Leachables/Extractables/Particulates

Implementation of the BPOG Extractables Testing Protocols: Comparing USP and BPOG Extractables Data for Autoclaved Polyethersulfone Filters

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Benefits of single-use technologies over traditional stainless-steel solutions in biopharmaceutical manufacturing include reductions in set-up times, cleaning/cleaning validation costs, elimination of cross-contamination risks, and smaller operating footprints. But despite increasing adoption of such systems, concerns remain about extractable and leachable (E&L) compounds from plastic single-use systems (SUS) components with the potential to compromise the efficacy and safety of final drug products. Such concerns are magnified by the growing number of SUS suppliers and the complex supply chain for SUS and…

February 16, 2018

Implementation of the BPOG Extractables Testing Protocols: Working with Multiple Single-Use Components

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Single-use technologies offer significant advantages over traditional stainless-steel solutions for biopharmaceutical manufacturing. Reductions in setup times, cleaning and cleaning-validation costs, elimination of cross-contamination risks, and smaller footprints are just some of the benefits they provide. Although adoption of single-use systems (SUS) for commercial manufacturing is expanding, concerns persist that extractable and leachable (E&L) compounds from plastic SUS components potentially can leach into final drug products and compromise efficacy and safety. Those concerns are magnified amid the growing number of SUS…

December 13, 2017

Particulate Contamination in Single-Use Systems: Challenges of Detection, Measurement, and Continuous Improvement

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Patients receiving particulate contamination through parenteral delivery of biopharmaceuticals presents a significant potential health risk. However, the severity of that risk often is unclear. It depends on the route of administration, dosage volume administered, particle properties and amount received, and the ultimate fate of particles within a patient’s body (1). The appearance of particulate contamination also can be a visible indicator of product quality. Consequently, when such contamination is discovered within biopharmaceutical manufacturing operations, often it triggers costly investigations and…

October 19, 2017

Extractables and Leachables: Standardizing Approaches to Manage the Risk

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The implementation, maturation, and benefits of single-use technologies in biopharmaceutical development and manufacturing are well documented and understood. As analytical methods and testing services also rapidly improve, it is clear that management of risk associated with extractables and leachables also must evolve. Standardization is universally accepted as a goal; how to define, implement, and educate the industry is where debate resides. The container–closure segment has had more experience dealing with leachables and extractables than those implementing single-use process components do…

March 29, 2017

Bioprocessing Standards for Single-Use Components Are Moving Forward

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With the escalating use of single-use technology in bioprocessing, suppliers have had to rapidly develop disposable components such as fittings, tubing, pumps, sensors, and flexible containers for bioprocessing. Single-use technology is growing so fast that the organizations tasked with guiding its growth are having difficulty keeping up. Contributing to this problem are factors such as company needs, regulatory requirements, market pressures, and costs. That growth has posed considerable concerns for the bioprocessing industry about the presence of organic and inorganic…

April 12, 2016

Evaluating New Film for Single-Use Bags: Growth Performance Studies with Animal and Human Cells

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In biopharmaceutical development and manufacturing processes, single-use technology has become widely accepted (1). Storage and cultivation bags are particularly common. They are fabricated from plastics consisting of multilayer films and are typically provided gamma-sterilized by suppliers (2). The bags offer several advantages such as savings in time and cost. Lowered contamination risk results from reduced cleaning and sterilization demands. However, some adverse effects of polymer films on cell growth and metabolism have been reported, both for storage and cultivation bags…

March 14, 2016

Quantitative Risk Assessment of Bioaccumulation Attributable to Extractables and Leachables in Cellular Immunotherapy Biomanufacturing

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Precious patient samples, contamination concerns, and limited product purification options have compelled manufacturers of cellular immunotherapies (iTx) such as chimeric antigen receptor T cells (CAR-T) and T-cell receptor (TCR) technologies toward the disposables industry. Such companies are implementing single-use technologies (SUTs) almost exclusively (1). But despite the dominance of disposable bioprocess platforms and their extraordinary growth in the iTx marketplace, researchers have made limited efforts to understand the perennial and critical bioprocessing risks of leachables and extractables. Here we outline…

November 16, 2015

Compatibility Assessment of a Model Monoclonal Antibody Formulation in Glass and Blow–Fill–Seal Plastic Vials

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PREPRINT October 2015 issue Blow–fill–seal (BFS) technology has been recognized by the industry as an advanced aseptic solution (1–3). Catalent Pharma Solutions has been commercially supplying sterile BFS products to the pharmaceutical industry for decades, primarily in the respiratory and topical ophthalmic markets. Such product formulations range from simple solutions to emulsions with drug substances from classical small molecules to large complex proteins such as biologics. The company also has optimized BFS processes and its Advasept plastic container system for…

July 13, 2015

Toward Industry Standardization of Extractables Testing for Single-Use Systems: A Collective BPSA Perspective

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Here we present a consensus position of the membership of the Bio-Process Systems Alliance (BPSA), the trade organization for the single-use industry based in Washington, DC. BPSA’s membership includes 48 corporate and institutional entities, among them component suppliers, systems integrators, end users, and independent testing laboratories. Consensus within this membership is reached through an official ballot of representative voting members, as provided for in the organization’s by-laws. The position outlined below was approved by such an internal consensus-balloting process. Building…

March 10, 2015

Extractables Profiles: A Comprehensive Approach Produces Long-Term Results

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Biopharmaceutical manufacturers spend years developing and testing new drug and biologic products to ensure their efficacy, safety, and usability for patients. Such knowledge is extremely valuable, but those same principles often get overlooked in selection of packaging and delivery systems. Decisions on packaging and delivery often are made almost as an afterthought. However, issues related to components such as extractables and leachables can affect patient safety and product quality. In addition, a lack of extractables and leachables data in filings…

March 10, 2015