Fill/Finish

Enabling Technologies

    We hear a great deal lately about the maturation of the biopharmaceutical industry — and much advancement over the past decade or so has been in business models, financing, and product pipelines. Meanwhile, regulators around the world have become more well versed in the subject matter and have adjusted their approaches to and expectations from the industry. However, the practical side of developing, characterizing, and manufacturing biotherapeutic products cannot be overlooked — nor its importance overstated. Many technological…

Drug Products for Biological Medicines

The California Separation Science Society (CASSS) held a Chemistry, Manufacturing, and Controls (CMC) Strategy Forum on drug products for biological medicines in July 2012 in Bethesda, MD. Topics included novel delivery devices, challenging formulations, and combination products. This CMC Strategy Forum aimed to promote an understanding of how best to increase the speed and effectiveness of drug product and device development for both large and small companies. Participants focused on areas that improve the likelihood for regulatory success, reduce risk,…

Drug Products for Biological Medicines

Traditionally, the CaSSS CMC Strategy Forum meetings have provided a scientific focus on the development of biotech drug substances and their manufacture and characterization, leaving the development of drug product formulation and filling, understanding primary containers, and considering novel delivery systems somewhat out of scope. Over recent years, however, the importance of investing more science and technology into drug product development has become evident as different product types, higher protein concentrations, and doses and requirements for improved delivery of biological…

Safety, Flexibility, and Efficiency

    International pharmaceutical and biotech companies are demanding solutions for current and future challenges of their industries — solutions that will stand the test of time while offering significant advances over current manufacturing techniques. Modern and highly proficient production lines for commercial manufacturing of parenteral drugs can represent a crucial criterion in the success of these companies. New and innovative high-speed filling lines for prefilled syringes present an excellent opportunity to meet current production demands. Following is an example…

A Decade of Fill–Finish and Packaging Solutions

    In 2003, BPI’s first year of publication, the Food and Drug Administration released a draft of its updated guidelines on aseptic processing. In it, the agency included the statement, “A well-designed positive pressure isolator, supported by adequate procedures for its maintenance, monitoring, and control offers tangible advantages over classical aseptic processing, including fewer opportunities for microbial contamination during processing” (1).That kind of statement, seemingly approving one technology over another, was unprecedented in an FDA guidance and perhaps an…

Glass Delamination and Breakage

    Although glass is widely considered to be the most traditional and cost-effective option for a parenteral drug container or delivery system, it may not always be the most economical or the best choice for certain products. With knowledge emerging about the suitability of materials in contact with drug products, it is time to look at alternatives that may offer a more appropriate choice and mitigate the risks associated with glass. As single-use technology finds its way into upstream…

Fill and Finish for Biologics

    As most novelists will tell you, if you make substantial changes to the beginning of a story, you may well need to revise your preestablished conclusion. Similarly, as approaches to process design and development change, new tools, technologies, and various shifting “paradigms” also affect the way companies approach final formulation, filling, and finish steps. As yet another ref lection of increased process understanding and quality-by-design’s (QbD’s) holistic approach to biopharmaceutical development, those final steps — traditionally outsourced by…

Implementing a Single-Use Solution for Fill–Finish Manufacturing Operations

    Fill–finish is the final operation in manufacture of sterile products (except for terminally sterilized products). This process requires sophisticated technology and machinery in a highly controlled, aseptic environment. Fill–finish assemblies must meet stringent requirements to ensure flow-path sterility and integrity, ensure operational safety and efficiency, and provide fill-volume accuracy to exacting requirements. Traditional fill–finish machinery comes as fixed systems comprising complex components that require assembly, cleaning and sterilization, disassembly, and material storage after filling is complete. Those operational…

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…