Usefulness of an IVIVC

Once a product is developed that meets a company s needs in terms of efficacy and safety, no one wants to change it. This is particularly true once in phase 3 trials, where there is a risk of compromising the safety and efficacy database. However, for many reasons, changes are inevitable. The key is to manage any changes so that they do not impact negatively on efficacy and safety. In the absence of an IVIVC, 

Panel a shows two lines, one for in vitro release (-) and the other 

The FDA guidance on IVIVC development and validation defines a number of circumstances where an IVIVC can be used to justify a biowaiver request in support of (1) level 3 process changes, (2) complete removal or replacement of non-release-controlling excipients, (3) level 3 changes in release-controlling excipients, (4) approval of lower strengths, and (5) approval of new strengths. Additionally, use of the IVIVC to justify biorelevant dissolution specifications is cited as the optimal approach. 

Pharmacokinetic Model for Simulation of Concentration-Time Profiles for Orally Administered Extended-Release Dosage Forms 

A generalized pharmacokinetic model that can be used to support prototype selection is shown below. 

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