An Example of Utilizing Mechanistic and Empirical Modeling in Quality by Design

In this case study, we present an approach for employing modeling to help define the design space for a reaction with potential to generate an impurity that could impact the quality of an API. Our approach broadly consisted of (1) evaluating the reaction parameters that can affect the critical impur...

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Bibliographic Details
Published inJournal of pharmaceutical innovation Vol. 5; no. 4; pp. 193 - 203
Main Authors Hallow, Daniel M., Mudryk, Boguslaw M., Braem, Alan D., Tabora, Jose E., Lyngberg, Olav K., Bergum, James S., Rossano, Lucius T., Tummala, Srinivas
Format Journal Article
LanguageEnglish
Published Boston Springer US 01.12.2010
Subjects
Biochemical Engineering
Biomedical and Life Sciences
Biomedicine
Biotechnology
Case Report
Industrial and Production Engineering
Pharmacology/Toxicology
Design space
Quality by Design
Mechanistic modeling
Verification
Empirical modeling
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Summary:In this case study, we present an approach for employing modeling to help define the design space for a reaction with potential to generate an impurity that could impact the quality of an API. Our approach broadly consisted of (1) evaluating the reaction parameters that can affect the critical impurity level to develop appropriate assumptions for a mechanistic model, (2) developing and evaluating a mechanistic model to predict the formation of the critical impurity, (3) defining a design space based on the model output to reduce in practice the acceptable parameter space to a practical number of parameters, and (4) verifying the design space through experimental testing. This work resulted in a verified design space that can be practically employed and includes wide parameters ranges for manufacturing flexibility.
ISSN:1872-5120
1939-8042
DOI:10.1007/s12247-010-9094-y