Stability clinical trial supplies

Stability samples and any samples used in evaluation programmes (including clinical trial supplies) should be subjected to QC evaluation inspections ... 

Clinical trial supplies which include full QC and supporting stability studies to show that product-pack is satisfactory for issue (i.e. IND stage in the USA). See also (8) below, paying usual attention to GMP, effectiveness of standard operation procedures (SOPs), etc. 

The product being crystallized was subject to a familiar set of constraints in the pharmaceutical industry. In early clinical trials, it was established that for bioavailability the active drug had to be supplied with a high specific surface area (2.3 -4.0 m /gm). On the other hand, it had to be highly crystalline, since (accelerated) stability testing had shown that partially (or totally) amorphous product, often encountered in the production of small (high surface area) particles, was subject to unacceptable... 

Once several batches of raw materials have been reviewed and tested to demonstrate that they will conform with the functional and quality requirements, the full excipient and packaging specifications can be finalised. Excipient and pack performance should be evaluated from a stability evaluation of the product and feedback from experience in clinical trials. Ideally, the specifications should be finalised for the start of Phase III clinical trials. If for some reason, the excipient or packaging material has to be changed for Phase III supplies, then some or all of the steps involved in the selection of materials, compatibility and stability studies may have to be repeated. 

While the practices of individual companies differ, the process description provided for the manufacture of API for use in the preparation of drug product formulations for pivotal clinical (e.g., the definitive bioavailability study) or stability trials should be documented to a level of detail approaching that to be included in the eventual marketing application. This will facilitate comparison of the synthesis of these key developmental batches with that to be used at the final manufacturing site supplying API for marketed product. At this time, it may be practical to include in-process acceptance criteria for key reactions or intermediates, and acceptance criteria for all raw materials used in this synthesis. 

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