Download Informal consultation on Strengthening Medicines Regulation and

Assessment of Medicines Regulatory
Authorities (MRAs)
WHO, Geneva, Switzerland
18 november 2009
Alain PRAT, Technical adviser, MRS/TCM/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, MRS/TCM/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 decisionmakers to obtain more support;
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Alain PRAT, MRS/TCM/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
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Request baseline information
Study of available information
Validation of the scope covered
Preparation of the assessment plan
Validation of the plan with the institution
Alain PRAT, MRS/TCM/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, MRS/TCM/HSS WHO/HQ Geneva
Mapping 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
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Alain PRAT, MRS/TCM/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
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1
2
Alain PRAT, MRS/TCM/HSS WHO/HQ Geneva
2
4
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, MRS/TCM/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, MRS/TCM/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, MRS/TCM/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
 Outcomes are very often difficult to assess
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Alain PRAT, MRS/TCM/HSS WHO/HQ Geneva
Outputs
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
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Alain PRAT, MRS/TCM/HSS WHO/HQ Geneva
MRA is a process in itself
Control Drug
Promotion
Quality Control
Product
Information
Marketing
authorization
Regulatory
Inspection
Pharmaco
vigilance
Few business processes
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Alain PRAT, MRS/TCM/HSS WHO/HQ Geneva
Import
Control
Licensing
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
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Alain PRAT, MRS/TCM/HSS WHO/HQ Geneva
Design of the assessment tool
 Same format for each modules / functions
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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
Alain PRAT, MRS/TCM/HSS WHO/HQ Geneva
Chapters of the tool
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Alain PRAT, MRS/TCM/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, MRS/TCM/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, MRS/TCM/HSS WHO/HQ Geneva
Marketing Authorization
Qualified personal
Equipments and
facilities maintained
Pertinent guideline
SOP implemented
Adequate legal
framework
Reception
Records
Evaluation
Pre-Market Inspection
Tests
Comittee
Planing and monitoring
Application
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Assessment process
Alain PRAT, MRS/TCM/HSS WHO/HQ Geneva
Decision
MA + Ann.
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, MRS/TCM/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, MRS/TCM/HSS WHO/HQ Geneva
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.
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Alain PRAT, MRS/TCM/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
– 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, MRS/TCM/HSS WHO/HQ Geneva
Usefulness of indicators
 Marketing Authorization
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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, MRS/TCM/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, MRS/TCM/HSS WHO/HQ Geneva
List of institutions to be visited and
Personnel to be met / 2

Representatives of Consumers' associations,
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Journalists.
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Non-governmental associations
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Procurement agencies, National medicines stores

Health research organizations

Chairmen or representatives of Advisory committee
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Chairmen or representative of IRB / IEC

Representative of university academician
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Alain PRAT, MRS/TCM/HSS WHO/HQ Geneva
Main source of documented evidence / 1

Regulatory authority
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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
Alain PRAT, MRS/TCM/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, MRS/TCM/HSS WHO/HQ Geneva
Issuance of Recommandations
 Based on the various life cycles of the activities
needed such as :
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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
Alain PRAT, MRS/TCM/HSS WHO/HQ Geneva
Guidance to use this tool

Regulatory assessment process
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For each regulatory function
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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
–
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Main steps of a Regulatory assessment
Different categories of assessment in the time
Duration
General advice about assessment
Templates
Alain PRAT, MRS/TCM/HSS WHO/HQ Geneva
MRA assessments worldwide
 44 Assessments performed on 40 Regulatory systems (with
the involvement of HQ)
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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, MRS/TCM/HSS WHO/HQ Geneva
MRA assessments in AFRO region
2008
2007
2006
2004
2003
2003
No
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Alain PRAT, MRS/TCM/HSS WHO/HQ Geneva
AFRO : Outcomes / Few examples
 Publication of the main drug law
8
7
6
5
4
3
2
1
0
Before 1979-1988 1989-1998 1999-2003 2004-2008
1979
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Alain PRAT, MRS/TCM/HSS WHO/HQ Geneva
AFRO : Outcomes / Few examples
 Various kinds of MRAs
5
3
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Alain PRAT, MRS/TCM/HSS WHO/HQ Geneva
13
MoH
Board
Agency
AFRO : Outcomes / Few examples
 Committees within the marketing authorization
processes
6
Committee in place
Committee not functional
11
4
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Alain PRAT, MRS/TCM/HSS WHO/HQ Geneva
No committee
AFRO : Outcomes / Few examples
 GMP requirements
Not required (42%)
Not in line with WHO (24%)
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Alain PRAT, MRS/TCM/HSS WHO/HQ Geneva
Not published (29%)
In line with WHO (5%)
Thanks for your attention
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Alain PRAT, MRS/TCM/HSS WHO/HQ Geneva