Substance Stability Data Submission

In the case of established drug substances (as used for OTC products), the formulator must be satisfied that adequate stability data exist (by reference searches) prior to using it in a formulation. These data also become part of any regulatory submission, independent of the source. It is too easy to assume that every other company s product has been thoroughly tested. Some examples of where problems have occurred, with reference to the above, are given below ... 

A drug substance should be adequately characterized (i.e., results of chemical, physical, and, when applicable, biological testing). Material produced at different sites should be of comparable quality. In general, 3 to 6 months of stability data on one to three site-specific drug substance batches, depending on the availability of sufficient primary stability data from another site, should be provided at the time of application submission. 

To avoid or limit problems in this area after submission of the NDA, the validation of analytical methods and the conduct of stability studies should be planned from the initial phases of clinical research. This will provide the type of data approvable by FDA. The reader is directed to the Guideline for Stability Studies for Human Drugs and Biologies and the final ICH Guideline for the Stability of Drug Substance and Drug Product for assistance in fulfilling this essential requirement. 

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