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CO u specifications are based on acceptable clinical, pivotal bioavailability and/or bioequivalence batches.

Biopharmaceutics issues depend on the route of administration as well as the kind of dosage forms (oral versus other routes of administration, immediate release dosage form, and modified release dosage forms). Some of these issues have been covered in the various chapters of this book.

The final formulation the sponsor wishes to market may not always be the one that has been used during the drug development. These formulation changes may be necessary due to variety of reasons ranging from aesthetic to overall improvement in formulation performance or to accommodate manufacturing convenience. It is essential to know that the to-be-marketed formulation will perform in the same way as the clinical trial formulation performed in the pivotal clinical studies. For an NDA, bioequi valence studies provide a link between the pivotal and early clinical trial formulation, a link between the formulations used in the pivotal clinical trial, and the to-be-marketed formulation or any other comparisons as appropriate. Bioequivalence studies provide information on the product quality and performance, when there are changes in components, composition and method of manufacture after approval of the drug product. The FDA has provided Guidance for the industry, such as BA/BE guidance [6], SUPAC-IR [7], and SUP AC-MR [8], to determine when the changes in the components and composition and/or method of manufacture of the drug product suggest a need to perform further in vitro/in vivo studies. Although, SUP AC stands for Scale-up and Post Approval Changes to the formulation, the same principals outlined in these guidances are utilized at the preapproval stage of the drug to determine the level of data needed for bio waivers.

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