The Good Manufacturing Practices (GMPs) are becoming more and more familiar in biotechnology, and concepts such as quality assurance or validation are now part of the background of clinicians and researchers involved in clinical trials. A recent European Community directive (2001/20/CE) states that GMPs should also be applied to investigational medicinal products and not only to products on the market. Vector supernatant is a so-called Active Pharmaceutical Ingredient (API) and is subject to the same guidelines as traditional drugs produced by the pharmaceutical industry. This has a deep impact in the field of gene therapy because clinical trials are often run by small biotech companies or, at least in the first phases, by academic centers. The field is continuously developing and, according to the progress of the clinical studies, new processes are necessary to produce large-scale amounts of vector supernatant in a safe and reproducible way…
Tag: <span>process development</span>
A growing number of separations’ scientists and process developers are looking beyond protein A sorbents for capture and initial purification of monoclonal antibodies. A variety of strategic and operational goals have prompted examination of alternative immunoglobulin-selective sorbents. Most broadly, many workers wish to eliminate design considerations associated with leached protein A. Also cited is a preference for sorbents that can withstand stringent cleanup using 1 M sodium hydroxide. In some applications, it is desirable to avoid the low-pH elution conditions typically employed with protein A sorbents — conditions that can foster aggregate formation. In still other cases, the target antibody may bind poorly to protein A. Finally, there may be interest in evaluation of immunoglobulin-selective sorbents less costly than protein A sorbents…
One of the biggest challenges in the production of recombinant therapeutic proteins, monoclonal antibodies, and vaccines is the clarification and separation of the product (typically a protein) from the cell culture or fermentation broth. The desired product is present in low concentrations and must be efficiently separated from the other components present in the bioreactor fluid. An overall objective in developing a clarification process is to achieve the highest level of product recovery (yield) and contaminant removal with the fewest number of unit processes. Understanding how each operational step affects the performance of the next step downstream is the challenge at hand. Centrifugation, in combination with depth filtration, is gaining acceptance as the preferred method for the removal of cells, cell debris, colloids, insoluble precipitants, aggregates, and other materials found in mammalian cell culture and bacterial fermentation fluids…
Process development is an investment. As with a personal retirement plan, the importance of making the investment is not in question, yet strategies for when, how much, and where to invest in process development vary significantly from company to company. For a personal retirement plan, the answers to these questions are straightforward: invest as early as you can and as much as you can, and take less risk the closer you get to retirement. This would also be sound advice for investing in process development (substituting “BLA filing” for “retirement”) were it not for two complicating factors. First, the majority of biotherapeutics that enter the clinic fail to make it to the market. This makes a large, early investment in process development less attractive. Second, there is extreme pressure to get into the clinic, and subsequently onto the market, as quickly as possible, minimizing the time available for process development…
With the advent of whole cell-based therapeutics has come a growing standardized quality control and quality assurance of the processes employed for developing and manufacturing cellular materials, similar to the controls over traditional drugs and biologicals. Cellular therapeutics present unique process and quality control challenges due to the innate complexities of living cells, making it important to use whole cell assays to provide detailed pictures of the status and consistency of cell preparations that will be used to treat patients. This article illustrates how a cellular assay from Guava Technologies addresses these issues…