cGLP Compliant Contract Research Organizations For Non-Clinical Animal Model Development Studies in Areas of Radiological and Nuclear (Rad-Nuc) Medical Countermeasuers (MCM)

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 August 23, 2019 1.0 DESCRIPTION 1.1 The Office of 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 on technical capabilities, data and materials from the public on current Good Laboratory Practice (cGLP) compliant research organizations that are capable of executing nonclinical animal model development studies in the areas of radiological and nuclear (Rad-Nuc) medical countermeasures (MCM). 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 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), intends to use responses obtain through this RFI for planning purposes toward the possible procurement of services from Nonclinical Contract Research Organizations (CROs). The Department of Health and Human Services, through the BARDA, requires the establishment of animal models for the development of medical countermeasures (MCM) for Chemical, Biological, Radiological, Nuclear (CBRN); 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: 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 June 2019 under the Pandemic and All-Hazards Preparedness and Advancing Innovation Act (PAHPAIA), 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. This Notice seeks information from contract research organizations with regard to their qualifications, experience and capability to conduct and manage studies related to the development of animal models in support of radiological and nuclear medical countermeasure development within BARDA's portfolio. 3.0 REQUESTED INFORMATION The following outline shall be used in the response document: 1) Capability to conduct animal models studies related to the development of animal models in support of radiological and nuclear medical countermeasure development including: a. Animal Model i. Animal species/strain ii. Maximum number of each on study iii. Unique capabilities b. Clinical Observations i. Cage-side procedures & frequency ii. Clinical procedures & frequency c. Laboratory Capabilities (Flow cytometry, PCR, FISH, etc...) d. Euthanasia Criteria including IACUC allowance of minimal supportive care if applicable 2) Capability to perform radioisotope exposure studies using internal delivery (Plutonium, Americium, Cesium, Strontium/Yttrium, Iridium, Uranium). 3) Capability to perform radiation exposure studies using Cs-137, Co-60, LINAC, X-ray or other accepted instrumentation for controlled exposures of animals to Beta-irradiation, lethal and non-lethal ionizing radiation within the constraint of acceptable dose rates, with uniform field flux and field sizes for large and small animals. a. Radiation Source b. AAPM dosimetry methods i. Calibration Frequency of Devices ii. Secondary Units c. Irradiator Availability i. Distance between irradiator and animal housing ii. Irradiator shared with any other research or clinical groups d. In-house dosimetry expertise e. Irradiation daily throughput f. ILPs for animals listed under animal husbandry g. Recalibration and performance verification schedule h. Partial body irradiation 4) Capability to provide routine care and health surveillance for laboratory animals, including afterhours/weekend necropsy, sample collection, onsite analytical capabilities, established protocols and on-call veterinary coverage 24 hours per day. 5) Capability to collect and store samples including the equipment, amount of space available and length of time for storage. a. Sterile tissue collection, storage, transport for microbiology b. RND/DNA sample collection c. Histology 6) Capability including throughput to perform onsite imaging analysis: in vitro and in vivo capabilities, whole body, and organ specific including vascular imaging techniques. 7) Capability including throughput to analyze hematology samples: coagulation assays, CBCs with differentials (WBC, RBC, neutrophils, platelets, lymphocytes, reticulocytes), bone marrow cellularity, flow cytometry and peripheral blood smears. 8) Capability to conduct pilot efficacy studies for candidate MCMs using new or existing animal models or tests (see C.1.1.) to establish the pathophysiology/natural history of threat agents in appropriate animal species. 9) Capability including throughput to report clinical chemistry values including species and site-specific reference ranges if applicable. 10) Capability to perform efficacy evaluations in various species on candidate compounds (e.g., drugs and biologics) as specified in the Task Order Statement of Work, 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). a. Pharmaceutical reconstitution i. Drug storage, administration and expiration SOPs ii. Other preparatory steps b. MCM and decorporation compounds experience 11) Capability to develop and/or provide acceptance criteria for the use of compound in animal model studies. 12) 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). 13) 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). 14) Capability to perform studies under GLP 15) Summary of systems for data management and control 16) Description of quality assurance program 17) 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). 18) The Offeror or its subcontractor shall possess Federal, State, and/or local licenses as required for the storage, use, and disposal of materials and training of all associated staff responsible for the use of such material. The Offeror or its subcontractor shall possess documentation from the Association for the Assessment and Accreditation of Laboratory Animal Care International (AAALAC) certifying accreditation or equivalent. The Offeror or its subcontractor shall possess U.S. Department of Agriculture (USDA) - licensed animal research facility, or equivalent. In all cases described above, the USG seeks laboratories with the capability to perform these procedures and studies in animal models of human 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, and a completed Capability Matrix (Attachment 1). 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, September 13, 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 (CMA) 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, September 4, 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 Rad-Nuc 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.