Streamlining process development has been the focus of the biotechnology industry over the past several years. To be financially viable in the current market, a company has to be competitive in all three of the following areas: quality, speed, and price (1). Attaining any two of the three attributes at a time is no longer sufficient. With new tools and technologies along with improved understanding of the cell-culture process, doing high-quality process development while reducing both cycle time…
2009
Software Simplifies Accounting for Batch Genealogy
As an updated US FDA guidance document emphasizes, the life sciences industry needs to use data to better understand manufacturing processes and sources of variation to minimize product risk and achieve better process control in future batches (1). Lessons learned through such efforts also can be applied to future process design, extending the value of data analysis. Bioprocess manufacturers typically rely on lot traceability to determine the composition of their final manufactured products. Lot traceability is only one…
Putting All the Pieces Together
Most people in the industry are struggling with quality by design and how it relates to the acceleration of process development. Many are confused by the new FDA approach to bioprocess development, unsure of the specific implications of QbD on the CMC section of their marketing applications, and unclear how the risk-based approach applies to their particular operations. Some have trouble understanding the precise link between CQA and CPPs under a life-cycle approach and are stuck considering the exact definitions…
Sailing Through Pharmaceutical Risk Management
The New World In 2002, responding to public outrage over a series of corporate accounting scandals, the US Congress enacted a law now generally referred to as “Sarbanes–Oxley” or SOX (2). Under this law, the US Securities and Exchange Commission (SEC) issued regulations defining new requirements. Promulgated for misdeeds arising in the financial sector and driven by the SEC, most analysts now view this legislation as financially unifunctional. The growing complexity of business organizations, however, and the interdependency of their…
50 Years of Sephadex Media
It has been 50 years since the first Sephadex paper was published (1). Readers of BioProcess International work in a field that was fundamentally affected by what happened after that paper appeared in 1959. So this anniversary is certainly worthy of a party and a few speeches. But there are lessons to be learned, too. Here we take a look at threads connecting events before and after the discovery of gel filtration chromatography and introduction of the Sephadex product. Interdisciplinary…
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).…
Investigating Flow Distribution and Its Effects on Scale-Up
Depth filtration is widely used in the biopharmaceutical industry to purify target proteins by removing whole cells, cellular debris, fines, aggregates, and colloidal particles from the fermentation broth (1,2). At large scale (>2,000 L), culture harvest from a bioreactor is typically processed with a disc-stack centrifuge to remove cells and cell debris. Although centrifugation is very effective for removing whole cells and larger debris, it cannot remove small-size particles, which remain suspended in the centrate. Depth filters are commonly used…
Interest in Hollow-Fiber Perfusion Bioreactors Is Growing
People who regularly culture animal cells become so comfortable with standard techniques that novel approaches can seem contrived or even unnatural. However, the typical cycle of seeding cells at very low density in an excess of medium and harvesting (often quite aggressively) just before the point of medium exhaustion is quite an unphysiologic process. Popular culture systems often take cells that originally grew attached to a porous matrix at high densities, with little variability in nutrient and oxygen supply, and…
A Practical Method for Resolving the Nucleation Problem in Lyophilization
Given the prevalence of lyophilization and the growing pipeline of sensitive biological drugs requiring stabilization, pharmaceutical development and manufacturing personnel need complete, reproducible control over the operation, scale-up, and transfer of their lyophilization processes. To address the nucleation problem, Praxair has developed a step-change technology that adds consistent control to the freezing step of lyophilization. This low-capital, plug-and-play option can be readily implemented on most existing freeze-dryers with minor equipment additions and controls integration. Adoption of the technology requires no…
Global Marketplace
Contamination Control Product: Endosafe-PTS glucan assay Applications: Biopharmaceutical process validation Features: The Endosafe-PTS glucan assay is a rapid test designed to help companies validate that products are free of (1,3)-β-D glucans. Glucans contaminate cell culture fluids, yeast protein production, air quality samples, and cellulose filter preparations. Glucans can cause false positive results in LAL assays. The Endosafe-PTS glucan cartridges have a sensitivity range of 10–1,000 pg/mL, yield results in