Transcript Overview of medicines regulation: regulatory cooperation and harmonization in the focus Dr Samvel Azatyan Manager, Medicines Regulatory Support Programme Quality Assurance and Safety: Medicines Essential Medicines.

Overview of medicines regulation:
regulatory cooperation and
harmonization in the focus
Dr Samvel Azatyan
Manager, Medicines Regulatory Support Programme
Quality Assurance and Safety: Medicines
Essential Medicines and Health Products
World Health Organization
E-mail: [email protected]
Advanced Technical Briefing Seminar : Quality Assurance and Safety of Medicines:
1 | Promoting Global Collaboration. 25–29 June 2012, WHO Headquarters, Geneva
Why regulation of medicines is needed?
What is special with medicines, compared to other goods /
commodities?
 As a rule, patients are not able to make independent
judgement about of the QUALITY, SAFETY and EFFICACY;
─ Even health professionals have difficulties, unless they are
specially trained;
Medicines regulation is the totality of all measures - legal,
administrative and technical - which governments undertake to
ensure the quality, efficacy and safety of medicines, as well as the
relevance and accuracy of the product information.
Advanced Technical Briefing Seminar : Quality Assurance and Safety of Medicines:
2 | Promoting Global Collaboration. 25–29 June 2012, WHO Headquarters, Geneva
Government's role is crucial
 Governments are obliged to intervene in the activities
of the private sector due to public health and safety
concerns;
 Medical products include: medicines, blood products,
vaccines and other biological and biotechnological
products, diagnostics, medical devices, traditional
medicines and other health-care products;
Regulation of medical products in the countries is
performed through National Regulatory Authorities
(NRAs)
Advanced Technical Briefing Seminar : Quality Assurance and Safety of Medicines:
3 | Promoting Global Collaboration. 25–29 June 2012, WHO Headquarters, Geneva
Role of a National Regulatory Authorities
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The overall objective of a National Regulatory
Authorities (NRAs) for medical products is to ensure
that all medical products (medicines, vaccines, blood
products and other biologicals) and medical devices
that are used in a country are of assured quality,
safety and efficacy and are accompanied by
appropriate information to promote their rational use.
NRAs need to be competent, independent, with strong
political backing and have clear authority to enforce
established regulations.
Advanced Technical Briefing Seminar : Quality Assurance and Safety of Medicines:
4 | Promoting Global Collaboration. 25–29 June 2012, WHO Headquarters, Geneva
The role of a National Regulatory Authority
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Medical products regulatory authority means a network (institution) that
administers the full spectrum of regulatory activities, including at least
the following functions:
Marketing authorization for new products and
variation of existing authorizations;
GMP, GCP, GLP inspections;
Licensing and post-license control of manufacturers,
wholesalers and other distribution channels;
Quality control laboratory testing;
Adverse drug reaction monitoring;
Provision of drug information and promotion of
rational drug use;
Enforcement operations;
Monitoring of Drug Utilization, etc.
Advanced Technical Briefing Seminar : Quality Assurance and Safety of Medicines:
5 | Promoting Global Collaboration. 25–29 June 2012, WHO Headquarters, Geneva
Main principles of medicines regulation –
although, not always observed..
Medicines regulation should:
 Have patient in the focus;
 Be evidence and science based;
 Be risk based;
 Bring added value;
 Respect interests of stakeholders and real possibilities;
 Be transparent but respect confidentiality;
 Be effective and flexible;
 Be part of broader overall pharmaceutical policy of the
country.
Advanced Technical Briefing Seminar : Quality Assurance and Safety of Medicines:
6 | Promoting Global Collaboration. 25–29 June 2012, WHO Headquarters, Geneva
Main principles of medicines regulation –
although, not always observed..
…But also keep in mind, that:
 Regulations must be attuned not to the wishes, but to
available resources (technical, human, financial, etc.);
 Due to the complexity and resource constrains, the
requirements developed and successfully implemented
in one country may not be equally successful in
another country;
 … Attempts to apply more sophisticated requirements
may have (at least, in short term) serious public health
implications.
Advanced Technical Briefing Seminar : Quality Assurance and Safety of Medicines:
7 | Promoting Global Collaboration. 25–29 June 2012, WHO Headquarters, Geneva
Differences in regulatory capacity globally
194 WHO Member States:
The reality is that due to
chronic shortages of
human, technical, financial
and other resources many
regulatory authorities don't
have the full capacity to
perform all core regulatory
functions
50%
20%
30%
Advanced Technical Briefing Seminar : Quality Assurance and Safety of Medicines:
8 | Promoting Global Collaboration. 25–29 June 2012, WHO Headquarters, Geneva
Developed
Variable
Limited
Assessments of medicines regulatory systems in
26 sub-Saharan African countries
 Guidelines and assessment procedures are not
up to international standards and are often of an
administrative rather than technical nature;
 Wide-ranging exemption clauses exist which are
not justified by a risk assessment, for example
for public sector imports or donations;
 Inadequate resources severely limited technical
assessment of dossiers;
 In spite of resource constraints only few
countries relied on decisions made by other
regulators (such as stringent NMRAs or by the
WHO Prequalification Programme);
 Regulatory decisions by other competent
authorities were not widely considered.
Advanced Technical Briefing Seminar : Quality Assurance and Safety of Medicines:
9 | Promoting Global Collaboration. 25–29 June 2012, WHO Headquarters, Geneva
Challenges and problems posed by a lack of
appropriate regulation
 In many low- and middle income countries most essential
medicines are not readily available and accessible due to
insufficient regulatory capacity and a lack of harmonized
technical requirements for medicines registration
 Poor uptake of new and existing health solutions costs
millions of lives across low-income countries
 A lack of essential medicines contributes to disparities in
health and life-expectancy between low- and middle
income and high-income countries
Advanced Technical Briefing Seminar : Quality Assurance and Safety of Medicines:
10 | Promoting Global Collaboration. 25–29 June 2012, WHO Headquarters, Geneva
WHO approaches to cope with increasing
demands and limited resources
 Avoid doing things that do not give added value;
 Concentrate on things that do give added value;
 Pragmatically and focus on priority issues, which are
most relevant for public health (risk-benefit approach);
 Increase effectiveness of internal operations;
 Co-operate with partners in order to eliminate
duplicated activities;
 Share your work with others – do what you can do
well and let others do what they could do better
Advanced Technical Briefing Seminar : Quality Assurance and Safety of Medicines:
11 | Promoting Global Collaboration. 25–29 June 2012, WHO Headquarters, Geneva
Prioritization of the regulatory activities
 Many NMRAs with limited resources may limit their scope
of activities to performance of those "core" regulatory
functions, which could potentially bring maximum added
value to the public health;
 Other regulatory functions could be more and more
shared with the colleagues in other NMRAs (especially in
the frameworks of existing RECs) and relying on the
opinions made and decisions taken by other regulators;
 This will allow WHO and other partners to prioritize the
support efforts and to introduce a system for accreditation
(or prequalification) of NMRAs for performance of specific
regulatory functions, in accordance with specific
international standards.
Advanced Technical Briefing Seminar : Quality Assurance and Safety of Medicines:
12 | Promoting Global Collaboration. 25–29 June 2012, WHO Headquarters, Geneva
More specific "innovative" (or heretic..)
approach
 Introduction of the concept of "levelling" for the
pharmaceutical products (essential medicines), according
to the "quality-related risk", into:
─ Low risk products
─ Medium risk products
─ High risk products
 This will create incentives and motivation for the
development, in case if NMRA wishes to "jump" a level
up, e.g., from regulation of low risk products to medium
risk products.
Advanced Technical Briefing Seminar : Quality Assurance and Safety of Medicines:
13 | Promoting Global Collaboration. 25–29 June 2012, WHO Headquarters, Geneva
What WHO/MRS is doing
to support regulators
 Developing evidence - assessments of regulatory systems worldwide
(more than 50 NMRAs assessed in all 6 regions);
 Providing direct technical support (capacity building, tools and
guidance) to regions and countries;
 Stimulating / initiating collaboration between
regulators from various countries on various
regulatory activities;
 Promoting and facilitating communication among national/regional
regulatory systems using ICDRA, specific network meetings (e.g. WHO
Annual Pharmacovigilance Centres meetings, and International
Regulatory Cooperation for Herbal Medicines (IRCH);
 Promoting regulatory collaboration and harmonization.
Advanced Technical Briefing Seminar : Quality Assurance and Safety of Medicines:
14 | Promoting Global Collaboration. 25–29 June 2012, WHO Headquarters, Geneva
Collaboration with other Programmes and
Units within EMP and outside
HSS/EMP
HSS/HDS
QSM (PQ, Safety)
QSM (Quality Assurance)
QSM (Blood products)
MAR (GGM)
TRM (IRCH)
FCH/IVB
QSS
(Regulatory pathways)
Disease-oriented
programmes
HTM/GMP
(Global Malaria
Programme)
Other Programmes
WHO Medicines Regulatory Support Programme
WHO Regional Offices
WHO Country Offices
National Medicines Regulatory Authorities
Advanced Technical Briefing Seminar : Quality Assurance and Safety of Medicines:
15 | Promoting Global Collaboration. 25–29 June 2012, WHO Headquarters, Geneva
Sharing regulatory information is a key to
faster access to medicines
 WHO is working with regulators to find out how best to
build confidence in regulatory decisions taken by other
regulators, including:
─ how to facilitate exchange
of consolidated information
about assessments and
inspections;
─ without challenging their
sovereignty.
Advanced Technical Briefing Seminar : Quality Assurance and Safety of Medicines:
16 | Promoting Global Collaboration. 25–29 June 2012, WHO Headquarters, Geneva
Sharing of expertise vs. recognition of
decision
Acceptance of expertise is not equal to acceptance
of decision:
 Acceptance of expertise
– is sovereign and complex regulatory decision of NRA based on
scientific arguments and confidence;
– may be applied case to case;
– is followed by formal independent decision according to national
legislation and mandate of national MRA;
 Acceptance of decision
– is a formal legal act, frequently requiring international treaties;
– may modify liabilities of involved parties and requires legal
specification of acceptance and non-acceptance.
Advanced Technical Briefing Seminar : Quality Assurance and Safety of Medicines:
17 | Promoting Global Collaboration. 25–29 June 2012, WHO Headquarters, Geneva
New regulatory approaches
Smaller or less resourced regulatory authorities more and
more starting to rely on the approvals or opinions issued by the
well-resourced regulatory authorities
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Examples of this type of initiatives include, but are not
limited to:
WHO PQP - HIV/AIDS, TB, malaria, RH, paediatric therapy;
US PEPFAR - HIV/AIDS;
EU Article 58 – assessment of products for use outside the
European Union territory;
Canada's Access to Medicines Regime – assessment of
products according to WHO Model List of Essential Medicines;
Other – orphan medicines, paediatric medicines.
Advanced Technical Briefing Seminar : Quality Assurance and Safety of Medicines:
18 | Promoting Global Collaboration. 25–29 June 2012, WHO Headquarters, Geneva
What we do mean under harmonization
 True harmonization goes further than just development
of common documentation;
 It requires effective communication and collaboration
aimed at building capacity and trust (e.g.,
information sharing, recognition and joint working);
 In combination, these activities can lead to similar or
collaborative approaches to medicines registration;
 Can prepare the ground for mutual recognition and/or
centralized registration in the longer-term future.
Advanced Technical Briefing Seminar : Quality Assurance and Safety of Medicines:
19 | Promoting Global Collaboration. 25–29 June 2012, WHO Headquarters, Geneva
What we definitely don't mean under
harmonization
 Harmonization doesn't mean a loss of national
sovereignty / autonomy (and certainly not in the early
stages);
 In all cases the registration decision itself remains
firmly in the hands of sovereign nations;
 Collaborative mechanisms, such as joint
assessments or inspections, does not imply
collaborative decision-making!
Advanced Technical Briefing Seminar : Quality Assurance and Safety of Medicines:
20 | Promoting Global Collaboration. 25–29 June 2012, WHO Headquarters, Geneva
Expectations from harmonization
 The primary aim of harmonizing technical requirements
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and processes for medicines registration is to improve
public health, by increasing timely access to safe and
effective medicines of good quality for the treatment
of priority diseases.
Access will be increased by reducing the time it takes for
essential medicines to be registered in‐country, without
compromising quality and, potentially, the time taken for
essential therapies to reach patients in need.
This will require capacity building to ensure transparent,
efficient and competent regulatory activities, including
assessment of registration dossiers and related
inspections, that are able to assure the quality, safety and
efficacy of registered medicines.
Advanced Technical Briefing Seminar : Quality Assurance and Safety of Medicines:
21 | Promoting Global Collaboration. 25–29 June 2012, WHO Headquarters, Geneva
Potential public health gains from
harmonization
 Less risk of being harmed by medicines as gradual
improvement of quality, safety and efficacy of products on
the markets is expected;
 More rapid access to needed medicines - high priority
essential medicines, new medicines;
 Better value for money - both for out of pocket and public
funds, as there will be no waste on substandard and of
poor-quality medicines.
Advanced Technical Briefing Seminar : Quality Assurance and Safety of Medicines:
22 | Promoting Global Collaboration. 25–29 June 2012, WHO Headquarters, Geneva
Potential gains have to be balanced with…
potential losses
 Increased price level of medicines (quality has its price);
 Reduced access – not all medicines on the market may
meet new harmonized standards;
 Increasing price for medicines regulation (harmonization
has its price too);
 Local industry may not always win;
 Wholesale and retail businesses may loose many of the
products that were bestsellers for them.
Advanced Technical Briefing Seminar : Quality Assurance and Safety of Medicines:
23 | Promoting Global Collaboration. 25–29 June 2012, WHO Headquarters, Geneva
Conclusions
 Medicines regulation is not anymore a "single-player"
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activity;
Prioritization of regulatory activities, work sharing and
collaboration can help reduce workload and improve
public health by improving overall regulatory
performance.
It can help to direct the expert knowledge and resources
to performance of the functions that can improve public
health and facilitate access to essential medicines;
Formation of effective networks between regulatory
authorities nationally and internationally may facilitate
sharing of scarce resources and eliminate duplicating of
activities.
Advanced Technical Briefing Seminar : Quality Assurance and Safety of Medicines:
24 | Promoting Global Collaboration. 25–29 June 2012, WHO Headquarters, Geneva
Graphic: www.eauc.org
Thank you!
www.who.int/medicines
Advanced Technical Briefing Seminar : Quality Assurance and Safety of Medicines:
25 | Promoting Global Collaboration. 25–29 June 2012, WHO Headquarters, Geneva