FAUCI ARCHIVE — EMAIL THREAD: Reminder about inputs for the potential White House Briefing on Sustainable Systems approach to MCM's https://faucisdiary.com/correspondence/reminder-about-inputs-for-the-potential-white-house-briefing-on-sustaina 2 messages, Jan 18, 2010 Text below is verbatim from the released PDFs, with the original line breaks. ============================================================================== Subject: RE: Reminder about inputs for the potential White House Briefing on Sustainable Systems approach to MCM's From: Anthony Fauci To: George Korch Cc: Michael Kurilla, Patricia Conrad, Greg Folkers, Anthony Fauci Sent: Mon, 18 Jan 2010 08:26:02 -0500 Source: Reading Room, pp. 431–432 of Reading-Room-FINAL.pdf Attachments named (files not released): NIH_-_R_and_D_for_Health_threats_-_1-pager_-_FINAL.docx ------------------------------------------------------------------------------ George: I am attaching our 1-pager as requested. Please let me know if you have any questons. Thanks, Tony -----Original Message----- From: Korch, George (OS) Sent: Monday, January 18, 2010 7:52 AM To: Fauci, Anthony (NIH/NIAID) [E]; Robinson, Robin (OS) Subject: Reminder about inputs for the potential White House Briefing on Sustainable Systems approach to MCM's Gentlemen: I will be assembling the information received on how to augment and improve the medical countermeasure enterprise from each of the partners to present to Heidi Avery and others on the NSC staff sometime tomorrow. Thanks in advance for sending your inputs to me so that I can craft a document to redistribute to all concerned. V/r, George A Research and Development (R & D) Strategy for Future Health Threats – The NIH Approach - 2010 GOAL: The nation must be prepared to protect its citizens and preserve national security with safe and effective medical interventions that can prevent, diagnose, and treat existing biological threats as well as respond rapidly and effectively to newly emerging threats that are either naturally occurring or deliberately propagated. TRADITIONAL STRATEGY: While the traditional medical countermeasure development approach is a sound and appropriate strategy for mitigation of known biological threats, time and resources limit the ability of this “one bug – one drug – one vaccine” approach to achieve a rapid and effective response to all possible threats. As a result NIH has been transitioning to a new paradigm with three “broad spectrum” strategies (products, platforms, and technology) that will underpin a more flexible and responsive medical countermeasure capability. FUTURE STRATEGY: 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 such that annual vaccinations would be eliminated and pandemic protection would already be pre-existing. b) Drugs. Given the virtually limitless number of organisms that can constitute public health threats, it is essential to pursue the broad spectrum approach towards therapeutics. In addition to a small number of drugs replacing a medicine cabinet of pathogen specific drugs, drug resistance would be less likely to develop. Truly broad spectrum products offer the potential not only to address the vast, existing infectious disease spectrum, but allow for effective countermeasures for emerging diseases that could not even be predicted. Broad Spectrum Platforms: The concept of new platforms pertains most readily to vaccines. Standardized recombinant DNA technologies must be made available 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. Platforms can be expanded to other aspects of the overall product development process such as diagnostic screening. Multiplexed platform diagnostics systems offer the capability to test for a wide array of potential pathogens, while at the same time, offering a simple and straightforward path for introduction of new tests as novel pathogens evolve or emerge. 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. 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. Taken together, this new R & D strategy will position us well to address existing health threats as well as the challenge of new and emerging threats. Subject: RE: Reminder about inputs for the potential White House Briefing on Sustainable Systems approach to MCM's From: George Korch To: Anthony Fauci Cc: Michael Kurilla, Patricia Conrad, Greg Folkers, Nicole Lurie, Monique Mansoura Sent: Mon, 18 Jan 2010 08:26:46 -0500 Source: Reading Room, pp. 433–445 of Reading-Room-FINAL.pdf ------------------------------------------------------------------------------ Thanks very much Tony ! I will send back a consolidated version sometime before early afternoon for everyone's edits. George -----Original Message----- From: Fauci, Anthony (NIH/NIAID) [E] Sent: Mon 1/18/2010 8:26 AM To: Korch, George (HHS/ASPR/IO) Cc: Kurilla, Michael (NIH/NIAID) [E]; Conrad, Patricia (NIH/NIAID) [E]; Folkers, Greg (NIH/NIAID) [E]; Fauci, Anthony (NIH/NIAID) [E] Subject: RE: Reminder about inputs for the potential White House Briefing on Sustainable Systems approach to MCM's George: I am attaching our 1-pager as requested. Please let me know if you have any questons. Thanks, Tony -----Original Message----- From: Korch, George (OS) Sent: Monday, January 18, 2010 7:52 AM To: Fauci, Anthony (NIH/NIAID) [E]; Robinson, Robin (OS) Subject: Reminder about inputs for the potential White House Briefing on Sustainable Systems approach to MCM's Gentlemen: I will be assembling the information received on how to augment and improve the medical countermeasure enterprise from each of the partners to present to Heidi Avery and others on the NSC staff sometime tomorrow. Thanks in advance for sending your inputs to me so that I can craft a document to redistribute to all concerned. V/r, George 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 For Official Use Only 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. Applied regulatory science can assist on issues such as:  Using biomarkers and more predictive animal models to increase indicators of efficacy.  Using “adaptive” and other flexible clinical trial designs and current information technology sciences to modernize clinical trial design, performance and analysis, reduce costs, and decrease development time  Facilitating more rapid scale up of production  Improving stability of products  Developing quality measurements, assays and standards for novel technologies such as stem cells and engineered tissues  Developing better or faster testing technologies like rapid microbial testing for vaccines to identify accidental or deliberate contaminants. 4. PRODUCT USE AND IMPROVEMENTS When new threats to population health appear, we must be able to rapidly recognize them from the noise of routine health-related activities. Highly flexible diagnostic technologies, such as the multi- array platforms described above, are needed to optimize detection and speed characterization of threats so that effective response actions can be initiated. The approaches taken for broad-spectrum applications and platforms in advanced development could expand into technologies or capabilities for surveillance needs. Performance of these surveillance and diagnostic technologies centers must filter back to the material developers to permit continuous improvement in these technologies. Once an etiology is identified, we must respond with highly effective deployment of the Emergency Public Health Supplies (vaccines, diagnostic tests, drugs and other medical devices and treatments such as ECMO) from publicly held stockpiles, or through enhanced supply mechanisms. Feedback on the success and failures in these deployments must translate back to the appropriate level of this product development enterprise to solve identified issues – thus recalibrating the product for optimized end use. commercially usable drugs, the tension between broad use leading to resistance development, vs.. preserving for resistance and MCM needs. Of interest, perhaps somewhat in between, and in some cases more realistic than truly broad spectrum, are interventions that may be dual or multi-use but not truly "broad spectrum" , such as an antibiotic that might be active both against terrorism threats and against specific resistant organisms in the health care setting. Or a radiation injury treatment that might be useful in cancer therapy, marrow transplantation and in radiation injury. I know this is what is intended by all of us but wanted to emphasize for discussions. One way to discuss for non-medical audiences might be that beyond a single only emergency use, dual use, multiuse and broad spectrum agents and platforms can be part of a more technologically advanced and strategic continuum that can increase economic incentives, US competitiveness, preparedness and health benefits. Thanks Jesse From: Korch, George (HHS/ASPR/IO) [mailto: @hhs.gov] Sent: Tuesday, January 19, 2010 4:31 PM To: Frieden, Thomas (CDC); Commissioner FDA; Fauci, Anthony S (NIH); Goodman, Jesse Cc: Sosin, Daniel M. (CDC); Kurilla, Michael G (NIH); Robinson, Robin (OS); Khabbaz, Rima F. (CDC); Parker, Gerald (OS) Subject: Sustainable systems for PHEMCE products (v8 0 NL)RM jl edits.doc Drs Frieden, Hamburg, Fauci and Goodman: Attached, please find the final version of the paper on the PHEMCE enterprise for discussion this evening with Ms. Heidi Avery and the NSS. Dr. Lurie has also asked that I have available the more fully developed texts that you all provided earlier to further inform the White House staff. V/r, George George W. Korch, Jr. Senior Science Advisor ASPR 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 For Official Use Only 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. Applied regulatory science can assist on issues such as:  Using biomarkers and more predictive animal models to increase indicators of efficacy.  Using “adaptive” and other flexible clinical trial designs and current information technology sciences to modernize clinical trial design, performance and analysis, reduce costs, and decrease development time  Facilitating more rapid scale up of production  Improving stability of products  Developing quality measurements, assays and standards for novel technologies such as stem cells and engineered tissues  Developing better or faster testing technologies like rapid microbial testing for vaccines to identify accidental or deliberate contaminants. 4. PRODUCT USE AND IMPROVEMENTS When new threats to population health appear, we must be able to rapidly recognize them from the noise of routine health-related activities. Highly flexible diagnostic technologies, such as the multi- array platforms described above, are needed to optimize detection and speed characterization of threats so that effective response actions can be initiated. The approaches taken for broad-spectrum applications and platforms in advanced development could expand into technologies or capabilities for surveillance needs. Performance of these surveillance and diagnostic technologies centers must filter back to the material developers to permit continuous improvement in these technologies. Once an etiology is identified, we must respond with highly effective deployment of the Emergency Public Health Supplies (vaccines, diagnostic tests, drugs and other medical devices and treatments such as ECMO) from publicly held stockpiles, or through enhanced supply mechanisms. Feedback on the success and failures in these deployments must translate back to the appropriate level of this product development enterprise to solve identified issues – thus recalibrating the product for optimized end use.