Fill/Finish

A Case Study in Qualification of Single-Use Filling Manifolds for Particles and Endotoxins

    Single-use technology is being examined for implementation in an increasing number of steps in the biopharmaceutical manufacturing process. Some examples of currently available disposable components include filter capsules, tubing, connectors, and biocontainers (for storage, mixing, and bioreactors), as well as devices for chromatography and multipass tangential-flow filtration (1,2). This technology was first implemented in upstream and API downstream processes such as media and buffer preparation, followed by upstream bioreactors and mixers (3). The single-use trend has most recently…

Optimizing Cryopreservation for Therapeutic Cells

    Biopreservation suppresses degradation and enables postpreservation recovery of structure, viability, and function. Although there are several biopreservation techniques (indicated in “Biopreservation Methods” box), most laboratories use either standard cryopreservation protocols (the far majority) or vitrification (much more limited in broad systems application) when freezing cells for research and clinical applications. Isopropanol freezing containers such as the Mr. Frosty device from Nalgene Labware have made cryopreservation easier in many applications, and controlled-rate freezers allow users to program and manipulate…

Minimizing Variation of Volume Withdrawn from a Vial Drug Package

Concerns for safety in administration of injectable drug products have escalated in recent years. As a result, scrutiny of administration practices has increased. Pharmaceutical manufacturers are placing greater emphasis on providing the best patient and caregiver experience as well as improving the convenience of drug administration. In fact, many drugs that are regularly administered for chronic conditions are now being offered for at-home preparation and administration. These trends highlight the importance of providing therapies that are not only effective, but…

Stability Considerations for Biopharmaceuticals: Overview of Protein and Peptide Degradation Pathways

To ensure product safety and efficacy, protein therapeutics must meet defined quality characteristics immediately after manufacture as well at the end of their designated shelf lives. Many physical and chemical factors can affect the quality and stability of biopharmaceutical products, particularly after long-term storage in a container–closure system likely to be subject to variations in temperature, light, and agitation with shipping and handling. Compared with traditional chemical pharmaceuticals, proteins are considerably larger molecular entities with inherent physiochemical complexities, from their…

Increasing Biopharmaceutical Quality Through Packaging Partnerships

Containers and administration devices are integral to the safety and efficacy of biopharmaceutical therapies and must be key considerations for all new drugs coming on the market. By partnering with packaging manufacturers early in development, biopharmaceutical manufacturers can increase efficiencies in their production processes while gaining expert advice and counsel throughout a drug’s lifecycle. Such an alignment can also improve product quality, enhance regulatory compliance, and contribute to the overall state of control by preserving biopharmaceutical stability, ensuring sterilization, and…

Single-Use Connections Enable Advancements in Aseptic Processing

    Today’s market demand for new drugs — combined with the difficult economic environment — is challenging bioprocessors to review their manufacturing systems and seek ways to make them more flexible, reliable, and cost effective. Increasingly, biomanufacturers are turning to single-use aseptic processing systems to meet or beat aggressive product-introduction timeframes while controlling costs. Innovative new single-use technologies continue to be introduced, giving pharmaceutical companies greater flexibility for replacing traditional stainless tubing, equipment, and even entire process suites with…

Strategies for Implementing a BPC in Commercial Biologics Manufacturing

Biopharmaceutical manufacturers use a range of bioprocess containers (BPCs) during the production and storage of biopharmaceuticals. Plastic bags, bottles, flasks, and carboys are all types commonly used in bioprocessing (1). A suitable BPC must be able to maintain aseptic integrity and be constructed of materials that will not harm product efficacy and/or purity. The trend of “single-use” or “disposable” BPC technologies in the biopharmaceutical industry enables greater flexibility and better use of production facilities that are increasingly designed for multiple…

Large-Scale Freezing of Biologics

Production of biologics is expensive. To optimize capacity use, bulk protein solution produced in manufacturing campaigns is often converted into drug product based on market demand, so it may be stored for relatively long periods. To decouple production of bulk solution from that of a final drug product, the bulk is often stored frozen. Transport of frozen bulk between sites offers several practical advantages over bulk transport in the liquid state (2–8 °C). Maintaining 2–8 °C requires accurate systems control…

Large-Scale Freezing of Biologics

Production of biologics is an expensive process, and to optimize capacity use, bulk protein solution is often produced in manufacturing campaigns. It is converted into drug product based on market demand and therefore may have to be stored for relatively long periods. To decouple the bulk solution production from that of the final drug product, bulk is often stored frozen. Transport of frozen bulk product between sites offers several practical advantages over its transport in the liquid state (2–8 °C).…

Applying Intelligent Flow Microscopy to Biotechnology

Ongoing requirements for additional insight and CGMP-compliant measurement have led to interest in new technologies that can be applied to the analysis of many different types of particle-containing fluids. Micro-Flow imaging (MFI) is a robust, versatile, and intelligent vision technology that is increasingly used for evaluating populations of microparticles encountered during bioformulation development (1). It is also being accepted in fill–finish processes and many other biotechnology applications. Features of MFI technology that have contributed to its rising popularity include the…