2010

Embracing Biotechnology

If you have ever gotten frustrated trying to explain what you do at work to friends and family, we can relate. One of the greatest challenges perennially facing the biotech industry is the lack of public understanding of what biotechnology is and the many ways it contributes to a better world. A lack of solid public acceptance and support can make it all the more difficult to advance our advocacy efforts in the United States Congress and in state legislatures…

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…

Minibodies and Multimodal Chromatography Methods

    Small, genetically engineered immunological constructs are being developed industry-wide for a growing range of in vivo applications. Examples include Fab, F(ab’)2, single-chain (sc) Fv, bis-scFV, diabodies, minibodies, and single-domain antibodies (1). Their small size potentially gives them access to tissues that are poorly accessible by intact antibodies; rapid clearance from blood and nontargeted tissues; lower immunogenic response; and eye-drop, inhalant, or oral administration. We report here on purification of an affinity-matured, humanized, antiprostate stem-cell antigen (PSCA) minibody for…

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…

Microanalytical Techniques for Identifying Nonprotein Contaminants in Biologics

Proteins can aggregate at any point during pharmaceutical manufacturing. Regulatory agencies pay special attention to aggregates that can enhance immune responses and cause adverse clinical effects and those that can compromise the safety and efficacy of a drug product. Biopharmaceutical companies have stringent quality control (QC) procedures in place to ensure that their final products are free of contaminants and defects, including protein aggregates. Trained QC inspectors, however, can typically see product defects or particulate material only as small as…

Hurry Up and Wait?

From time to time we each experience the hurry to get somewhere, only to end up waiting for someone or something else. Today’s air travel seems to be nothing but “hurry-up-and-wait”: After you race to the airport two hours before your flight time, the plane ends up departing two hours late. Businesses suffer from the same disorder. For example, in the biopharmaceutical industry, this phenomenon is often evident in all the documentation that must be completed before a product can…

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…

PAT-Based In-Line Buffer Dilution

    Technological advancement has taken protein expression titers from concentrations measured in mg/L to those measured in g/L over just a few years (1). Annual demand for antibodies has reached several metric tons, which has spurred production of >100 kg batches of protein at a time (2). As upstream yields continue to increase, downstream purification involving process solution preparation and delivery must increase in proportion to keep pace with demand. That has placed facility and instrumentation capacity constraints front…