sultan ghani who prequalification programme of priority essential medicines, 11-13 october 2010, abu...
TRANSCRIPT
Sultan Ghani
WHO Prequalification Programme of Priority Essential Medicines, 11-13 October 2010, Abu Dhabi, U.A.E.
Dossier Requirements for Generic Medicines and Quality Guidelines
WHO Prequalification Programme of Priority Essential Medicines, 11-13 October 2010, Abu Dhabi, U.A.E.
Focus of PresentationFocus of Presentation
Part A: Organization and principal of assessment
Part B: Organization of data and regulatory dossier
Part C: Introduction to PQP Guidelines
Part D: Other Relevant Documents and Guidelines
WHO Prequalification Programme of Priority Essential Medicines, 11-13 October 2010, Abu Dhabi, U.A.E.
PART A: PART A: Organization and principal
of assessment
PART A: PART A: Organization and principal
of assessment
WHO Prequalification Programme of Priority Essential Medicines, 11-13 October 2010, Abu Dhabi, U.A.E.
IntroductionIntroductionIntroductionIntroduction WHO Procedure of assessment is based on the
following principles: Reliance of the information supplied by DRA Understanding of production and quality
control of the manufacturer Assessment of data and information on safety,
efficacy and quality GMP compliance of sites for APIs and FPPs GCP / GLP compliance Random sampling and testing Distribution recalls and complaints
WHO Prequalification Programme of Priority Essential Medicines, 11-13 October 2010, Abu Dhabi, U.A.E.
Steps of the ProcedureSteps of the ProcedureSteps of the ProcedureSteps of the Procedure
SOD
EPO
S.D.N.S.D.
Screening
Dossier Assessment
Site Inspection
Report and Outcome of Evaluation
Assessment Results
Expression of Interest
Submission of Dossiers
SUBMISSION OF DOSSIER
Multisource generic product
- Detail of the Product (See Presentation)
Standard Dossier submitted to DRA – Innovator Product- WHO-type Certificate of Pharmaceutical Product- Assessment Report- WHO-type Batch Certificate- Different packaging requires stability data
WHO Prequalification Programme of Priority Essential Medicines, 11-13 October 2010, Abu Dhabi, U.A.E.
Testing of SamplesTesting of SamplesTesting of SamplesTesting of Samples
Random Sampling
In case of failure investigation
WHO will provide written report and recommendation for action
Relevant DRA will be invited to participate in inspection or investigation
WHO Prequalification Programme of Priority Essential Medicines, 11-13 October 2010, Abu Dhabi, U.A.E.
Other IssuesOther IssuesOther IssuesOther Issues
Cost recovery
Confidentiality and undertaking (inspectors and evaluators)
Conflict of interest
WHO Prequalification Programme of Priority Essential Medicines, 11-13 October 2010, Abu Dhabi, U.A.E.
PART B: Organization of data and
regulatory dossier
WHO Prequalification Programme of Priority Essential Medicines, 11-13 October 2010, Abu Dhabi, U.A.E.
CTD FORMAT – ICH RequirementsCTD FORMAT – ICH Requirements
The CTD is not a “Global Dossier” !
It is an agreed-upon common format for the “modular” presentation of summaries, reports and data
Incorporates relevant ICH guidelines
It is organized into five sections:
All “modules” harmonized except Module 1 – regional specific
Raw data per regional requirements
WHO Prequalification Programme of Priority Essential Medicines, 11-13 October 2010, Abu Dhabi, U.A.E.
Module 1
Regional Administrative
Information
NonclinicalOverviewQuality
OverallSummary Clinical
Summary
Module 3
Quality
Module 4
NonclinicalStudy Reports
Module 5
ClinicalStudy Reports
ClinicalOverview
NonclinicalSummaries
Not Part of CTD
CTD
Module 2NDS
Result was the CTD Triangle
WHO Prequalification Programme of Priority Essential Medicines, 11-13 October 2010, Abu Dhabi, U.A.E.
CTD StructureCTD Structure
Full dossier contains 5 “Modules” - -
- Only Modules 2-5 are “CTD”
Module 1 – region-specific but always included in complete CTD structure
Module 2- All summaries / overviews
Module 3 – CMC (“Quality”)
Module 4 – Preclinical
Module 5 - Clinical
WHO Prequalification Programme of Priority Essential Medicines, 11-13 October 2010, Abu Dhabi, U.A.E.
Module 2 - CTD SummariesModule 2 - CTD Summaries
2.1 Overall CTD ToC
2.2 CTD Introduction
2.3 Quality Overall Summary
2.4 Non-Clinical Overview
2.5 Clinical Overview
2.6 Non-Clinical Written and Tabulated Summaries
2.7 Clinical Summary
WHO Prequalification Programme of Priority Essential Medicines, 11-13 October 2010, Abu Dhabi, U.A.E.
2.2 CTD Introduction2.2 CTD Introduction
General introduction to the pharmaceutical, including
Pharmacologic class
Mode of action
Proposed clinical use
Typically 1 page
WHO Prequalification Programme of Priority Essential Medicines, 11-13 October 2010, Abu Dhabi, U.A.E.
2.3 Quality Overall Summary - Content2.3 Quality Overall Summary - Content
A Summary that follows the scope and outline of the Body of Data in Module 3
Emphasize and discuss critical key parameters of the product
Discuss key issues to integrate information from Module 3 and other modules
Typically 40 pages, excluding tables, figures
WHO Prequalification Programme of Priority Essential Medicines, 11-13 October 2010, Abu Dhabi, U.A.E.
2.3 Quality Overall Summary - Format2.3 Quality Overall Summary - Format
2.3 Introduction
2.3.S Drug Substance
2.3.P Drug Product
2.3.A Appendices
2.3.R Regional Information
WHO Prequalification Programme of Priority Essential Medicines, 11-13 October 2010, Abu Dhabi, U.A.E.
Submission of CMC Information in CTD Format
Submission of CMC Information in CTD Format
3.2.S
3.2.S.1
3.2.S.2
3.2.S.3
3.2.S.4
3.2.S.5
3.2.S.6
3.2.S.7
DRUG SUBSTANCE
General Information
Manufacture
Characterization
Control of Drug Substance
Reference Standards or Materials
Container Closure System
Stability
WHO Prequalification Programme of Priority Essential Medicines, 11-13 October 2010, Abu Dhabi, U.A.E.
Submission of CMC Information in CTD Format (cont’d)
Submission of CMC Information in CTD Format (cont’d)
3.2.P3.2.P.1
3.2.P.23.2.P.33.2.P.43.2.P.53.2.P.63.2.P.73.2.P.8
DRUG PRODUCTDescription and Composition of the
Drug ProductPharmaceutical DevelopmentManufactureControl of ExcipientsControl of Drug ProductReference Standards or MaterialsContainer Closure SystemStability
WHO Prequalification Programme of Priority Essential Medicines, 11-13 October 2010, Abu Dhabi, U.A.E.
Submission of CMC Information in CTD Format (cont’d)
Submission of CMC Information in CTD Format (cont’d)
3.2.A
3.2.A.1
3.2.A.2
3.2.A.3
3.2.R
APPENDICES
Facilities and Equipment
Adventitious Agents Safety Evaluation
Excipients
REGIONAL INFORMATION
WHO Prequalification Programme of Priority Essential Medicines, 11-13 October 2010, Abu Dhabi, U.A.E.
Submission of CMC Information in CTD Format
Submission of CMC Information in CTD Format
The CTD Quality Module is unique in that it is a combination of historical development and future commitments that apply to the commercial, post-approval production period.
WHO Prequalification Programme of Priority Essential Medicines, 11-13 October 2010, Abu Dhabi, U.A.E.
Impact of the CTDImpact of the CTD
The ICH CTD represents one of the most ambitious and successful international harmonization activities undertaken
It will significantly reduce time and resources needed by industry to compile applications for global registration
WHO Prequalification Programme of Priority Essential Medicines, 11-13 October 2010, Abu Dhabi, U.A.E.
Benefits of the CTDBenefits of the CTD
More “reviewable” applications
Complete, well-organized submissions
More predictable format
More consistent reviews
Easier analysis across applications
Easier exchange of information
Facilitates electronic submissions
WHO Prequalification Programme of Priority Essential Medicines, 11-13 October 2010, Abu Dhabi, U.A.E.
CTD FORMAT – WHO Documents CTD FORMAT – WHO Documents RequirementsRequirements
CTD FORMAT – WHO Documents CTD FORMAT – WHO Documents RequirementsRequirements
1. Characteristics of the Finished Pharmaceutical Product (FPP)1.1 Detail of the Product
- Names, Dosage Forms & Strength- Description of Product & Packaging (Bottle, Blister, Bulk)
1.2 Sample- all proposed market presentations
1.3 Regulatory Situation in Other Countries- CANADA, USFDA, PEPFAR, EU, etc.
WHO Prequalification Programme of Priority Essential Medicines, 11-13 October 2010, Abu Dhabi, U.A.E.
2. Active Pharmaceutical Ingredient(s) (APIs)2.1 Nomenclature
- INN, Compendial Name, Chemical Name, Drug Substance Code, USAN, CAS Number.
2.2 Properties of APIs- API not described in Pharmacopoeia - API described in Pharmacopoeia- Structure Elucidation, Isomerism, Polymorphs, Particle Size Distribution (PSD), Critical additional characteristics (solubility, partition coefficient, etc.), Literature references.
CTD FORMAT – WHO Documents CTD FORMAT – WHO Documents Requirements Requirements (cont’d)(cont’d)
CTD FORMAT – WHO Documents CTD FORMAT – WHO Documents Requirements Requirements (cont’d)(cont’d)
WHO Prequalification Programme of Priority Essential Medicines, 11-13 October 2010, Abu Dhabi, U.A.E.
CTD FORMAT – WHO Documents CTD FORMAT – WHO Documents Requirements Requirements (cont’d)(cont’d)
CTD FORMAT – WHO Documents CTD FORMAT – WHO Documents Requirements Requirements (cont’d)(cont’d)
2. Active Pharmaceutical Ingredient(s) (APIs)
2.3 Site(s) of Manufacture - DMF(s), API-MF, GMP Certificate & Manufacturing licence, - - Specify: if inspected by WHO or any other Regulatory Agency.
2.4 Route(s) of API Synthesis- Specifications of Raw Materials & Intermediates- Controls of Critical Steps & Intermediates- Process Validation or Evaluation. - Impurities (organic, inorganic, catalysts, etc.).- Residual Solvents.
WHO Prequalification Programme of Priority Essential Medicines, 11-13 October 2010, Abu Dhabi, U.A.E.
2. Active Pharmaceutical Ingredient(s) (APIs)2.5 Specifications
- Complete specifications, signed & dated- Batch analysis- Summary of analytical results of relevant batches used in clinical or comparative studies.- Justification of specifications.- Reference Standards or Materials.
CTD FORMAT – WHO Documents CTD FORMAT – WHO Documents Requirements Requirements (cont’d)(cont’d)
CTD FORMAT – WHO Documents CTD FORMAT – WHO Documents Requirements Requirements (cont’d)(cont’d)
WHO Prequalification Programme of Priority Essential Medicines, 11-13 October 2010, Abu Dhabi, U.A.E.
2. Active Pharmaceutical Ingredient(s) (APIs)2.6 Container Closure System
- Specifications & Test Methods - IR identification tests to be
performed.2.7 Stability Testing
- Stress testing, Accelerated testing, long-term
testing
CTD FORMAT – WHO Documents CTD FORMAT – WHO Documents RequirementsRequirements (cont’d)(cont’d)
CTD FORMAT – WHO Documents CTD FORMAT – WHO Documents RequirementsRequirements (cont’d)(cont’d)
WHO Prequalification Programme of Priority Essential Medicines, 11-13 October 2010, Abu Dhabi, U.A.E.
3. Finished Pharmaceutical Product (FPP) 3.1 Marketing & Manufacturing Authorization3.2 Pharmaceutical Development
- API characterization studies- Compatibility of API & Excipients- Selection of excipients- Formulation development- Overages
CTD FORMAT – WHO Documents CTD FORMAT – WHO Documents Requirements Requirements (cont’d)(cont’d)
CTD FORMAT – WHO Documents CTD FORMAT – WHO Documents Requirements Requirements (cont’d)(cont’d)
WHO Prequalification Programme of Priority Essential Medicines, 11-13 October 2010, Abu Dhabi, U.A.E.
3. Finished Pharmaceutical Product (FPP) 3.3 Formulation
- Standard unit composition- Clinical batch composition- Proposed commercial batch- Highlight differences (if any)
CTD FORMAT – WHO Documents CTD FORMAT – WHO Documents RequirementsRequirements (cont’d)(cont’d)
CTD FORMAT – WHO Documents CTD FORMAT – WHO Documents RequirementsRequirements (cont’d)(cont’d)
WHO Prequalification Programme of Priority Essential Medicines, 11-13 October 2010, Abu Dhabi, U.A.E.
3. Finished Pharmaceutical Product (FPP)3.4 Site(s) of Manufacture
- Name & address of the facility3.5 Manufacturing Process
- Flow chart of manufacturing process - In-process control- Identification of critical steps- Target limits (if any)
CTD FORMAT – WHO Documents CTD FORMAT – WHO Documents RequirementsRequirements (cont’d)(cont’d)
CTD FORMAT – WHO Documents CTD FORMAT – WHO Documents RequirementsRequirements (cont’d)(cont’d)
WHO Prequalification Programme of Priority Essential Medicines, 11-13 October 2010, Abu Dhabi, U.A.E.
3. Finished Pharmaceutical Product (FPP)3.6 Control of Critical Steps & Intermediates
- Tests (according to dosage form)- Methods (compendial, In-house,
etc.)3.7 Process Validation
- Types of validation - Purpose- Validation Protocol- Batch Size- Batch Number- Commitment
CTD FORMAT – WHO Documents CTD FORMAT – WHO Documents RequirementsRequirements (cont’d)(cont’d)
CTD FORMAT – WHO Documents CTD FORMAT – WHO Documents RequirementsRequirements (cont’d)(cont’d)
WHO Prequalification Programme of Priority Essential Medicines, 11-13 October 2010, Abu Dhabi, U.A.E.
3. Finished Pharmaceutical Product (FPP)3.8 Specifications of Excipients
- Pharmacopoeial Grade- Non-Pharmacopoeial Grade
3.9 Control of FPP- Specifications- Justification of specifications- Test Methods
3.10 Container Closure System- Type of container closure system- Blister, HDPE Bottle, Bulk
CTD FORMAT – WHO Documents CTD FORMAT – WHO Documents RequirementsRequirements (cont’d)(cont’d)
CTD FORMAT – WHO Documents CTD FORMAT – WHO Documents RequirementsRequirements (cont’d)(cont’d)
WHO Prequalification Programme of Priority Essential Medicines, 11-13 October 2010, Abu Dhabi, U.A.E.
3. Finished Pharmaceutical Product (FPP)3.11 Stability Testing
- Stability protocol- Stability specifications- Selection of batches- Long term conditions- Accelerated conditions- Proposed shelf-life pf FPP
commitmentbatches
- Stability studies3.12 Container Labelling
- outer, inner labels
CTD FORMAT – WHO Documents CTD FORMAT – WHO Documents RequirementsRequirements (cont’d)(cont’d)
CTD FORMAT – WHO Documents CTD FORMAT – WHO Documents RequirementsRequirements (cont’d)(cont’d)
WHO Prequalification Programme of Priority Essential Medicines, 11-13 October 2010, Abu Dhabi, U.A.E.
3. Finished Pharmaceutical Product (FPP)3.13 Product Information for Health
Professionals3.14 Patient Information & Package Insert3.15 Differences in the product in various
countriesissuing the submitted WHO-type
certificate(s).
CTD FORMAT – WHO Documents CTD FORMAT – WHO Documents RequirementsRequirements ((cont’d)cont’d)
CTD FORMAT – WHO Documents CTD FORMAT – WHO Documents RequirementsRequirements ((cont’d)cont’d)
WHO Prequalification Programme of Priority Essential Medicines, 11-13 October 2010, Abu Dhabi, U.A.E.
PART C: Introduction to PQP Guidelines
WHO Prequalification Programme of Priority Essential Medicines, 11-13 October 2010, Abu Dhabi, U.A.E.
Introduction to PQP GuidelinesIntroduction to PQP Guidelines
PQP Dossier Submission Requirements:
Prequalification website addresswww.who.int/prequal/
WHO Prequalification Programme of Priority Essential Medicines, 11-13 October 2010, Abu Dhabi, U.A.E.
Introduction to PQP GuidelinesIntroduction to PQP Guidelines
Covering letter
Product Dossier
Product Sample e.g. 1 x 100 tablets
Site Master File
WHO Prequalification Programme of Priority Essential Medicines, 11-13 October 2010, Abu Dhabi, U.A.E.
PART D:Other Relevant Documents and
Guidelines
PART D:Other Relevant Documents and
Guidelines
WHO Prequalification Programme of Priority Essential Medicines, 11-13 October 2010, Abu Dhabi, U.A.E.
Relevant Documents and GuidelinesRelevant Documents and GuidelinesRelevant Documents and GuidelinesRelevant Documents and Guidelines
Marketing Authorizations of Pharmaceutical Products with Special Reference to Multi-source (Generic) products. A Manual for Drug Regulatory Authority – Regulatory support series No. 5 (WHO / DMP / RGS / 98.5)
Quality Assurance of Pharmaceuticals. A compendium of guidelines and related materials, Vol. 2, Good Manufacturing Practices and Inspection, Geneva. World Health Organization
Guidance for Industry – Q7A Guidance for Good Manufacturing Practices for Active Pharmaceutical Ingredients, August 2001
WHO Prequalification Programme of Priority Essential Medicines, 11-13 October 2010, Abu Dhabi, U.A.E.
Relevant Documents and Guidelines Relevant Documents and Guidelines (cont’d)(cont’d)
Relevant Documents and Guidelines Relevant Documents and Guidelines (cont’d)(cont’d)
World Health Organization WHO Technical Report Series No. 850 Annex 3, Guidelines for Good Clinical Trials on Pharmaceutical Products
World Health Organization WHO Technical Report Series No. 902, 2002 Annex 3, Good Practices for National Pharmaceutical Control Laboratories
UNDP / World Bank / WHO Special Programme for Research and Training in Tropical Diseases (TDR) Handbook. Good Laboratory Practices (GLP)
Pre-assessment of Product Files (new submission) multi-source (generic) products, January 2007 (SOP)
WHO Prequalification Programme of Priority Essential Medicines, 11-13 October 2010, Abu Dhabi, U.A.E.
Relevant Documents and Guidelines Relevant Documents and Guidelines (cont’d)(cont’d)
Relevant Documents and Guidelines Relevant Documents and Guidelines (cont’d)(cont’d)
World Health Organization WHO Technical Report Series No. 937, 2006, Annex 7, Multisource (generic) pharmaceutical products: guidelines on registration requirements to establish interchangeability
Guidelines on Submission of Documentation for Pre-Qualification of Multisourced generic finished product used in the treatment of HIV / AIDS, malaria and tuberculosis
World Health Organization WHO Technical Report Series No. 943, 2005, WHO Expert Committee on Specifications for Pharmaceutical Preparations
WHO Prequalification Programme of Priority Essential Medicines, 11-13 October 2010, Abu Dhabi, U.A.E.
Relevant Documents and Guidelines Relevant Documents and Guidelines (cont’d)(cont’d)
Relevant Documents and Guidelines Relevant Documents and Guidelines (cont’d)(cont’d)
Procedure for Assessing the Acceptability, in principle, of Active Pharmaceutical Ingredients for use in Pharmaceutical Products (draft – under discussion)
Pharmaceutical Development for Multisource (generic) Pharmaceutical Products. Draft.
Good Trade and Distribution Practices for Pharmaceutical Ingredients. WHO Expert Committee on Specifications for Pharmaceutical Preparations. Thirty-eight report. Geneva, 2004. Technical Report series No. 917, Annex 2.
WHO Prequalification Programme of Priority Essential Medicines, 11-13 October 2010, Abu Dhabi, U.A.E.
Relevant Documents and Guidelines Relevant Documents and Guidelines (cont’d)(cont’d)
Relevant Documents and Guidelines Relevant Documents and Guidelines (cont’d)(cont’d)
WHO Pharmaceutical Active Ingredients Certification Scheme (SMACS) Guideline on Implementation. In: WHO Expert Committee on Specification for Pharmaceutical Preparation. Thirty-eight report. WHO 2004. Technical Report Series N. 917, Annex. 3
WHO Good Manufacturing Practices: Main Principles for Pharmaceutical Products. In: WHO Expert Committee on Specification of Pharmaceutical Preparations. Thirty-seventh Report. WHO 203. Technical Report Series No. 908. Annex 4
ICH Quality Guidelines, e.g. Q1, Q6A, Q8, etc.
WHO Prequalification Programme of Priority Essential Medicines, 11-13 October 2010, Abu Dhabi, U.A.E.
Thank youThank you
WHO Prequalification Programme of Priority Essential Medicines, 11-13 October 2010, Abu Dhabi, U.A.E.