Deficiencies in generic product dossiers as submitted to the WHO Prequalification of Medicines Programme

Abstract

This study was undertaken to determine the type and extent of deficiencies in generic product dossiers in the therapeutic areas of HIV/AIDS, tuberculosis, malaria and reproductive health, as submitted to the WHO Prequalification of Medicines Programme. There were considerably more quality-related deficiencies in tuberculosis, malaria and reproductive health dossiers compared to HIV dossiers, especially in the category specification of active pharmaceutical ingredients, development pharmaceutics, manufacturing method and finished pharmaceutical product specifications. The deficiencies related to the efficacy/safety portion of the dossiers displayed a trend similar to that observed in the quality portion in that the most critical deficiencies such as an incorrect study design, the use of an unacceptable comparator or the failure to include a study occurred considerably more frequently in the tuberculosis, malaria and reproductive health dossiers than in the HIV dossiers. The frequency of dossier-related deficiencies as determined on screening and assessment of the dossiers seemed to be inversely related to the number of product dossiers that had been prequalified by the end of 2010. The results of this study stress the need for continued capacity building of local generic manufacturers, further development of pharmacopoeial monographs by WHO (PhInt) and other pharmacopoeial commissions, not least to promote development of generic products, as well as development of new guidelines (WHO guidelines for development of generic and paediatric products and a technology transfer guidance document are currently being finalized). To our knowledge, this is the first comprehensive review of the quality and efficacy/safety portions of generic product dossiers, originating from pharmaceutical companies in emerging markets, and comparison of dossier deficiencies across four critically important therapeutic areas.

Keywords

Prequalification dossier deficiencies generic medicines quality bioequivalence HIV/AIDS tuberculosis malaria reproductive health

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