I have compiled a list of our most popular 10 Blogs for 2016. Here are the top Downstream Column blogs in alphabetical order.
At this year’s Boston Biotech Week the 2016 BioProcess International Award Winners were announced. These awards recognize outstanding achievements in the area of biotherapeutic development and manufacturing processes. This year individuals and companies that made significant contributions to improving biotherapeutics were recognized. Novel technologies in upstream, downstream and analytical application areas were also awarded. I have listed the winners and finalists along with a brief description of the winning achievements for downstream technologies here. For a list of upstream and analytical technology winners, please see 2016 BioProcess International Award Winners – Upstream and Analytical….
Aramus Single Use Bag Assembly – Provides Advantages over Existing Storage and Transportation of Intermediate and Drug Substance
Safe and efficient transportation of drug substance from one location to another requires considerable time and resources. With the rise in the use of Contract Manufacturing Organizations (CMOs) and Contract Fill/Finish providers, there is an increasing need for efficient tools to enable these processes and an increase in the logistics required….
This year was the first year that the BioProcess International Conference (BPI East) became Boston Biotech Week and incorporated a Cell Therapy track. I was excited to attend and to see what the format for the new conference was going to be. I felt that the content was very relevant and covered a wide breadth of topics, from cell culture to commercial manufacturing and I was particularly interested to see how this translated to cell therapy. Overall Boston Biotech Week delivered talks focused on improving the manufacturing process for biopharmaceuticals and cell therapies, enabled industry networking opportunities, and provided the chance to see the latest products and technologies. One area that I focused on was downstream manufacturing including recovery and purification, and drug product manufacturing including fill/finish….
The concentration of biological drug substances may be necessary at various stages in the drug manufacturing process. Examples include post harvest, pre-capture or in-process volume reduction. Concentration may also be needed between chromatography steps. The most widely used method for concentrating biologics is tangential flow filtration (TFF). In this method, the feed stream passes parallel to the membrane face as one portion passes through the membrane (permeate) while the remainder (retentate) is recirculated back to the feed reservoir. When the desired concentration is reached, the process is stopped. TFF is an efficient means for concentrating biologics, however sensitive proteins may have a problem with the recirculation of process fluids and aggregation or product degradation can occur….
Clarification using Acoustic Wave Separation offers Advantages including -Continuous Process Solution
The harvest and clarification of cell culture bioprocess fluids removes cells and cell debris and provides clarified cell culture harvest fluid for downstream purification. The success of the clarification step can greatly impact efficiency and ease of downstream purification. Improvements in cell culture techniques have resulted in both higher cell densities and higher product titers, and so the clarification step has become more challenging. As a result, there has been a need to develop technologies to improve the efficiency of harvest and clarification. In addition, the interest in moving toward a continuous process has also spurred advances in clarification because traditional clarification steps like centrifugation and depth filtration are typically done in batch mode….
Enzymes such as Trypsin and Collagenase are often critical components for product processing, modification of proteins and cell preparation for stem cell therapies. As these final cell-based products are intended for administration into patients, it is important that any residual enzyme material from the production process be assessed and its final concentration minimized to reduce risk. Potential negative impacts of residual enzymes could include immunogenic activity, reduced efficacy of the final product, and toxicity in patients. Although there are no specific regulatory guidelines at this time to specify allowable amounts of residual Trypsin or Collagenase, these are still considered process residuals and potential product contaminants, and thus should be assessed as part of an overall risk mitigation strategy….
Because Protein A is a valuable resource in any mAb purification strategy, companies often search for ways to improve the productivity of their affinity chromatography step. One strategy worth further investigation is variable column loading. By varying residence time (RT) over the loading phase, productivity from an affinity chromatography step can be significantly improved….
A vital part of the biomanufacturing process is being able to move fluid under sterile conditions using sterile connections. However, this activity requires considerable time and resources. One challenge is that in most cases, current disposable sterile connectors only allow users to make a single sterile connection per device, which then requires the use of multiple devices per unit operation. In addition, the flow path must be dry and non-pressurized during connection and disconnection. Due to these limitations, sterile liquid transfer can be very inefficient….
The first step of the study was to screen four Protein A resins from leading industry vendors for use in a capture step, those resins included: Amsphere™ A3, platform resin referred to as Agarose S, and two other polymeric resins referred to as Polymer H and Polymer E. The resins were evaluated at 10% breakthrough utilizing the purified Herceptin biosimilar at two protein concentrations, 2.5 and 5.0 mg/ml and 1 ml columns at 4 minutes residence time. It was observed that substituting Amsphere A3 in the platform capture process led to a 40% increase in dynamic binding capacity relative to two of the resins tested and a 25% dynamic binding increase over the third resin. (Figure 1)….
Purpose-designed Protein A resins for Improved Downstream Process and Cost Efficiency in MAb purification
The use of Protein A affinity chromatography is commonplace in biopharmaceutical manufacturing. This form of chromatography is both simple to use and very effective at binding the target molecule. However, the Protein A chromatography step can be costly, thus binding capacity and efficiency is something that is closely evaluated as a way to get the most out of a company’s Protein A Resin investment….