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Draft The Center will initially focus on projects that have demonstrable value for all parties. Such projects could focus on: • Comparatively advanced manufacturing platforms with which FDA already has some familiarity (e.g., monoclonal antibodies, therapeutics based on RNA interference (RNAi), various protein expression systems for vaccines and therapeutics, novel adjuvants, widely available automated high throughput diagnostic platforms for nucleic acids, proteins and antibodies); • Good Laboratory Practice (GLP) animal-efficacy model development for new vaccines, antibiotics and antiviral medications; • Validation of improved potency and rapid sterility assays; and • New approaches to statistical analysis of clinical trials. Over time, the Center could expand its focus to address other regulatory challenges, including: • Development and validation of biomarkers for use as alternative clinical endpoints and to enhance prediction of safety; • Cell culture and in silico modeling of efficacy; • Non-animal toxicological and safety evaluation; • Defining pathways for novel vaccine manufacturing platforms (e.g., virus-like particles and DNA vaccines targeted to novel antigens); and • Defining pathways for point-of-care diagnostics with ability to subtype influenza or detect antimicrobial resistance. IV. Product Development and Manufacturing Services Advanced development and manufacturing account for a large proportion of the total cost of medical countermeasure development. These costs represent a substantial barrier to the participation of large pharmaceutical firms, which prefer a more favorable return on investment, and to the progress of smaller biotechnology firms, which typically lack the necessary capital and expertise required to succeed. Compounding these problems, the Federal contracting mechanisms most often used to support advanced development and manufacturing can impose long lead times and significant transaction costs. Contracts may further impose a form of reverse moral hazard, in that the difficulty and publicity associated with their cancellation often lead program staff and government agencies to become more failure-averse. Federal contracting must be streamlined and accelerated, and future contracts to support the development of medical countermeasures against public health threats must be structured in a way that facilitates early down-selection of projects that are not making appropriate progress. Given the high attrition rates associated with drug development, government agencies must configure themselves to be highly tolerant of failure and to have mechanisms that allow projects, if they are to fail, to "fail fast and fail cheap." Going forward, and as needs dictate, the U.S. Government will also employ other mechanisms, including service and cooperative agreements, other transaction authorities, and challenge grants to facilitate public-private partnerships and expedite countermeasure development and manufacturing. Such mechanisms will augment the more traditional contracting processes currently used to support advanced development and manufacturing activities, enabling the Enterprise to be more flexible,