cGLP Compliant Contract Research Organizations For Non-Clinical Animal Model Development Studies in Areas of Chemical Medical Countermeasures (MCMs)

U.S. Department of Health and Human Services (HHS) Office of the Assistant Secretary for Preparedness and Response (ASPR) Biomedical Advanced Research and Development Authority (BARDA) Division of Non-Clinical Development REQUEST FOR INFORMATION June 24, 2019 1.0 DESCRIPTION 1.1 The Biomedical Advanced Research and Development Authority (BARDA), within the Office of the Assistant Secretary for Preparedness and Response (ASPR) at the U.S. Department of Health and Human Services (HHS), is seeking information from the public regarding technical capabilities, data, and materials, on current Good Laboratory Practice (cGLP) compliant contract research organizations that are capable of executing non-clinical animal model development studies in the areas of Chemical medical countermeasures (MCMs) against at least one of the following: 1.1.1 Pulmonary agents, cyanide, opioids, and toxic industrial chemicals (TICs); AND/OR 1.1.2 Nerve agents and vesicants (including sulfur mustard), and other OPCW schedule 1 chemical agents. 1.2 THIS IS A REQUEST FOR INFORMATION (RFI) ONLY. This RFI is issued in accordance with Federal Acquisition Regulation (FAR) provision 52.215-3, Request for Information or Solicitation for Planning Purposes, and is solely for information gathering and planning purposes. The RFI does not constitute a Request for Proposal (RFP) or a promise to issue an RFP in the future. BARDA intends to use responses to this RFI for planning purposes towards the possible procurement of services from Non-Clinical Contract Research Organizations (CROs). This notice does not commit the Government to contract for any supply or service whatsoever. Further, BARDA is not seeking proposals at this time and will not accept unsolicited proposals. Respondents to the RFI are advised that the U.S. Government will not pay for any information or administrative costs incurred in response to this RFI; all costs associated with responding to this RFI will be solely at the interested party's expense. Not responding to this RFI does not preclude participation in any future RFPs, if any are issued. If a solicitation is released, it will be synopsized on the Federal Business Opportunities/FedBizOpps website (https://www.fbo.gov/). It is the responsibility of the interested parties to monitor the site for additional information pertaining to this RFI or potential requirement. 2.0 BACKGROUND The U.S. Department of Health and Human Services, through the BARDA, requires the establishment of animal models, for the development of medical countermeasures (MCMs) against Chemical, Biological, Radiological and Nuclear (CBRN) threats, Pandemic Influenza, and Emerging Infectious Diseases (EID). The mission and priorities of the HHS Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) are articulated in the PHEMCE Implementation Plan (link: https://www.medicalcountermeasures.gov/BARDA/documents/2017-phemce-sip.pdf). The Pandemic and All-Hazards Preparedness Act (PAHPA), signed into law on December 19, 2006, and reauthorized in March 2013 under the Pandemic and All-Hazards Preparedness Reauthorization Act of 2013 (PAHPRA), codifies HHS as the lead entity of Federal public health and medical response to public health emergencies and National Response Plan incidents, and specifies that one of the duties of the HHS Assistant Secretary for Preparedness and Response is to oversee advanced research, development, and procurement of qualified countermeasures and qualified pandemic or epidemic products. Section 319L (a)(6): Advanced Research and Development subsection (b) "activities includes": ii) Design and development of tests or models, including animal models, for such testing. The development of animal models is a key element in the successful development of medical countermeasures for CBRN, influenza, and emerging infectious agents, particularly since efficacy of products against most of these threats could never be verified using clinical studies. In 2002, the FDA amended its regulations for drugs and biologics to permit approval or licensure of medical countermeasures based on substantial evidence of effectiveness in animals when adequate and well-controlled efficacy studies in humans are not feasible or ethical. This includes lethal or disabling agents for which exposure to healthy human volunteers would be unethical. This change in the regulations (21 CFR 314.600 for drugs and 21 CFR 601.90 for biologics), commonly referred to as the "Animal Rule," made the design and conduct of adequate efficacy studies in appropriate animal models of paramount regulatory importance, since the inference of efficacy in humans is based on efficacy data derived in animals. 2.1 Discussion: This Notice seeks information from contract research organizations with regard to their qualifications, experience and capabilities to conduct and manage studies related to the development of animal models in support of chemical medical countermeasure development within BARDA's portfolio. The USG seeks laboratories with the capability of controlled exposure of various animal species to chemical agents, to develop models to evaluate the efficacy of potential medical countermeasures: 2.1.1 To pulmonary agents, cyanide, toxic industrial chemicals (TICs), and other potential chemical agents of concern by inhalation ingestion and tropical routes; AND/OR 2.1.2 To nerve agents and vesicants, including sulfur mustard by inhalation, ingestion, and topical routes. Note that responding laboratories must address at least one of the above conditions. The United States Government (USG) seeks appropriate Good Laboratory Practices (GLP) facilities that are adequate and available to establish new or existing animal tests and/or models for the development of CBRN MCMs. In these models, the challenge dose generally should be the same as that which produces the human disease or condition, and the pathophysiological mechanism of its toxicity should be reasonably well-understood and mimic the human disease/condition as closely as possible. When these models are used to test the efficacy of potential MCMs for Chemical agents, the mechanism of action of the countermeasure will need to establish the utility of the animal model as a surrogate for humans. 3.0 REQUESTED INFORMATION The following outline shall be used in the response document: 1) Capability of controlled exposure of various animal species to chemical threat agents in order to develop models to evaluate the efficacy of potential countermeasures to: a. Pulmonary agents, cyanide, opioids, toxic industrial chemicals (TICs); AND/OR b. Nerve agents and vesicants (including sulfur mustard), and other chemical agents by inhalation, ingestion and topical (including ocular) routes. 2) Current approved Federal, State and/or local licenses/certifications for animal work. The USG seeks to conduct work in accordance with all applicable Federal, state and local laws, codes, ordinances and regulations (or if foreign, equivalent regulatory oversight). 3) Capability to provide routine care and health surveillance for laboratory animals, including established protocols and on-call veterinary coverage 24 hours per day. 4) Capability to conduct pilot efficacy studies for candidate MCMs using new or existing animal models or tests to establish the pathophysiology/natural history of threat agents in appropriate animal species. 5) Capability to perform efficacy evaluations in various species on candidate compounds (e.g., drugs and biologics), to permit further product development including, but not limited to, the assessment and optimization of the formulation, route of administration, effective dose level, dose schedule, therapeutic index (i.e. the ratio of the drug/biologic's adverse event plasma concentration over the plasma concentration sufficient for efficacy), and timing of administration (pre-exposure, post-exposure, delayed administration). 6) Capability to develop and/or provide acceptance criteria for the use of challenge material in animal model studies. 7) Capability to provide analytical support to monitor the progression of disease in animal models and demonstrate prospective correlates of protection (e.g., clinical laboratory capabilities and adoption of novel biomarker testing). 8) Statistical and pharmacokinetics support to analyze and predict experimental hypotheses for models, including pharmacokinetic modeling (both individual animal and population approaches using compartmental and non- compartmental methods). 9) The Respondent, or its affiliate/subcontractor, shall possess Federal, State, and/or local licenses, as required, for the storage, use and disposal of chemicals, and training of all associated staff responsible for the use of such material. The Respondent, or its affiliate/subcontractor, shall possess documentation from the Association for the Assessment and Accreditation of Laboratory Animal Care International (AAALAC), certifying accreditation or equivalent. The Respondent, or its affiliate/subcontractor, shall possess a U.S. Department of Agriculture (USDA)-licensed animal research facility, or equivalent. 10) [Only for laboratories responding to 2.2.2] For laboratories approved to work with chemical warfare agents (OPCW Schedule 1), it is expected that the Respondent, or its affiliate/subcontractor, has ready access to chemical threat agents and maintains qualified laboratories with the requisite experience, facilities, capabilities and personnel to handle Schedule 1 agents under all applicable laws. The Respondent, shall provide a detailed narrative demonstrating this capability. In all cases described above, the USG seeks laboratories with the capability to perform these procedures and studies in animal models that may be predictive of human response within all populations, including at-risk and special populations (e.g., pediatric, geriatric, pregnancy, etc.). 4.0 RESPONSES - RFI WHITE PAPER 4.1 Interested parties are requested to respond to this RFI with a white paper. 4.2 RFI white papers shall be in Microsoft Word 2016-compatible format, include two sections as requested below, and due no later than 12:00PM ET on Friday, July 19, 2019. White papers shall be submitted via e-mail only to the Contracting Officer listed below. Please be advised that all submissions become Government property and will not be returned. Enrique Man, Contracting Officer Division of Contracts Management and Acquisition (DCMA) Biomedical Advanced Research and Development Authority (BARDA) E-mail: enrique.manan@hhs.gov 4.3 Page limitations: Section 2 of the white paper shall be limited to five (5) letter-sized pages. The number of pages in Section 1 of the white paper do not count against the 5-page limitation indicated for Section 2 (i.e. the 5-page limitation applies only to Section 2 of the white paper). 4.4 Section 1 of the white paper shall provide administrative information, and shall include the following as a minimum: 4.4.1 Respondent name, mailing address, overnight delivery address (if different from mailing address), phone number, and e-mail address of designated point of contact. 4.4.2 Business type (large business, small business, small disadvantaged business, 8(a)-certified small disadvantaged business, HUBZone small business, woman-owned small business, very small business, veteran-owned small business, service-disabled veteran-owned small business) based upon North American Industry Classification System (NAICS) code 541714, Biotechnology research and development laboratories. "Small business concern" means a concern, including its affiliates that is independently owned and operated, not dominant in the field of operation in which it is bidding on Government contracts, and qualified as a small business under the criteria and size standards in 13 CFR part 121. A small business concern for the purposes of this RFI is generally defined as a business, including its affiliates, with no more than one thousand (1,000) employees. Respondents are cautioned, however, that this is a general description only. Additional standards and conditions apply. Please refer to FAR Part 19 for detailed information on Small Business Size Standards. The FAR is available at http://www.acquisition.gov. 4.5 Section 2 of the white paper shall answer the issues addressed in Section 3.0, Requested Information, of this RFI. Proprietary information, if any, should be minimized and MUST BE CLEARLY MARKED. To aid the Government, please segregate proprietary information. 5.0 QUESTIONS Questions regarding this announcement shall be submitted via e-mail only to the Contracting Officer listed in Section 4.0 of this RFI. Verbal questions will NOT be accepted. The Government does not guarantee that questions will be addressed if received after Wednesday, July 3, 2019. 6.0 SUMMARY THIS IS A REQUEST FOR INFORMATION (RFI) ONLY, IAW FAR 52.215-3, issued to identify current Good Laboratory Practice (cGLP)-compliant contract research organizations that are capable of executing non-clinical animal model development studies in the areas of Chemical medical countermeasures. The information provided in the RFI is subject to change and is not binding on the Government. BARDA has not made a commitment to procure any of the services discussed, and release of this RFI should not be construed as such a commitment or as authorization to incur cost for which reimbursement would be required or sought. All submissions become Government property and will not be returned.