SYNOPSIS: This is a Request for Information (RFI) for planning purposes only, as defined in Federal Acquisition Register (FAR) 15.201e. This is not a solicitation or request for competitive proposals. Responses to this notice are not offers and cannot be accepted by the Government to form a binding contract. It is not to be construed as a commitment by the Government nor will the Government pay for the information solicited. No solicitation document exists or is guaranteed to be issued as a result of this RFI. Respondents are advised that the Government is under no obligation to acknowledge receipt of the information received or provide feedback to respondents with respect to any information submitted. (Note: this RFI is separate from the previously released Chemical, Biological, Radiological, and Nuclear (CBRN) Medical Countermeasures Prime Systems RFI, W9113M-RFI-090001. Responses are requested regardless of whether a response to the previous RFI was submitted). BACKGROUND: The Chemical Biological Medical Systems (CBMS) Medical Identification and Treatment Systems (MITS) Joint Project Management Office (JPMO) is responsible for the development, procurement, fielding, and sustaining of medical treatment and prophylactic capabilities against chemical, biological, radiological and nuclear agents. The current CBMS-MITS portfolio includes therapeutics, pretreatments and prophylactics at varying stages of clinical development, including FDA-approved drugs. PURPOSE AND OBJECTIVES: The Department of Defense has a requirement for a capability to rapidly treat the effects of nerve agent poisoning in the central nervous system. The Centrally-Acting Nerve Agent Treatment System, (CANATS), will encompass the development and addition of a centrally-acting therapeutic to the existing therapy, atropine/oxime/anti-convulsant, as well as to future treatment regimens in order to improve the efficacy of these countermeasures against traditional and non-traditional nerve agents. Current treatment options do not easily cross the blood-brain barrier to counteract the central symptoms of nerve agent poisoning. Research indicates that the addition of such centrally-acting compounds increases survival, reduces morbidity, decreases neurological damage to the brain and improves other treatment outcomes in animal models. The new treatment must provide broad spectrum protection against nerve agent exposure. The objective of issuing this RFI is to gather information that will assist in the determination of a suitable contract solution for the advanced development, FDA-approval, manufacture, and production of the CANATS. As such, CBMS-MITS is seeking information on current industry capabilities from interested entities with potential to meet ANY of the following criteria, IN WHOLE OR IN PART: (1) Description of your company's experience with the program management of technically complex efforts, to include: * Existing capabilities to manage pharmaceutical product development efforts through FDA approval, to include assuming product sponsorship. a. Product(s) taken to FDA licensure/approval, including product type. Examples include small molecule therapeutics, large molecule therapeutics, vaccine, etc. b. Current products under development expected to achieve FDA licensure. Include explanation of product type and current stage of development. Examples include small molecule therapeutics, large molecule therapeutics, vaccine, etc. c. Experience with product development under 21 CFR 314 Subpart I or 601 Subpart H (i.e., the Animal Rule). Include any animal subject concerns. (2) Description of your company's technical expertise in pharmaceutical product development, to include: * Ability to design and conduct non-Good Laboratory Practices (GLP) as well as GLP-compliant testing sufficient to support the filing of an Investigational New Drug (IND) application for clinical testing in humans. a. Experience conducting the following types of research and development studies: efficacy studies; genetic and reproduction toxicology studies; short-term and long-term toxicology studies; range-finding toxicology, toxicokinetic/pharmacokinetic studies; absorption, distribution, metabolism and excretion (ADME) studies; safety pharmacology analysis; mechanism of action studies. b. Experience with designing and developing well characterized animal models. * Ability to manufacture current Good Manufacturing Practices (cGMP)-compliant clinical material to support Phase 1 and/or Phase 2 clinical studies. a. Experience with performing chemistry, manufacturing, and controls (CMC) studies and activities to include: standard characterization; assay development and validation; process development and validation; process scale-up assessments; preparation of technology transfer packages; formulation preparation and analysis; clinical trial formulation development; clinical dose delivery; container closure/extractables/leachables/compatability and sterilization. b. Estimate of small and/or large-scale cGMP-compliant manufacturing capability. c. Experience implementing International Conference of Harmonization (ICH) stability test programs to establish product shelf life, storage conditions and stability; experience conducting stability and compatibility testing of the pharmaceutical with the delivery device. * Ability to manage and conduct clinical study activities, Phase 1 dose escalation/pharmacokinetic studies and Phase 2 expanded safety/drug-drug interaction studies, in accordance with FDA regulations and Good Clinical Practices (GCP) guidelines. a. Experience designing GCP-compliant clinical protocols, informed consent forms, and case report forms sufficient for submission to the Human Subjects Research Review Board (HSRRB). b. Experience managing day-to-day clinical study operations, to include study drug and study supplies inventory management, severe adverse event management, and safety monitoring board management. Experience with clinical study data management, archiving and final study report generation. c. Experience with the design and conduct of the bioanalytical and pharmacokinetic (BA/PK) aspects of human clinical trials as well as with the analysis and evaluation of BA/PK data from human clinical trials. d. Experience with statistical planning and analysis should include developing a detailed statistical analysis plan, developing a subject randomization scheme, conducting interim and final analyses, and preparing a final statistical report. e. Experience in designing clinical protocols to evaluate a multi-drug treatment regimen. (i.e., evaluate drug-drug interactions for concomitantly administered pharmaceuticals) * Ability to evaluate and incorporate enabling technologies critical to enhance and/or prolong the drug product shelf life. a. Individual unique identification (IUID) and visual temperature to time indicator (TTI) product labeling, other than syringe and needle administration, and stabilizing technologies to ensure stability across a wide range of temperatures. (3) Description of your company's experience with FDA regulatory interactions leading to product approval/licensure, to include: a. Ability to manage activities related to the development of an IND application and New Drug Application (NDA)/Biologics License Application (BLA) submissions. Describe experience with submissions in an electronic Common Technical Document (eCTD) format. b. Engaging in meetings, Types A, B and C, with the FDA and preparation of pre-meeting information packets. c. Preparation and submission of Special Protocol Assessments. Respondents are invited to provide materials related to their capabilities to fulfill ALL or ANY of the requirements specified above. Respondents should provide whether their level of interest and current capability is to fulfill the entire scope of the effort, or a limited aspect of the effort, such as teaming as a subcontractor with another firm. The Government will retain comments and information received in response to this RFI. Proprietary information should be identified as Company Proprietary. Do not use Government Security classification markings. Questions regarding this RFI should be forwarded to the CBMS e-mail address listed below within five (5) days after RFI release. SUBMISSION INSTRUCTIONS: All written responses must be received within fifteen (15) days of issuance of this RFI. Submissions should: (1) use Microsoft Word or Adobe Portable Document Format (PDF); (2) be sent to
[email protected]; (3) be minimum 11 font on 8.5" X 11" paper; (4) be complete, sufficiently detailed, and organized in a manner that tracks to the information requested in this RFI; (5) include a single company point of contact with name, title, address, telephone and fax numbers, and e-mail address(es); and (6) not exceed 10 single sided pages in total (not including cover page and cover letter). Other media types (i.e. CD, printed technical information) that meet the submission criteria above will be accepted and should be sent to the US Army Research, Development and Engineering Command, ATTN: Leo Fratis, 64 Thomas Johnson Drive, Frederick, Maryland 21702. Material that is advertisement only in nature is not desired.