Leachables/Extractables/Particulates

The Changing Landscape of Single Use in Bioprocessing: An Interview with Stefan Schlack and Jean-Marc Cappia

Single use in bioprocessing has changed significantly in recent years. To find out how a leading supplier to the biopharmaceutical industry is redefining its technology to align with new market challenges, science writer, Sue Pearson, had the opportunity to interview Stefan Schlack, Head of Bioprocess Marketing, and Jean-Marc Cappia, Head of Segment Marketing Vaccines, both at Sartorius Stedim Biotech (SSB) in Goettingen, Germany. Redefining Single Use Pearson: Sartorius Stedim Biotech is a recognized leader in single-use technology, and you’ve recently…

Development and Biomanufacturing Strategies for Next-Generation Antibody-Drug Conjugates

The development and manufacture of antibody-drug conjugates (ADCs) requires a series of complex steps. ADC manufacturers must comply with guidelines for both the small-molecule linker-drug and the monoclonal antibody (MAb). The authors describe their company’s development of its lead ADC product. They review process decisions, including the issues that factored into their selection of single-use systems, manufacturing challenges (differences between ADCs and MAbs), and testing methodologies for extractables and leachables. Synthon began as a small-molecule generics company in 1991. During…

Development of a Standardized Extractables Approach for Single-Use Components: General Considerations and Practical Aspects — A Manufacturer’s Perspective

The subject of extractables for single-use bioprocess contact materials has been a subject of heated debate since roughly the summer of 2012, when the first ISPE paper was published issuing a call to action to develop a standardized extractables protocol for the industry (1). As a supplier that pioneered the science of extractables (2‒11) and has published extractables data for our products for over 20 years, Sartorius Stedim Biotech (SSB) took the opportunity to look back, take stock, rationalize, and…

A Product–Packaging Interaction Study to Support Drug Product Development

Drug packaging is subject to a number of regulatory requirements, including those for product containers and packaging. For example, according to the federal Food, Drug, and Cosmetic Act (FD&C) section 501(a)(3), a drug is considered adulterated “if its container is composed, in whole or in part, of any poisonous or deleterious substance which may render the contents injurious to health.” And 21 CFR states that drug packaging “shall not be reactive, additive, or absorptive so as to alter the safety,…

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

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…

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

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…

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

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…

Extractables and Leachables: Standardizing Approaches to Manage the Risk

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…

Bioprocessing Standards for Single-Use Components Are Moving Forward

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…

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

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…