SOURCES SOUGHT
A -- Studies of the Absorption, Distribution, Metabolism, and Excretion (ADME) of Compounds in Animal Model Systems
- Notice Date
- 8/11/2010
- 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 of Environmental Health Sciences, Office of Acquisitions, Office of Management, 530 Davis Drive, Durham, North Carolina, 27713, United States
- ZIP Code
- 27713
- Solicitation Number
- NIHES2010105
- Archive Date
- 9/28/2010
- Point of Contact
- David C. Sedgley, Phone: (919)541-4027, WANDA M. HOLLIDAY, Phone: 919-541-0943
- E-Mail Address
-
sedgley@niehs.nih.gov, hollida1@niehs.nih.gov
(sedgley@niehs.nih.gov, hollida1@niehs.nih.gov)
- Small Business Set-Aside
- N/A
- Description
- THIS IS A RESEARCH AND DEVELOPMENT SOURCES SOUGHT NOTICE. THIS IS NOT A SOLICITATION ANNOUNCEMENT FOR PROPOSALS AND NO CONTRACT WILL BE AWARDED FROM THIS ANNOUNCEMENT. The National Institute of Environmental Health Sciences is requesting information to determine the availability of interested businesses to compete for a contract to study the absorption, distribution, metabolism, and excretion (ADME) of compounds in NTP Animal Model Systems. The purpose of the sources sought notice is to ascertain the interest in this effort by offerors which have the capability of performing the studies which have or do not have the capability to meet Good Laboratory Practices (GLP). NIEHS is also interested in hearing from independent organizations that have the capability of providing GLP capabilities to organizations that do not currently provide that capability. The contractor shall procure detailed Absorption, Distribution, Metabolism, and Excretion (ADME)/CHEMICAL DISPOSITION data from a number of studies of selected environmental contaminants or model compounds per year. Most of these studies will be required in laboratory rodents of various strains specified by the Contracting Officers Technical Representative (COTR). Studies may be conducted in animals of different age groups representing different potential periods of susceptibility to toxicants. Most studies will address the fate of organic chemicals; however, studies of inorganic compounds may also be requested. Individual studies may vary in complexity from preliminary investigations of chemical absorption to detailed studies of all phases of ADME Chemical Disposition, toxicokinetics, and mechanism. The immediate goal of these studies is to facilitate the design (accurate determination of doses) and interpretation of National Toxicology Program (NTP) bioassay studies and support the research objective of the NTP Host Susceptibility Program. The long-range goal is the accumulation of data that will permit a better assessment of structure-activity relationships, chemical absorption, metabolism and disposition in laboratory animals and to better interpret the significance of these data to man. A secondary goal is to add expertise and capacity for new NTP animal model systems that require both characterization of chemical disposition (ADME) in multiple inbred and out bred species and genetically defined inbred strains or genetically-defined out bred stocks of those species as well as genetically-modified animal models in order to identify polymorphic genetic loci of genic or non-genic, including epigenetic, sequences that influence ADME pathways and toxicity outcomes. Therefore, this statement of work reflects the nature and substance and specifications required by NTP nominations for both conventionally used species and strains as well as new models that incorporate genetic diversity and genetic definition in populations of those species to model human population level genetic diversity. For example, current ADME studies with benzene are being conducted using a complement of 20 inbred mouse strains (as described http://mouse.perlegen.com/mouse/index.html and http://phenome.jax.org/pub-cgi/phenome/mpdcgi and other strains as necessary. Together, these studies aim to quantify individual genetic differences (e.g. populations of inbred strains or outbred stocks) in ADME and toxicity phenotypes, which will provide valuable data for hazard identification and risk assessment procedures and data required from animal models for extrapolation to human exposure. The multi-strain ADME mouse studies with benzene for NTP in progress have been substantially completed. The preliminary findings for benzene ADME indicate significant differences (2-10X) between the 18 strains analyzed for all kinetic parameters and at least one major unique metabolite was identified in one strain. Significant between strain and tissue site-specific differences were observed between male and females mice as hypothesized. Completions of these studies and analysis of the studies by NTP scientists and collaborators for both modeling and quantitative trait analysis and the identification of candidate polyvariant genes will make a significant contribution to toxicology. Determining a genetic and mechanistic basis for these differences between strains is critical. Investigation of ADME kinetic parameters following benzene exposure in multiple strains of mice has shown significant and variable range of differential response in the kinetics of benzene exposure and disposition. Analysis of data from multiple inbred strains of mice that show significant differences between strains for ADME kinetics may alter the requirements and methods for PBPK modeling and toxicokinetics and toxicodynamics and ultimately offer mechanistic explanations for in vivo toxicity and carcinogenicity results critical for hazard identification and human risk assessment. To assist in this effort, it will be required that offertory provide data to the Contracting Officer's Technical Representative (COTR) in a form that will facilitate more in-depth analysis by bioinformatics and genomic approaches (at NIEHS or under an independent NIEHS subcontract). This will usually consist of providing individual animal data in a commonly used spreadsheet program such as Excel, FileMaker Pro, Adobe Acrobat etc. or tab-delimited text. It is anticipated this will add little or no increase in cost, since most data is tabulated in such formats. Since these projects may be dissimilar in design, the COTR requires close communication with the PI. The COTR will specify agents for study and in coordination with the PI a study design will be developed. During the conduct and reporting of the study, weekly communication with the PO via email, telephone, fax, etc. is anticipated. The ultimate goal of all these studies is publication in quality peer reviewed journals and NTP peer reviewed technical reports. b. Specific Requirements (1) The contractor shall complete one or more studies each contract year depending on the complexity of the study. A study shall consist of the determination of absorption, distribution, metabolism and excretion of one exposure concentration of a selected compound in multiple strains of a given species. Identification of unknown metabolites may be complex enough to be considered a separate study. Estimation of toxicokinetic parameters may be requested for selected chemicals and will be considered a separate study. One or more studies per year may be requested to investigate comparative metabolism of chemicals in human and rat liver microsomes or hepatocytes in vitro. The complete characterization of the ADME/CHEMICAL DISPOSITION of a chemical could consist of several studies depending on the needs of the Program. For costing purposes, 2 studies per year may be conducted using the strains described on the NTP Mouse Genome Resequencing Project (http://mouse.perlegen.com/mouse/index.html or http://phenome.jax.org/pub-cgi/phenome/mpdcgi and other strains/stocks as necessary, plus appropriate founder strains for cohorts of 20 or more strains) in one or both sexes of each strain or stock. A study will require a minimum of 25 animals per sex/strain held for a maximum of 4 weeks. Blood, urine and 3 tissues will be analyzed for total isotope concentrations for up to 96 hours and one or more strains analyzed for parent and metabolite profiles in blood and urine, including unknown metabolites. Further details are described below. (2) The compounds for study shall be selected by the COTR. Unless a satisfactory analytical procedure is available for unlabeled compounds and both parties agree to its use, radioisotope or stable-isotope labeled compounds shall be procured from a commercial source to facilitate the assay. 3) The protocol for each study shall be developed by the COTR in cooperation with the Principal Investigator and the scientist in charge of the toxicology studies working with the study design team. The protocol for study may include but is not limited to such items as the following: a) Determination of dermal, intravenous, and/or gastrointestinal absorption of radioisotope or stable-isotope labeled test compounds, b) Development of analytical methodology to separate and to quantitative parent compound and metabolites in tissue extracts and biological fluids; c) Isolation and identification of major metabolites by standard analytical chemical techniques including extraction, chromatography and analysis by HPLC and HPLC-mass spectrometry (HPLC-MS) and nuclear magnetic resonance spectroscopy (NMR); d) Measurement of excretion of parent compound and/or metabolite(s) in expired air, urine, feces and bile; e) In vitro studies to confirm site and primary types of metabolism involved in chemical degradation including studies with rodent or human liver microsomes, enzymes, microsomes, gut microbes, isolated hepatocytes or other primary cell cultures, and/or perfusion of tissues/organs; f) Routine chemical synthesis, including derivatization and simple organic synthesis of putative metabolites or other intermediates of metabolism; g) Estimation of kinetic rate constants for absorption, distribution, and elimination. The government estimates that the project will require the work of one professional man-year and three and a half technical/administrative personnel man-years in each contract year. The Government would prefer that the Principal Investigator and Co-Principal Investigator have a minimum of 5 years relevant Post-Doctoral Degree experience. The estimated annual level of effort is 9,360 labor hours. Award of one cost-reimbursement, level of effort contract on an open competition basis is contemplated as a result of this solicitation. The contract obtained under this solicitation will continue the work of a similar contract, N01-ES-45529. The period of performance for the contract is five years, beginning on or about September 2011 through September 2016. The contract would have one base year and four one year option extensions. The following is a list of equipment and special facilities required under contract: 1) Facilities for animal receipt, housing treatment and care, 2) Facilities for safe receipt, storage and use of toxic and radio-labeled chemicals, 3) Metabolism cages which permit humane housing of rats and mice for extended times and separate collection of urine, feces, exhaled volatiles and C02, 4) Equipment for quantitative chemical analysis e.g. HPLC, HPLC-MS, gas liquid chromatography, UV-visible spectrophotometer, mass spectrometer, nuclear magnetic resonance spectrometer, HPLC-MS, plus the usual complement of minor laboratory equipment, 5) Equipment for quantitative analysis of radioactivity in chemical and biological samples, e.g. liquid scintillation counter, biological sample oxidizer and HPLC radio-detector, and 6) Equipment for studies of chemical metabolism in vitro, e.g., liver perfusion apparatus, incubator, and homogenizer, centrifuges, water baths and extraction apparatus. The facility must be AAALAC approved (or the equivalent). Interested organizations should submit two (2) copies of their capability statement, not to exceed fifteen (15) pages in length, excluding standard brochures, for receipt by the agency within thirty (30) days from the date of this announcement. Standard company brochures will not be considered a sufficient response to this sources sought synopsis. In the capabilities statements, contractors should provide their size status for the NAICS Code (541712) and whether or not they are a certified HUBZone, 8(a), Woman-Owned, Small Disadvantaged and/or Service Disabled Veteran-Owned or Veteran-Owned Small Business concern. An RFP will be synopsized on the FedBizOpps Website at a later date. Mail capability statements to: David Sedgley, P.O. Box 12874, Research Triangle Park, NC 27709; or by PDF to e-mail address sedgley@niehs.nih.gov. For commercial delivery, send to David Sedgley, 530 Davis Drive, Durham, NC 27560. NAICS Code is 541712. 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. Information provided will be used to assess tradeoffs and alternatives available for the potential requirement and may lead to the development of a solicitation. 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. Any solicitation resulting from the analysis of information obtained will be announced to the public in Federal Business Opportunities in accordance with the FAR Part 5. Respondents will be added to the prospective offerors list for any resultant solicitation. However, responses to this notice will not be considered 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 solicitations.
- Web Link
-
FBO.gov Permalink
(https://www.fbo.gov/spg/HHS/NIH/NIEHS/NIHES2010105/listing.html)
- Record
- SN02236840-W 20100813/100811235434-7368e721ad69980c34bd494960a7a787 (fbodaily.com)
- Source
-
FedBizOpps Link to This Notice
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