guide to master formulae final 2012 - who.int

1 guide to master formulae WHO/FWC/IVB/QSS/VQR 2011 guide to master formulae Guidance Document 1 This guidance document guide TO master formulae is one of a series developed by WHO/FWC/IVB Quality, Safety & Standards team upon request from the manufacturers members of the Developing Countries Vaccine Manufacturers Network (DCVMN), with funds of USAID. A set of priority topics have been identified by the manufacturers for WHO to provide guidance on expectations from the vaccine prequalification programme.

2 The guidance document guide TO master formulae is targeted primarily at manufacturers who are new to the prequalification of vaccines and who require detailed guidance about the level of detail needed for the development of batch production records. It may also be a useful guide to National Regulatory Authorities (NRAs) in vaccine producing countries. These are not official WHO documents but rather notes for guidance on expected standards to be followed for the prequalification of vaccines.

3 They are based on WHO recommended requirements but providing further explanations with examples on how these can be actually implemented. guide to master formulae Guidance Document 2 guide TO master formulae Table of Contents: Page 1) Introduction 4 2) Terms for master Formula (MF) 4 3) Definitions of Batch / Lot 5 4) master formulae needed 5 5) GMP guidelines on master documentation 5 6) Required Contents of a MF 6 7) MF and corresponding Batch Records 11 8) Formats for MF 11 9) Issuing of MF copy as a blank batch record 12 10) Electronic MF and Batch Records 13 11) Batch Records versus master Formula 14 12)

4 Batch record review checklist 14 Appendix 1: Extract from: World Health Organization, Technical Report Series, No. 908, 2003; Annex 4: good manufacturing Practices for pharmaceutical products: main principles. Appendix 2: Extract from: EUDRALEX; Volume 4 - Medicinal Products for Human and Veterinary Use: good manufacturing Practice: Chapter 4 Documentation. Appendix 3: Extract from: Pharmaceutical Inspection Convention Co-operation Scheme PE 009-3, 1 January 2006; guide to good manufacturing Practice for Medicinal Products; Documentation.

5 Appendix 4: Extract from Canadian GMP Guidelines, Health Canada, Health Products and Food Branch Inspectorate. good manufacturing Practices Guidelines, 2002 Edition, Version 2. guide to master formulae Guidance Document 3 Appendix 5: Extracts from US Code of Federal Regulations (CFR) and US FDA Guidelines. App 5-1) US Regulations for master Production Records for Finished Pharmaceuticals. Extract from: CFR 21, Chapter I, Subchapter F: Biologics, Part 211 Current good manufacturing Practice for Finished Pharmaceuticals; Subpart F--Production and Process Controls, Sec.

6 Written procedures; deviations; and Subpart J--Records and Reports; Sec. master production and control records. App 5-2) US Regulations for Batch Records for Finished Pharmaceuticals: Extract from: CFR 21, Chapter I, Subchapter F: Biologics; Subchapter C: Drugs General; Part 211 Current good manufacturing Practice for Finished Pharmaceuticals; Subpart J--Records and Reports; Sec. Batch production and control records. App 5-3) US Regulations for Batch Records for Biological Products: Extract from: CFR 21, Chapter I, Subchapter F: Biologics, Part 600 Biological Products: General; subpart B Establishment Standards, Sec Records App 5-4) US FDA Guidelines for Batch Records for Sterile Products: Extract from: Guidance for Industry.

7 Sterile Drug Products Produced by Aseptic Processing Current good manufacturing Practice. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER); Center for Biologics Evaluation and Research (CBER); Office of Regulatory Affairs (ORA). September 2004 (Pharmaceutical cGMPs). Appendix 6: Sample master formula for a hypothetical biological product Appendix 7: Example one of a master Formula Appendix 8: Example two of a master Formula Appendix 9: Example three of a master Formula guide to master formulae Guidance Document 4 1) Introduction In the 1997 WHO guidance document: WHO/ : (A WHO guide to good manufacturing practice (GMP) requirements.

8 Part 1: Standard operating procedures and master formulae ) some basic explanations and instructions were given for preparing various documents required by good manufacturing Practice guidelines from WHO and from several regulatory authorities. GMP guidelines include the requirements for documents (individual), documentation (the systems and formats for documents), and documenting (recording) of production and control activities. Most GMP guidelines provide the same or very similar information as the principles of good manufacturing Practice are now international in scope.

9 In this guidance document, the requirement for master manufacturing instructions and the requirements as given in different GMP documents, different names for these documents and various forms that they can take will be described. This is to guide vaccine manufacturers who are applying for prequalification or re-qualification of their product(s) in the preparation or improvement of current documents for manufacturing operations. 2) Terms for master Formula (MF) WHO identifies manufacturing instructions as master Formula.

10 Other terms used in GMP guidelines and regulations are manufacturing Formula , master Production and Control Record , but all mean the same thing an approved master document that describes the full process of manufacturing for the batch of product with at least cross-reference to the support operations for a batch of a specific product. Individual companies may give internal names to these documents ( manufacturing instructions, monographs, etc). In this guidance document the WHO term master Formula (or MF) will be used.