(571ac) A Design Space Approach towards the Development of the Viral Filtration and Tangential Flow Ultrafiltration Unit Operations for the Commercial Purification Process of a Monoclonal Antibody

A design space approach was implemented towards the development of the viral filtration and ultrafiltration / diafiltration (UF/DF) unit operations within the manufacturing scale purification process for a monoclonal antibody. Traditionally, development of these and other purification unit operations have been centered around assuring that process performance and product quality attributes met acceptance criteria at and around target manufacturing operating conditions. The design space approach enhances conventional development by exploring process parameters and parameter ranges outside those traditionally explored, to determine the multidimensional combination and interaction of process parameters that assure product quality and process consistency.

The implementation of a design space approach towards development of purification processes has the potential to result in expanded manufacturing operating ranges and process flexibility as well as a better understanding of factor effects on process and product quality responses. Expanded operating ranges decrease the potential of deviations at manufacturing scale, and in the case a deviation does occur, the increased process knowledge gained during development can aid in determining the root cause of a deviation. Additionally, process changes within the design space should decrease future development and reduce regulatory filings associated with such changes.

The Viral filtration and UF/DF unit operations are ideal candidates for the implementation of a design space approach towards development because of their place in the purification process and the number of input parameters associated with each unit operation. These two unit operations are the last two unit operations in the purification process prior to bottling. Therefore, assurance that operating ranges encountered at manufacturing scale do not adversely affect product quality is essential. Additionally, the statistical analysis and modeling implemented in a design space approach are ideal for finding significant parameters from the myriad of factors associated with the viral filtration and UF/DF unit operations.

The development performed resulted in statistical process models that were utilized to set VF and UF/DF operating parameter ranges at manufacturing scale.