CMC Forums

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…

Essentials in Quality By Design

Quality by design (QbD) is a systematic approach to drug development. It begins with predefined objectives and emphasizes product and process understanding and process control, all based on sound science, data-based decision making, and quality risk management (QRM). As introduced by the US Food and Drug Administration (FDA), QbD brings modern drug development methodologies to chemistry, manufacturing, and control (CMC) teams working on biologics, pharmaceuticals, and vaccines. The innovations associated with QbD are not so much the development concepts (which…

Reference Standards for Therapeutic Proteins: Current Regulatory and Scientific Best Practices

Sponsors developing and manufacturing protein therapeutic products use a variety of analytical tests (e.g., cell-based potency and chromatographic assays) to assess quality attributes of their active ingredients and drug products. Those tests are used to assess product quality in a number of activities, including characterization, comparability, lot release, and confirmation product quality and stability. Reference standards play a critical role in calibrating and confirming the suitability of such tests and in helping analysts to draw scientifically sound conclusions from data…

Biosimilar Products

The Chemistry, Manufacturing, and Controls (CMC) Strategy Forum held on 22 January 2012 in San Francisco, CA, focused on selected scientific and regulatory aspects in the development of biosimilar products. Such products are an increasingly important area of interest for both the biopharmaceutical industry and its regulatory agencies. Biosimilars are highly complex, so scientists have been unable to demonstrate identity to a level typically possible for small molecules. Consequently, specific scientific and regulatory approaches are required to ensure the high…

Drug Products for Biological Medicines

Traditionally, the CaSSS CMC Strategy Forum meetings have provided a scientific focus on the development of biotech drug substances and their manufacture and characterization, leaving the development of drug product formulation and filling, understanding primary containers, and considering novel delivery systems somewhat out of scope. Over recent years, however, the importance of investing more 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…

Rapid Pharmaceutical Product Development

    A Chemistry, Manufacturing, and Controls (CMC) Strategy Forum was held in January 2012 in San Francisco, CA, to examine the topic of rapid pharmaceutical product development. The purpose of this meeting was to promote an understanding of how best to increase the speed of product development, focusing on areas that improve chances of regulatory success while lessening the time it takes to get a product through development and onto the market. Participants also sought to identify and discuss…

Analysis and Immunogenic Potential of Aggregates and Particles

    The conclusion of this CMC Forum continued to focus on the latest developments in detection and characterization of protein aggregates (1). Afternoon sessions detailed the most recent experiments probing the role of protein aggregates in immunogenicity, with discussions on the best models to use and initial results. Topics included potential thresholds for immunogenicity, linking laboratory and clinical data, and predicting and testing potential immunogenicity of products throughout a development lifecycle.     Afternoon Sessions   Amy Rosenberg (Division…

Analysis and Immunogenic Potential of Aggregates and Particles

    The number of biotherapeutics on the market has rapidly increased during the past several years. Such proteins commonly exhibit a concentration-dependent propensity for self-association, which often leads to the formation of aggregates that range in size from nanometers (oligomers) to microns (subvisible and visible particles). Publications two years ago focused attention on the potential immunogenicity of active-ingredient aggregates ((1,2,3,4). The authors discussed lack of specificity of compendial measurements and inability of other current methods to address potential effects…

Glycosylation of Therapeutic Proteins

    ACMC Strategy Forum held in Washington, DC, on Sunday 28 January 2007, focused on two topics related to protein structure and function. First, analytical techniques used in the glycan analysis characterization included recent advances and correlations among the various tools. And second, current understanding glycosylation’s functional relevance to therapeutic proteins was discussed in the context of its effects on biological activity, pharmacokinetics, and Fc effector functions (for monoclonal antibodies, MAbs). Progress has been made in the field of…