Wednesday, October 28, 2015

BPI 2015: Day One Recap

The 12th annual Bioprocess International (BPI) Conference & Exposition began with a series of technical sessions, many of which broke new ground. BPI 2015 also proved to be an invaluable forum for scientists and engineers with its poster presentations and product announcements, as well as keynote talks from industry leaders. Here are some highlights of Day 1.

Keynote Addresses
Market leaders from Merck & Co., Novartis Pharma, and the Duke School of Medicine gave compelling and insightful keynote presentations on Tuesday at BPI 2015. And it is fitting that in Boston, one of the keynote speakers noted that there is a “revolution” underway in fighting cancer.


Innovating mAb Production to Support the Immunotherapy Revolution was given by David J. Pollard, PhD, Executive Director, BioProcess Development, Merck & Co., Inc.  Dr. Pollard began the keynote session by stating it was an “exciting time in immunotherapy” and that a revolution is now underway in cancer treatment. To be successful in this revolution, the industry needs to be agile and flexible so it can quickly adapt to change.

To that point, Dr. Pollard emphasized the importance of there being a “collaboration between suppliers and end users” to help lower costs and increase throughput. “Working as a community we can help create a facility of the future,” he stated.

Such a “facility of the future” will create a tremendous opportunity to lower the cost of manufacturing while also being able to handle increased capacities, according to Dr. Pollard. He explained that a modular approach will be taken to develop these facilities so they can easily be built out as needed.

Dr. Pollard stated this next-generation manufacturing approach will improve acceleration to clinical trials and that technology will be used to de-bottleneck activities. This will create high-throughput workflows using enabled formulations from cell line development, process development (both upstream and downstream), and formulation.

Another challenge during this revolution is to create a bridge from IV to subcutaneous. The goal is to achieve the necessary high concentration of >150 mg/mL while also addressing viscosity issues. Dr. Pollard stated that, while it is early proof of concept, Merck has done research in which novel excipients have been added to meet this challenge. 

Next to speak was Spencer Fisk, Global Head, Biologics Process, R&D, Novartis Pharma, AG who spoke of Innovative Process Development Strategies to Drive the Rapid Clinical Introduction of Emerging Biologics. Fisk challenged the industry go beyond the “heavily walked path” and push boundaries to speed drug development and improve efficacy.

Fisk’s approach to accelerating drug development was for his colleagues to not avoid taking risks. He suggested to “use data to guide us” so scientists and engineers can approach the “edge of the cliff.” Using data, risk levels can be determined and comfort levels established with the end result of more quickly selecting the proper candidate for development.  

Choosing the best candidate requires evaluating all the variables such as the biology and the ability to develop the candidate. Each variable has its own elements. For example, in the case of biology, binding, potency and efficacy need to be assessed. In terms of development there are a number of aspects, including stability, that need to be determined.

Risk factors not only need to be established, they should be classified as critical (red), moderate (yellow), and low (green), suggested Fisk. If the risks are predominantly low, then the candidate should be moved ahead. “Green means go,” stated Fisk. The results will be favorable the majority of the time.

“If we get it right >80% of the time, we have significant time savings. In many cases, the 20% that does not work is simply due to the fact that more time is needed,” said Fisk.

Taking this approach will create a cycle that will benefit the market, as well as society. Once scientists have “walked to the edge” and realized it was not as close as they originally believed they will push the boundaries further, creating a continuum of accelerating drug development, according to Fisk.

The final keynote, Novel Approach to Developing and Producing Human Experimental Vaccines for HIV, was given by Michael Anthony, M.D., Chief Medical Officer, Associate Professor of Pediatrics, Duke Human Vaccine Institute, Duke School of Medicine. Dr. Moody emphasized that because HIV is a unique and challenging virus it poses many challenges. Vaccines that are developed and aim to be effective must deal with an incredible diversity of circulating strains.

“By locating and neutralizing antibodies we can prevent disease but this is not an easy task. Antibodies at a sufficient level can target many strains of HIV1,” said Dr. Moody.

One question posed by Dr. Moody during his session was if information gathered from those patients who are infected can be used to make antibodies. “But it’s not that simple. There are many changes to the immunosystem that we may need to mimic with adjuvants to be successful,” he explained.

Novel adjuvants will need to be developed, according to Dr. Moody. Human trials are in the planning stages but there is no guarantee that the answers will be found. There is a paradox in the bnAb development – mutations develop. As a result, Phase I human testing is required. Within that context, two important elements are needed:
·         Targeting of multiple lineages
·         Multiple immunogens, likely in sequence

“Industry, academia and government will need to come together, as one of these alone cannot muster the resources needed to be successful,” emphasized Dr. Moody.

Technical Session Highlights
New Data on Continuous Manufacture in Downstream Process: In the Recovery and Purification technical track, Michael Bavand, PhD, Chairman and CEO of ChromaCon AG, released new data during his presentation entitled Data Based Comparison of Capture and Polishing Steps in a Continuous Mab Process.

Dr. Bavand spoke of a study conducted in which four resins were compared using batch mode, dynamic flow load, and continuous chromatography. The experiment evaluated five outputs – recovery percentage, high molecular rate (HMW%), productivity, host cell protein, and 0.1M NaOH tolerance. The results revealed:
·         Very little difference in recovery percentage, as all the conditions were > 90%
·         Slight reduction in HMW% in the continuous condition
·         Host cell protein (ng/mg) was equivalent or better in continuous condition
·         All DBC levels were > 90% initially after 100 cycles; resin 4 showed reduction in DBC after first measurement

A model was generated with all the productivity data. Validation cost estimates, lab scale system purchase, GMP system purchase, FTE estimates, and the number of new molecules arriving in a plant annually were all accounted for by the model. The model was used to estimate return on investment across the number of new molecules to come into a pilot plant every 12 months. Using a baseline of two new molecules per year, the initial estimates were that cost savings would be realized after three years.

Dr. Bavand also discussed a second part of the experiment that studied a process using MCSGP with a membrane adsorber to determine if it would have equivalent or better outputs than a cation exchange (CEX) resin step in terms of recovery, productivity, and impurity levels. Through the experiment, a Flow Through MCSGP was demonstrated to have equivalent purity and recovery with significant higher productivity levels than batch mode.

As revealed by the results, higher productivity and large cost savings are possible using a continuous chromatography system for both capture and polishing steps. Additional verification of these processes is needed before they can be implemented into a pilot plant concluded Dr. Bavand.

Poster Highlight
Essential Pharmaceuticals’ poster entitled Novel Lipid Based Supplement Increases Protein Yield in Single Use Bioreactor presented the use of a lipid supplement using various strategies to improve protein yield.

The poster stated that by adding the lipid supplements at the beginning of the culture, the yield in titer antibody protein production increased 30% from CHO cells without increasing proliferation. Further, when the metabolic profile was examined, it was discovered that there were no differences in any of the metabolites.

The poster also stated that the supplement was used as a feed and there were two notable effects: 1) increasing the titer yield by 25% and 2) extending the window for peak protein production from one day to two. These results show that there are windows for further optimization of protein production using lipids. It is possible the use of lipids reduces the energy requirement for new cell formation and, therefore, can be used for protein production. 

Product Highlight 
Pall Life Sciences is showcasing key components of its biopharmaceutical portfolio in its booth (#309). A host of updated and new portfolio products will be on display, with particular emphasis on continuous solutions Pall has available for downstream processing support.

Included in the BPI 2015 booth will be:
  • The disruptive Acoustic Wave Separation technology for cell-culture clarification in either fed-batch or perfusion applications
  • A preview of Pall’s latest advance in depth filtration: Stax™ Depth Filters with Hyperion Flow technology, for direct mammalian cell harvest with a new filter to remove cells and cellular debris effectively and efficiently
  • The award-winning Cadence™ Inline Concentrator single-pass tangential flow filtration system for direct flow-through and in-process volume reduction in an integrated or stand-alone format
  • The recently introduced BioSMB® System for single-use or multicolumn continuous chromatography featuring a disposable flow path with a proprietary integrated valve cassette to service up to 16 columns or devices.

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