The manufacturing of cell-based therapies requires harmonized processing protocols to ensure consistent quality. Expanded adipose-derived mesenchymal stromal cells (ASC) are among the most promising candidates for such therapies due to their regenerative and immunomodulatory properties. However, transitioning these therapies to large-scale production presents challenges related to cell recovery, formulation, and in-process cell counting (IPC). The Gibco CTS™ Rotea™ multipurpose Counterflow Centrifugation System enables multiple workflow operations—including cell separation, concentration, washing, and buffer exchange—and is designed to operate within a GMP environment. From a cell concentration perspective, the Rotea system can also formulate concentrated cells in different types of media, including fetal bovine serum…
BioProcessing Journal Posts
With growing interest in process intensification in the biopharmaceutical industry, implementing cost-effective purification strategies has become increasingly important, particularly for the expensive protein A affinity capture step in monoclonal antibody production. This study compares traditional resin-based batch chromatography (rbBC), multi-column chromatography (MCC), and membrane chromatography (MC) using small-scale experiments with commercially available formats. Performance metrics including yield, elution volume, and impurity reduction were evaluated. The best-performing conditions for MC and MCC were used to project cost and productivity for mAb purification at the 1,000 L bioreactor scale. Both MC and MCC demonstrated significant advantages over rbBC. MC achieved the highest productivity (234–236 g/L/h, 19–20-fold higher than rbBC) and the lowest media costs, resulting in up to 91% reduction in cost-of-goods (CoG) per batch. MCC also showed notable improvements, with 4.6–5.1-fold higher productivity than rbBC, and up to 72% CoG savings. Due to its operational similarity to rbBC and compatibility with existing infrastructure, MC was selected for further evaluation. Optimization was performed using a 3.5 mL membrane over 50 cycles, followed by scale-up to a 58 mL membrane tested on a pilot-scale skid representative of clinical or commercial manufacturing. The process was successfully run for 55 cycles, demonstrating comparable yield, impurity reduction, and elution profiles to rbBC. These results support the feasibility of membrane chromatography as a scalable and economical alternative for protein A capture in intensified downstream processing.
The number of cellular therapies in clinical trials and on the market has continued to rise significantly in recent years—and so does the need to maintain strict control over all manufacturing steps in order to reduce batch-to-batch variability. One potential source of product variability is the manual thawing of cryopreserved cells in a water bath, which can differ between operators. Additionally, water baths pose a significant contamination risk, making them less suitable for GMP environments. To overcome these challenges, several companies have developed water-free thawing devices that offer better control of the thawing process. However, these devices either accommodate only one vial at a time or lack U.S.
FDA 21 CFR 11 compliance in producing a computer-generated audit trail. Hence, we have developed a novel, water-free and dry-heat-based, fully programmable thawing device that is capable of thawing up to ten vials simultaneously and complies with 21 CFR11 requirements…
This study assessed a novel statistical approach using space-filling designs (SFDs) and self-validating ensemble modeling (SVEM) machine learning to efficiently identify key process factors using recombinant adeno-associated virus type 9 (rAAV9) gene therapy manufacturing as a case study. Based on risk assessment of parameters that may impact rAAV9 production, we have evaluated six process parameters using 24-run SFDs generated by the JMP statistical software. SFDs are a new class of design of experiment (DoE) created with the objective of covering the entire design space as completely as possible; this in turn allows more accurate modeling of complex response surface behavior typically found in bioprocesses.
M&As continue at a dizzying pace even while so many organizations are just trying to hang on. Apparently some of the biggest firms still have excess money or access to cheap money, and they would rather spend it acquiring than building or solidifying what they have. But if they have so much money, why are they laying so many people off? At a biotech business meeting I recently attended in DC, I kept hearing that “companies have a lot of money.”
But when I followed-up on this point with a panelist, I was told that much of this money could not be used for
operations. Apparently because of the off-shore location, or other locations where it’s hiding, it can only be used to buy stock…
I’ve seen little to tell me the major biopharma firms, or the larger supply firms, have learned anything. They’re stuck on the concepts of slashing vital resources—such as R&D and capacity—to “do deals” plus pay executive
bonuses, investment bankers, and hordes of attorneys. As a result, we’ve seen a burgeoning of Business-to-Business (B2B) meetings where the talks are geared toward selling companies and acquisition services. So we continue to see these large firms hoarding cash, acquiring companies, and cutting strategic resources…
We just completed our 6th ISBioTech Spring Meeting, and it was a resounding success. And while the attendee numbers were up considerably, the more important aspects for me were that we had the “right” people, plus incredibly valuable content. Then what impressed me the most was the happiness and hopefulness I saw during the meals, receptions, and the banquet. We’ve been organizing these meetings for over 20 years, and I haven’t experienced anything like this since our earliest days in Williamsburg…
European organizations have been doing business with Cuba during its last 30 years of biotechnology development, and have benefited from both licensing and distribution agreements for generic pharmaceuticals, as well as vaccines and other biologicals. However, as far as direct US/Cuban interactions, we’ll probably have to go through a period of “low-level” scientific exchanges before there is much interaction. As a starting point, it has been proposed by the American Association for the Advancement of Science (AAAS) that an official scientific and technology agreement be established to form a broader framework for interactions…
As an industry, we need to do far more to implement technologies and work with FDA, not only to keep them informed, but to make sure they are aware of industry trends and newer technologies. Remember that CBER and
CDER have their own labs, and in many cases, they will want to bring in the technologies you want to use and see how they work in their own experiments…