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FDA and industry weigh broader use of prior knowledge in biotechnology testing and production.
Efforts to streamline the development of new medicines, particularly breakthrough therapies, are focusing attention on strategies to clarify and enhance the use of data and information gained over time from process development and validation. This prior knowledge has become more recognized as useful in limiting redundant product testing and informing new drug development. The wide variety in the scope and nature of such data held by biopharma manufacturers is prompting industry to seek more assurance from regulatory authorities that references to prior knowledge in testing protocols and submissions will be accepted and help support regulatory decisions.
These issues were addressed this week at CASSS CMC Strategy Forum in Washington, DC, building on a workshop in London in November 2017 on prior knowledge and its use in regulatory applications sponsored by the European Medicines Agency (EMA). Participants at the EMA meeting have prepared a report on the value and use of prior knowledge in product and process development, and a white paper on the topic is expected from the organizers of the CASSS Forum.
The topic is timely because, after 20 years of producing monoclonal antibodies, manufacturers have extensive prior knowledge that can support the assessment of quality attributes, validation of analytical methods, establishment of control strategies, and design of viral clearance and other studies. Quality standards established by the International Council for Harmonisation (ICH) refer to prior knowledge of process and product in establishing relevant testing plans and specifications. Leveraging prior knowledge, explained Josefine Persson, associate director for purification development at Genentech, at the CASSS forum, can lead to smaller validation studies, enhance process understanding, and speed the commercialization process.
To better use prior knowledge in product development, manufacturers now seek more clarity from regulators on how and where to submit established information in dossiers and to support manufacturing changes through the product lifecycle. Prior knowledge is critical in developing clinically relevant product specifications but has to be documented in a form that is clearly communicated and understood in regulatory filings, pointed out Barbara Rellahan, director of product quality at Amgen.
FDA recognizes the value of prior knowledge in designing manufacturing processes, product formulations and control strategies for biologics, noted Cristina Ausin, team leader in the Office of Biotechnology Products in the Center for Drug Evaluation and Research (CDER). She cited the value of utilizing previous experience with similar formulations in developing control strategies and risk assessment, noting that such approaches may lead to faster product development and enhanced manufacturing efficiency. But while prior knowledge can be leveraged to confirm data, it should not override the need to establish controls and specifications that reflect the unique properties of every regulated product or replace the need for extensive product specific knowledge, Ausin said. A concern for FDA, she added, is manufacturer over-reliance on prior knowledge in justifying development strategies; while prior knowledge can support expectations, manufacturers still need data to provide a basic assurance of quality.
There’s agreement that regulators will consider leveraging prior knowledge on a case-by-case basis, based on a consideration of product attributes and clinical experience. But manufacturers would like to see more clarity and convergence on where prior knowledge can help eliminate redundant testing and optimize process development. A clear benefit of utilizing prior knowledge is to accelerate development programs for new products that appear to offer important advances for patient treatment. Risk evaluation is key in weighing how much to assess earlier experience with similar products with the need for new product-specific data to support product approvals.