Reading Room Production — page 472

Draft adaptive, and responsive in engaging with industry to promote medical countermeasure development. The opportunity costs and risk assumed by private sector partners can be lowered substantially through the direct provision of advanced product development and manufacturing services. To provide such services, the U.S. Government must work with industry to establish prioritized access to advanced development and manufacturing capabilities for these countermeasure products. The capabilities specified and prioritized by the U.S. Government would build on an existing domestic infrastructure composed of an integrated network of industrial facilities able to provide assistance in product development or in manufacturing clinical investigational lots or commercial scale lots of countermeasure products. Components of this advanced product development and manufacturing services capability could be assembled in multiple, non-exclusive ways by establishing contract partnerships with academia, contract research and manufacturing organizations, and industry, or by establishing Manufacturing and Development Centers of Excellence or a non-profit, Federally Funded Research & Development Center or Centers. In whatever form the capability is established, it would provide a full range of pre-clinical and advanced product development services2 (including animal-efficacy model development and validation) as well as dedicated scale-up, validation, and production capabilities using flexible manufacturing technologies. Technical expertise in scale up and manufacturing process development as well as commercial scale manufacturing will be provided by Biodefense Advanced Research and Development Authority (BARDA) to industry partners in need of these skills. The infrastructure required to provide this end-to-end range of services would be operated by industry under U.S. Government oversight. Important downstream benefits of establishing this capability are that it will make life cycle management and replenishment of needed countermeasures more cost effective and provide expanded domestic emergency manufacturing capacity. One of the core product development services the U.S. Government will provide is identifying and addressing regulatory challenges prospectively and providing assistance with regulatory filings. Regulatory officers from NIH, BARDA, and DoD with deep knowledge of the "animal rule" and FDA concerns will provide expert support to private-sector partners and facilitate and participate in formal and informal interactions with FDA. By providing subject matter and animal model expertise, developing and validating screening and GLP animal models, anticipating and addressing regulatory challenges prospectively, and establishing an advanced development and manufacturing capability, the U.S. Government will drastically reduce the opportunity costs and other barriers that limit investment by the pharmaceutical and biotechnology industries in public health countermeasure projects. This intensive and direct support by the U.S. Government will reduce the absolute investment of company resources in particular projects and fundamentally alter the calculus of return on investment. A much more favorable return on investment will, in turn, enable pharmaceutical and 2 For example, Good Laboratory Practice (GLP) toxicology and safety pharmacology studies, formulation methodology, current Good Manufacturing Practice (cGMP) manufacturing support, stability studies, non-pivotal screening and efficacy evaluations, GLP pivotal efficacy studies in validated animal models, and support for Phase I clinical safety and pharmacokinetic studies.