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(@niaid.nih.gov>, "Heilman, Carole (NIH/NIAID) [E]" /niaid.nih.gov> Subject: One pager and its integration into the HHS package Date: Tue, 19 Jan 2010 16:52:41 -0500 Importance: Normal Attachments: Sustainable_systems_for_PHEMCE_products_(v8_0 NL)RM_jl_edits.doc; NIH__R and _D_for Health threats _-_1-pager_- FINAL.docx Attached you'll find a one pager that NIAID assembled over the weekend as part of an HHS document to be presented to Heidi Avery (National Security Council Deputy Assistant to the President) this evening. The larger document is the "shortened" version of the HHS package (there is a 10 page version as well). Michael G Kurilla, MD-PhD Director, Office of BioDefense Research Affairs Associate Director for BioDefense Product Development esda, z Iam interested in how to live in a world we dont understand very well --in other words, while most human thought (particularly since the enlightenment) has focused us on how to turn knowledge into decisions, Iam interested in how to turn lack of information, lack of understanding, and lack of "knowledge" into decisions - Nassim Nicholas Taleb For Official Use Only Information Paper on Developing a Systems Approach for Managing the Public Health Emergency Medical Countermeasure Enterprise A. BACKGROUND • Despite significant effort and research expenditure to develop public health emergency medical countermeasures (vaccines, drugs, diagnostics, devices) there are insufficient products in the current development pipeline to address these natural or man-made threats. • The current pathway for product development involves multiple steps which include: defining product characteristics, discovery, advanced development, manufacturing, procurement, storage, distribution, and patient administration. • What we currently lack is a 'systems" or end-to-end approach for product development B. AIM We require a unified management approach for this product pipeline, potentially under a single decision authority, that incorporates metrics for success and continually monitors the progress of products through a sustainable, long-range and properly-structured enterprise. We propose to improve the current system by focusing on four components of the countermeasure development process: 1). science and technology investments, 2). advanced development and manufacturing capability, 3). regulatory science, laws and regulations and 4). product use and improvement In addressing these components, we anticipate 1) advancing science and technology, for national and global health security, 2) improving our preparedness and ability to respond to natural and man-made disasters, 3) aligning financial and market incentives for these products 4) creating public-private partnerships (government, academia and industry) for cutting edge, scientifically-based manufacturing, which 5) creates substantial job opportunity for a highly-skilled workforce. 1. SCIENCE AND TECHNOLOGY INVESTMENTS An integrated, systems approach begins with a science and technology effort that keep the end-users in mind, and builds a target product profile based on those needs. This ultimately contributes to the best "return on investment". At a minimum, we require rapid, facile point of care and multiplexed diagnostics; new broad-spectrum antimicrobial drugs and vaccines; user-expedient vaccine delivery methods; room temperature long term stability and field-friendly equipment that improves management of life support. The NIH has been transitioning to a new paradigm to address these types of needs with three "broad spectrum" strategies (products, platforms, and technology) to achieve a more flexible and responsive medical countermeasure capability that moves beyond the traditional medical countermeasure approach of "one bug - one drug - one vaccine". The goal is for these science and technology investments to be able to translate products more effectively into the advanced development process. A. Broad Spectrum Products: Existing anti-infective products possess narrow activity across the wide range of potential pathogens, a) Vaccines. Using Influenza as an example, vaccines are exquisitely targeted such that a new influenza vaccine is required annually. Cross-protective vaccine concepts offer the potential for a universal influenza vaccine, eliminating annual vaccines and essentially providing pre-existing pandemic protection, b) Drugs. Given the virtually limitless number of natural and potential organisms that could constitute public health threats, it is essential to pursue the broad spectrum approach towards therapeutics. Truly broad spectrum products offer the potential not only to address the vast, existing and emerging infectious disease spectrum, but to produce effective countermeasures for 'unpredictable' diseases, c) Diagnostics. Highly multiplexed methods that take advantage of the specificity in nucleic acid, antibody and other protein signatures are well recognized as the approaches needed to develop rapid, sensitive and specific diagnostic tools, but challenges lie in miniaturization, cost, computational analysis of multiplexed information and signal to noise issues. B. Broad Spectrum Platforms: The concept of new platforms pertains most readily to vaccines and other biologics. Standardized recombinant DNA technologies must be developed for immediate application in the context of emerging infectious diseases. Standardized methods offer the potential to significantly reduce the complexity, time, and cost required to bring medical countermeasures to general use. In addition, multiplexed platform diagnostics systems offer the capability to test for a wide array of pathogens that are already recognized, while at the same time, offering a simple and straightforward path for diagnosis as novel pathogens evolve or emerge. C. Broad Spectrum Technology: Technological enhancements offer greater capabilities in storage, dispersal, and utilization of countermeasures. NIH has focused on temperature stabilization and alternative delivery for vaccines as ancillary technologies with potential applicability to existing as well as future vaccines. This focus reflects the end-user needs for products that are less reliant on cold chain, and can be self administered with a single dose. For example, temperature stabilization allows for room temperature stockpiling which reduces storage and shipment costs as well as extending the shelf life of the vaccine. The potential to improve the vaccination effectiveness in the 3rd world where cold chain capability can be limited is enormous. 2. ADVANCED DEVELOPMENT AND MANUFACTURING CAPABILITY Successful efforts at the bench prove their worth in the advanced development stages of candidate product development. Platform technologies must succeed against the increasing levels of regulatory scrutiny during the scale up and testing process, and ultimately must produce a specific vaccine, drug or diagnostic, and not just a general demonstration of technology feasibility. Currently, challenges to advanced development include lack of product and manufacturing expertise among innovative sponsors which are often small biotech companies, strong reliance on animal models for efficacy data in lieu of trials in humans, insufficient methods to address safety and discard those products likely to cause unacceptable toxicity in human trials, or to ensure product reliability and stability, and lack of flexible capacity to surge or dampen manufacturing capacity based on population and market needs. Early alignment of the biotechnology / innovator communities with skilled advanced developers from the larger pharmaceutical organizations appears to be the best strategy to accomplishing this end goal. Opportunities to enhance successful delivery of approved products through advanced development will require:  Fostering broader spectrum indications to increase market attractiveness  Offering long-term (> 10 years) product acquisition contracts with minimum warm-base manufacturing to guarantee markets  Establishing government/private sector-sponsored facilities for advanced development, and domestic pilot lot and commercial scale manufacturing;  Creating more domestic fill-finish capability  Building more flexible and robust high-level biocontainment facilities to conduct regulated animal challenge studies for safety and efficacy testing. 3 . REGULATORY SCIENCE, LAWS AND REGULATIONS There is an urgent need to invest in applied regulatory science (ARS) and to strengthen the underlying research contributing to a more robust and agile regulatory process. This is necessary to ensure that the potential benefits of these public health medical countermeasure candidates translate into approved products. Such science is distinct from basic discovery research, typically done in academia with NIH support, or industry research intended to develop one specific product. ARS can improve the likelihood of success for a product at all stages from preclinical studies through stockpile, distribution and dispensing. Other areas may include revisiting regulations pertaining to the Animal Rule (AR) and Emergency Use Authorization (EUA). Finally, there may be a benefit to exploring alternate regulatory paradigms and pathways for these specific products for public health emergencies.