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Integrating Critical Early Development Activities

Wednesday Sep 3, 2014

By Susan Dana Jones  (sjonesatbptcdotcom)  

Integrating Critical Early Development Activities to progress From Clone to Clinic® cost-effectively is the theme of IBC’s newly launched track on Success Factors for Early Stage Biologics and the topic of what is sure to be a lively discussion panel hosted by BPTC. This track, part of the BioProcess International Conference & Exhibition held in Boston this fall, will take place on Wednesday October 22 starting at 10:30 AM. The content of this panel will range from funding strategies, manufacturing decisions, and “doing more with less,” all of which is designed specifically to provide management and staff of biotech start-up companies with a road-map of the “must-have”, “nice-to-have”, and “can be postponed without major risk” CMC development activities.

Many start-up biotech companies don’t have their own development capabilities and therefore seek the services of a qualified CRO or CMO to perform the different activities. However, it is the sponsor, not the CRO or CMO, who is responsible for the proper conduct of all development activities, the risk assessment of proceeding with a sub-optimal process, and the eventual quality of the product produced for human clinical evaluation. Managing the sponsor-CMO or CRO relationship is therefore a critical activity in developing new biopharmaceuticals. For biosimilar development, the sponsor company must be even more vigilant to insure that the CRO/CMO expectations and activities are fully aligned with the goal of designing a process to produce a product that is comparable in all the required ways to the reference, innovator product.

Cell line development is the first, and critical path, activity for any development program and this is a potentially lengthy activity for products that must be expressed in a mammalian system. With a multitude of options available through service providers and enabling technologies available through purchase or license, the decision of how and where to initiate this activity sets the strategy and risk profile for the entire development program. The history of the production cell line will be carefully reviewed by regulatory authorities worldwide and therefore any risks taken at this early stage could impact the eventual request to initiate trials in human subjects. Does this mean that cell line development must be lengthy and expensive? Not necessarily. We don’t believe that it needs to take more than 4-5 months to obtain a clonal, genetically stable, high expressing mammalian cell line for products that don’t require novel enzymatic processing, co-factors to assist in folding or secretion, or other unusual elements. The bigger question in early development is what else can be done while the cell lines are under construction?

The IBC track is focused on integration of all activities, minimization of upfront cash flow while mitigating the most likely risks in early development, and achieving a product that performs as desired in animals and patients. BPTC’s panel discussion at 4:30 PM will include seasoned industry veterans from both BPTC’s team of expert consultants and from companies developing novel, first-in-class or biobetter products. By drawing together experts in all aspects of early development and accessing the breadth of knowledge across this group, BPTC and IBC hope to implant the importance of well-managed, well-thought out development strategies starting with lead candidate selection through to delivery of the drug to patients in need of new therapies. If you still haven’t registered for the conference, you can register using BPTC’s discount code, BP14SKRE3, for 20% off the standard rates.

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Cell Culture World Congress USA 2014

Monday Sep 1, 2014

Join BPTC at Terrapinn’s Cell Culture World Congress USA conference, co-located with the HPAPI Congress, in Boston, MA from September 15-16.  We look forward to mingling with fellow cell culture experts to discuss process enhancements, innovative technologies, and bottle-neck reduction opportunities. Please come visit us at booth 13 to learn how we can help improve your upstream process and accelerate your development programs.

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2014 BioProcess International Conference & Exhibition

Friday Aug 29, 2014

Join BPTC at IBC’s 11th Annual BioProcess International Conference & Exhibition in Boston, MA from October 20-23, 2014. In addition to exhibiting at the conference (booth #810), BPTC consultants will be actively participating in a number of sessions.  Susan Dana Jones, Vice President and Principal Consultant, will be leading a panel discussion on “Identifying and Integrating Critical Early Development Activities to Enable Successful Progression from Discovery to First-in-Human Clinical Trials” on October 22 at 4:30PM. Susan will also be leading a course titled, “Introduction to BioPharmaceutical Development and Manufacturing” with Sheila Magil, Senior Consultant.  This course will provide an overview of the technical considerations and activities required to progress a biopharmaceutical from discovery through early process development and manufacturing. If you still haven’t registered, take advantage of our discount code, BP14SKRE3, for 20% off the standard rates. See you there! For more information, visit: http://bit.ly/1zVjTJt.

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Has the time come to embrace continuous processing?

Tuesday Aug 26, 2014

By: Howard Levine  (hlevineatbptcdotcom)   and Frank Riske  (friskeatbptdotcom)  

As in years past, the Recovery of Biological Products XVI Meeting in Rostock, Germany (July 27‑31) provided a forum for lively debate on new technologies for downstream processing, new applications of old technology, and glimpses of what the future of our industry might hold. High among the topics of interest at the conference was continuous processing as a replacement for traditional batch processing of monoclonal antibodies and other recombinant proteins. Jon Coffman (Boehringer Ingelheim) began the conference pointing out that the cost of manufacturing per se is not limiting our ability to deliver products at a cost effective level but rather the high failure rate of products in clinical trials and the time required for overall product development were more critical in driving the cost of medicines today. Jon then showed how continuous processing might help accelerate production of material for clinical trials, allowing companies to shorten overall timelines to commercialization. This was followed by a presentation from Charlie Cooney (MIT) in which he reviewed the evolution of continuous processing for traditional pharmaceuticals and argued that the biopharmaceutical industry can also benefit from the efficiencies and flexibility continuous processing can provide.

Later in the program, Veena Warikoo (Genzyme), Oliver Kaltenbrunner (Amgen), and Alex Xenopoulos (Merck Millipore) presented their views on the development and implementation of integrated, fully continuous processes for recombinant proteins and monoclonal antibodies. While there was discussion and some disagreement over implementation of “end to end” continuous processes, these presentations and several posters at the meeting, did make the case for the use of continuous perfusion cell culture and continuous chromatography for initial product capture for recombinant proteins that are relatively unstable (e.g. Factor VIII) and helped define the objectives for implementing continuous processing for more stable products such as monoclonal antibodies. In these cases, continuous processing, whether for a single unit operation such as Protein A capture or a more fully integrated end-to-end process, there may be economic and/or productivity gains to be had through continuous (or semi-continuous) processing. Furthermore, advances in process analytical technology (PAT) may also favor using aspects of continuous downstream processing. With FDA and most industry experts embracing the concept of continuous processing, it is likely that some level of continuous processing will become commonplace in biopharmaceutical industry in the near future. Looking toward this future, Karol Lacki (GE Healthcare) gave an excellent presentation on a unified approach to process development that supports batch, semi-, and fully continuous processing without a need to repeat costly process development and process characterization studies should a switch be made from one operational mode to another later on.

The case for sticking with batch processing was made in comments by Brian Kelley (Genentech). According to Brian, conventional batch processes can be economical and suitable for production of biopharmaceuticals, even if very large columns or multiple cycles per column are required to process increasing levels of product in the harvest from large volume bioreactors. For a company like Genentech, with a large base of installed capacity and manufacturing assets, perhaps this is true. However, as companies look toward designing and building “factories of the future,” smaller facilities incorporating some aspects of continuous (perfusion) cell culture and continuous chromatography may be more cost effective and productive than larger facilities built around traditional batch processing. In conclusion, a company decision to use aspects of continuous processing may well depend on the stability of the protein, and an economic and risk analysis of placing such technology into an existing facility, or planned new construction.

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CHIs 6th Annual BioProcessing Summit

Monday Aug 4, 2014

Drs. Susan Dana Jones and Sheila Magil will be leading a 1.5-day training course titled, “Introduction to Bioprocessing” from August 18-19, 2014 at the Renaissance Waterfront Hotel in Boston, MA, to be held in conjunction with CHI’s Bioprocessing Summit (running August 18-22). This training seminar offers a comprehensive survey of the steps needed to produce today’s complex biopharmaceuticals from early development through commercial.  The seminar begins with a brief introduction to biologic drugs and the aspects of protein science that drive the intricate progression of analytical and process steps that follows.  We then step through the stages of bioprocessing, beginning with the development of cell lines and ending at the packaging of a finished drug product.  The seminar also will explore emerging process technologies, facility design considerations and the regulatory and quality standards that govern our industry throughout development. The important roles played by the analytical and formulation in developing and gaining approval for a biopharmaceutical are also examined. This 1.5-day class is directed to attendees working in any aspect of industry, including scientific, technical, business, marketing or support functions, who would benefit from receiving a detailed overview of this field. For more information and to register for this seminar, please click here. Interested in learning more about BPTC’s CMC consulting expertise? Please email Julie Adam  (jadamatbptcdotcom)   to pre-arrange a meeting at the conference.

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