BPTC is pleased to be exhibiting at the 2014 Biotechnology Industry Organization’s International Convention to be held in sunny San Diego, CA from June 23-26. We hope you’ll take some time to visit us at Booth 1214 in the Bioprocessing Zone to learn more about our extensive biopharmaceutical product development and manufacturing expertise and to enter our daily raffle to win two hours of free consulting. To pre-arrange a meeting to discuss your specific needs, please email Julie Adam (jadambptccom) . We look forward to seeing you in CA.
Dr. Keith Wells (kwellsbptccom) has been invited by Dr. Milana Boukhman Trounce, Clinical Associate Professor of Surgery, Divsion of Emergency Medicine, Stanford University School of Medicine, to serve as a special guest lecturer for her class entitled, “Biosecurity and Bioterrorism Response“. Dr. Wells will be speaking on Monday, 19 May at the Alway Building on the Stanford University School of Medicine Campus, and will be providing his perspectives on the technical potential for non-state actors to create strategic biological weapons and the development of a biodefense posture to counter that potential based on his 17+ years in the biodefense arena.
By Patti Seymour (pseymourbptccom)
Although the United States still has yet to work out the regulatory details to obtain approval for biosimilars, Europe and other countries, particularly growth markets, offer market potential for biosimilars. DCAT’s 2014 BioPharmaceutical Forum: Biosimilars—Development, Regulatory, and Marketing Experiences, held March 13, 2014, examined both the opportunities and challenges in biosimilar development and commercialization.
Assessing the opportunity
Biosimilars are a small, but growing segment of the global biopharmaceutical market accounting for 0.4% of the $137-billion biologics market in the so-called “mature eight” markets of the United States, EU5 (France, Germany, Italy, Spain, and United Kingdom), Canada, and Japan in 2012, according to IMS (1). In growth markets, biosimilars accounted for 10.7% of a $15-billion biologics market in 2012. By 2017, biosimilars are expected to represent 3–5% of an estimated $205-235 billon global biologics market(1).
For biosimilars in general and particularly with the opportunity of more complex molecules, such as monoclonal antibodies to become biosimilars, developers face the challenge of developing a manufacturing process that can achieve comparability to the reference product. Development activities center on replicating the process conditions of the reference product to drive the process toward producing a “highly similar product”. Because innovators do not typically publically disclose their manufacturing processes, biosimilar developers have to ascertain the process conditions that will allow them to achieve comparability, or “biosimilarity”. An added complication facing biosimilar developers is whether to take advantage of advances in cell line development and bioprocessing innovations to develop a more efficient manufacturing process to produce a biosimilar. The industry has seen titers increase from less than 1 g/L in 2000 to titers of 10 g/L or more in 2014. A fundamental issue for a biosimilar developer in evaluating the cost and time for biosimilar development is deciding whether to take advantage of innovative manufacturing processes that may result in better yields and more efficient manufacturing processes, but may generate a product sufficiently different from the reference standard that it would not be considered a “biosimilar.”
Biosimilar developers also face quandaries in cell-line development. In terms of conventional host cells systems, mammalian cell culture systems (primarily Chinese hamster ovary (CHO) cells) account for the majority of host cells or 56% of the systems used and E. coli comprise 29% of the host cells used in biopharmaceutical production. (2). An important issue in biosimilar development is determining whether a host cell system that is different from what was used by the innovator can be used for biosimilar development and commercialization.
Applying highly sophisticated analytical techniques to characterize these molecules and the potential to take advantage of a more advanced host cell and expression technology in the development of biosimilars is likely possible. However, regulatory authorities may be cautious and maintain a high bar regarding meeting the “biosimilar” criteria when a technology different from the innovatory process is used. In the U.S., we won’t know how the FDA will view the use of different technologies until they issue their long awaited guidance documents on development of biosimilars.
1. G. Lewis, “Pharma Transformation in Turbulent Times,” presented at DCAT Week 2014 (New York, 2014).
2. T. Fritz, C. Lightcap, and K. Shah, “Manufacturing Strategies for Biosimilars,” Pharma Manufacturing, June 12, 2012.
By: Patti Seymour (pseymourbptccom)
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.
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!