Both the United States and the European Union offer guidance on a life-cycle approach to process validation. This goes beyond the traditional three to five lots run at the center point of proposed ranges for operating parameters. New approaches leverage product design and process development information. They facilitate adapting the QbD paradigm to allow for a science- and risk-based selection of critical process parameters, key process indicators, and appropriate specification criteria. The number of runs for process performance qualification (PPQ) must be determined using a risk-based understanding and control of process variability.
This approach allows for more comprehensive use of multiple data sources to strengthen process understanding. Once process performance qualification has been executed, a stage of continued process verification begins for ensuring that a qualified control strategy is sufficient and that the process remains in a state of control. Following an appropriate time frame, process verification can be reduced to standard continuous process monitoring levels for ensuring process robustness and stability.
The January 2013 CMC Strategy Forum in Washington, DC, examined available regulatory guidances and attempted to answer certain remaining unanswered questions regarding implementation of the new process validation paradigm. Chaired by Rohin Mhatre (Biogen Idec) and Wassim Nashabeh (Genentech/Roche), the forum addressed such issues as process qualification planning and execution, continuous verification, and routine process monitoring. The day encompassed two sessions, each comprising presentations followed by an interactive panel discussion. Moderators facilitated questions and comments from the audience.
The Morning Session: Mats Welin, a senior expert at the Swedish Medical Products Agency, opened with “Process Validation: What to Put in the File — EU Perspective.” The second presenter was Robert Kuhn of Amgen Inc., who spoke on “Integration of Prior Knowledge, Small-Scale Studies, and Manufacturing Data for Efficient and Effective Process Design.” The third speaker was Nathan McKnight of Genentech/Roche, who presented “Scale-Down Model Qualification and Use in Process Characterization.” Morning session talks were followed by a roundtable discussion of specific questions posed to the presenters, who were joined by Christian Klock of Sanofi Pasteur.
The Afternoon Session: The first afternoon presentation was “Process Validation for Biotech Products: The Compliance Perspective,” by Linda Ng of FDA CDER. The second talk was “Executing PPQ Runs and Demonstrating a High Degree of Assurance at the End of Stage 2,” by Wendy Lambert of Abbott Laboratories. The third presentation was “Developing the Control Strategy for Continued Verification: Enhanced Testing,” by Graham Tulloch of Eli Lilly and Company. And the last speaker was Rick Schicho of Bristol Myers Squibb, who presented “Continued Process Verification for a Legacy Product: From Site Transfer Through Post Marketing Changes.” A Q&A panel discussion followed the afternoon presentations, with Ranjit Deshmukh (MedImmune), Lambert, Linda Ng (FDA CDER), Schicho, and Tulloch.
For more detail from these sessions, see the full article archived online (1).
1 Beck G, et al. Raw Material Control Strategies for Bioprocesses. BioProcess Int. 7(8) 2009: 18–29