The application of MicroCal VP Capillary DSC at a contract development organization
See how you can use DSC to save you money in your contract development lab. This paper provides an overview of the workflow typically associated with preformulation projects at a contract development organization as well as provides a general framework for conducting preformulation studies that leverages the application of biophysical techniques such as DSC and traditional analytics by employing statistical design. A case study involving the formulation development of a monoclonal antibody is presented to detail the utility and potential limitations of DSC in support of preformulation for a variety of protein products.
The application of Microcalorimetry at a contract development organization
See how you can use DSC to save you money in your contract development lab.
This paper provides an overview of the workflow typically associated with preformulation projects at a contract development organization and also provides a general framework for conducting preformulation studies that leverages the application of biophysical techniques, such as DSC and traditional analytics, by employing statistical design. A case study involving the formulation development of a monoclonal antibody is presented to detail the utility and potential limitations of DSC in support of preformulation for a variety of protein products.
Introduction
Although biopharmaceuticals represent a rapidly growing segment for ethical products, the ability to progress these products from research to development and ultimately manufactured products can be hindered by the complex structures and multiple degradation pathways that are associated with biopolymers.1,2,3
Traditional pharmaceutical development has often relied on real-time stability studies and standard analytics to develop product formulations that confer the two year shelf life typically required for drug products. Although these approaches have proven useful, there is a need to develop and apply techniques that report on the structural stability of biopharmaceuticals and reduce the need to rely on real-time stability studies so extensively. Differential scanning calorimetry, which monitors the apparent excess heat capacity of a protein solution as a function of temperature, is one of several tools that have been proven to be useful in this setting. 4,5 Even when used in a comparative or rank-ordered fashion DSC can provide data on protein stability that correlates well with real-time stability studies.
A key element in the ability to apply DSC or any other technique that may report on protein structure or stability is an organized approach that allows for the rigorous statistical evaluation of preformulation data. Recent regulatory guidance6 has highlighted the need both for well-characterized biopharmaceutical products as well as a systematic development approach that allows for the understanding of both critical parameters that affect product stability as well as any interactions between those factors that may exist. Here, we describe a systematic approach to preformulation development that leverages biophysical characterization and standard analytics in the context of statistical design with the goal of shortening the pharmaceutical development cycle while improving the quality of the development studies.
