Strategies for Commercialization Track Sessions
Strategies for Commercialization Track 1: Positioning for Phase III Manufacturing
Thursday 5/19/2011
Time: 7:45am - 8:45am
CMC needs to be “locked-in” for a pivotal clinical trial (typically Phase 3), which takes place when the clinical safety and proof of concept has been established. There is a window of opportunity before the start of the pivotal trial to make decisions and investments to ensure manufacture of a product of consistent quality and commercial success. This session will focus on the activities, decisions, and investments to align the need for compliance with regulatory requirements and commercialization of a cell based product before the start of a pivotal clinical trial.
Strategies for Commercialization Track 2: Cell Characterization, Potency, and Comparability Studies
Thursday 5/19/2011
Time: 11:00am - 12:15pm
Effective characterization testing is the cornerstone of successful cell therapy product and process development. A basic understanding of key characteristics is essential from the outset. This characterization foundation - of the product, cellular raw material, and process intermediates - grows more detailed and extensive in the course of preclinical and clinical development. Characterization testing is commonly thought of in terms of safety, purity, identity, potency, and stability. Of these, potency testing, measurement of the product’s relevant biological function, presents particularly formidable challenges, from selecting and controlling assays, to establishing specifications, and to qualification and validation. The product’s biological function may involve interactions with device components, local cell populations, and other microenvironment effects. In vitro measurement of product function may require multiple functional and non-functional assays, and unique reference standards. Multiple candidate potency assays may be evaluated, necessitating qualification studies to bridge changes in test methods. This session will review common questions in potency testing development and qualification, current European and US regulatory guidance and expectations, guidelines for controlling and validating potency testing, and strategies for effective qualification studies to bridge changes in assay methods.
Strategies for Commercialization Track 3: Advanced Automation for Autologous Processing
Thursday 5/19/2011
Time: 3:30pm - 5:00pm
As Autologous and Patient-specific products continue through clinical development, it is important to prepare for commercialization of these unique therapies. Once these therapies are on the market, tens of thousands of patient product doses will be required to be manufactured for a variety of products. At this level of processing, greater than 100 patient samples must be received every day, and the same number of final products must be processed, tested, and released daily. This level of manufacturing will require extensive automation at almost every step, including processing, analytical testing, and product release. This session will outline different approaches to automation, some technologies available today, and importantly when to begin planning for, and implementing automation during clinical development.
Strategies for Commercialization Track 4: Risk Assessments
Friday 5/20/2011
Time: 7:30am - 8:30am
The concept of manufacturing quality risk management (QRM) has been endorsed by regulatory authorities in the ICH regions and beyond for some time in the form of ICH Q9. ICH Q9 was not written with cell-based products in mind, but this session will explore how this might be approached and discuss the outcomes of one such attempt. Taking the concept of risk management further, the EMA’s guideline on cell-based medicinal products and a recent revision of the requirements for marketing authorisation for ATMP’s introduced the concept of a risk-based approach. Although only at the concept paper stage, the risk-based approach appears to go further than manufacturing QRM and offer the opportunity to focus the whole of product development based on risk. The session will discuss whether the risk-based approach offers a short-cut for ATMP development or is this merely an acknowledgment of the difficulties in developing them?
Strategies for Commercialization Track 5: Decreasing Corporate Risk for Cell Therapy Programs
Friday 5/20/2011
Time: 10:45am - 12:15pm
This session will focus on key strategies companies can employ in order to decrease the risk associated with investing in cell therapy commercialization programs. Strategies to decrease time to market, increase odds of clinical success, improve globalization and Regulatory compliance, and to allocate risk across programs will be explored.
Dr Natalie Mount will discuss Pfizer’s approach to smart clinical trial design, David James of Invetech will present an argument on why, when and how to invest in process automation, and Paul Anderson of OrthoCell will discuss portfolio diversification for regenerative medicine companies. Dr Dawn Driscoll will Chair, and will briefly discuss the FDA’s SPA program, as part of a corporate risk reduction strategy.
Strategies for Commercialization Track 6: Challenges of commercial development of pluripotent hES
Friday 5/20/2011
Time: 3:30pm - 5:00pm
This session will focus on the bottlenecks and difficulties which can be anticipated to challenge the commercialization of hES-derived therapies. First, quantitative modeling will be used to translate anticipated patient populations, dosages and market penetrance into predicting the demands which will be placed on cell therapy manufacturing unit operations. Secondly, these will be mapped onto the equivalent challenges which have faced classical biologics, with consideration of how this field overcame the difficulties. Thirdly, a similar approach will be taken to analyze the regulatory path taken by biologics and areas of commonality and difference with cell therapies.
Strategies for Commercialization Track 7: Personalized approach to cell and gene therapy
Saturday 5/21/2011
Time: 7:30am - 8:30am
This session will present and discuss cell and gene therapies that have reached the stage of Phase 2 clinical trial.
Dr. Ronnda Bartel of Aastrom Biosciences will present "Ixmyelocel-T - A New Therapy for Severe Chronic Cardiovascular Disease". Ixmyelocel-T is a disease modifying therapy with multi-functional properties including tissue remodeling, immuno-modulation and the promotion of angiogenesis, which is targeted to address the multiple underlying causes of many severe, chronic cardiovascular diseases such as CLI. This patient specific cell therapy is manufactured from the patient’s own bone marrow using Aastrom’s proprietary, automated closed manufacturing system. Ixmyelocel-T is composed of a mixture of cell types normally found in bone marrow as well as expanded mesenchymal stromal cells and alternatively activated macrophages. This presentation will give an overview of the ixmyelocel-T product manufacture, preclinical characterization and interim results of the Phase 2 clinical study in critical limb ischemia.
Dr. Philippe Leboulch of the Unversity of Paris (CEA-INSERM) and Harvard Medical School will present “Lentiviral therapies for genetic disorders: illustration with adrenoleukodystrophy and the b-hemoglobinopathies”, the two first approved human trials worldwide that make use of lentiviral vectors for the treatment of genetic diseases. After years of optimization, gene therapy has seen clear evidence of clinical benefit in selected patients, and bluebird bio of Cambridge, MA, is developing these approaches towards commercialization. The b-hemoglobinopathies (b-thalassemia and sickle cell disease) are the most prevalent inherited disorders worldwide. Gene therapy of these diseases is especially challenging given the requirement for massive hemoglobin production and the lack of selective advantage for corrected hematopoietic progenitors. Our trial shows that, 4 years after lentiviral b-globin ex vivo gene transfer to hematopoietic stem (HSC) cells, an adult patient with severe bE/b0-thalassemia dependent on monthly transfusions since early childhood has become transfusion independent for the past 3 years. Potential safety issues will also be discussed. X-linked adrenoleukodystrophy (ALD) is a severe brain demyelinating disease in boys that is caused by a deficiency in ALD protein. Four children with the disease were submitted to lentiviral gene therapy. Up to 4 years later, disease progression slowed down or even halted, a clinical outcome comparable to that achieved by allogeneic transplantation.
Strategies for Commercialization Track 8: Strategies for Allogeneic Cell Therapy Commercialization
Saturday 5/21/2011
Time: 1:15pm - 2:45pm
Mesenchymal cell therapies: from concept to clinic
A number of groups that develop allogeneic mesenchymal cell-based therapies have made considerable advances towards the commercialization of their products. This session will describe and discuss the potential benefits of different tissue sources such as bone marrow and placenta, and their different cell populations, for the successful commercial development of off the shelf cell therapies. Key commercial considerations include raw material availability, intrinsic mechanistic capacity, ease and cost effectiveness of production, utility, distribution logistics and reimbursement.
