SOLICITATION NOTICE
A -- Development of Improved DTPA for Radionuclide Chelation
- Notice Date
- 4/26/2005
- Notice Type
- Solicitation Notice
- NAICS
- 541710
— Research and Development in the Physical, Engineering, and Life Sciences
- Contracting Office
- Department of Health and Human Services, National Institutes of Health, National Institutes of Allergy and Infectious Diseases, Contract Management Program 6700 B Rockledge Room 3214 MSC7612, Bethesda, MD, 20892-7612
- ZIP Code
- 20892-7612
- Solicitation Number
- RFP-NIH-NIAID-DAIT-05-46
- Response Due
- 6/8/2005
- Archive Date
- 6/23/2005
- Description
- This notice is a COMBINED SYNOPSIS/SOLICITATION for other than commercial items. This announcement constitutes the only solicitation; offers are being requested and a written solicitation will not be issued. This procurement is being conducted under the Simplified Acquisition Procedures (SAP) set forth in FAR Part 13. This notice is being issued as a Request for Proposal (RFP) support the discovery and demonstration of proof-of-concept of prodrugs or alternative (oral, inhalation, or transdermal) formulations of DTPA that deliver plasma levels sufficient to decorporate systemic transuranyl compounds for use by the general public in case of radiation emergencies. Background The potential for radiation exposures to occur from terrorist acts, radiation accidents or nuclear detonation mandates that the health care system develop and implement preparedness plans that include the stockpiling of radioprotective drugs and therapeutics. Radiation exposure can occur from external irradiation, external contamination with radioactive materials, and internal contamination by inhalation, ingestion or absorption through skin or wounds. The removal of internal radioactive contaminants can be accomplished by administering chelating agents that can preferentially complex with radionuclides in the body and increase their rate of clearance, thereby decreasing radiation exposure. Pentetate (diethylenetriaminepentaacetate) calcium trisodium (Ca-DTPA) and pentetate (diethylenetriaminepentaacetate) zinc trisodium (Zn-DTPA) have been shown to be effective in treating internal contamination with radionuclides such as plutonium, americium, or curium. DTPA increases the rates of elimination of these substances from the body through the exchange of calcium or zinc ions with the transuranium element. The transuranium-DTPA complex is stable and is excreted in urine. The calcium salt is 10X more effective than the zinc salt of DTPA in the first 24 hours following internal contamination, but after 24 hours, the salts are similarly effective. DTPA has been available for distribution from the Radiation Emergency Assistance Center/Training Site under an IND and formulations of Ca-DTPA and Zn-DTPA suitable for intravenous administration, or inhalation via nebulizer, were approved by the FDA in August 2004. Other formulations (for example oral, inhalation or transdermal) would be more easily administered than the injectable formulations, making DTPA easier to use in a mass casualty situation; however, because of its hydrophilicity, DTPA is poorly absorbed when administered by these routes. The NIAID is interested in facilitating the discovery and demonstration of proof-of-concept of prodrugs, alternative formulations, or alternative delivery methods of DTPA that provide for plasma levels sufficient to decorporate systemic transuranic compounds for use by the general public in the case of a radiation emergency. In addition, the NIAID is interested in facilitating the development of prodrugs, alternative formulations, or alternative delivery methods that provide for lung clearance of transuranic compounds and that can be used in a mass casualty situation. The ultimate goal of the DTPA development effort is to identify effective candidates that could be evaluated for inclusion in the Strategic National Stockpile. The NIAID anticipates awarding up to three (3) contracts based on technical merit, available funds, scientific priority, and programmatic balance. The NIAID estimates that the average total cost (direct and indirect cost combined) for these contracts will be greater than $1 million per contract; however, it is anticipated that the total cost for each award may vary depending upon the scope of the project and the technical objectives of the award. The length of time for which funding is requested should be consistent with the nature and complexity of the proposed research. The period of performance is expected to be a total of twenty-one (21) months. The anticipated base contract period (Phase 1) will be fourteen (14) months with Option 1 (Phase 2), if exercised, being seven (7) months. Statement of Work Independently and not as an agent of the Government, the Offeror shall furnish the necessary service, qualified personnel, material, equipment and facilities not otherwise provided by the Government as needed to perform the work described below. The Offeror is expected to develop and execute a plan for the development of an alternative structure (specifically a prodrug which can be metabolized to yield DTPA), formulation or delivery method of DTPA that does not require intravenous injection in order to achieve sufficient levels in plasma and sufficient decorporation of systemic transuranic compounds, or improved clearance of transuranic compounds or ease of use in the case of inhaled transuranic compounds. This contract will provide for initial discovery of lead compound(s) or formulations to the proof-of-concept stage (demonstration of adequate pharmacokinetics and effective elimination of transuranic compounds) and will be funded in two phases; therefore, funding for Phase 2 is contingent upon acceptance of progress by the NIAID Project Officer and program staff in consultation with the Offeror. Phase 1 will include the planning, synthesis, assay development and screening of drug candidates or formulations. Phase 2, which will be funded after successful completion of Phase 1 and selection of lead candidates in consultation with and after approval of the NIAID Project Officer, will include the evaluation of pharmacokinetics and decorporation efficacy of lead candidates. The results will be evaluated to select the best candidates for further testing and development under a separate contract. The ultimate goal of the DTPA development effort is to identify effective candidates that could be evaluated for inclusion in the Strategic National Stockpile. Specifically, the Offeror will: Phase 1: 1. Design a strategy and technical approach to develop effective DTPA prodrugs, formulations or delivery methods that allow for the rapid absorption and bioavailability of DTPA at rates and quantities equivalent to intravenous administration or improved ease-of-use in the case of lung clearance of inhaled radionuclides. The strategic plan should include how cGMP manufacture would be accomplished. The Offeror should be aware of the patent licensing and exclusion issues regarding their product innovation(s) and describe the steps that the Offeror has taken to ensure that the resulting product may be developed for use as nuclear contamination countermeasures. 2. Synthesize and formulate quantities of DTPA drug candidates for evaluation of physiochemical properties, in vitro and/or in vivo absorption kinetics, bioavailability in vivo and radionuclide chelation efficiency. 3. Develop and conduct a screening strategy to select appropriate DTPA prodrugs and formulations for further testing (such as partition coefficients, in vitro absorption models, in vivo absorption models, in vitro chelation models). 4. Develop analytical methods for the detection and measurement of DTPA both in product formulations and in biological fluids. If DTPA has been covalently modified to form a prodrug, a method for the discrimination of native and modified DTPA shall be included. 5. Provide a Phase 1 Milestone Report including strategy and technical approach for Phase 2. Phase 2 (Option ? Funding contingent upon acceptance of Phase 1 DTPA prodrugs, formulations or delivery method.): 1. Conduct in vivo studies in rodents to compare absorption kinetics, bioavailability and decorporation efficacy of DTPA administered intravenously and selected lead candidate(s) of modified DTPA administered by appropriate route (such as oral, inhalation or transdermal). These studies will include general observations to assess toxicity of the formulation and an estimate of the Maximum Tolerated Dose. Offeror must have or have access to facilities licensed to perform in vivo chelation experiments using appropriate transuranic elements or their equivalents. 2. Provide Phase 2 and Final Reports. References: http://www.fda.gov/cder/guidance/6455fnl.htm - Guidance for Industry, Calcium DTPA and Zinc DTPA Drug Products ? Submitting a New Drug Application. http://www.fda.gov/cder/guidance/6394dft.htm - Guidance for Industry, Internal Radioactive Contamination ? Development of Decorporation Agents. http://www.fda.gov/cder/foi/label/2004/021749lbl.pdf - Ca-DTPA Package Insert. http://www.fda.gov/cder/foi/label/2004/021751lbl.pdf - Zn-DTPA Package Insert. Review and Award Criteria Selection of an Offeror for contract award will be based on an evaluation of proposals against three factors. The factors in order of importance are: (1) technical merit and (2) cost and (3) past performance. Although technical factors are of paramount consideration in the award of the contract, cost is also important to the overall contract award decision; however, all evaluation factors other than cost or price, when combined, are significantly more important than cost or price. In any case, the Government reserves the right to make an award to that Offeror whose proposal provides the best overall value to the Government. In accordance with FAR 15.3, the award will be subject to a cost realism analysis by the Government. The NIAID reserves the right to make an award without discussions. The evaluation will be based on the demonstrated capabilities of the prospective Offerors in relation to the needs of the project as set forth in the RFP. The merits of each proposal will be carefully evaluated. Each proposal must document the feasibility of its plan to successfully achieve the objectives of the RFP. Offeror must submit information sufficient to evaluate their proposals based on the detailed criteria listed below. 2. TECHNICAL EVALUATION CRITERIA The technical evaluation committee will use these evaluation criteria when reviewing the technical proposals. Proposals will be judged solely on the written material provided by the Offeror. The criteria below are listed in the order of relative importance with weights assigned for evaluation purposes. CRITERIA Scientific and Technical Approach to Statement of Work Points: 60 Technical approaches for proposals submitted will be evaluated with respect to the following: 1) Technical adequacy and feasibility of proposed screening strategy (as proposed in the Statement of Work ? Phase 1) to determine lead candidates and technical adequacy and feasibility of analytical methods to be used to detect, differentiate and quantitate DTPA and modified DTPA (if applicable) and chelated target molecule(s) (25 points) 2) Technical adequacy and feasibility of proposed methods for in vivo testing of the lead candidates (as proposed in the Statement of Work ? Phase 2) for proof of concept (bioavailability and efficacy). (20 points) 3) Comprehensiveness of the approach and scientific soundness of the methodology proposed to develop and synthesize DTPA prodrug(s), formulation(s) or delivery method(s) for DTPA and plans for cGMP production as described in the Statement of Work. (15 points) Personnel Qualifications Points: 30 1) Documented evidence of the qualifications, experience, and availability of Principal Investigator in managing drug development projects, preferably in the field of metal chelation. (15 points) 2) Documented evidence of the qualifications, experience, and availability of all technical personnel in working with drug development tasks; in particular, compound synthesis, detection assay development, pharmacology and metal chelation assays. Adequacy of the management plan, staffing and organizational structure. (15 points) Facilities and Resources Points: 10 Adequacy and availability of appropriate laboratories, and animal care facilities (including AAALAC accreditation or equivalent), equipment, and resources, including radiation licensing and safety procedures, necessary to safely and efficiently accomplish the studies proposed. Also, an offeror needs to provide a letter, signed by an authorized official, indicating their agreement to a pre-award site visit of their facility. The Government reserves the right to perform a pre-award site audit, if necessary. Total: 100 Points 3. EVALUATION OF PAST PERFORMANCE An evaluation of Offeror?s past performance information will be conducted subsequent to the technical evaluation. However, this evaluation will not be conducted on any Offeror whose proposal would not be selected for award based on the results of the evaluation of factors other than past performance. The evaluation will be based on information obtained from references provided by the Offeror, other relevant past performance information obtained from other sources known to the Government, and any information supplied by the Offeror concerning problems encountered on the identified contracts and corrective action taken. The government will assess the relative risks associated with each Offeror. Performance risks are those associated with an Offeror?s likelihood of success in performing the acquisition requirements as indicated by that Offeror?s record of past performance. The assessment of performance risk is not intended to be a product of a mechanical or mathematical analysis of an Offeror?s performance on a list of contracts but rather the product of subjective judgment by the Government after it considers relevant information. When assessing performance risks, the Government will focus on the past performance of the Offeror as it relates to all acquisition requirements, such as the Offeror?s record of performing according to specifications, including standards of good workmanship; the Offeror?s record of controlling and forecasting costs; the Offeror?s adherence to contract schedules, including the administrative aspects of performance; the Offeror?s reputation for reasonable and cooperative behavior and commitment to customer satisfaction; and generally, the Offeror?s business-like concern for the interest of the customer. The Government will consider the currency and relevance of the information, source of the information, context of the data, and general trends in the Offeror?s performance. 4. PRE-AWARD SITE AUDIT An evaluation of the adequacy of the facilities and resources provided by the Offeror may be conducted at the discretion of the Government prior to award. When assessing the facilities and resources, the Government will focus on the adequacy and availability of appropriate laboratories, equipment and animal care facilities and will include an audit of the Offeror?s radiation licensing and safety procedures. Deliverables The Offeror shall provide the following information to the NIAID Program Officer and Contracting Officer: 1) Quarterly Progress Report: Every 90 days the Offeror shall submit a Quarterly Technical Progress Report. A Quarterly Progress Report will not be required for the periods when the Milestone or Final Reports are due. Preprints and reprints of papers and abstracts shall be submitted with the Milestone or Final Reports. Such reports shall include the following specific information: a. Cover Page: List the contract number and title, the period of performance being reported, the Offeror's names and address, the author(s), and the date of submission. b. SECTION I (Introduction): Describe the purpose and scope of the contract effort for the period covered. c. SECTION II (Results): Detail, document, and summarize the results of work done during the period covered. These reports shall be in sufficient detail to explain the results achieved. The description shall include pertinent data and/or graphs in sufficient detail to explain any significant results achieved and preliminary conclusions resulting from analysis and scientific evaluation of data accumulated to date under the project. A one-page summary of each ongoing and completed protocol shall be submitted at this time. d. SECTION III (Substantive Performance): Describe the current technical or substantive performance and any problems encountered and/or which may exist along with proposed corrective action. Also to be included is an explanation of any difference between planned progress and actual progress, why the differences have occurred, and if behind planned progress, what corrective steps are planned. e SECTION IV (Experimental Plan) Summarize the work proposed for the next reporting period. 2) Phase 1 Milestone Report: When the work in Phase 1 has been completed, the Offeror shall submit a comprehensive Milestone Report. The Milestone Report shall detail, document and summarize the results of the first phase of work performed to fulfill the requirements as specified in the Statement of Work and shall be comprised of a cover page and Sections I and II as specified for the Quarterly Progress Report, above. A strategic plan for the work proposed in Phase 2 will also be included in the Milestone Report. Preprints and reprints not submitted previously shall be submitted. The Offeror will also prepare and present results and plans to the NIAID Project Officer, and other individuals involved in the Radiation/Nuclear Program prior to consideration for Phase 2 funding. A decision regarding funding for Phase 2 will be made within 30 days of the presentation of Phase 1 data. 3) Phase 2 (if funded) and Final Report: By the expiration date of the contract, the Offeror shall submit a comprehensive Phase 2 and Final Report. This Report shall detail, document and summarize the results of the second phase of the contract and the entire contract work for the period covered, and shall be comprised of a cover page and Sections I and II as specified for the Quarterly Progress Report, above. Preprints and reprints not submitted previously shall be submitted. Full reporting of inventions (including name(s) of inventor(s), title(s) of invention(s) and date each invention was reported to NIH) first conceived or actually reduced to practice, as well as any copyrights produced, under the contract will also be included in the Phase 2 and Final Report. The Offeror will also prepare and present results and plans to the NIAID program officials. Submission: Three (3) hard copies, comprising of two (2) copies to the Project Officer and one (1) copy to the Contracting Officer, and one (1) electronic copy of each report shall be sent to the Project Officer. Addresses/Distribution: Contracting Officer, NIAID, 6700-B Rockledge Drive, Bethesda, MD 20892 and Project Officer, NIAID 6610 Rockledge Drive, Bethesda, MD 20892 Point of Contact Donald E. Collie, Contract Specialist, Phone 301-496-0992, Fax 301-480-4675, Email dc128b@nih.gov ? Olga Acosta-Polston, Senior Contracting Officer, 301-435-4322, Fax 301-480-4675, Email oapolston@niaid.nih.gov
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