Alain PRAT, Technical adviser, QSM/EMP/HSS WHO - Geneva Assessment of Medicines Regulatory Authorities (MRAs) Technical Briefing Seminar on Essentials medicines Policies WHO, Geneva, Switzerland November 2010 Alain PRAT, Technical adviser, QSM/EMP/HSS WHO - Geneva

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

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 / 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 / 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 actors Related actors / Institutions Regulatory functions MoH Manufacturers, distribution channel licensing NRA Registration Inspectorate Regulatory Inspections NQCL Quality control laboratory National Vigilance center Safety monitoring of marketed products Institutional Review Boards Clinical trial Drug Information Center Control of drug promotion

Mapping the processes / Historical findings based on 21 assessments Marketing authorization Licencing Regulatory Inspection Quality Control Pharm.Vigilance 3 2 6 1 4 Number of MRA = 21

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 

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

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

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

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

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

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

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

Chapters of the tool

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

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

Marketing Authorization Planing and monitoring 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

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

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

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.

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

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)

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)

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

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

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

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

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

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 ???

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

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

AFRO : Outcomes / Few examples Various kinds of MRAs

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

AFRO : Outcomes / Few examples GMP requirements

Thanks for your attention