Manufacturing Innovation for the Production of Cell-Based Cancer Immunotherapies

Description:

Fast track proposals will be accepted. Direct-to-Phase II proposals will not be accepted. Number of anticipated awards: 2-4 Budget (total costs, per award): Phase I: up to $400,000 for up to 9 months; Phase II: up to $2,000,000 for up to 2 years PROPOSALS THAT EXCEED THE BUDGET OR PROJECT DURATION LISTED ABOVE MAY NOT BE FUNDED. Summary Cancer immunotherapy is a therapeutic approach that directs a patient’s own immune system to eradicate their tumor cells. Past and current NCI investments in adoptive T cells, CAR-T cells, NK cells, and other cell-based cancer immunotherapies have resulted in the translation of many lab-specific approaches into early clinical trials. Importantly, reproducible and robust production methods are critical to ensure that advances in basic research result in successful translation of cell-based therapies. Clinical development of such therapies requires multi-center, randomized clinical trials that must be supported with high quality, consistent, and reproducible cell-based products. Patient-specific autologous or allogeneic lots must be adequately characterized to ensure that similar products are given to all patients. For non-patient specific cell-based therapies, large-scale and reproducible manufacturing technologies are needed to produce high-quality products with uniform identity and potency. Current limitations in cell manufacturing can increase both the cost and time required to bring a therapy to market and can result in missed opportunities to evaluate promising new cell-based therapies. Product failures can be attributed to poor product design and characterization, as well as inadequate scale-up and manufacturing processes; therefore, further investments are needed to develop state-of-the art manufacturing technologies and processes to advance cell-based cancer immunotherapies at the commercial-scale. Effective use of science and engineering principles during the early development phase of a cell-based therapy can improve both the efficiency and reliability of the manufacturing process and the quality of the final product. Moreover, it is anticipated that standardized approaches to manufacturing, process analytics, release testing, and product characterization will result in more rapid, cost-effective product development and a higher level of regulatory success. Achieving the desired level of standardization for current and future cell-based cancer immunotherapy products will require both pragmatic research to establish consistent manufacturing processes, as well as the development of new innovations and technologies. Project Goals The overall goal of this contract topic is to facilitate the development of innovative methods and technologies capable of improving and modernizing product manufacturing processes for cell-based cancer immunotherapies. This includes the use of autologous, allogeneic, or pluripotent cells. Offerors submitting proposals under this solicitation are strongly encouraged to establish collaborative relationships with clinical product development companies focused on the development of specific cell-based products. In all cases, it is expected that offerors will demonstrate the utility of their innovation(s) in the context of at least one cell-based product, which is representative of a particular class of cell-based cancer immunotherapies. Examples of manufacturing innovations/advancements might include, but are not limited to: • Automated closed systems for cell separation, genetic modification, differentiation, and/or expansion; • Low-cost, high-efficiency methods for genetic modification to support cell engineering; • Standardized assays and/or surrogates to evaluate cell attributes that ensure lot-to-lot consistency in terms of phenotype, functionality, quality, and potency; • Real-time, non-destructive test methods with sensors and/or imaging technologies to assess critical quality attributes (e.g., contamination); and/or • Process analytics capable of feedback control in response to real-time changes in critical attributes of the cell product. It is expected that Phase I proposals will focus on novel inventions related to innovations or improvements in cell manufacturing processes, including in-line or on-line (i.e., continuous) process analytics to support product consistency and safety, as well as GMP production of a particular class of cell therapies. Phase II proposals should demonstrate the scalability and validation of the production platform or process improvements developed in Phase I. Engineering and process solutions must be capable of regulatory compliance with FDA Guidelines. The long-term goal of this initiative is to provide the tools necessary for efficient, high-quality manufacturing of novel products in the emerging field of cell-based cancer immunotherapies. Phase I Activities and Deliverables • Develop a device/technology/process to support commercially-relevant manufacturing advancements or improvements for the production of a specific class of cell-based cancer immunotherapies (e.g., CAR-T cells, adoptive T-cells, NK cells) • Establish defined specifications, assays and/or metrics to interpret scientific data supporting the feasibility of the device/technology/process, with respect to reproducible product manufacturing, process analytics, and/or process controls Page 71 • Demonstrate the suitability of the device/technology/process to improve relevant manufacturing metrics (e.g., product uniformity, quality, efficiency, cost-effectiveness) for at least one cell-based product, which is representative of a particular class of cell-based cancer immunotherapies • Provide proof of collaboration or partnership with an entity that is developing a representative cell-based therapeutic agent OR otherwise demonstrate access to a representative cell-based therapeutic agent through other means (e.g., internal drug development program), that can be used for validation of the device/technology/process • Demonstrate pilot-scale beta-testing of the production process to demonstrate reproducible performance within appropriate specifications for identity, purity, potency, and/or other relevant metric for the chosen cell-based immunotherapy product Phase II Activities and Deliverables • Generate scientific data demonstrating the proposed scalability (e.g. scale-up, scale-out, point-of-use) of the production platform, process analytics and/or process controls • Develop an at-scale prototype of the device/technology/process with detailed specifications for hardware/software that supports the production platform or process analytics/process controls improvements • Validate the production innovation and/or process improvements, including standards for calibrating any novel process analytics or process controls that monitor production

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