There are many examples of efforts to make biosimilar products, such as every time a product is taken to a larger
scale, and when an established product is transferred to another facility, including a contract manufacturing site.
While most of these examples have resulted in products which were indistinguishable for all practical purposes,
others revealed troubling differences during product characterization or clinical administration…
Tag: <span>biologics</span>
Call me jaded. One of the latest fads in the production of biologics is “continuous processing.” So let’s concede that the upstream realm can lend itself to continuous processing, but the really hard stuff was always on the downstream side. Here we’ve had to deal with product clarification and purification, which typically involve crossflow (tangential) filtration and chromatography run in a batch mode, with regeneration steps in between whatever was considered a batch…
I bet you are expecting me to rant and rave about M&A-focused business plans and how they are to blame for just about everything that is wrong with the biotech industry. Well, I guess I will a little, but I’m going to take a slightly different approach this time or you’ll probably quit reading my opinion pieces. So why not step back and look at this financial board game a little differently, where you consider employees to be a far better long-term investment than any company or technology you can buy?
Thankfully, recent market fluctuations have made M&As less attractive, and we can see more firms committed to building the businesses they already have, and developing strategic partners instead of acquisition targets. For this issue, I want to address the developments that may mean we are entering some lofty times in the biotech industry…
While I could be deluding myself with wishful thinking, I may be seeing the “new normal” evolving for the biotech industry. The “new normal” may very well be that the mass closing of R&D facilities and the cancellation of major programs is freeing up the CSOs and other entrepreneurs who will start their own companies…
In an attempt to express and isolate BoLA-NC3*00101, a bovine, non-classical, major histocompatibility complex (MHC) class I protein, the mouse mastocytoma cell line P815 was transfected with the NC3*00101 transgene. The transfected cells were checked for expression by flow cytometry and positive stable transfectants were sorted using a fluorescence-activated cell sorter (FACS). A large amount of purified protein is required for the generation of monoclonal antibodies in order to immunize the mice and then boost the host for several months to get highly-specific antibodies. To avoid using a large number of cell culture flasks and shorten the time required to obtain a sufficient quantity of protein, stably-transfected BoLA-NC3*00101-expressing cells were grown in a pitched-blade bioreactor. One week of culturing in the bioreactor yielded a large cell mass which was used to isolate and purify the protein…
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…
Biotechnology companies — those that research and manufacture products through the use of biological techniques such as genetic engineering and the development of specialized strains of biological substances — constitute an increasing segment of the US economy. These companies might: (a) create a new type of insect- or drought-resistant corn by the modification of genes; (b) alter naturally occurring enzymes to aid in manufacturing or to help produce foods; (c) use recombinant DNA to create medicines that are remarkably effective in curing or treating disease; or (d) use any of a number of other techniques to create beneficial and potentially lucrative products. Just like other industries, biotechnology groups can be faced with recalls of their products, either voluntary or government-mandated, or claims that their products have caused bodily injury or property damage to their customers. Because biopharmaceuticals are produced by — or extracted from — a biological source, the chances of a product recall are higher than that of a synthesized drug. In April 2012, a report by GBI Research, an independent research firm, concluded that biologics were involved in more recalls, voluntary or mandatory, than drugs from other sources for the four-year period from 2007 through 2010…
The objective of this study was to optimize process conditions for the effective partitioning of bovine serum albumin (BSA) using response surface methodology (RSM). Initially, four different salts (tripotassium citrate, tripotassium phosphate, sodium carbonate, and sodium sulphate) were tested for the ability to partition BSA. Among the salts chosen, tripotassium citrate was observed to yield a high partition coefficient. The effect of phase forming components: concentration, PEG molecular weight, and pH were studied for a PEG/tripotassium citrate system and the information obtained was utilized to fix the ranges in RSM studies. Four different independent variables (PEG 2000, tripotassium citrate, NaCl concentrations, and pH) were considered for RSM studies and the responses generated were partition coefficient (k) and percentage yield. A statistical model was developed and the values obtained were 99% within the confidence level. Optimal conditions of the system were found as: 0.25 M sodium chloride, 32% PEG 2000 (w/w), 16% tripotassium citrate (w/w), pH 6.0, a partition coefficient of 6.03, a recovery of 91.76%, and a controlled operating temperature of 303.15 K…
Single-use, stirred-tank bioreactor systems have been used in large-scale production for a number of years. Bench-scale, stirred-tank bioreactors have not been commercially-available for single-use until recently. The New Brunswick™ CelliGen® BLU pitched-blade bioreactor was introduced in 2009, and the CelliGen BLU packed-bed bioreactor, in 2012. Little information is currently available on the utility of these bioreactors for bench-scale production of recombinant products. Thus, we designed this study to perform multiple comparisons with these single-use bioreactors and their traditional glass vessel counterparts. The data comparisons included: (1) CelliGen BLU pitched-blade vs. glass pitched-blade; and (2) CelliGen BLU pitched blade in batch mode vs. CelliGen BLU packed-bed in perfusion mode. Chinese hamster ovary (CHO) cells were used to measure alkaline phosphatase (ALKP) production in each bioreactor. The final measured concentration of ALKP, after eight days of batch-mode culture in the single-use, pitched-blade bioreactor, was 1.6 U/mL compared to 2.1 U/mL in the reusable bioreactor. After six perfusion harvests in the single-use, packed-bed bioreactor, the combined ALKP production was 16.2 U/mL compared to 17.4 U/mL in the reusable bioreactor in batch mode. Multiple batch culture runs in the pitched-blade bioreactor would be required to match the output of a single run in the packed-bed bioreactor in perfusion mode. Results demonstrate that there are no significant differences between the reusable and single-use systems for bench-scale production of recombinant proteins. Our results also suggest that the CelliGen BLU packed-bed bioreactor, when operated in perfusion mode, is superior to the CelliGen BLU pitched-blade bioreactor when operated in batch mode, confirming our studies from 2012…