WHO, Geneva, Switzerland 18 november 2009

1. WHO, Geneva, Switzerland18 november 2009 Alain PRAT, Technical adviser, MRS/TCM/HSS WHO - Geneva Assessment of Medicines Regulatory Authorities (MRAs)

2. Plan of the session • The assessment process • The process approach • The content of the assessment tool • Some figures and outcomes

3. 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;

4. Main 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

5. Main 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

6. Mapping the regulatory actors

7. Mapping the processes / Historical findings based on 21 assessments

8. Assessment 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 

9. Documented 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

10. Documented 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

11. Mapping 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 Structures/ Inputs Outputs Processes Outcomes

12. Mapping 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

13. MRA is a process in itself Control Drug Promotion Quality Control Product Information Marketing authorization Regulatory Inspection Pharmaco vigilance Licensing Import Control Few business processes

14. Recent 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

15. Design 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

16. Chapters of the tool

17. Institutional structure / 1 • Legal basis • Governance structure • Organization in place • Quality management system • Funding • Management of human resources

18. Institutional structure / 2 • Independence and impartiality • Transparency and confidentiality • Management of committees and external expertise • Infrastructure and equipment • Monitoring and accountability • IT Management

19. Marketing Authorization Equipments and facilities maintained Qualified personal Pertinent guideline SOP implemented Adequate legal framework Records Reception Evaluation Pre-Market Inspection Tests Comittee Planing and monitoring Application Decision MA + Ann. Assessment process

20. 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

21. Examples of key findings and gaps (Inspections) / 2 • 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

22. Examples of key findings and gaps (Inspections) / 3 • 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.

23. Examples of key findings and gaps (Inspections) / 4 • 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

24. Usefulness 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)

25. 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)

26. List of institutions to be visited and Personnel to be met / 2 • 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

27. Main 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

28. Main 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

29. Issuance 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

30. Guidance 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

31. MRA 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 • ???

32. MRA assessments in AFRO region 2008 2007 2006 2004 2003 2003 No

33. AFRO : Outcomes / Few examples • Publication of the main drug law

34. AFRO : Outcomes / Few examples • Various kinds of MRAs

35. AFRO : Outcomes / Few examples • Committees within the marketing authorization processes

36. AFRO : Outcomes / Few examples • GMP requirements

37. Thanks for your attention