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

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Alain PRAT, Regulatory Support QSM/EMP/HSS WHO/HQ Geneva

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;

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Alain PRAT, Regulatory Support QSM/EMP/HSS WHO/HQ Geneva

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

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Alain PRAT, Regulatory Support QSM/EMP/HSS WHO/HQ Geneva

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

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Alain PRAT, Regulatory Support QSM/EMP/HSS WHO/HQ Geneva

Mapping the regulatory actors

Regulatory functions

Manufacturers, distribution channel licensing Registration Regulatory Inspections Quality control laboratory Safety monitoring of marketed products Clinical trial Control of drug promotion

Related actors / Institutions

MoH NRA Inspectorate NQCL National Vigilance center Institutional Review Boards Drug Information Center

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Alain PRAT, Regulatory Support QSM/EMP/HSS WHO/HQ Geneva

Mapping 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 7 |

Alain PRAT, Regulatory Support QSM/EMP/HSS WHO/HQ Geneva

1 6 2 3

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

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Alain PRAT, Regulatory Support QSM/EMP/HSS WHO/HQ Geneva

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

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Alain PRAT, Regulatory Support QSM/EMP/HSS WHO/HQ Geneva

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

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Alain PRAT, Regulatory Support QSM/EMP/HSS WHO/HQ Geneva

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

Structures/ Inputs

Processes

Outputs

 Outcomes are very often difficult to assess Outcomes

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Alain PRAT, Regulatory Support QSM/EMP/HSS WHO/HQ Geneva

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

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Manage supporting activities



Manage continuous improvement 12 |

Alain PRAT, Regulatory Support QSM/EMP/HSS WHO/HQ Geneva

Product Information

MRA is a process in itself

Control Drug Promotion Quality Control Marketing authorization Regulatory Inspection Pharmaco vigilance Licensing Import Control

Few business processes

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Alain PRAT, Regulatory Support QSM/EMP/HSS WHO/HQ Geneva

Recent improvement for the tool

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Chapter on clinical trial developed

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Chapter on vigilance aspects developed

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New chapter on Narcotics

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New chapter on International cooperation

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Quality management system for NRAs

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No more open question

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All chapters reviewed and design consolidated 14 |

Alain PRAT, Regulatory Support QSM/EMP/HSS WHO/HQ Geneva

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 15 |

Alain PRAT, Regulatory Support QSM/EMP/HSS WHO/HQ Geneva

Chapters of the tool

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Alain PRAT, Regulatory Support QSM/EMP/HSS WHO/HQ Geneva

Institutional structure / 1

 Legal basis  Governance structure  Organization in place  Quality management system  Funding  Management of human resources

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Alain PRAT, Regulatory Support QSM/EMP/HSS WHO/HQ Geneva

Institutional structure / 2

 Independence and impartiality  Transparency and confidentiality  Management of committees and external expertise  Infrastructure and equipment  Monitoring and accountability  IT Management

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Alain PRAT, Regulatory Support QSM/EMP/HSS WHO/HQ Geneva

Marketing Authorization

Qualified personal Pertinent guideline Equipments and facilities maintained SOP implemented Adequate legal framework Reception Evaluation Pre-Market Inspection

Planing and monitoring

Tests Records Comittee

Application

Assessment process

Decision MA + Ann.

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Alain PRAT, Regulatory Support QSM/EMP/HSS WHO/HQ Geneva

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

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Alain PRAT, Regulatory Support QSM/EMP/HSS WHO/HQ Geneva

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

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Alain PRAT, Regulatory Support QSM/EMP/HSS WHO/HQ Geneva

Examples of key findings and gaps (Inspections) / 3

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QMS and SOP

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No periodicity defined for performing inspection and inadequate duration of inspection

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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.

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Alain PRAT, Regulatory Support QSM/EMP/HSS WHO/HQ Geneva

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

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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

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Alain PRAT, Regulatory Support QSM/EMP/HSS WHO/HQ Geneva

Usefulness of indicators

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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)

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Alain PRAT, Regulatory Support QSM/EMP/HSS WHO/HQ Geneva

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)

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Alain PRAT, Regulatory Support QSM/EMP/HSS WHO/HQ Geneva

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

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Alain PRAT, Regulatory Support QSM/EMP/HSS WHO/HQ Geneva

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

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Alain PRAT, Regulatory Support QSM/EMP/HSS WHO/HQ Geneva

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

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Alain PRAT, Regulatory Support QSM/EMP/HSS WHO/HQ Geneva

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 29 |

Alain PRAT, Regulatory Support QSM/EMP/HSS WHO/HQ Geneva

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 30 |

Alain PRAT, Regulatory Support QSM/EMP/HSS WHO/HQ Geneva

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 – ???

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Alain PRAT, Regulatory Support QSM/EMP/HSS WHO/HQ Geneva

MRA assessments in AFRO region

2008 2007 2006 2004 2003 2003 No 32 |

Alain PRAT, Regulatory Support QSM/EMP/HSS WHO/HQ Geneva

AFRO : Outcomes / Few examples



Publication of the main drug law 8 7 6 5 4 3 2 1 0 Before 1979 1979-1988 1989-1998 1999-2003 2004-2008 33 |

Alain PRAT, Regulatory Support QSM/EMP/HSS WHO/HQ Geneva

AFRO : Outcomes / Few examples

 Various kinds of MRAs

5 M oH Board Agency 3 13 34 |

Alain PRAT, Regulatory Support QSM/EMP/HSS WHO/HQ Geneva

AFRO : Outcomes / Few examples



Committees within the marketing authorization processes 6 11 Com m ittee in place Com m ittee not functional No com m ittee 4 35 |

Alain PRAT, Regulatory Support QSM/EMP/HSS WHO/HQ Geneva

AFRO : Outcomes / Few examples



GMP requirements

Not required (42%) Not in line with WHO (24%) 36 |

Alain PRAT, Regulatory Support QSM/EMP/HSS WHO/HQ Geneva

Not published (29%) In line with WHO (5%)

Thanks for your attention

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Alain PRAT, Regulatory Support QSM/EMP/HSS WHO/HQ Geneva