SOURCES SOUGHT
A -- The Synthesis and Preclinical Studies of New Treatments for Neurodegenerative Disease, Diabetes Mellitus, Congestive Heart Failure, Oncologic and Immunologic Disease
- Notice Date
- 4/23/2009
- Notice Type
- Sources Sought
- NAICS
- 541712
— Research and Development in the Physical, Engineering, and Life Sciences (except Biotechnology)
- Contracting Office
- Department of Health and Human Services, National Institutes of Health, National Institute on Mental Health, Contracts Management Branch, 6001 Executive Blvd, Rm 8154, MSC 9661, Bethesda, Maryland, 20892-9661
- ZIP Code
- 20892-9661
- Solicitation Number
- HHS-NIH-NIA-SBSS-09-006
- Point of Contact
- Drake Russell,, Phone: 301-443-0212, Teresa A. Baughman,, Phone: (301) 443-1193
- E-Mail Address
-
russeldr@mail.nih.gov, baughmat@nida.nih.gov
- Small Business Set-Aside
- N/A
- Description
- SOURCES SOUGHT NOTICE RFP Number: HHS-NIH-NIA-SBSS-09-006 This is a Small Business Sources Sought notice. This is NOT a solicitation for proposals, proposal abstracts, or quotations. The purpose of this notice is to obtain information regarding: (1) the availability and capability of qualified small business sources; (2) whether they are small businesses; HUBZone small businesses; service-disabled, veteran-owned small businesses; 8(a) small businesses; veteran-owned small businesses; woman-owned small businesses; or small disadvantaged businesses; and (3) their size classification relative to the North American Industry Classification System (NAICS) code for the proposed acquisition. Your responses to the information requested will assist the Government in determining the appropriate acquisition method, including whether a set-aside is possible. An organization that is not considered a small business under the applicable NAICS code should not submit a response to this notice. BACKGROUND: Within the various laboratories of the National Institute on Aging (NIA), Intramural Research Program (IRP) are several lines of investigational drugs that are not only providing insight into fundamental mechanisms of aging and age-related diseases, but also provide potential targets and agents for therapeutic intervention. This work has resulted in the identification of a number of new chemical entities, which represent lead drug candidates for the treatment of cardiovascular, neurodegenerative, oncologic, and immunological diseases as well as other clinical states associated with the aging process. Initially this work was done under three (3) contracts: N01-AG-3-1008 (Preclinical Toxicology), N01-AG-3-1009 (Synthesis of Lead Compounds), and, N01-AG-3-1011 (Synthesis of Bulk Chemicals and Drugs for Preclinical and Clinical Studies). This program was successfully applied to the identification of (R,R')-fenoterol as a lead drug for the treatment of congestive heart failure and the steps up to the initial "first-into-human" study. The program also indentified a new chemical entity, methoxyfenoterol, as a second generation agent as well as the development of a pharmacophore describing binding to the 2-adrenergic receptor. This pharmacophore lead to the synthesis of additional, highly selective agents. The present contract will be a continuation of the initial program and will include the development of methoxyfenoterol up to the "first-into-human" stage. The program will also work on the development of other possible lead drug candidates identified in the NIA laboratories including agents active in the Central Nervous System (CNS) and inflammatory diseases following the protocols developed during the first project. PURPOSE AND OBJECTIVES: The NIA is planning to procure services in the area of the development of new drug candidates from conception to submission of Investigational New Drug (IND) applications to the FDA. The services are in the following areas: 1) The synthesis and physicochemical characterization of related series of compounds, the structures of which have been determined to be likely to be active at the relevant receptor/target; 2) The screening of synthesized compounds in relevant molecular, cellular, and animal models to determine relative pharmacological activity, the establishment of quantitative structure activity relationships and molecular models necessary to permit the selection of compound(s) for additional studies; 3) The synthesis of selected compound(s) in sufficient quantity under standards of Good Manufacturing Practice (GMP) for use in toxicological evaluations and human studies; and, 4) The evaluation of the acute and chronic toxicity in rodents and dogs of drug candidates including pharmacokinetic study to provide data for interspecies scaling. These drug candidates in the areas of congestive heart failure, neurodegenerative disease, diabetes mellitus, oncologic and immunologic diseases will have toxicological evaluation to the extent that permits filing of an IND to the FDA in order to receive approval to use the drug in humans. For drug candidates selected to be introduced into human, compound stability studies and an appropriate pharmaceutical formulation will be developed. PROJECT REQUIREMENTS: All work shall be done as directed by a Work Assignment (WA). The Contractor shall synthesize, purify, characterize, and submit to the NIA, target compounds of high purity and small libraries of analogs of lead compounds as needed. The total number of target compounds to be delivered per year shall be no less than five (5) nor more than 100. A target compound is defined as one that is assigned by the Project Officer for synthesis, purity evaluation or determination of physio-chemical properties such as stability, solubility, and spectroscopic data. The Contractor shall conduct toxicology and pharmacology studies in accordance with the complete protocol requirements developed by the NIA for each agent. The protocols and required studies will be determined based upon each compound's in vitro cytotoxicity, biochemistry and schedule dependence as well as in vitro activity. The Contractor shall be required to perform the following types of studies: 1) Drug Synthesis Phase: Develop synthesis of required compounds and establish identity and purity using analytical methods such as chromatography and spectroscopy (e.g. IR, NMR, MP, MS, or other emerging methodologies designed by the Project Officer). Develop and validate the procedures for the assay of targeted compounds in biological fluids. 2) Pharmacological Screens: Conduct in vitro receptor binding and activity studies in appropriate cell lines and tissues. Determine drug transporter selectivity and function in appropriated cell lines. Determine presystemic and microsomal metabolism using appropriate cell lines, and sub cellular preparations. Conduct mutagenicity and genotoxicity studies according to FDA requirements. Where appropriate, conduct molecular biology studies of the effect of the lead/test compounds on gene and protein expression(s) using standard techniques such as: Western and Northern blotting, confocal microscopy and gene arrays. Determine construction of Quantitative Structure - Activity Relationships (QSAR) and molecular models (such as CoMFA-Models) to describe and predict receptor ligands interactions. 3) Pharmacokinetic Phase: Plasma elimination kinetics shall be determined in one or both of the following species: beagle dogs and rodents, after a single intravenous dose of drug. Other routes and ministrations such as oral, intraperitoneal, subcutaneous and intramuscular may be necessary to evaluate as well. Bioavailability of non parenteral routes and plasma clearance rates shall be determined in order to establish the dose required to produce effective drug concentrations and plasma for future toxicity studies. 4) Preliminary Phase: For each drug, establish a maximum tolerated dose (MTD) and dose limiting toxicities (DLT) in both beagle dogs and rodents. 5) IND Directed Toxicity Phase: For each drug, establish toxicity and safety in relation to drug plasma concentrations or area under the curve in both beagle dogs and rodents. The types of studies in this phase may include the following, but are not limited to: Single or multiple dose schedules such as Dx1, q3hr x 3, 18hr x 15, etc.; Up to 90 days are repeated administration of drug to rodents and/or beagle dogs; Special studies such as cardiotoxicity, neurotoxicity, immunotoxicity and mutagenesis; and, Canine in murine bone marrow toxicity assessment in vitro and correlation with toxicity occurring in vitro. Rat and monkey marrow as necessary for certain agents under consideration. The desired materials will involve a wide variety of compounds. Methods of synthesis or literature citations will be available for many, but not all WAs. The Contractor shall develop new and/or existing synthetic procedures and process development for scale up to commercial size lots as required. All materials submitted shall be analyzed and checked for identity and purity by accepted procedures. All materials produced or procured shall be accounted for, and will remain Government property, and shall be delivered and distributed as directed by the Project Officer. Appropriate laboratory safety controls and procedures shall be followed in carrying out the activities of this project. The Contractor shall be registered with the FDA as a manufacturer of bulk drugs and maintain such registration throughout the life of the contract. Facilities shall meet FDA standards in accordance with GMP regulations throughout the life of the contract (see: http://www.fda.gov/CDRH/DEVADVICE/32.html ). The Contractor shall be required to comply with Occupational Safety and Health Act (OSHA), Environmental Protection Agency (EPA) regulations regarding the discharge of water and air pollutants and assure that disposal of all chemical residues meet current EPA regulations (see: http://www.osha.gov/ and http://www.epa.gov/ ), as well as, FDA and International Conference on Harmonization (ICH) Guidelines (see: http://www.fda.gov/cber/ich/ichguid.htm ) REPORTS/DELIVERABLES: The following reports will be required: Monthly Technical Progress Report, Final Work Assignment Reports, Annual Technical Progress Report, Report of Unexpected Event, and Final Report. ANTICIPATED PERIOD OF PERFORMANCE: The anticipated period of performance is five (5) years from 3/1/10 through 2/28/15 with one 6-month option period thereafter. OTHER IMPORTANT CONSIDERATIONS: The following Mandatory Qualification Criteria must be met at the time of initial proposal submission: 1) The laboratory facility must be in compliance with the Food and Drug Administration's (FDA) Good Laboratory Practice Regulations (GLP) as published in the December 22, 1978 Federal Register (Volume 43, No. 247, pp. 59986 60025). GLP Regulations are available on the World Wide Web (WWW) at www.fda.gov/ora/compliance_ref/bimo/glp/87finalrule.htm and GLP Regulations Questions and Answers are available at www.fda.gov/cder/guidance/old004fn.pdf. Compliance is documented in an FDA inspection report. A copy of the two (2) most recent FDA GLP inspection reports must be included in the proposal. If only one (1) report exists, it is acceptable to include only that one (1) report. 2) The Laboratory Facility must be in compliance with the Food and Drug Administration's (FDA) Good Manufacturing Processes (GMP) as published in the http://www.fda.gov/CDRH/DEVADVICE/32.html#introduction and the http://www.fda.gov/cdrh/comp/gmp.html. GMP Regulations Questions and Answers are available at http://www.fda.gov/cdrh/devadvice/16.html and http://www.fda.gov/cdrh/devadvice/ide/faq.shtml. A copy of the two (2) most recent FDA GMP inspection reports must be included in the proposal. If only one (1) report exists, it is acceptable to include only that one (1) report. The following Mandatory Qualification Criteria must be met at the time of receipt of Final Proposal Revisions (FPRs) is: The Contractor's animal facilities must be accredited by the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) International as indicated by providing the latest accreditation report. Information about AAALAC accreditation is available on the WWW at www.aaalac.org. The Contractor must also provide an animal welfare assurance indicating compliance with the Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals, information for which is available on the WWW http://grants.nih.gov/grants/olaw/references/phspol.htm and http://grants.nih.gov/grants/olaw/olaw.htm CAPABILITY STATEMENT/INFORMATION SOUGHT: Respondents to this notice must provide, as part of their responses, a capability statement to include the following: (1) information regarding respondents': (a) staff expertise, including their availability, experience, and formal and other training; (b) current in-house capability and capacity to perform the work; (c) prior completed projects of similar nature; (d) corporate experience and management capability; and (e) examples of prior completed Government contracts, references, and other related information; (2) provide any catalog/list prices for services described in this notice; (3) respondents' DUNS number, organization name, address, point of contact, and size and type of business (e.g., 8(a), HUBZone, etc) pursuant to the applicable NAICS code; and (4) any other information that may be helpful in developing or finalizing the OPDIV's acquisition requirements. INFORMATION SUBMISSION INSTRUCTIONS: Respondents should provide responses accordingly: (1) submit information both electronically and by mail. No telephone and facsimile responses will be accepted; (2) format capability statements using Microsoft Word or Adobe PDF including attachments, resumes, charts, etc. Use single space, 12 font minimum and 8 ½ x 11 size paper; (3) organize material in such a manner that clearly identifies and address capability requirements and provide an executive summary; (4) capability statement should not exceed ten (10) single sided pages including references; (5) respondents must send two original copies via mail and one electronic copy via email; (6) responses should be received no later than May 11, 2009 at 1:00 PM Local Time; (7) include respondents' technical and administrative points of contact, including names, titles, addresses, telephone and fax numbers, and e-mail addresses; and (8) send responses to this notice via email to russelldr@mail.nih.gov The original statements mailed using the U.S. Postal Service should be sent to ATTN: Drake Russell, National Institutes of Health, Office of Acquisitions - NIDA Neuroscience COAC, NIA R&D Contracts Management Section, 6001 Executive Boulevard, Room 8154, MSC 9661, Bethesda, MD 20892-9661. If using a courier service such as the UPS, Federal Express, etc., change the City, State and Zip Code to Rockville, MD 20852. (Please be aware that the U.S. Postal Service's "Express Mail" DOES NOT deliver to the Rockville, Maryland address.) DISCLAIMER AND IMPORTANT NOTES: This notice does not obligate the Government to award a contract or otherwise pay for the information provided in response. The Government reserves the right to use information provided by respondents for any purpose deemed necessary and legally appropriate. Any organization responding to this notice should ensure that its response is complete and sufficiently detailed to allow the Government to determine the organization's qualifications to perform the work. 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. After a review of the responses received, a pre-solicitation synopsis and solicitation may be published in Federal Business Opportunities. However, responses to this notice will not be considered adequate responses to a solicitation. CONFIDENTIALITY: No proprietary, classified, confidential, or sensitive information should be included in your response. The Government reserves the right to use any non-proprietary technical information in any resultant solicitation(s)."
- Web Link
-
FedBizOpps Complete View
(https://www.fbo.gov/?s=opportunity&mode=form&id=9cd3fbdc3164ce6b3b63471c9e3f5d5c&tab=core&_cview=1)
- Place of Performance
- Address: Not applicable, United States
- Record
- SN01800462-W 20090425/090423220221-9cd3fbdc3164ce6b3b63471c9e3f5d5c (fbodaily.com)
- Source
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FedBizOpps Link to This Notice
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