OR WAIT null SECS
Regulatory officials and industry scientists participated in a CMC Strategy Forum sponsored by CASSS in July 2015.
To ensure that biotech manufacturing processes can consistently deliver high quality products through high-yield systems, biotech companies are developing systems to monitor and evaluate key product attributes and process factors during manufacturing to identify the need to modify control mechanisms. This process involves continued process verification (CPV), which has emerged as a main strategy for managing change over the product lifecycle, according to regulatory officials and industry scientists participating in the July 2015 CMC Strategy Forum sponsored by CASSS. A CPV provides a manufacturer with assurance that a validated process remains in a validated state during commercial manufacturing.
Emanuela Lacana, associate director for policy in the Office of Biotechnology Products (OBP) in the Center for Drug Evaluation and Research (CDER), discussed how a CPV provides a basis for continued assurance that the process maintains a state of control, with monitoring and sampling adjusted as needed. A CPV should be established during the design of the manufacturing process, Lacana noted, and should include a set of controls that can assure process performance and product quality.
A CPV also can be important in identifying ways to improve the process and changes needed to maintain product quality. FDA’s guidance defining “Established Conditions” supports this approach by further defining key elements of a control strategy needed to assure quality performance of an approved product, which should be part of a CPV strategy. Established conditions include specifications for analytical procedures, starting materials and procedures, as well as components and specifications for container-closure systems. But Lacana added that batch records, development data, validation results, and batch analysis data generally are not established conditions. Clearly defined established conditions, which should be negotiated and finalized at time of product approval, should reduce submission of unnecessary supplements, encourage continual process improvements, and provide a more flexible, risk-based approach for FDA to regulate post-approval changes, Lacana concluded.
A number of biotech manufacturers examined CPV as it relates to product lifecycle management, integration with quality systems, monitoring strategies, quality control tools, novel data analysis methods, and the relation to control strategies and to process analytical technology. One issue is whether process validation can be sufficiently flexible to facilitate development and approval of critical, lifesaving biotech therapies. Participants at the Forum noted that CPV plans are particularly useful as internal management tools, which then can be tapped to provide additional information to regulatory authorities during inspections or as part of efforts to define planned improvements. Leading biotech companies are developing a roadmap for CPV within a framework established by the BioPhorum Operations Group (BPOG) on continuous process verification.
A detailed summary of the Forum by consultant Nadine Ritter highlights how a CPV strategy formalizes a firm’s procedural, logistical, and mechanistic expectations for a “state of control.” Discussion will continue on how signals from a CPV should interface with deviation systems and support established clinical ranges of product safety and efficacy, and how CPV programs can help implement process changes by defining design space and processes. CPV implementation requires good IT database management and a highly knowledgeable cross-functional team to deliver real results. Both regulators and manufacturers remain uncertain about how they will interact on CPV plans and to what extent information will be shared with the agency, or used by manufacturers internally to support monitoring and decision making.