Title: WHO Essential Drugs Strategy
1 Follow-up of the Recommendations made at the 9th
International Conference of Drug Regulatory
Authorities (ICDRA), 1999
3rd Pan American Conference on Drug Regulatory
Harmonization 24-26 April 2002, Washington, D.C.,
USA
Lembit Rägo, MD, PhD, Coordinator Quality
Assurance and Safety Medicines Essential Drugs
and Medicines Policy Health Technology and
Pharmaceuticals Cluster World Health
Organization E-mail ragol_at_who.ch
2International Conference of Drug Regulatory
Authorities (ICDRA)
- An unique forum where regulators from both
developing and developed world gather - ICDRA has been held every two years since 1980
- 9th ICDRA was held in Berlin, Germany in April
1999, with 280 participants from 90 countries - Objectives
- Promoting collaboration between national drug
regulatory authorities - Achieving a consensus on matters of mutual
interest - Facilitating timely and adequate exchange of
technical information - Discussing topical issues of international
relevance - Many important World Health Assembly Resolutions
have originated in ICDRA
3Topics of 9th International Conference of Drug
Regulatory Authorities (ICDRA) (I)
- Good Regulatory Practice
- Good Certification Practice
- Counterfeit drugs Challenges and solutions
- Current issues in regulation and quality
- ICH Implementation and Implications
- ICH Common technical document
- Drug utilization studies
- Global and national efforts to reduce tobacco use
4Topics of 9th International Conference of Drug
Regulatory Authorities (ICDRA) (II)
- Electronic communication in the regulatory
process - Transparency in monitoring the safety of
medicines - Pharmaceutical products for use in special
population - Need for bioequivalence
- Antimicrobial resistance
- Safety of plasma-derived medicinal products
- Herbal medicines
- Regulation and access to essential drugs
59th ICDRA- Recommendations and their follow-up
- Recommendations were made at the each session
- Recommendations to WHO
- Recommendations to national drug regulatory
authorities - Follow-up of the recommendations to WHO
- What has WHO achieved since then?
- What are the obstacles to implement the
recommendations? - What needs to be done further?
- What is the Impact of WHOs work on drug
regulatory authorities? - 10th ICDRA will be held in Hong Kong, Special
Administrative Region of China, from 24-27 June
2002
6Good Regulatory Practice
- Recommendations to WHO
- WHO should develop guidelines to define good
regulatory practice and develop appropriate
indicators to measure performance. These
guidelines should be made available over the WHO
website to enable countries to formulate their
own standard operating procedures (SOPs).
7Good Regulatory Practice
- What has been achieved?
- A Multicountry study on effective drug regulation
(10 countries in total) was carried out to
compare country experience and it includes
concepts, methods and indicators for assessing
regulatory performance (The final text is in
press and will be available soon on the WHO
website) (http//www.who.int/medicines/) - The joint initiative between EDM/QSM and VAB/ATT
to visit countries and assess the regulatory
capacities for both drugs and vaccines was
launched. Guidelines to assess the regulatory
capacities (Rapid Assessment Tool) will be
developed, which will help develop a strategic
work plan to strengthen national authorities
8Good Certification Practice
- Recommendations to WHO
- WHO should continue to promote the use of the
Certification Scheme with a view to assuring its
global application - WHO should trigger feedback information on the
practical utility of the Scheme, including the
certification needs of importing countries, ways
to prevent falsification of certificates, and how
to improve the effectiveness of the Scheme - WHO should work with national authorities to
develop appropriate, safe and reliable mechanisms
to permit exchange of verifiable product
certificates and information on the Internet
9Good Certification Practice
- Recommendations to WHO (cont.)
- WHO should foster further development of the
Certification Scheme to (a) include provisions
for additional information on manufacturers, and
(b) address the case of products with no
marketing authorization in the certifying
country. A declaration by the company's
authorized person before the certifying country
authority, including information on product
development, stability testing, and prior
marketing should be given
10Good Certification Practice
- What has been achieved?
- World Health Assembly Resolution on the Revised
Drug Strategy in May 1999 (WHA52.19) requested
WHO to prepare a new scheme for the certification
of starting materials in international commerce - The draft of the guideline and the model
certificate for the starting materials was
discussed at the WHO Expert Committee on
Specifications for Pharmaceutical Preparations in
October 2001
11Counterfeit drugs Challenges and solutions
- Recommendations to WHO
- Liaison officers of the WHO anti-counterfeit
drugs network should be utilized for information
exchange and investigation of counterfeit drugs.
The draft WHO guidelines for the development of
measures are useful instruments and will be made
available on the WHO website. - International cooperation should be strengthened
and involve international agencies such as WHO,
UNICEF and Interpol. WHO and Interpol should
develop initiatives to improve the exchange of
information. International agencies should give
specific consideration to the conflict between
the need for regulatory authorities to know of
the circulation of counterfeit products and the
need for confidentiality when criminal
investigations are under way.
12Counterfeit drugs Challenges and solutions
- What has been achieved?
- Guidelines for the development of measures to
combat counterfeit drugs and Counterfeit and
substandard drugs in Myanmer and Viet Nam were
published - Materials (poster, videotape, booklets) to raise
awareness of the problems were prepared - Working Group which includes international
pharmaceutical associations and NGOs were created - Workshops and meetings on counterfeit drugs
involving industry and international agencies
have been organized regularly at international /
regional level - Training workshops for regulators have been
organized
13(No Transcript)
14Current issues in regulation and quality
- Recommendations to WHO
- WHO should
- Continue to serve as a platform for the exchange
of information on important regulatory decisions
of worldwide implication - Take measures to reinforce the collaboration
between drug regulatory and criminal
investigation authorities internationally, in
particular Interpol and the World Customs
Organization, to deal with criminal activities
involving pharmaceutical products and materials - Implement recommendations on safe trade and
control of starting materials as set out in
document WHO/PHARM/98.605, including risk
assessment of starting materials.
15Current issues in regulation and quality
- Recommendations to WHO (cont.)
- WHO should
- Develop safe trading practices in close
collaboration with brokers, traders and other
international organizations and institutions - Support training of assessors for new drug
applications and good manufacturing practice
(GMP) inspectors in countries with limited
resources, in collaboration with national health
authorities
16Current issues in regulation and quality
- What has been achieved?
- The draft guideline and the model certificate of
WHO Certification Scheme for the starting
materials was discussed at the WHO Expert
Committee (EC) on Specifications for
Pharmaceutical Preparations in October 2001 - Draft of Good Trade and Distribution Practices
(GTDP) of pharmaceutical starting materials was
discussed at the EC - The WHO basic training modules on GMP (CD-ROM)
was developed and several training workshop for
inspectors were held - Training workshops for assessors of drug
applications were held in Africa and Asia
17ICH Implementation and implications
- Recommendations to WHO
- WHO should continue to play an important role by
taking into account the implications for non-ICH
members. - WHO should explore the feasibility of integrating
ICH products and WHO guidelines into a
comprehensive set of guidelines - Since ICH guidelines cover new products and many
countries manufacture, register and use generic
drugs, WHO is encouraged to continue work on
guidelines on requirements for registration of
generic drugs
18ICH Implementation and implications
- What has been achieved?
- An independent review team was convened to assess
the implications of ICH on non-ICH countries and
options for the future role of WHO were proposed
result article in WHO Drug Information vol. 14,
No.3, 2000 - Based on the above, an informal consultation was
held to discuss considerations on the Impact of
ICH in non-ICH member countries - (September 2001, the report is in press)
- Review of WHO-GCP has been initiated to explore
the harmonization with other guidelines including
ICH-GCP - The discussion summary of the ICH meetings have
been disseminated to non-ICH countries to receive
more feedback
19Drug utilization studies
- Recommendations to WHO
- WHO should assist drug regulatory authorities by
- Encouraging studies of actual use and consumption
of drugs by relating pharmacotherapy to the
actual disease - Promoting quality of the data by ensuring that
the source of the data is accurate and
establishing a system of data collection - Raising awareness of how Anatomic-
Therapeutic-Chemical (ATC) and Defined Daily
Doses (DDDs) are developed through educational
programmes in order to prevent misinterpretation
and misuse of ATC/DDD.
20Drug utilization studies
- Recommendations to WHO (cont.)
- WHO should assist drug regulatory authorities by
- Adopting or adapting manuals for use of the
ATC/DDD classification at local level with
reference to the manuals prepared by the WHO
Collaborating Centre on Drug Statistics
Methodology in Oslo, Norway - Promoting greater awareness of changes in the
ATC/DDD classification system and establishing
conditions for the regular updating of national
classification systems
21Drug utilization studies
- What has been achieved?
- Several studies on the use of antimicrobials and
antihypertensive drugs have been carried out and
will soon be published - A manual entitled, Introduction to Drug
Utilization Research is in press (2002) - A regional training course for regulators and
other users of the system is being planned in
October 2002 - (The application of ATC/DDD methodology in
drug utilization research)
22Electronic communication in the regulatory process
- Recommendations to WHO
- WHO should set up an electronic communication
system to permit effective, prompt and secure
Information exchange among drug regulatory
authorities - WHO should further promote the implementation of
computer-assisted drug registration in order to
contribute to effective drug regulation
23Electronic communication in the regulatory process
- What has been achieved?
- WHODRA Electronic Discussion Group was
established as a tool for communication among
national drug regulatory authorities and WHO,
however, it was deemed impossible to have a
closed discussion after some experiences - WHO has been working with the European Medicines
Evaluation Agency (EMEA) on a new version of
Model System for Computer-assisted Drug
Registration (SIAMED), which will be ready in
late summer 2002. A user guide is under
development.
24Transparency in monitoring the safety of medicines
- Recommendations to WHO
- Networks for electronic exchange of drug
information, in particular relating to safety and
which allow for rapid communication, should be
established. WHO should take the lead in this
endeavour - Principles of good communication should be
developed by WHO with input from WHO Member
States and regional authorities
25Transparency in monitoring the safety of medicines
- What has been achieved
- More information on website, immediate posting
- WHO Collaborating Centre for International Drug
Monitoring (UMC) in Uppsala, Sweden has created a
Vigimed network in which all representatives of
National Pharmacovigilance Centres that have an
e-mail address are included. It is being used
for rapid distribution of drug safety alerts and
general information exchange - A document which discusses the principles of good
communication in pharmacovigilance and the roles
of various players is in press with the help of
the UMC - WHO Pharmaceuticals Newsletter merged with UMCs
Adverse Reactions Newsletter for wider and more
effective dissemination of safety information -
available on website
26Need for bioequivalence
- Recommendations to WHO
- WHO should
- Develop common definitions and guidelines
indicating when in vivo equivalence studies are
needed - Coordinate the development of model guidelines
for harmonization purposes to determine when
in-vitro studies are acceptable - Make the list of international comparator
products widely available, including advice on
how it can be used by drug regulatory authorities
within their national context for viral and other
transfusion transmitted diseases
27Need for bioequivalence
- Recommendations to WHO (cont.)
- WHO should
- Take the lead in identifying where there is a
need for training in each region and arrange for
access by drug regulatory authorities and
interested parties - Develop and promote the introduction of
appropriate guidelines for the accreditation of
drug quality control laboratories
28Need for bioequivalence
- What has been achieved?
- Provisional list published in WHO Drug
Information, list of international comparator
products with the note on how it can be used is
in press - WHO has decided to review the Guidelines on
Registration Requirements to Establish
Interchangeability (based on the recent thinking
on the establishment of interchangeability,
including inter alia, Biopharmaceutical
Classification System set out in the US FDAs
guidance and other evidence available)
29Antimicrobial resistance
- Recommendations to WHO
- WHO is invited to
- Bring together national authorities for human and
veterinary drug regulation to exchange
information and to consider Joint action - Provide guidance on the clinical development of
antimicrobial drugs, in particular to optimize
efficacy while minimizing the risk of resistance - Establish a common format for product information
and patient information leaflets, specifically
addressing antimicrobial resistance issues
Special attention should be given to improving
the communicative potential of the information
provided. This information should be regularly
updated in the light of prevailing resistance
patterns
30Antimicrobial resistance
- Recommendations to WHO (cont.)
- WHO is invited to
- Continue efforts, as set out in WHO resolution
WHA 51.17, to make antimicroblal drugs available
on a prescription-only basIs - Stimulate drug regulatory authorities to share
all relevant information on clinical trials
involving antimicrobial drugs, with public health
authorities
31Antimicrobial resistance
- What has been achieved?
- The WHO global strategy for containment of
resistance was launched in September 2001 - The exchange of information programme among drug
regulatory authorities is being enhanced - The WHO Model Prescribing Information - Drugs
used in Bacterial Infections providing clinical
information on antimicrobials was published in
2001
32Safety of plasma-derived medicinal products
- Recommendations to WHO
- WHO should
- collaborate with Member States to strengthen the
technical expertise of national control
authorities in the regulation of plasma products - Promote the regulation of blood bank facilities
by National Control Authorities in order to
ensure compliance with GMP principles - Facilitate the development of educational
programs and training opportunities for National
Control Authorities involved in regulation and
control of blood products. WHO should promote
regional cooperation and training
33Safety of plasma-derived medicinal products
- Recommendations to WHO (cont.)
- WHO should
- Assist Member States in the development of
appropriate guidelines for plasma fractionation
contract activities - Provide guidelines on information to be included
in batch release certificates in order to
facilitate acceptance of imported plasma products
by national control authorities
34Safety of plasma-derived medicinal products
- What has been achieved?
- The WHO Guidelines on Viral Inactivation and
Removal Procedures Intended to Assure the Viral
Safety of Human Blood Plasma Products were
established in November 2001 - Global Project for Quality Assurance and Safety
of Blood Plasma Derived Medicinal Products was
initiated. - A WHO Regional Workshop on Quality Assurance and
Safety of Plasma Derivatives was organized in
PAHO - An Aide Memoire on Blood Products and other
Biologicals and Information Sheets for Regulators
were developed - Intense activity had also been generated in the
preparation of international biological reference
materials for the standardization and assessment
of in vitro diagnostic tests, in particular for
Hepatitis B, C and HIV, and Human Transmissible
Spongiform Encephalopathies (TSE), see
http//www.who.int/biologicals/
35Herbal medicines
- Recommendations to WHO (excerpt)
- WHO should continue to co-operate with
governmental Institutions in developing and
updating guidelines on the assessment of the
quality, safety and efficacy of herbal medicines - WHO should continue to compile knowledge on the
safety and efficacy of herbal medicines,
including development of WHO monographs on
selected medicinal plants - WHO should collaborate with Member States to
strengthen the safety monitoring of herbal
medicines
36Herbal medicines
- What has been achieved
- General guidelines for methodologies on research
and evaluation of traditional medicine was
published - WHO monographs on selected medicinal plants,
Volume 2 is in press and Volume 3 4 in
preparation - Good Sourcing Practices for Medicinal Plants and
update of GMP for herbal medicines are in
discussion - Safety of herbal medicines were discussed in the
last two Annual Meeting of National
Pharmacovigilance Centres and the guidelines on
safety monitoring of herbal medicines are in
discussion - Training workshops for regulators have been
organized in PAHO - National survey to update the regulation of
herbal medicines in the Member States has started
37Conclusions
- Learning from past and looking ahead
- ICDRA remains a unique Global forum for national
DRAs - ICDRA recommendations have served as a valuable
guidance for WHO in its work - in normative area
- in regulatory support area
- Considerable progress has been achieved both by
countries and WHO, but resource constraints have
been a limiting factor
38