Regulatory Requirements for Stability Testing of Generics

Abstract

The Office of Generic Drugs (OGD) of the Food and Drug Administration (FDA) believes that stability of drug products is best ensured through quality-by-design. Quality-by-Design (QbD) in the context of stability means that a sponsor identifies potential mechanisms for instability and designs the formulation, container-closure system and manufacturing processes to mitigate the potential for instability. Under OGD’s new question-based review system, quality-by-design is documented in the pharmaceutical development report. However, the stability of generic drug products must still be demonstrated with data. On June 1, 2006, the FDA withdrew the 1998 draft stability guidance leaving the ICH Q1 documents as the only advice to sponsors. The scope of the ICH Stability Guidance is limited to new molecular entities and associated products. However, many sections of the ICH Q1 documents could apply to the new Abbreviated New Drug Applications (ANDAs). For example the storage temperature and relative humidity that are specified in ICH Q1 for accelerated, long term, and other conditions could be used for ANDAs. This talk will attempt to cover those recommendations which differ from ICH Q1 (e.g., initial submissions for new ANDAs), those for which no guidance is provided in the ICH document (e.g., post-approval changes), and those for which additional information is provided (e.g., data to support in-use conditions).