WHO Essential Drugs Strategy

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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
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International 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

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Topics 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

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Topics 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

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9th 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

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Good 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).

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Good 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

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Good 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

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Good 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

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Good 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

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Counterfeit 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.

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Counterfeit 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

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Current 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.

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Current 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

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Current 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

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ICH 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

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ICH 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

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Drug 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.

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Drug 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

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Drug 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)

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Electronic 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

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Electronic 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.

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Transparency 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

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Transparency 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

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Need 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

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Need 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

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Need 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)

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Antimicrobial 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

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Antimicrobial 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

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Antimicrobial 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

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Safety 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

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Safety 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

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Safety 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/

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Herbal 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

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Herbal 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

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Conclusions

• 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

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