The WHO Prequalification of Medicines Programme Dossier Assessment

1. The WHO Prequalification of Medicines ProgrammeDossier Assessment Rutendo Kuwana Technical Officer Prequalification of Medicines Program WHO

2. The PQ Process Flow Its simple, straight forward and designed for complete product review – just like a Stringent Regulatory Authority

3. Dossier for FPP pre-qualification Information requested Applicant Screening Dossier accepted for assessment Information requested Optional GMP API manufacturing sites FPP manufacturing sites Clinical research sites. Review of GMP Certification, Inspection reports, Site Master Files (SMF). Efficacy/Safety Part of Dossier Biowaivers Bioequivalence studies Clinical trials Quality Part of Dossier API FPP Applicant APIMF Corrective and preventive actions APIMF holder Assessment Information requested Information requested Information requested Accepted Assessment Applicant Assessment Manufacturers Inspection Accepted Accepted Accepted Final decision on prequalification Variations Complaints Random sampling Requalification (5 years after listing) Listing on WHO website

4. Dossier Screening Conclusion • Accepted for assessment • Accepted under certain conditions • Not acceptable. • Rejected Applicant still receives extensive comments on any deficiencies EMP TBS, 5 November 2010

5. Use of Biopharmaceutics Classification System • Requirement for in vivo bioequivalence testing may be waived under certain conditions • Solubility of drug substance • Permeability of drug substance • Uncomplicated drug substance • Immediate-release dosage form • Acceptable dissolution characteristics of dosage form EMP TBS, 5 November 2010

6. Application of BCS in PQP • PQP has reviewed existing information on the bioavailability and dissolution data of the invited medicines • Identified some drug substances as eligible for a BCS-based biowaiver application - either monocomponent or fixed-dose combination (FDC) products • Monocomponent or FDC products containing other drug substances must be supported with in vivo BE data EMP TBS, 5 November 2010

7. What's New in PQP? • New guidelines for submitting new dossiers • Clarifications on guidelines for submitting Variations • Requalification of medicines • Prequalification of APIs • Joint assessments EMP TBS, 5 November 2010

8. The new draft generic quality guideline:Key Features EMP TBS, 5 November 2010 • Common Technical Document (CTD) structure • Electronic summary: Pharmaceutical Quality Information Form (PQIF) replaced by Quality Overall Summary (QOS)) • Elaboration of current requirements • Updated requirements • Some key reduced requirements

9. PQ Dossier Variation Guidance Three categories of variations, according to potential impact to quality of product and current timelines we aim to achieve (achieved already) • Notification - no or minimal impact: 30 days • Minor change - potential minor impact: 60 days • Major change - potential major impact: 60 days EMP TBS, 5 November 2010

10. Requalification Procedure for prequalification of pharmaceutical products requires holders of WHO-prequalified products to submit a quality review after five years from the date of prequalification of the product, or when requested to do so by PQP (whichever date is earlier) EMP TBS, 5 November 2010

11. Upcoming Enhancers • Dossiers to be submitted in CTD format • Increased access to assessors for applicant queries –guideline and procedure for meetings/contacts with applicants under development • Publish list of prequalified APIs and their specific attributes • Publish prevailing timelines for key processes • Share with stakeholders relevant information about prequalified products EMP TBS, 5 November 2010