SOLICITATION NOTICE
R -- COMPETITIVE BINDING ASSAY
- Notice Date
- 8/28/2003
- Notice Type
- Solicitation Notice
- Contracting Office
- Environmental Protection Agency, Office of Acquisition Management, RTP Procurement Operations Division, E105-02, 4930 Page Road, Research Triangle Park, NC, 27711
- ZIP Code
- 27711
- Solicitation Number
- RFFQ--RT-03-00207
- Response Due
- 9/11/2003
- Archive Date
- 10/15/2003
- Point of Contact
- ROBIN HARRIS HARRIS, CONTRACT SPECIALIST, Phone 919.541.0955, Fax 919.541.4273,
- E-Mail Address
-
harris.robin@epa.gov
- Description
- THIS IS A COMBINED SYNOPSIS/SOLICITATION FOR COMMERCIAL ITEMS PREPARED IN ACCORDANCE WITH THE FORMAT IN FAR SUBPART 12.6, AS SUPPLEMENTED WITH ADDITIONAL INFORMATION INCLUDED IN THIS NOTICE. THIS ANNOUNCEMENT CONSTITUTES THE ONLY SOLICITATION. PROPOSALS ARE BEING REQUESTED AND A WRITTEN SOLICITATION WILL NOT BE ISSUED. This solicitation is for FULL AND OPEN COMPETITION. The North American Industry Classification System (NAICS) Code is 541710-Chemical Research and Development Laboratories or Services and the small business size standard is $6 million. The solicitation number is RFQ-RT-03-00207, and the solicitation is being issued as a Request for Quote (RFQ). The solicitation document and incorporated provisions and clauses are those in effect through Federal Acquisition Circular 01-15. A firm, fixed-price purchase order is anticipated to result from the award of this solicitation. This procurement is for Ki Experiments to Improve Training Data Set for Estrogen Receptor Quantitative Structure Activity Relationship (QSAR) Computer Stimulation Model. STATEMENT OF WORK: A. Background and Purpose- In response to emerging concerns that environmental chemicals may have adverse effects on human health by altering the function of the endocrine system, the Food Quality Protection Act mandated that the U.S. EPA develop and implement an endocrine disruptor screening program (EDSP). Working toward this goal, the U.S. EPA is currently implementing a proposed EDSP that is designed to detect chemicals that alter the estrogen, androgen, and thyroid systems in human, fish and wildlife (http://www.epa.gov/scipoly/oscpendo/index.htm). To date, the U.S. EPA has implemented the program on two fronts: (1) the development of the ED Priority Setting Database which will be used to establish priorities for screening compounds; and (2) the prevalidation and validation of the Tier I and Tier II assays that are likely to be included in the final testing battery. Studies are currently ongoing within the Agency to develop, standardize and validate a number of in vitro and in vivo mammalian and ecotoxicological assays for use in a Tier I Screening Battery (TIS). Additionally, the Agency has recently completed an extensive evaluation of two Quantitative Structure Activity Relationship (QSAR) computer stimulation models that were designed to detect chemicals that would be likely to bind with the estrogen receptor (ER) based upon the molecular structure of the substance. Each model was tested for its ability to predict the ER relative binding affinity (RBA)1 for chemicals within a subset of those currently under EPA's purview. Approximately 300 of these chemicals were chosen for laboratory analyses, and the actual RBAs were then compared to the predicted RBAs. Results from these tests demonstrated that additional ER binding data were needed to improve the sensitivity, specificity, and positive predictive probability of these QSAR models. A problem with the current ER QSAR models is that they were developed using competitive binding data from multiple laboratories, and that some of the data included in the models may not be indicative of a true competitive inhibition (e.g., the chemical may have altered the ER binding by alterative mechanisms). Thus, to improve the QSAR models, a review of the data is necessary, as well as the refinement of the model by incorporating additional data from a broader group of structurally diverse chemicals. Since the Agency currently has the competitive binding data for the 300 chemicals used to test the models, these chemicals would be an excellent source of new information. However, prior to being used in the models, the ER binding characteristics need to be further defined by Ki2 experiments to determine whether or not the chemicals exhibit true competitive inhibition. Of the 300 chemicals, approximately 10 - 15% exhibited some ability to displace estradiol from the ER. By conducting Ki experiments on those chemicals, it can be determined which of these chemicals are actually competitive inhibitors, and more precise estimates of ER binding affinity can be incorporated into the QSAR models. The purpose of this Professional Services Contract is to: (1) conduct competitive binding assays and Ki experiments for approximately 40 - 50 chemicals; (2) to provide accurate Ki and IC503 data for each chemical tested; and to (3) to document which of the chemicals display true competitive inhibition. Data from these experiments will provide a well-defined data set for incorporation into the QSAR models. Additionally, these data be included in the protocol for the in vitro ER binding assay of the Agency's EDSP to document examples of the ?profile' of ER competitive binding curves that can be obtained from a structurally diverse group of chemicals. NOTES: (1Relative Binding Affinity (RBA)- Calculated as the ratio of concentrations of E2 and competitor required to reduce the specific radioligand binding by 50% (ratio of IC50s); 2Ki- Inhibition constant (Calculated from Ki experiment); 3IC50- Concentration of competitor required to reduce the specific radioligand binding by 50%; 4Kd- Equilibrium dissociation constant of radioligand; 5Bmax- Maximum binding capacity (e.g., total receptor capacity) ) B. Contractor Requirements-The contractor shall conduct the experiments using protocols provided by the EPA. An example of the competitive binding assay using rat cytosolic ER is available at: http://iccvam.niehs.nih.gov/methods/endodocs/final/erbndbrd/erbndall.pdf (Appendix B5, 1-14). General methods for the Ki experiments are described in Toxicology 112:173-182 (1996) and Nature 375(6532):581-585 (1995). The Scope of Work will be completed through multiple tasks, and written deliverables (electronic and hard copy) documenting the findings. Completion and approval of each task is required before proceeding to the next task. Problems or technical difficulties should be reported immediately to the EPA technical point of contact (to be defined at contract award). C. Government responsibilities - Two weeks prior to beginning each task, EPA shall provide the contractor with test chemical to be tested. Upon receipt of the results from each task, EPA will examine the data and provide feedback to the Contractor within 30 days after the completion of each task. D. Reporting requirements- The contractor shall file a report within 30 days after the completion of each task. The report will consist of a hard copy and an electronic version of the data, graphs, analyses, and conclusions. Formats for electronic data should be submitted in a lotus or excel spreadsheet suitable for further data analyses. Graphs may be submitted as PRISM, Lotus Freelance, Powerpoint or pdf files. The time frame for each task is as follows: Task I (3 months); Task II (6 months); and Task III (6 months). E. Quality Assurance (QA)- Quality Assurance Documentation must be submitted to the EPA Project Officer within 60 days after the effective date of the purchase order. A hybrid version of the Quality Management Plan and the Quality Assurance Plan (see EPA website) may be submitted to meet this requirement. No work involving direct measurements or data generation, compilation of data from literature or electronic media shall be initiated under this project until the EPA Project Officer has approved the quality assurance documentation. Additional QA guidance documents can be found on the internet at http://es.epa.gov/ncer/guidance/qa.html. F. Delivery Schedule- Task 1 (within 3 months after the effective date of the order), Task 2 (within 6 months after the completion and acceptance of Task 1), and Task 3 (within 6 months after the completion and acceptance of Task 2). All Final Reports and Data are due with the completion of Task 3. G. Equipment- The contractor shall provide all necessary equipment for the project. EPA shall provide the selected chemicals for testing in accordance with "Government Responsibilities" found in paragraph C above. H. Security- Although the research to be conducted under this award is not considered to be of a sensitive nature, it is expected that data safeguards will be incorporated under the study design. I. Place of Performance- The submitted proposal shall indicate where the studies are to be conducted, and EPA reserves the right to conduct periodic site visits and QA audits at the research organization. J. Period of Performance- The period of performance is 15 months from the effective date of the award. Task I: Determine the variety of test chemicals to be evaluated and the complexity of ER binding data analyses and interpretation. EPA will provide a set of 10 test chemicals that is expected to exhibit the range of possible outcomes (e.g., chemicals that are true competitive inhibitors of ER binding, chemicals that interfere with the ER binding assay, chemicals that may present solubility issues) two weeks prior to the task. Required assays and data are: (A) Competitive binding assays (IC50 estimates) for inert estradiol and 10 test chemicals. (Note: Each assay will included 8 concentrations (in triplicate) of the test chemical and 6 concentrations (in triplicate) of inert estradiol) . Three concentrations of each test chemical will be determined from the competitive binding assays for use in the Ki experiments; (B) Ki experiments (Ki, IC50 ) for inert estradiol and 10 test chemicals. (Note: The Ki experiment for each test chemical will consist of 4 sets of saturation assay tubes (in duplicate)). General methods for these experiments are described in the following references: SC Laws et al., Toxicology, 112:173-182 (1996) and WR Kelce et al., Nature, 375(6532):581-585 (1995); and (C) Data analyses (Scatchard analyses, IC50, Ki). Analyses and conclusions should also document whether or not each test chemical is a true competitive inhibitor, interferes with the ER binding assay, or if there are most likely solubility problems. The Final report should include a copy of the actual protocol used (e.g., dilutions of chemicals, etc. ), raw data from each assay, graphs of binding curves/saturation plots, Scatchard analyses, Kd4, Bmax5, IC50, Ki, estimates of intra-assay variation. Documentation of solubility problems, or any technical issues relevant to protocol standardization for the EDSP should also be included in the final report. Task II: Competitive binding assays (IC50 ) and Ki experiments for 10 - 20 chemicals. Required assays and data are: Competitive binding assay (IC50 and optimal competitor concentrations for Ki experiment) and Ki experiment (Ki, IC50 ) each test chemical. -Data analyses (Scatchard analyses, IC50, Ki) and interpretation of results (e.g., true competitive ER binder, etc.) The report should include a copy of the actual protocol used (e.g., dilutions of chemicals, etc. ), raw data from assays, graphs of binding curves/saturation plots, Scatchard analyses, Kd, Bmax, IC50, Ki, and estimates of intra-assay variation. Task III: Competitive binding assays (IC50 ) and Ki experiments for another set of 10 - 20 chemicals. Required assays and data are: Competitive binding assay (IC50 and optimal competitor concentrations for Ki experiment) and Ki experiment (Ki, IC50 ) each test chemical. Data analyses (Scatchard analyses, IC50, Ki) and interpretation of results (e.g., true competitive ER binder, etc.) The report should include a copy of the actual protocol used (e.g., dilutions of chemicals, etc. ), raw data from assays, graphs of binding curves/saturation plots, Scatchard analyses, Kd, Bmax, IC50, Ki, and estimates of intra-assay variation. Proposal Instructions and Evaluation Criteria: The Government intends to award a single purchase order to the responsible offeror whose technically acceptable proposal offers the 'Best Value' to the Government cost and other factors considered. For this requirement 'best value' will be determined based on technical capability, past performance and price. For this RFQ, the technical factors for approach and knowledge demonstrating that the contractor has both the technology for performing the work described, and the scientific expertise in receptor biochemistry to appropriately design, analyze and interpret the data will be significantly more important than all other factors combined. This procurement shall be awarded based on the following 'best value' criteria: 1. Technical (a). Demonstrated Approach and Knowledge. The offeror shall submit a detailed technical approach that demonstrates ability to perform the requirements out lined in the areas (B, D, and E-J) and tasks (I, II, III) above. Examples of data from contractor's laboratory (e.g., show actual data and graphs for scatchards, competitive binding and Ki data, data to demonstrate intra- and inter-laboratory variation, publications, etc.) may be submitted to demonstrate technical expertise. The complete technical proposal may not exceed 15 pages in length. (b). Past Performance. Demonstrated successful past performance of the offeror and any major subcontractors as evidenced by information gathered concerning (1) previous history of successful conduct of research under contract; and/or (2) the successful completion of similar scale projects within time and cost estimates. Include the following information for each contract and subcontract listed: (a) name of contracting agency (b) contract number (c) contract title (d) brief description of contract or subcontract and relevance to this requirement (e) total contract value (f) contract type (g) period of performance (h) contracting officer and telephone number (i) program manager/project officer and telephone number. 2. Price- The pricing proposal shall include sufficient information to enable the Contracting Officer to perform a price analysis in accordance with FAR 15.404-1(b). NOTE: All offerors are to include with their offer a completed copy of provision 52.212-3, Offeror Representations and Certifications -Commercial Items. The following FAR provisions apply to this solicitation: 52.212-1, Instructions to Offerors--Commercial Items. The following FAR clauses apply to this acquisition: 52.212-4, Contract Terms and Conditions-Commercial Items. The following additional FAR clauses which are cited in clauses 52.212-5 are applicable to the acquisition: 52.222-26, Equal Opportunity; 52.222-35, Affirmative Action for Disabled Veterans and Veterans of the Vietnam Era; 52.222-36, Affirmative Action for Handicapped Workers; 52.222-37, Employment Reports on Special Disabled Veterans and Veterans of the Vietnam Era; 52,225-1, Buy American Act, 52.225-3, Buy American Act--North American Free Trade Agreement, 52.232-33, Payment by Electronic Fund Transfer-Central Contractor Registration. Offerors should review any other information posted with this Request for Quotation on EPA's website at the following address: http://www.epa.gov/oam/rtp_cmd. Arrow down to the REQUEST FOR QUOTATION section and click on the solicitation. Please submit two copies of the technical and price proposal to U.S. Environmental Protection Agency, RTP Procurement Operations Division (E105-02), Attn: Robin S. Harris, Contract Specialist, 4930 Page Road, Durham, NC 27703. All offers are due by September 11, 2003, 4:30 p.m., EDT. No telephonic or faxed requests will be honored. E-mail proposals are acceptable and should be e-mailed to: harris.robin@epa.gov
- Record
- SN00415438-W 20030830/030828214011 (fbodaily.com)
- Source
-
FedBizOpps.gov Link to This Notice
(may not be valid after Archive Date)
| FSG Index | This Issue's Index | Today's FBO Daily Index Page |