CMO
2016 Wrap-Up: Looking Ahead to 2017 and Beyond
Bikash Chatterjee
President and Chief Science Officer Pharmatech Associates
As we bid farewell to 2016 to face the opportunities and challenges of 2017, the global life sciences industry can be best described as being on the cusp of great change. For the last ten years, U.S. market growth has been transitory, with M&A activity defining the primary defensive strategy to stifle global competition and pricing pressures. Yet, continued growth in the virtual biotech sector elevates the importance of a cohesive outsourcing strategy for the successful development of a commercial product. The FDA’s new fast-track and breakthrough drug regulatory programs have been embraced by both industry and FDA as a conduit for novel drugs to get to market faster. However, the combination of faster review and approval cycles and outsourcing as the primary development framework has put greater emphasis on CDMOs and CROs to support the CMC and quality elements of the development program that were historically reserved for the drug developer.
Better Diagnostics Drive Insight
Change is driven by several factors. First is the unprecedented evolution of better tools, i.e. the trend to new therapies that rely on new sources of data made available as technology advances. Genetic engineering is a case in point. CRISPR - Clustered Regularly Interspaced Short Palindromic Repeats - a genome-editing tool, gives researchers the ability to quickly and easily target and study particular DNA sequences in the vast expanse of a genome, even providing the potential for treating disease by editing the genes of human embryos. Scientists have been able to edit genomes for nearly a decade but early techniques were expensive, costing $5000 or more per test. CRISPR costs as little as $30 per test and is a big reason for the breakneck pace we see in the field of genome research. With gains in speed and ease of use, editing DNA is but one trick that the CRISPR tools can be used for. Scientists are hacking the tools so that they can send proteins to precise DNA targets to toggle genes on or off, and even engineer entire biological circuits with the long-term goal of understanding cellular systems and disease.
New data brings new diagnostic capability and is the catalyst for the escalating interest in Companion Diagnostics. A companion diagnostic can be an in-vitro diagnostic device or an imaging tool that provides essential information for the safe and effective use of a corresponding therapeutic product. The use of companion diagnostics will allow physicians to identify patients who have specific disease states derived from specific root causes such as a specific genetic anomaly.
Personalized medicine, sometimes called precision medicine, seeks to stimulate the body’s own immune system to attack cancer cells. Combined with a companion diagnostic the potential for precisely tailoring of a drug therapy is unprecedented and represents the potential for a huge change in disease therapy. CAR-T cells (Chimeric Antigen Response-T cells) are engineered proteins composed of two distinct functional components. The first consists of an antibody fragment or
target-binding domain that allows CARs to recognize targets that are present on the surface of cancer cells. The second provides signals that rapidly and powerfully activate the T-cell to attack and kill cancer cells. The personalized element is that the treatment uses the patient’s own white blood cells to modify the T-cells.. The challenge industry and FDA regulators face is how to modify the current definition of fit for use. The quality definition for conventional drug products and processes is based upon demonstrating process reproducibility and an effective control strategy. That paradigm goes out the window when you are only making one lot, along with autologous white cells to build a single lot with targeted functionality and critical quality attributes. Stage 2 process validation no longer applies in the conventional sense. How industry and FDA define the quality requirements will influence how quickly personalized medicine programs gains traction.
Outsourcing’s Responsibilities Escalate
Outsourcing has long been a component of the drug development lifecycle but the last decade has shown decided growth in the breadth and depth of responsibilities assumed by Contract Service Providers (CSPs). The move to a global supply chain has caused industry to rely upon CSPs for everything from early molecule identification to clinical and commercial manufacturing. This evolution creates challenges for organizations that were historically built and operated on vertical development and manufacturing models, particularly as they relate to the Quality Management System. Accommodating collaboration models between multiple developers confounds the roles and responsibilities that are typically solely the domain of the development organization. Within the U.S., virtual biotech continues to be a growing presence and the sector is utilizing CSPs for everything from method development to process design and regulatory filings. The challenge with each of these market evolutions is to align quality and development systems with the capabilities and constraints of each CSP. To embrace outsourcing as the core development model means having to modify the quality structure and formalize how and where all operational and quality systems interact.
Another driving factor behind the growth of biotech and virtual biotech has been the evolution of combination products as a vehicle for broadening the potential patient population for many disease therapies. By moving away from IV infusion as the route of delivery for many biologic drug therapies, auto-injectors and prefilled syringes make it possible to treat disease without a hospital or clinical visit. However, there is complexity associated with merging drug and device quality systems. The FDA has made major strides toward clarifying their minimum expectations by issuing 21 CFR Part 4 which articulates, at a minimum, what parts of CFR 210/211 and 820 are applicable. However, the practical challenges of aligning both quality paradigms remain.
Pharmaceutical Outsourcing | 20 | November/December 2016
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