Development of CTD for registration of medicines for EAC Medicines Regulatory Harmonization Programme

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• Development of CTD for registration of medicines
  for EAC Medicines Regulatory Harmonization
  Programme
• Country National Stakeholders Consultation
  Meeting dd/mm/yy

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Outline

• Background
• Composition of the TWG-MER
• Responsibility
• Progress
• Challenges
• Way forward
• Conclusion

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Background

• Chapter 21 (Article 118) of the EAC Treaty
• Provides for harmonization of drug registration
  and regulation
• Harmonize drug registration procedures
• Harmonize national health policies and regulation
  and promote the exchange of information on health
  issues in order to achieve quality health within
  the Community.

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Harmonization of medicines registration procedures

• Purpose To harmonize medicines registration in
  the EAC Partner States in order to
• increase the rapid availability of safe,
  efficacious and good quality essential medicines
  in the region
• enable free movement of pharmaceuticals within
  the region to complement the implementation of
  the EAC Customs Union operational since 2010
• Goal To have a harmonized and functioning
  medicines registration system within the East
  Africa Community in accordance with national and
  internationally recognized policies and standards
  i.e. WHO ICH

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Composition of TWG on Medicines Evaluation and
Registration (MER)

• Constituted by 12 members drawn from all the 6
  EAC Partner States NMRAs. i.e.
• Kenya Pharmacy and Poison Board (future KFDA)
• National Drug Authority of Uganda
• Tanzania Food and Drugs Authority (TFDA) Lead
  country
• Zanzibar Food and Drug Board (ZFDB)
• Rwanda Pharmacy Task Force (future RFMA)
• Department de la Pharmacie, du Médicament et des
• Laboratoires (DPML) of Burundi (Future ABREMA)

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Responsibilities

• To develop harmonized technical requirements and
  guidelines for registration of human medicines.
• Develop EAC Common Technical Document (CTD)
  format for application for registration of human
  medicines in EAC.
• Present the developed CTD, technical requirements
  and guidance for application for registration of
  medicines in EAC to the Steering Committee for
  approval.

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Responsibilities (cont)

• Develop assessment guidelines and Standard
  Operating Procedures (SOPs) for assessment of
  medicines dossiers.
• Identify and develop a list of vital essential
  and necessary (VEN) medicines that will be
  jointly assessed by EAC Partner States and
  present to the project Steering Committee for
  approval.
• Facilitate domestication of the agreed technical
  document for registration of medicines,
  guidelines and SOPs for application and
  assessment of dossiers.

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Progress made TWG on MER

• Meetings held
• 23 Video conferences - between July 2012 and
  August 2013
• 3 face to face meetings- in July, October 2012
  and May 2013
• Drafting and Development of EAC
  guidelines/documents

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Progress made (2)

• 1. EAC Guidelines on Submission of Application
  for registration of Medicines Common Technical
  Document (CTD) with appendixes mother document
  
• Provide guidance for applicants preparing a
  Common Technical Document for registration of
  medicines
• Describes how to organise applications based on
  the International Conference on Harmonisation of
  Technical Requirements

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Progress made (3)

• The CTD consists of 5 modules
• Module 1 Prescribes Administrative Information
  and Prescribing Information requirements,
• Module 2 Quality overall summary (QOS),
• Module 3 Quality (API and FPP),
• Module 4 Non-clinical,
• Module 5 Clinical

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Progress made (4)

• Annexes
• Annex I Covering letter.
• Annex II EAC application form
• Annex III Expert report.
• Annex IV Letter of access for DMF/CEP.
• Annex V Quality Overall Summary
• Annex VI Quality review requirements.

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Progress made (5)

• 2. Quality overall summary of module 2 and
  module 3 quality
• Assist applicants on the preparation of the
  Quality Module for generic medicinal products
• Provides clear general guidance on the format of
  presenting information
• Provide guidance on the technical and other
  general data requirements.

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Progress made (6)

• Quality overall summary (QOS)
• Overview of Module 3
• Emphasize critical key parameters of the product
• Key issues that integrates information from
  sections in the Quality Module and supporting
  information from other Modules (e.g.
  qualification of impurities via toxicological
  studies).

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Progress made (7)

• Module 3
• Main data on quality of API and FPP
• API data submission
• Options 1 EAC-Active pharmaceutical ingredient
  master file (EAC-APIMF) or
• Option 2 Full details in the Marketing
  Application Dossier (MAD).
• FPP full documentation

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Progress made (8)

• 3 . Requirements for stability studies
• Active pharmaceutical ingredient
• Finished pharmaceutical ingredient
• Address new and existing APIs/FPP
• Not applicable for biologicals vaccines
• Stress stability
• Regulatory stability accelerated and long term
• Long-term
• 30 C 2 C/75 RH 5 RH
• Accelerated
• 40 C 2 C/75 RH 5 RH 6 months

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Stability studies

• Storage conditions requirements for FMPs intended
  for storage in a refrigerator
• Long-term
• 5 C 3 C 12 months
• Accelerated
• 25 C 2 C/60 RH 5 RH or
• 30 C 2 C/65 RH 5 RH or
• 30 C 2 C/75 RH 5 RH
• FMPs intended for storage in a freezer
• 5 C 3 C or 25 C 2 C or 30 C 2 C)

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Therapeutic equivalence

• Specify the requirements for the design, conduct,
  and evaluation of bioequivalence studies
• Immediate release and modified release dosage
  forms with systemic action
• Stipulates exemptions for carrying out in vivo
  bioequivalence (BE)
• In vitro dissolution tests as a surrogate for in
  vivo BE studies
• Other studies
• Comparative pharmacodynamics studies
• Comparative clinical studies

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Procedural aspects for applications

• Outline procedures from submission of a dossier
  to the final outcome, timeframe and procedure for
  competent authorities to amend, where necessary
  the conditions of marketing authorization of a
  particular product.
• Provide guidelines on general requirements
  language, font size etc
• Outline procedures for different types of
  applications new, renewal variation

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Completed guidelines ready for approval by
National Stakeholders (1)

• EAC guidelines on submission of application for
  registration of human medicinal products (main
  guideline).
• EAC guidelines on therapeutic equivalence
  requirements.
• EAC guidelines on registration of fixed-dose
  combinations (FDCs
• EAC guidelines on biowaiver
• EAC list of standard terms for pharmaceutical
  dosage forms and routes of administration.

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Completed guidelines ready for approval by
National Stakeholders (2)

• EAC guidelines on procedural aspects of
  application for registration of human medicinal
  products.
• EAC guidelines on stability requirements.
• EAC guidelines on labeling requirements.
• EAC common glossary of terms used in medicines
  registration.

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Completed guidelines ready for approved by
National Stakeholders (3)

• 10. Annexes to the EAC guidelines on submission
  of application for registration of human
  medicinal products (main guideline)-
• Annex I Covering letter.
• Annex II EAC application form for marketing
  authorization of medicinal product.
• Annex III Expert report.
• Annex IV Letter of access for DMF/CEP.
• Annex V Quality Overall Summary Product
  dossier.
• Annex VI Quality review requirements.

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Request to the National Stakeholders

• To consider and approve the developed draft
  documents as listed above, and which have already
  been approved by the projects regional steering
  committee, for further approval processes
• Also
• -To continue supporting the national and regional
  initiatives and efforts that are towards the
  improvement of peoples lives
• -To continue participating in the approval
  processes that will follow at the regional level
• Build more consensus and advocacy for
  strengthening the existing national Medicines
  Regulatory Agencies

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Work in progress

• EAC guidelines on selection of comparator
  products
• EAC guidelines on application for variation of a
  registered medicinal product.
• EAC common assessment procedure.
• Training modules on evaluation
• EAC Active Pharmaceutical Ingredient (API)
  procedure
• Guidelines on requirements for registration of
  biological/biotechnological products

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Challenges

• procedures for internationalization of the
  approved guidelines in Partner States regulatory
  systems is not yet in place
• Few face to face meetings versus workload
  (development of documents)
• All the 6 NMRAs involved in the project activitie
  are not at the same level and more funds than
  budgeted will be required to build capicities in
  Rwanda, Burundi and United Republic of Tanzania
  (ZFDB)

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Way forward

• Capacity building activities planned/underway
• a) Twining programme (2nd quarter - 2013/14)
• b) Training on dossier assessment (3rd quarter )
• c) Joint assessments (4th quarter)
• d) WHO/EAC joint assessment sessions (July and
  Sept 2013.....continuing)
• Appointment of TWG members for replacement
• More interactive sessions face to face meetings
  at least 3 for this financial year

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Thank you very much