The WHO Prequalification of Medicines Programme Dossier Assessment

Rutendo Kuwana Technical Officer Prequalification of Medicines Program WHO

The PQ Process Flow

Its simple, straight forward and designed for complete product review – just like a Stringent Regulatory Authority

APIMF Optional APIMF holder Information requested Assessment Accepted Quality Part of Dossier API FPP Assessment Accepted Applicant Information requested

Dossier for FPP pre-qualification

Screening Information requested Applicant Information requested Assessment Variations Complaints Random sampling Dossier accepted for assessment Efficacy/Safety Part of Dossier Biowaivers Bioequivalence studies Clinical trials GMP API manufacturing sites FPP manufacturing sites Clinical research sites.

Review of GMP Certification, Inspection reports, Site Master Files (SMF).

Information requested Applicant Corrective and preventive actions Inspection Manufacturers Accepted Accepted Final decision on prequalification Listing on WHO website Requalification (5 years after listing)

Dossier Screening Conclusion

 Accepted for assessment  Accepted under certain conditions  Not acceptable.

 Rejected

Applicant still receives extensive comments on any deficiencies

4 EMP TBS, 5 November 2010

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 5 EMP TBS, 5 November 2010

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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

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

7 EMP TBS, 5 November 2010

The new draft generic quality guideline: Key Features

 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 8 EMP TBS, 5 November 2010

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

9 EMP TBS, 5 November 2010

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 ) 10 EMP TBS, 5 November 2010

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 11 EMP TBS, 5 November 2010