CMC Forums

Analysis and Structure Characterization of Monoclonal Antibodies

On 6 January 2003, 129 attendees participated in the second Well-Characterized Biotechnology Product (WCBP) Chemistry and Manufacturing Controls (CMC) strategy forum, titled “Analysis and Structure Characterization of Monoclonal Antibodies (MAbs),” held in San Francisco to discuss lot release and characterization test issues specific to MAbs (1). The objective of the meeting was twofold: to identify a “core” set of assays most useful for lot-release testing of MAbs and to define a mechanism for selecting appropriate potency tests. Two separate workshops…

Lot Release and Characterization Testing of Live-Virus–Based Vaccines and Gene Therapy Products

The January 2005 CMC Strategy Forum was devoted to a discussion of live virus vaccines and viral vectors used for gene therapy. The purpose of the meeting was to determine whether consensus positions could be reached among the delegates regarding lot release, stability, characterization, and comparability testing. Part 1 of this two-part report on that meeting describes factors influencing the choices of lot-release assays for vaccines and gene-therapy products (1). Part 2 presents potency testing, characterization, and comparability studies, including…

QBD Manufacturing Strategies: The CMC Strategy Forum Series, Part 2

The CMC Strategy Forums provide a venue for biopharmaceutical product discussion. They focus on relevant chemistry, manufacturing, and controls (CMC) issues throughout the life cycle of a therapeutic and thereby foster collaborative technical and regulatory interaction. Forum chairs share information with regulatory agencies to help them merge good scientific and regulatory practices. Outcomes of the forum meetings are published in BioProcess International and on the CASSS website. This process is meant to help ensure that biopharmaceutical products manufactured with advancing…

New Paradigms for Process Validation: A Practical Approach

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)…

Raw Material Control Strategies for Bioprocesses

The 15th WCBP CMC Strategy Forum, “Raw Material Control Strategies for Bioprocesses,” met on Sunday, 11 January 2009 in San Francisco, CA. This forum considered the design and implementation of control strategies for complex raw materials used in bioprocessing. Discussion focused on key approaches and application of risk assessment tools that can be used to identify and assist in mitigating potential safety and efficacy concerns that can affect the quality of biological products. Two Sessions To fully explore the topic,…

Multiproduct Facility Design and Control for Biologics: Challenges and Considerations

Multiproduct facilities are increasingly integral to corporate biologics network and supply chain strategies. Manufacturing capacity strategies ensuring appropriate facility design and procedural controls to manage the risks of producing multiple products are critical to the successful deployment of commercial and clinical supply plans. A Chemistry, Manufacturing, and Controls (CMC) Strategy forum was held in Bethesda, MD, in August 2011 to highlight various challenges, risks, and control strategies associated with multiproduct facilities. Multiproduct strategies for the manufacture of a variety of…

Drug Products for Biological Medicines: Novel Delivery Devices, Challenging Formulations, and Combination Products

The importance of investing science and technology into drug product development has become evident as different product types, higher protein concentrations, and doses and requirements for improved delivery of biological drug products have increased. The need to give patients larger and more concentrated doses has challenged formulation scientists and driven development of new technologies that can deliver those doses. Delivery devices fall under device regulations and have distinctly different design, development, and validation requirements from those of protein drug products…

Expanded Change Protocols: Benefits, Cost Considerations, and Regulatory Views

The US FDA Office of Biotechnology Products’ quality by design (QbD) pilot program defines an expanded change protocol (eCP) as a particular type of comparability protocol that will “describe the quality by design, risk- based approach linking attributes and processes to product performance safety, and efficacy” (1). Sponsors have explored a wide range of potential applications for eCPs (e.g., movement within or beyond an established design space, site transfers, and additional process modifications supported by either a QbD or traditional…

The CMC Strategy Forum Series, Part 1 – QbD and Risk Management

Introduction by Cheryl Scott The CMC Strategy Forum series provides a venue for biopharmaceutical product discussion. The meetings focus on relevant chemistry, manufacturing, and controls (CMC) issues throughout the life cycle of a therapeutic and thereby foster collaborative technical and regulatory interaction. Forum chairs share information with regulatory agencies to help them merge good scientific and regulatory practices. Outcomes of the forum meetings are published in BioProcess International. This process is meant to help ensure that biopharmaceutical products manufactured with…

Accelerated Product Development: Leveraging Industry and Regulator Knowledge to Bring Products to Patients Quickly

A Chemistry, Manufacturing and Controls (CMC) Strategy Forum titled “Accelerated Product Development: Leveraging Combined Industry and Regulator Knowledge to Bring Products to Patients More Quickly” was held in Washington, DC, on 27 January 2014. Biological therapeutics in development are demonstrating remarkable results in the clinic for many indications. So companies are seeking ways to accelerate the approval of these therapies and rapidly bring them to market. Many such products take the form of well-characterized proteins (e.g., IgG1 or IgG2 monoclonal…