WHO, Geneva, Switzerland 18 november 2009

WHO, Geneva, Switzerland18 november 2009

Alain PRAT, Technical adviser, MRS/TCM/HSS

WHO - Geneva

Assessment of Medicines Regulatory Authorities (MRAs)

Alain PRAT, MRS/TCM/HSS WHO/HQ Geneva2 |

Plan of the sessionPlan of the session

The assessment process

The process approach

The content of the assessment tool

Some figures and outcomes


Why an assessment tool ?Why an assessment tool ?

In line with one of the strategic objectives – To strengthen National Regulatory Authority's capacities

To assess in order to to identify strengths and weaknesses

To make recommendations on identified gaps for improvement

To propose/suggest supporting activities to satisfy the identified needs

To use assessment results as a tool for convincing decision-makers to obtain more support;


Main steps of the assesssment / 1Main steps of the assesssment / 1

Expression of a need– Internal / External

– Scope of the assessment– Objectives and expected outcomes

Assessment team – Qualification, experience, availability

– Minimun 2– Staff from the organization assessed

Preparation works – Request baseline information– Study of available information

– Validation of the scope covered– Preparation of the assessment plan

– Validation of the plan with the institution


Main steps of the assessment / 2Main steps of the assessment / 2

Opening session– Presentation of assessment team, objectives, methodology

– Presentation of the authority

Conducting the visit – Follow planned activities,

– Collection of evidence

Closing session– Presentation of the main findings and related recommendations

– Presentation of the institutional plan– Closing remarks

Follow up– Provide for the draft report, collect the comments and finalize

– Initiate/consider supportive actions


Mapping the regulatory actorsMapping the regulatory actors

Regulatory functions Related actors / Institutions

Manufacturers, distribution channel licensing

MoH

Registration NRA

Regulatory Inspections Inspectorate

Quality control laboratory NQCL

Safety monitoring of marketed products

National Vigilance center

Clinical trial Institutional Review Boards

Control of drug promotion Drug Information Center


Mapping the processes / Historical findings based on 21 assessmentsMapping the processes / Historical findings based on 21 assessments

Marketing authorization

Licencing

Regulatory Inspection

Quality Control

Pharm.Vigilance

Number of MRA = 21

1 2 2 4 1 6 2 3


Assessment methodologyAssessment methodology

Not based on impressions, feelings or any subjective considerations

Based on objective evidence

Evidence collected through interviews should, whenever possible, be confirmed by more objective means

Possible deficiencies or gaps should be thoroughly investigated and validated

Consensus should be reached at the end with auditees


Documented evidenceDocumented evidence

Interviewing personnel

Reviewing manuals, guidelines developped

Studying records

Reading reports

Scanning files or applications

Analyzing data, indicators

Observing activities performed and facilities where they are performed

Examining conditions during these activities


Documented evidenceDocumented evidence

Investigations not only to check the presence or the absence of a document (law)

But to pursue to find the evidence on the implementation

And ideally the evidence that it provides the desire results…..

Examples : – Law has been issued and Regulation is missing– Law and regulation are published but no guidance is provided to

applicants– Administratives procedures are established but no records are

demonstrating its implementation– Administratives decisions are published but without any legal

framework


Mapping the processes / 1Mapping the processes / 1

Ressources are input for the process– Results are the outputs of the process

Outputs from the process N – are inputs for the process N+1

Outcomes are very often difficult to assess

ProcessesStructures/

InputsOutputs

Outcomes


Mapping the processes / 2Mapping the processes / 2

Manage vision, mission, strategies, policies

Manage the ressources needed : human and others

Manage the relation with patient and customers

Manage the production of products and/or services

Manage supporting activities

Manage continuous improvement


MRA is a process in itselfMRA is a process in itself

Marketing authorization

Regulatory Inspection

Product Information

Pharmacovigilance

Import Control

Licensing

Control Drug Promotion

Quality Control

Few business processes


Recent improvement for the toolRecent improvement for the tool

Chapter on clinical trial developed

Chapter on vigilance aspects developed

New chapter on Narcotics

New chapter on International cooperation

Quality management system for NRAs

No more open question

All chapters reviewed and design consolidated


Design of the assessment toolDesign of the assessment tool

Same format for each modules / functions– Legal basis, framework– Guideline and Documentation– Organisation and structure– Planning and internal procedures– Human and other Ressources– Records and others outputs– Availability of these information


Chapters of the toolChapters of the tool


Institutional structure / 1Institutional structure / 1

Legal basis

Governance structure

Organization in place

Quality management system

Funding

Management of human resources


Institutional structure / 2Institutional structure / 2

Independence and impartiality

Transparency and confidentiality

Management of committees and external expertise

Infrastructure and equipment

Monitoring and accountability

IT Management


Application DecisionMA + Ann.

Marketing Authorization

Qualified personal

SOP implemented

Assessment process

Adequate legal framework

Equipments and facilities maintained

Evaluation Pre-Market Inspection Tests

Planing and monitoring

Records

Comittee

Pertinent guideline

Reception


Examples of key findings and gaps (Inspections) / 1


Regulation– No regulations for compliance with good manufacturing practices

(GMP) and good distribution practices (GDP)

Guideline– The available GMP guidelines are not updated to comply with WHO

guidelines.– There are no Good Distribution, Storage or Wholesaling Practice

Guidelines – Written official GMP guidelines do not exist at the moment except the

unfinished draft– There is no official National GMP guideline and the WHO GMP

guidelines have not been officially adopted, although they are being used




Human resources– Lack of competency in GMP auditing – Limited human resources in GMP and GDP activities– Some of the staff have received limited but not adequate training in

GMP inspection. They also lack experience.– There is no legal officer in the department.– The number and skills of inspectors is not adequate, considering the

number of manufacturers to be inspected.

Independence/Impartiality– No code of conduct for inspectors– No provision or guidelines regarding conflict of interest of inspectors

exist




QMS and SOP– No periodicity defined for performing inspection and inadequate

duration of inspection– No quality management system for inspectorate and in particular no

documented procedure for documentation control, no internal periodic review or auditing

– Documented procedure for planning, preparation, inspection and follow up not finalized

– No procedure for qualification as inspector and inspection team leader– ProcedureS for follow up of deficiencies identified during inspections

do not exist.– Written checklist and plans for inspection of manufacturers and

distribution channels are not available.




Equipment / IT– Limited access to the internet– Inadequate logistical support i.e. communication tools on the

field, vehicles and computers

Organisation– Poor communication with the regional inspectors– No coordination or collaboration or exchange of information on

inspection activities– No mechanism to demonstrate that all inspectors in the country

follow the same procedure

Records and outcomes– No consolidated list of inspection activities performed


Usefulness of indicatorsUsefulness of indicators

Marketing Authorization– Number of application received, Number of MA delivered .– Time to acknoledge receipt of application ;– Time to deliver a MA ;– Time/delay to publish MA with related Product Information.

Inspection– Number of inspection– Time between two inspections ;– Time between initial inspection and follow up inspections (in

case of non compliance)


List of institutions to be visited and Personnel to be met / 1


Ministry of Health / Ministry of industry,

Representatives of the Regulatory authority and any other organizations involved in the regulatory functions,

Staff of Regulatory authority or organization,

Representatives of the Industry Association of manufacturers, distributors, importers and exporters,

Representatives of the Professional Association of general practitioners, nurses and pharmacist,

Professionals councils (medical practitioners council, pharmacists council)




Representatives of Consumers' associations,

Journalists.

Non-governmental associations

Procurement agencies, National medicines stores

Health research organizations

Chairmen or representatives of Advisory committee

Chairmen or representative of IRB / IEC

Representative of university academician


Main source of documented evidence / 1Main source of documented evidence / 1

Regulatory authority– Act, Law, Decree or circular establishing the Regulatory authority– Corporate, strategic and business plan of the NRA– Mission, vision, objectives and indicators of the NRA, i– Quality manual,– List of Internal procedure– List of internal forms and templates– List of the fees applicable for licensing, registration or authorization– Organigram/organization charts– Code of conduct/code of ethics– List of staff with their qualification– List of external experts– Annual report, self-assessment report


Main source of documented evidence / 2Main source of documented evidence / 2

Regulatory functions (Registration, Licensing, Inspection, Clinical Trail, Pharmaco-vigilance, Market control, Import Control, Quality Control Laboratory, control of drug promotion– Act, Law, Decree or circular establishing legal provisions for

each regulatory functions– Guidance published on this domain– Internal procedure– List of equipment– Job descriptions– Decision, Authorization and their annexes


Issuance of RecommandationsIssuance of Recommandations

Based on the various life cycles of the activities needed such as :– To convince politicians– To change laws or decrees– To develop a guidance with consultative process– To reorganise and reshape the structure

(centralized/decentralized activities)– To implement QMS, to develop procedures and planning– To manage HR– To change records– To implement communication strategy


Guidance to use this toolGuidance to use this tool

Regulatory assessment process– Main steps of a Regulatory assessment– Different categories of assessment in the time– Duration– General advice about assessment

For each regulatory function– Brief narrative description of the function– List of questions– Quantitative indicators of activities, of performances– Documented evidence to be reviewed (plan, procedures, reports, job

descriptions, etc)– References to be consulted, based on WHO bibliography

Annexes– Templates


MRA assessments worldwideMRA assessments worldwide

44 Assessments performed on 40 Regulatory systems (with the involvement of HQ)

– AFRO - 21 COUNTRIES / 24 ASSESSMENTS– EURO - 2 COUNTRIES / 2 ASSESSMENTS– EMRO - 4 COUNTRIES / 5 ASSESSMENTS– SEARO - 4 COUNTRIES / 4 ASSESSMENTS– WPRO - 7 COUNTRIES / 7 ASSESSMENTS– PAHO - 2 COUNTRIES / 2 ASSESSMENTS

WHO Regional assessments– ????

Self-assessments– ???


MRA assessments in AFRO regionMRA assessments in AFRO region

2008

2007

2006

2004

2003

No

2003


AFRO : Outcomes / Few examplesAFRO : Outcomes / Few examples

Publication of the main drug law

01

2

34

5

67

8

Before1979

1979-19881989-19981999-20032004-2008



Various kinds of MRAs

133

5

MoH

Board

Agency



Committees within the marketing authorization processes

11

4

6

Committee in place

Committee not functional

No committee



Not required (42%) Not published (29%)Not in line with WHO (24%) In line with WHO (5%)

GMP requirements


Thanks for your attention

Documents

WHO, Geneva, Switzerland 18 november 2009