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…
Manufacturing
Polymers and Additives Used in Fabrication of Disposable Bioprocess Equipment
The materials used to fabricate single-use processing equipment for biopharmaceutical manufacturing are usually polymers, such as plastic or elastomers (rubber), rather than the traditional metal or glass. Polymers offer more versatility because they are light-weight, flexible, and much more durable than their traditional counterparts. Plastic and rubber are also disposable, so issues associated with cleaning and its validation can be avoided. Additives can also be incorporated into polymers to give them clarity rivaling that of glass or to add color…
Effect of Sterilization on the Mechanical Properties of Silicone Rubbers
Silicone rubber is widely used in the pharmaceutical industry, where sterilizability is an essential requirement for all fluid transfer equipment. Pharmaceutical products are sterilized frequently and repeatedly by high-level energy and/or chemical vapor to eliminate bacterial surface contamination. Such treatments may also affect the molecular structure of silicone rubbers, causing changes in their physical properties and performance. Several studies on this topic have been reported; until now, however, no systematic investigation has been performed on the effect of…
The Time Has Come for Automation in Bioprocessing
As early as 1997, automation was ready to offer potential benefits to the bioprocess industry (1). Professor Bernhard Sonnleitner of the Zürich University of Applied Sciences’ Institute for Chemistry and Biological Chemistry suggested a “standard operating procedure†and pointed to the opportunities, requirements, and potential pitfalls of applying the principles of automation to bioprocess development and operations. If “boring and less interesting routine tasks†could “more efficiently and reliably be handed down to machines,†he explained, then personnel…
Biopharmaceutical Information Infrastructure 2.0
This two-part article explores related tools and technologies that biopharmaceutical companies can leverage to build an efficient mechanism for capturing and delivering valuable information. In BioProcess International’s December 2009 issue, part 1 of the series focused on infrastructure selection and how hardware, software, and information systems form a kind of ecosystem (1). Simplicity, sustainability, and scalability can be achieved only when that trio is designed holistically. Part 1 further explored structured data capture and analysis tools, whereas this…
Improved HCP Quantitation By Minimizing Antibody Cross-Reactivity to Target Proteins
Host cell proteins (HCPs) are process-related impurities derived from a host cell expression system that may be present in trace amounts in a final drug substance. During biologics development, it is important to demonstrate that a bioprocess is efficient in removing HCPs and that it provides consistent control of HCP levels. Several techniques are typically used for detection, quantitation, and risk evaluation of HCPs in biologics. The most common are enzyme-linked immunosorbent assays (ELISAs), Western blotting, sodium-dodecyl-sulfate polyacrylamide…
Nutrient Supplementation Strategies for Biopharmaceutical Production, Part 3
Scale-up studies are needed for assessing cell culture production system options and for testing nutrient supplementation techniques as well. With the many supplementation options available, choices need to be made as early in product development as possible because advantages can change with scale. One published fed-batch scale-up study testing from 3 L up to 2,500 L highlights items to be considered in addition to the nutrient supplementation process such as the impact of pH and CO2 control (1).…
Primary Clarification of Very High-Density Cell Culture Harvests By Enhanced Cell Settling
In recent years biopharmaceutical manufacturing has demonstrated major improvements in MAb production, exhibiting product titers as high as 25 g/L often associated with very high cell densities (1). High-density cell cultures with >150 million cells/mL pose a great challenge in clarification and further downstream processing because of a need to remove a large amount of biomass and increased levels of contaminants from cell debris generated during cell culture and harvesting. Production of biological substances (MAbs, in particular) usually…
Biopharmaceutical Information Infrastructure 2.0
Availability of the right information to the right people at right time is critical for understanding and improving existing processes within an organization. For a data-intensive industry such as biopharmaceuticals development and manufacturing, access to data and information enables companies to understand and streamline their operating and business processes. But most organizations fail to leverage such information for better decisions because they mismanage it. Some try to fill the gap between information and end users by introducing various applications and…
Accelerating Bioassay Transfer in a GMP Environment
Most products in discovery by pharmaceutical companies today are biopharmaceuticals. Made by living organisms, these are typically large–molecular-weight products that rely on their secondary and tertiary structure for therapeutic effectiveness. Synthetic small molecules and biopharmaceuticals both require analytical verification for release, but only biopharmaceuticals require functional potency assays for investigational new drug (IND), biological license application (BLA), and new drug application (NDA) submissions. Those activities often require elaborate transfers of diverse, biological, product specific assays that carry greater chances of…