Biopharmaceutical manufacturing concludes with mixing a drug substance into a formulation that can be injected or otherwise introduced to patients — then filling and packaging the resulting drug product for delivery and distribution. Aseptic processing is key to making sure that biologic drugs are safe for patients. From buffers and excipients to containers and closures to specialized devices, this featured report centers on biopharmaceutical drug products and the types of controls used to ensure their quality, safety, and efficacy.

Aseptic Considerations in Formulation, Fill–Finish: Choosing Between Barrier and Isolator Technologies
Patrick Nieuwenhuizen
The primary objective of aseptic processing is contamination control. Several different sources raise significant risks from microbiological contamination within the complex, multistep formulation and fill–finish process. Those include personnel, materials, container closures, equipment, and the facility itself. In this article, a consultant from PharmaLex Ireland compares restricted-access barrier system (RABS) and isolator technologies that biologics manufacturers can apply to bolster their contamination-control strategies. The author also describes essential scientific, operational, and business-related considerations for implementing technologies for aseptic processing.

Creative Formulation: A Useful Approach to Patient-Centered Drug Development
Jan Jezek
Creative formulation technologies can provide several benefits to biopharmaceutical drug products, including improved stability properties, reduced product viscosity, tunable rates of active-ingredient release from an injection site, and large-volume delivery capabilities. Thus, such technologies are becoming a fundamental part of patient-focused product-development efforts in the biopharmaceutical industry — and their importance is likely to increase over time. Herein, an executive from Arecor Limited overviews promising advances in creative formulation technologies and explains how those could help to improve the biopharmaceutical industry’s responsiveness to patient requirements.

Analysis of Trace-Level, High-Risk HCPs: Proteomics Advances for Preventing Degradation of Polysorbates in Biotherapeutic Formulations
Xuanwen Li and Douglas D. Richardson
Polysorbates are commonly applied in formulation of biotherapeutic products, both for preventing surface adsorption and as stabilizers against protein aggregation. Their degradation can cause turbidity and potential formation of subvisible particles, mainly from poorly soluble, hydrophobic, free fatty acids. Recently, prevention of polysorbate degradation has become an industry-wide priority, especially because its risk increases with higher cell densities and titers in bioprocess and with higher drug concentrations in biologics formulation. Some residual host-cell proteins (HCPs) affect polysorbate degradation. LC-MS/MS–based proteomics provides a means for both identification and quantification of HCP impurities simultaneously and has emerged as an orthogonal assay for HCP characterization. It aids in development of control strategies to mitigate that risk and adapt a testing strategy across the product development and commercialization life cycle. Herein, the authors review the latest advances in proteomic assessment, including activity-based protein profiling (ABPP).

A Holistic Approach: Bridging the Gap Between Suppliers and Biomanufacturers
Scott Ewan
This article describes how two BioPhorum workstreams are facilitating communications about drug-product development between suppliers and biomanufacturers. The author focuses especially on the members’ ongoing efforts to develop a holistic approach to container–closure integrity testing (CCIT). Such an approach seeks to apply quality and risk management tools to CCIT in ways that simultaneously enhance manufacturing efficiency, maintain patient supplies, design quality into products and processes, and reduce the incidence of unnecessary compatibility and stability testing.

Closed-System Transfer Devices: Collaboration Provides Tools to Guide Compatibility and Stability Testing Strategy
Elaine E. S. Stokes
The application of closed-system drug-transfer devices (CSTDs) has increased significantly in recent years due to United States Pharmacopeia and National Institute for Occupational Safety and Health recommendations that they be used for preparation and administration of potentially hazardous drugs. Although CSTDs help to reduce occupational exposure to harmful compounds, they must be assessed for compatibility with biopharmaceutical preparations before use. To that end, the BioPhorum has developed an approach to assessing the compatibility of biologics with CSTD components. This clinical in-use piece focuses on approaches to determining compatibility and in-use stability studies of formulations to enable biopharmaceutical drug product administration.