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Prequalification Update - 10 November 2010

 

Introduction to the new quality guidelines:

Guideline on submission of documentation for a multisource (generic) finished pharmaceutical product (FPP): Preparation of Product Dossiers (PDS) in Common Technical Document (CTD) Format

and,

Guideline on submission of documentation for a multisource (generic) finished pharmaceutical product (FPP): Quality Part

The above guidelines on the preparation of dossiers in CTD format and the quality data to be provided therein are now available.  These have been provisionally accepted by the WHO Expert Committee on Specifications for Pharmaceutical Preparations, with the intention that they are to be implemented on a pilot basis in the Prequalification Programme, while the period to comment on these documents has been extended. 

These guidelines have been developed to provide the following:

1)  ICH CTD structure has been adopted and the guidelines provide full details on preparation of dossiers in this format.    Accordingly, the previous PQIF template has been replaced with the CTD QOS-PD template (available on the     Prequalification website).

2) The quality guideline is more extensive than previous guidelines.  Note that this is not indicative of an increase in requirements.  Instead, the guideline has been updated to reflect current requirements and at the same time, additional details have been provided on how to meet the current requirements.   Included in this expansion is detailed guidance on the three options of submitting API data (CEP, APIMF or full details in the dossier). In addition it can be used for guidance on how to prepare an APIMF.

3)  Certain reductions in requirements are described.  The principle reduced requirements are as follows:

a) There is a reduced requirement for the number of FPP batches required to establish the shelf-life, for both complicated FPPs* (minimum three pilot batches reduced to minimum two pilot batches) and uncomplicated FPPs (minimum three pilot batches reduced to minimum one pilot batch and a second batch which may be smaller).

b) There is a reduced requirement regarding process validation of primary (pilot) batches.  We no longer require a process validation report for the pilot lots. Instead, we require only a demonstration of the uniformity of the batch(es) used in bioequivalence or biowaiver studies, either through blend uniformity, or extensive post-compression uniformity testing.

c) Reduced requirements for pharmaceutical development and process validation for "established multisource products" are elaborated, as follows: 
 
 Established multisource products are those that have been marketed by the applicant or manufacturer associated with the dossier for at least 5 years, and either 10 batches were produced in the past year, or 25 batches were produced in the past 3 years. 
 
For established multisource products, instead of process validation and certain pharmaceutical development data, applicants may provide data as outline in Appendix 2, ie a product quality review (PQR).  In summary, the PQR replaces the developmental pharmaceutics data in the sections on 1) formulation development (P.2.2.1 a)) and 2) manufacturing process development (P.2.3 a)).  In addition, it replaces the section on process validation, P.3.5. 

*The term "complicated FPP" includes sterile products, metered dose inhaler products, dry powder inhaler products and transdermal delivery systems. Other specific products under "complicated FPP" include ritonavir/lopinavir FDC tablets and FDCs containing rifampicin or an artemisinin. As the invitations for EOI change over time, the listing of individual "complicated" FPPs is not meaningful and applicants should contact the Head of Assessments, Prequalification of Medicines Programme in case of doubt.

Related Link:   

For new dossiers submitted from 1 March 2011 onwards, it is mandatory that the completed QIS/QOS templates be provided with the dossier(s). The applicant is encouraged to submit these templates before this, whenever possible.

For new dossiers submitted from 1 September 2011 onwards, it is mandatory that the dossier(s) be presented in CTD format.  The applicant is encouraged to submit in CTD format before this, whenever possible.