage the MHRA toexplore the potential for a more outcome-focused approach, for example, in the useof other sources of assurance such asinternal audit quality assessment. Thismight follow models used in the devicesand BROMI regimes.

87 We welcome the MHRA’s approach tosystematising its already good awarenessof risk into a formal risk-based inspectionmodel, and we would encourage it tocontinue to communicate clearly and workclosely with industry regarding itsdevelopment.

We would encourage the MHRA to work in the international arena to develop Memoranda ofUnderstanding with non-EUcountries so that internationalGood Manufacturing Practiceinspections of business can be minimised

88 Industry in the pharmaceutical sector facesthe cumulative burden of multiple nationalinspectorates from other nations looking atsimilar issues regarding the manufacture ofmedicines. One site we visited estimatedthat this in effect meant that they had, onaverage, an inspection from apharmaceutical regulatory agency once amonth. The MHRA is working with partnersto try to minimise the need for multipleoverlapping international inspectionsthrough a mutual recognition arrangement.We support this and encourage further workinternationally, although we understand that


the MHRA can be constrained in this to adegree by a need to approve mutualrecognition procedures through the EMEA.

89 We believe that the MHRA could use its‘international capital’ to drive this agendaforward. Given the globalised nature of thepharmaceutical industry, and the rise ofother international competentinspectorates, this will be an expandingarea in future.

The MHRA’s inspector selectionand training is rigorous, and wewould encourage moves toimprove continuous professionaldevelopment

90 The MHRA puts a great deal of effort into

ensuring that they recruit the right peopleto be an inspector. The selection processinvolves both psychometric testing and anassessment centre. There is thus a highpersonality-type ‘hurdle’ to pass, in additionto the technical knowledge required, tobecome an inspector.

91 This selection process is then followed andsupplemented by an approach to ensurequality and continuous professionaldevelopment, with a minimum of ten daysbeing assigned each year to the continuedprofessional development of inspectors.The MHRA is considering improving itsongoing professional development forinspectors and we would support thismove.


Sanctions

Key findings

• The MHRA takes a strong outcome-focused approach to the use of sanctions. The emphasisis on compliance, and there is a strong recognition that the use of advice and guidance isoften more effective than formal enforcement action.

• The MHRA has a clear and effective system for prioritising investigation and enforcementcases.

• There are however gaps in the sanctions available to the MHRA which limit its flexibility inpractice to deal with serious cases.

• Feedback from enforcement action, or failures of enforcement action, is put to good usethroughout the Agency.

Hampton & Macrory principles

“The few businesses that persistently break regulations should be identified quickly, andface proportionate and meaningful sanctions.”

“Regulators should be transparent in the way in which they apply and determineadministrative penalties.”

“Regulators should avoid perverse incentives that might influence the choice of sanctioningresponse.”

“Regulators should follow-up enforcement actions where appropriate.”

Background

92 The MHRA is, essentially, a licensing, and– on the devices side – an accreditationbody. This has implications for itsenforcement activity: where it is dealingwith non-compliance by a licence holder, ithas a number of sanctions available to it,including review, variation to and,potentially, withdrawal of a licence. Thisgives the MHRA considerable flexibility inbringing licence-holders into compliance.

93 Where no licence is held, the Agency’smain sanctioning tool is prosecution; theMHRA takes forward approximately 20prosecutions per year and has quite wide-ranging powers to deal with non-

compliance. The MHRA publicly statesthat it tries to work with industry to ensurecompliance. In the event of seriousbreaches, or wilful failure to comply, arange of possible sanctions exists, suchas:

• Withdrawal of a product from the market;• Suspension of a clinical trial;• Referral of individuals to the appropriateprofessional body (e.g. the GeneralMedical Council);

• Forfeiture orders for unsafe products;• Criminal prosecutions.

94 Most criminal prosecutions that the MHRAtakes are in relation to medicines andrelate to supply of counterfeit or illegal


supply of medicines (e.g. clinics supplyingViagra without either a medical examinationor a legal prescription).

95 The MHRA may prosecute under theMedicines Act and the Trade Marks Act.The Proceeds of Crime Act is also used aspart of its enforcement strategy.Prosecutions for medical devices can takeplace under either the Medical DevicesRegulations or the General Product SafetyRegulations.

96 In 2007-08, the MHRA opened 302 newinvestigations, of which 22 were referred toGovernment lawyers. Thirteen furtherprosecutions were completed, 38 formalcautions for breaches were handed out andin 200 cases, compliance was achievedthrough the MHRA issuing warnings andadvice.

97 In the use of sanctions as elsewhere, theMHRA works in a highly globalised context:one of the most serious enforcementchallenges facing the MHRA is the need todeal with counterfeit medicines andmedical devices, many of which are theproduct of crime operating on aninternational level.

Review Findings

The MHRA takes a strongoutcome-focused approach to theuse of sanctions. The emphasis ison compliance, and there is astrong recognition that the use ofadvice and guidance is often moreeffective than formal enforcementaction

98 The MHRA staff that we spoke to had aclear understanding of the sanctioningoptions available to them, and acommitment to only using serioussanctions that warrant formal action: thecritical factors here are the extent of harmthat may have been caused to a patient,and the level of criminality involved.

99 In other cases, the MHRA believes thatadvice and guidance are the mostappropriate initial responses to cases ofnon-compliance.

100 The MHRA routinely follows up on allallegations of non-compliance in thedevices sector. Many of these will involvequestions about devices which areproduced by micro-businesses that aredoing their best to comply with the lawwithin the limited resources available tothem. In these cases the MHRA works withthe business to put things right, and tominimise the anxiety and disruption that aninteraction with the regulator can mean forthe business. We found that the MHRAcombined this approach with adetermination to take swift and decisiveformal action where it is necessary. TheMHRA also publishes the results of suchaction where this would send out a usefulmessage to the sector.


101 The MHRA basic approach is thoroughlycompatible with the Hampton and Macroryprinciples in practice. The Review Teamnotes however that is has not published anenforcement policy that would set theseprinciples and processes out for the benefitof stakeholders. We have seen a draft ofthis policy and we would encourage theMHRA to publish it as soon as possible.

102 Stakeholders that we spoke to whooperated within the licensing regime werestrongly supportive of the action MHRAtakes to prosecute counterfeit operators.

The MHRA has a clear andeffective system for prioritisinginvestigation and enforcementcases

103 The MHRA deals with a large number ofreferrals relating to cases of possible non-compliance in any given year, both reactiveand proactive. The MHRA prioritises itswork according to a system of scoringwhich takes into account risk factors (likethe number of people on whom the casewould potentially impact), and factors likethe compliance record of the individualsand businesses involved.

There are however gaps in thesanctions available to the MHRAwhich limit its flexibility in practiceto deal with serious cases

104 The costs and administrative burdensassociated with criminal prosecution for aregulator can be prohibitive, and carefulconsideration is given before a caseprogresses to court.

105 The MHRA has recognised that some ofthe sanctions available under theRegulatory Enforcement and Sanctions Act2008 – notably Variable MonetaryPenalties – would allow for more flexibleand effective sanctioning for low levelregulatory breaches in practice. Theywould allow, for instance, for theimposition of a level of fines under a civilprocedure which would reflect the serious-ness of the case, or, where appropriate,‘naming and shaming’ of offenders.

106 The MHRA is currently exploring how thisexpanded range of sanctions might beapplied, particularly in respect ofadvertising of medicinal products, EUimposed deadlines for submitting data,variations to existing marketingauthorisations and the implementation ofthe Paediatric Medicines Regulation.

Feedback from enforcementaction, or failures of enforcementaction, is put to good usethroughout the Agency

107 Elsewhere in this Report we havecommented on the extent to which workbetween parts of the MHRA are co-ordinated: the same is true with itsenforcement staff.

108 Where in a serious recent case it becameclear that prosecution would not bepossible on grounds relating to theexisting law on disclosure requirements,the MHRA developed both proposals forchanges to UK law (which are now inplace) and to strengthen EU law.


Focus on Outcomes

Key findings

• The MHRA has a strong sense of its ultimate outcome – to secure public health.

• However, measuring the Agency’s input and contribution towards public health outcomes is difficult.

• The MHRA should ensure that the quality of the regulatory service that it provides to industryis consistent.

• The MHRA has made good efforts to avoid ‘silo’ working across its regulatory regime.

Hampton principle

“Regulators should measure outcomes and not just outputs.”

Background

109 The MHRA’s performance and deliveryagainst its 2007-08 Key Targets, and its2008-09 Key Targets, together with theassociated performance measures, areset out in its 2007-08 annual report.There are 12 targets for 2008-09 under 4 headings:

• Safeguarding public health• Communicating effectively• Shaping a balanced regulatoryframework

• Running a successful organisation

These represent a good attempt to set outhow the MHRA will take forward itsstatutory objectives and to focus ontangible outcomes.

110 The Agency’s 2008-09 Business Plan and2008-13 Corporate Plan set out how theMHRA will deliver on its key targets at theworking level. Additionally, the MHRA hasa Communications Plan to the end of2010 setting out in detail how it will

communicate with stakeholders (industry,healthcare professionals and the public).

111 The MHRA has specific targets to turnaround some applications, for examplefor completing assessments for clinicaltrials authorisations within 30 days.Information on its performance againstthese targets is published annually andavailable to stakeholders.


Review Findings

The MHRA has a strong sense ofits ultimate outcome – to securepublic health

112 Public health is emphasised and appears tobe widely understood as the overarchingoutcome of the MHRA, and there is aconsistent view on this ultimate outcomewithin and outside of the Agency.

113 We were impressed with the strong senseof outcome-focus from staff at all levels ofthe MHRA. This cascades well fromcorporate targets to individual work plans.For example, staff working both onenforcement and on giving advicedemonstrated a clear understanding thatcompliance is key to achieving regulatoryoutcomes and is the best means ofachieving this.

However, measuring the MHRA’sinput and contribution towardspublic health outcomes is difficult

114 The Review Team recognises the difficultyand complexity of measuring the MHRAinput to such a broad outcome as‘securing public health’. But we werereassured that the MHRA has developed aprocess of monitoring the impact of itsprogrammes through discrete pieces ofresearch work. A good example of thiswould be its work to establish the impactof its decision to withdraw the painkiller co-proxamol from the market.

115 A key issue for the MHRA has been to findand define proxy measures for it to assessits impact, and on a project level there hasbeen some success here: for example, onthe judgements to be made in licensing newproducts and developing a balance betweenthe risk of harm and the immediatetherapeutic impact. This allows new drugs tocome onto the market, but with a specificrisk-management plan. In this way the drugis released as early as possible (therapeuticbenefit), whilst still recognising that there

may be risks associated with this actionthat need to be specifically managed(reducing the risk and impact of harm).

116 We would encourage the MHRA to continueto develop its thinking on this area, and wewould encourage it to ensure that its proxymeasures cover all aspects of the MHRA’sactivities, and so provide a full measure ofthe success of the organisation.

The MHRA should ensure that thequality of the regulatory servicethat it provides to industry isconsistent

117 Whilst the MHRA generally understands theimpact of its work on the industry, there isone sector of the industry which perceivesitself as a ‘Cinderella sector’.Representatives of the over-the-countermedicines sector put it to us that its needsare being trumped by the prioritisation itdeems the MHRA gives to Europeandecentralised Marketing Authorisation work.These decentralised processes havemandatory timescales for approval andindustry feel the Agency’s prioritisation ofthis work has negatively affected the qualityand timeliness of the regulatory service itprovides to other sectors.

118 The MHRA accepts that the assessments it performs on behalf of the EMEA, orapplications processed within the MutualRecognition or Decentralised Procedures,often have priority over nationalapplications which are being delayed as a result.

119 In practice, this means there is littlediscipline placed on the MHRA to give low-risk applications the priority thatbusinesses need to get their products onthe market quickly. It also means that thereis no clarity for industry on the length oftime approval could take – which can have(sometimes serious) commercialimplications. We understand that the MHRArecognises this issue, and is recruiting


additional staff and making processimprovements. Transparency is also anissue. While the MHRA states that it hastime metrics that are agreed with tradeassociations and are published on amonthly basis, these targets, andperformance against them, need to bemore prominent amongst their ownpriorities and in communications to theindustry.

The MHRA has made good effortsto avoid ‘silo’ working across itsregulatory regime

120 The MHRA was formed from the merger oftwo regulatory bodies in highly differentways due to major differences in legislative

approach. Despite having been merged forsome 5 years, it has largely maintained anorganisational distinction between its workon medical devices and on medicinesregulation. The Review Team found thisapproach was justified given thefundamental differences in legislativebasis. However, this did not appear to haveled to ‘silo’ working within the MHRA as itis good at forming collegiate groups whencross-cutting work is discussed.

121 We consider the MHRA to be joined up andoutcome-focused. We consider it a strengthof the MHRA that it has policy, enforcementand inspection all in one place.


Appendix 1: Review Team membership

Trish Davies is the Deputy Chief Executive and Director of Regulation of the HumanFertilisation and Embryology Authority (HFEA),having joined the organisation in March 2004.Before then, Trish was the Director ofCorporate Policy and Communications for theNational Care Standards Commission, whichshe joined at its inception in 2001, from theDepartment of Health, where she was theproject manager for National MinimumStandards during the development of the CareStandards Act 2000. Her previous careerincludes two years as an inspector in theSocial Services Inspectorate, five years asHead of Inspection in Hertfordshire, setting upand managing a joint unit between the CountyCouncil and the Health Authorities and fiveyears as Assistant Regional Director with NCH.Trish is a qualified social worker and has alsoworked in social work education, staffdevelopment and family placement.

Paul Holland is an Audit Manager at theNational Audit Office, responsible for theFinancial Audits of a number of bodies withinthe Department of Health, including the MHRA.He has previously worked on the audits of anumber of central government organisations,including the Electoral Commission; House ofCommons and House of Lords and the Ministryof Defence.

Dawn Muspratt was, until recently, ActingDeputy Chief Executive of the NationalConsumer Council (NCC) working as part of theleadership on the merger with energywatch andPostwatch. Before then Dawn was Head ofOrganisational Development at NCC working atBoard level and across the National, Scottishand Welsh Consumer Councils implementingimproved structures and systems and staffdevelopment. Dawn is a qualified youth andcommunity worker and has a strongbackground in the voluntary sector. She spenta number of years working for voluntaryorganisations in inner London in communitydevelopment and youth work where shefundraised and delivered multi-million poundbuilding redevelopment projects.

Elizabeth Surkovic was, at the time of thereview, a Director at the Better RegulationExecutive within the Department for Business,Enterprise and Regulatory Reform (BERR). Herbackground is in chemicals, having spent 20years in that industry. She more recently movedto the Civil Service where she has worked inDefra and the Cabinet Office.


Appendix 2: Key findings and conclusions of the Hampton andMacrory reports

• Regulators, and the regulatory system as awhole, should use comprehensive riskassessment to concentrate resources on theareas that need them most

• No inspection should take place without areason

• Regulators should provide authoritative,accessible advice easily and cheaply

• All regulations should be written so that theyare easily understood, easily implemented,and easily enforced, and all interestedparties should be consulted when they arebeing drafted

• Businesses should not have to giveunnecessary information, nor give the samepiece of information twice

• The few businesses that persistently breakregulations should be identified quickly, andface proportionate and meaningful sanctions

• Regulators should recognise that a keyelement of their activity will be to allow, oreven encourage, economic progress and onlyto intervene when there is a clear case forprotection

• Regulators should be accountable for theefficiency and effectiveness of their activities,while remaining independent in the decisionsthey take

• Regulators should be of the right size andscope, and no new regulator should becreated where an existing one can do thework

• When new policies are being developed,explicit consideration should be given to howthey can be enforced using existing systemsand data to minimise the administrativeburden imposed

Source: Hampton Report, Box E2 page 7

Hampton principles of inspection and enforcement


A sanction should:

1. Aim to change the behaviour of the offender;

2. Aim to eliminate any financial gain or benefit from non-compliance;

3. Be responsive and consider what isappropriate for the particular offender andregulatory issue, which can includepunishment and the public stigma thatshould be associated with a criminalconviction;

4. Be proportionate to the nature of the offenceand the harm caused;

5. Aim to restore the harm caused by regulatorynon-compliance, where appropriate; and

6. Aim to deter future non-compliance.

Regulators should:

1. Publish an enforcement policy;

2. Measure outcomes not just outputs;

3. Justify their choice of enforcement actionsyear on year to stakeholders, Ministers and Parliament;

4. Follow up enforcement actions whereappropriate;

5. Enforce in a transparent manner;

6. Be transparent in the way in which they applyand determine administrative penalties; and

7. Avoid perverse incentives that might influencethe choice of sanctioning response.

Source: Macrory Report, Box E1 page 10

Macrory’s principles and characteristics of an appropriatesanctioning regime


Appendix 3: Review scope and methodology

The review focused on those aspects of theMHRA’s activities where we considered that itsactions have the most impact on business.These areas included the majority of its work onmedicines, devices and clinical trials regulation.

The following areas were excluded from thescope of the review

• MHRA activity facing towards non-industrygroups such as enforcement and sanctionsaction against criminals

• Advice and guidance to patients (exceptwhere this leads to disproportionate impactson industry)

• Some of Agency’s ‘niche’ areas, such asblood products, tissue engineering andnanotechnology

Our methods included:

• interviews with a wide range of MHRA staffincluding senior managers;

• interviews with other stakeholders includingthe trade bodies in the pharmaceutical sectorand medical devices sector and businessrepresentative groups;

• focus groups of MHRA inspectors, policy staffand enquiry staff

• observational visits including GoodManufacturing Practice inspection and GoodClinical Practice inspection; and

• document review, including the MHRA’s highlevel strategies and plans.

The review process is described in HamptonImplementation Reviews: Guidance for ReviewTeams. It is not the same as a full value-for-money audit of economy, efficiency andeffectiveness and the Review Team’sconclusions are both evidence- and judgement-based. These judgements, however, have beenmade drawing on a range of evidence fromdifferent sources, including those describedabove. Judgements have not been based onevidence from a single source – the ReviewTeam has sought to bring together evidencefrom a number of different businesses ororganisations, and from MHRA front-line staff,policy officials and senior managers.



Better Regulation ExecutiveDepartment for Business, Enterprise and Regulatory Reform3rd Floor1 Victoria StreetLondon SW1H 0ET

Website: www.berr.gov.uk/bre

Publication date: April 2009

URN: 09/821

© Crown copyright 2009

The text in this document may be reproduced free of charge in any format or media withoutrequiring specific permission. This is subject to material not being used in a derogatorymanner or in a misleading context. The source of the material must be acknowledged asCrown copyright and the title of the document must be included when being reproduced aspart of another publication or service.

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