Monday, June 26, 2023 Daily Archives

Chromatographic Purification: Data Science, Chemistry, and Process Engineering Are Driving Bioprocess Innovation Forward

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When people decry “the lack of innovation” in biomanufacturing, I often find myself scratching my head. Maybe we’re working from different angles on the concept — for some, it might mean only those advances that are truly disruptive and replace a previous paradigm completely. But what I see in the biopharmaceutical industry currently is an explosion of new ideas, fresh approaches to established technologies, and incremental improvements that all add up to paint a dynamic picture of innovation indeed. “Creativity…

June 26, 2023

Demystifying Mixed-Mode Chromatography Resins: Emerging Applications for Purification of Non-MAb Protein Therapeutics

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Although monoclonal antibodies (MAbs) still represent the most common and most lucrative drug class in the biopharmaceutical industry, enthusiasm is growing for other recombinant-protein products. Clinical pipelines and even commercial portfolios are beginning to feature a breadth of nonantibody proteins and fragments as well as variations on the conventional-antibody theme: e.g., single-chain variable fragments (scFvs), fragment antigen-binding (Fab) products, and single-domain antibody fragments (also called nanobodies). By exploring such formats, drug developers hope to continue leveraging the efficacy advantages of…

June 26, 2023

Platform Optimization for Efficient AAV Purification: Insights from a CDMO

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The number of clinical studies continues to increase for candidate gene therapies based on adenoassociated virus (AAV) vectors. Application of different AAV serotypes has enabled drug developers to target a large panel of tissues and to address a breadth of diseases — but with the drawback that each serotype necessitates a distinctive purification process. Such development work requires considerable resources and results in long process-development timelines, which can cause significant delays to entering clinical trials. Thus, gene-therapy companies and contract…

June 26, 2023

Intensification of Fab-Fragment Purification: Multicolumn Chromatography Using Prepacked Protein L Columns

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Antibody fragments — such as fragment antigen-binding (Fab) domains, single-chain variable fragments (ScFvs), and heavy-chain variable domains (nanobodies) — have emerged as increasingly important therapeutic and diagnostic alternatives to full-length monoclonal antibodies (MAbs) for a multitude of diseases. Whereas MAb downstream processing is well established and easy to scale based on protein A capture, the purification of antibody fragments is just on the verge of standardized processing. The most promising candidate for effective capture of those containing a kappa light…

June 26, 2023

June 2023: From the Editor

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The pandemic forced many companies in many industries around the world to rethink how to get work done with much less in-person interaction than ever before. For the few of us who already worked from home at least part time, it wasn’t quite business as usual — but only because the circumstances brought technological and procedural improvements in how we work remotely. For most of our colleagues, however, it was a bit like getting tossed into the deep end of…

June 26, 2023

Standard Operating Procedures in a Good Practice Environment: Benefit or Burden?

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I was both excited and curious the day I started a new job in the quality affairs department of a pharmaceutical company. As usual, I attended onboarding meetings and received a training plan that contained a list of standard operating procedures (SOPs). So far, so good. But once I looked into the company’s training documents, my excitement turned to surprise. The SOP training included more than 150 good practice (GxP) SOPs, several of them longer than 50 pages and full…

June 26, 2023

Post-COVID Supply-Chain Challenges Are Easing, Part 1: New Competition Is Changing Industry’s Buying Behavior

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The SARS-CoV-2 pandemic created unprecedented stresses on bioprocessing and healthcare supply chains as suppliers struggled to find materials to meet demand for COVID-19 vaccines and therapeutics. BioPlan Associates, with BioPhorum and its members, recently researched the biomanufacturing industry’s response to the pandemic and prepared a white paper, Impact of COVID-19 on the Bioprocessing Supply Chain (1). Before COVID-19, the bioprocess supply industry had been growing consistently at 12–14% (nearly doubling revenue every five years) since 1990. During COVID, growth in…

June 26, 2023

Measurement of Particulates in Single-Use Systems for Cell and Gene Therapies Manufacturing — Part 1: Misapplication of USP <788>

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Particulates are mobile, undissolved particles other than gas bubbles that are unintentionally present in an injectable drug product. Patient safety can be compromised by the amounts and types of particulates present in a drug product (1). They differ in nature (e.g., metal, glass, dust, fiber, rubber, polymer, mold, and degradant precipitates) and can be divided into three categories: intrinsic, inherent, and extrinsic particulates. Intrinsic (native) particles are derived from operation of a manufacturing process or its equipment, a product formulation,…

June 26, 2023

Continued Process Verification: A Multivariate, Data-Driven Modeling Application for Monitoring Raw Materials Used in Biopharmaceutical Manufacturing

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Biologics manufacturing entails multiple complex unit operations across three key process areas: cell culture, purification, and sterile fill–finish (Figure 1). Numerous raw materials are used to formulate reagents that are vital to those processes. For example, bioreactors require cell-culture media, and buffer solutions are used during both drug-substance filtration and drug-product final formulation. Changes in raw-material properties can introduce variation in the performance of intermediate processes and in product quality attributes. Therefore, raw-material properties must be monitored to help ensure…

June 26, 2023

Degradation of Biopharmaceuticals During Cleaning Processes: Comparing Two Different Analytical Methods for Assessment with Bispecific Antibodies

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Before June 2015, pharmaceutical manufacturing of certain types of drugs required dedicated facilities. The European good manufacturing practice (GMP) guidelines state that to minimize the risk of cross-contamination, “dedicated and self-contained facilities must be available for the production of particular medicinal products, such as highly sensitizing materials (e.g., penicillin) or biological preparations (e.g., from live microorganisms). The production of certain additional products, such as certain antibiotics, certain hormones, certain cytotoxics, certain highly active drugs, and nonmedicinal products should not be…

June 26, 2023