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Does innovation in biologics CMC really matter?

Friday Apr 18, 2014

By: Patti Seymour  (pseymouratbptcdotcom)  

IBC’s Biopharmaceutical Development and Production Week, usually held somewhere in southern California in March to attract the winter weary from the east coast and mid-west, was, as usual, very worthwhile in spite of the less than perfect weather typically expected in that part of the country. I found the two key notes given by Dr. Jens Vogel of Boehringer Ingelheim and Tina Larson of Genentech particularly enjoyable. Both talks focused on innovation and efficiency in process development and manufacturing.

Dr. Vogel began his talk by asking, “Does innovation in biologics CMC matter in a platform world?” He was referring to the increasing use of platform processes to reduce development time and cost to Proof of Concept (PoC) to develop the five to ten molecules it takes to successfully launch one molecule. Market forecasts show predict no, or limited, growth for branded pharmaceuticals in “developed” markets, i.e., US and Europe, and this is driving the markets towards generics and cost controls. In contrast, emerging markets are driving global pharmaceutical growth. These markets have rising incomes, the population of which can now afford more expensive biopharmaceuticals; however pharmaceutical companies serving these areas may require local manufacturing for access to certain emerging markets. Based on these trends, it’s logical to question the significance of innovation in biologics CMC when global markets require fast and flexible development, fine control of critical quality attributes (CQA), and flexible manufacturing concepts.

While Dr. Vogels’ talk focused on development stage products, Ms. Larson approached the innovation and efficiency question from the commercial manufacturing perspective. She posed the question, “Is there any need for ‘innovation’ in an industrializing sector?” Ironically, even with Genetech’s extensive batch history, batch inconsistency is still a problem for some of their commercial products. Ms. Larson discussed manufacturing technology approaches to address batch inconsistencies which included equipment and facility design such as flows, sanitization and chromatography column packing; automation such as algorithms and manufacturing execution systems (MES); sensors and data technology such as trouble shooting and fault detection and prevention; and raw materials such characterization and specifications and monitoring and control. She went on to describe several examples of manufacturing innovation driven by the maturation of the antibody industry that included overall data management, at-line cell culture analysis, improved purification measurement, at-line endotoxin testing, column packing robustness, cleaning and materials of construction, disposable chromatography equipment, novel drug formats like knob-into-hole bi-specific antibodies and ADCs, facilities of the future and drug delivery.

Both talks gave a thorough overview of the multiple innovations being used throughout the industry for both early phase development and commercial manufacturing. Clearly, CMC innovation is still vitally important for the development and commercial maintenance of biopharmaceuticals. I expect the CMC sector of the industry will continue to transform how we traditionally have developed and managed processes if not to gain a competitive advantage then surely out of necessity.

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10th Annual PEGS

Tuesday Apr 15, 2014

We are pleased to announce that we will be joining over 1,600 anticipated participants in Boston’s vibrant seaport district at CHI’s 10th Annual PEGS: the essential protein engineering summit to be held from May 5-9, 2014.  We invite you to visit our booth (#210) to learn how we can support your early product development programs.  With significant expertise in trouble-shooting complex technical issues ranging from characterizing higher-order protein structure to developing high-expressing cell lines to manufacturing targeted antibodies (i.e., bi-specifics, ADCs, fusion proteins), we are well-suited to help you move your product forward.  Still not convinced?  Try bioSELECT and see how we can help!

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Three strikes for traditional “fixed-point” process validation

Friday Apr 4, 2014

By Susan Dana Jones  (sjonesatbptcdotcom)  

Last week’s cold and dreary weather in San Diego did not hinder the casual exchange of information in hallways and seminar rooms, the sharing of technical and business success stories, the launch of new technologies and products, and the input from regulatory authorities that has come to characterize IBC’s annual “BDP Week” conference. The only activity impacted by the weather was the outdoor reception, bravely attended by participants who huddled around the heat lamps while enjoying the food, drink, and camaraderie with colleagues.

This year’s conference contained so many information-packed tracks that it was sometimes a challenge to decide which room to migrate to after the breaks. On one day when I was torn between two or three equally compelling sessions, I fortunately elected to attend a lively session in the Process Validation and Continued Process Verification track. In this session a talk from Genentech on changing the traditional approach to process validation from a “three batches and you’re done” approach to a Lifecycle/continuous review approach was followed by Frank Zettl from Roche Penzberg presenting the underlying details behind Roche’s first FDA approval based on a QbD submission. The astute among you have already realized that these talks were from the same company in two different locations and together these excellent presentations provided the rest of the industry with justification for requesting extra funds to support early development activities based on QbD.

David Reifsnyder of Genentech described a massively parallel effort to align Genentech and Roche Quality Systems, resulting in issuing over 100 new documents in less than two years. Under the unified Quality System, process validation and post-approval monitoring commitments for legacy products that continue to be manufactured at their currently licensed sites would not be changed but for any product that was subject to technology transfer to a new site or even a new scale QbD elements would be implemented that would supersede the “three batches and you’re done” approach. Frank Zettl’s talk focused on Gazyva (obinutuzumab), the recently approved glyco-engineered anti-CD20 antibody that has close to 100X greater antibody-dependent cellular cytotoxicity (ADCC) activity than their current blockbuster product Rituxan. For Gazyva, the critical quality attributes (CQA) were well understood and were those than impacted CD20 binding or ADCC activity. Design space for the product was defined using accurate scale-down models that enabled assessment of the impact of each combination of process parameters on the CQA. With the data to support the design space, Roche proposed a conservative process control strategy and committed to a post-approval lifecycle monitoring plan (PALM) in their submission. Following FDA approval, the PALM became a binding contract and Roche must adhere to the agreed upon testing program. While the pros and cons of lifecycle management versus the three batch process validation approach could be debated, the truth is that lifecycle management provides greater process consistency, earlier warning of a process trending towards the limits of the design space, and improved patient safety. Small companies on lean budgets should learn from the industry leaders and should apply similar strategies throughout their development programs.

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Navigating the Analytical Development Challenges for Bioprocess Residuals and Impurities

Monday Mar 10, 2014

To ensure the safety and efficacy of biopharmaceutical products administered to patients, manufacturers are expected to measure and control impurities in their products, including the host cell components and process additives that may leach into the process stream and final product. Tracking the clearance of these residuals is an essential part of process development and characterization.  Since residuals are typically present at varying levels throughout the process, analytical method development and optimization can be challenging.  In addition, detailed regulatory guidance on acceptable limits does not exist for all residuals.

In this 75-minute Biopharm International webinar sponsored by Eurofins Lancaster LaboratoriesDr. Sheila Magil, Senior Consultant, will provide an overview of manufacturing challenges presented by residuals in biopharmaceutical manufacturing, as well as regulatory expectations.  We encourage you to register for this webinar to learn about challenges presented by residuals in biopharmaceutical manufacturing, regulatory expectations, analytical approaches for cell- and process-associated residuals, a platform method technology for residuals, and matrix effects. In the meantime, if you like to learn more about BPTC’s CMC analyticalquality, and/or regulatory consulting services, please email Julie Adam  (jadamatbptcdotcom)  .

 

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New Technologies, New Vaccines

Monday Mar 10, 2014

Dr. Keith Wells, Senior Consultant, will be presenting at the IABS International Scientific Workshop, “New Technologies, New Vaccines,” being held from March 23-26 in Wilmington, Delaware.  This conference is the eighth in a series that began in 2006, and was previously titled “New Cells, New Vaccines”.  Over the years the conference has followed the progress of new vaccines made using new cell substrates and new technologies from concept through clinical development to new products.  Keith’s talk on “QbD in Process Development of Live Virus Vaccines” will be presented on the afternoon of Tuesday, March 25 and will focus on the application of quality by design (QbD) principles to the early stages of live virus vaccine development. To learn more about BPTC’s expertise in vaccine development, please contact Keith  (kwellsatbptcdotcom)   to pre-arrange a meeting at the conference.

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