Author Archives: Barry Cherney

eBook: Production of Cell-Line Development and Control of Product Consistency During Cultivation — Myths, Risks, and Best Practices

Health authorities are requesting substantial details from sponsors regarding practices used to generate production cell lines for recombinant DNA–(rDNA) derived biopharmaceuticals. Authorities also are asking for information about the clonality of master cell banks (MCBs) and control strategies to minimize genetic heterogeneity. Such requests are prompted by recent reports indicating “nonclonality” for certain production cell lines. To address these and related issues, the CASSS CMC Strategy Forum on “Production Cell Line Development and Control of Product Consistency During Cell Cultivation:…

CMC Strategy Forum Special Focus Series: Part 2 Product-Related Impurities, An Overview

Introduction by Cheryl Scott The CMC Strategy Forums 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 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 technologies in a regulated environment…

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…

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…