RFP No. NIH-NIAID-DMID-96-13 Title: "VACCINE PRODUCTION FACILITY" Issued by: Cyndie Cotter Contracting Officer NIH/NIAID Contract Management Branch Solar Building, Room 3C07 6003 Executive Boulevard MSC 7610 Bethesda, Maryland 20892-7610 DATE ISSUED: NOVEMBER 29, 1995 PROPOSAL DATE DUE: JANUARY 19, 1996, 4:30 P.M. (EST) Ladies and Gentlemen: You are invited to submit a proposal in accordance with the requirements of this RFP (NIH-NIAID-DMID-96-13) for a "Vaccine Production Facility." The Government contemplates the award of one (1), five (5) year, cost-reimbursement, completion-type contract as a result of this RFP. The documents included with this electronic RFP package are as follows: I. Streamlined RFP a. Introduction and Work Statement (Parts A and B), dated November 29, 1995 (Attachment 1) b. Deliverables and Reporting Requirements, dated November 29, 1995 (Attachment 2) c. Evaluation Factors for Award, dated November 29, 1995 (Attachment 3) II. Specific RFP Instructions and Provisions, dated November 29, 1995 (Attachment 4). III. Applicable RFP References, dated November 29, 1995 (Attachment 5) In addition to the information listed above, a listing of the applicable Government clauses/provisions, sample contract format, and terms and conditions which will be incorporated into the eventual contract document may be obtained either through accessing the NIH Gopher system or by sending a request to Cyndie Cotter, Contracting Officer, using the internet electronic mail listed below. The attachments listed above represent all the necessary information required for the submission of a proposal for this acquisition. Following proposal submission and review, additional information will be requested by the Contracting Officer from all offerors intended to comprise the competitive range. NOTE: The Representations and Certifications must be submitted with the offeror's proposal (this form can be found in this RFP Gopher under the REPRESENTATIONS AND CERTIFICATIONS subdirectory found in C. RFP REFERENCES). DUE TO THE NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES' CURRENT BUDGET RESTRICTIONS, IT IS RECOMMENDED THAT ANY PROPOSED ANNUAL INCREASE IN COSTS FOR INFLATION BE LIMITED TO NO MORE THAN 4% OF TOTAL COSTS PER YEAR WHICH IS ALSO THE MAXIMUM CURRENTLY ALLOWED BY THE NIH FOR RESEARCH PROJECTS. The original and twenty (20) copies of your technical proposal and the original and five (5) copies of your business proposal must be received by the Contracting Officer no later than January 19, 1995, at 4:30 p.m. local time at the address listed in Attachment 4, Item 5. You are reminded that the "Technical Proposal Cover Sheet" must be completed in full detail and used as the cover sheet for each copy of your technical proposal (a copy of this form is contained in the NIH Gopher under the FORMS, FORMATS, AND ATTACHMENTS subdirectory found in C. RFP REFERENCES). New policies require submission of more detailed information than has been previously required. It is important that you list all professional personnel and organizations named in the proposal who have any role in the proposed work, including: staff of the primary organization (offeror), subcontractors, collaborating organizations, and consultants. Organizational affiliation(s) must be indicated for every person named. You may use additional sheets, as needed, following the format shown in the Technical Proposal Cover Sheet. This information will be used to ensure that there will be no conflict of interest when selecting review committee members. Your attention is further directed to the "Proposal Intent" form contained in Attachment 4, item 11. Please complete this form and return it to this office on or before December 19, 1995. This will allow us to expedite preparations for the peer review of proposals. PLEASE NOTE THAT ATTACHMENT 4, ITEM 10. PROVIDES GUIDELINES FOR TECHNICAL PROPOSAL PAGE LIMITATIONS AND TABLE OF CONTENTS. Funds are not presently available for this requirement. The Government's obligation under a resulting contract is contingent upon availability of appropriated funds from which payment for contract purposes can be made. Please note that in addition to telephone and fax numbers, the INTERNET addresses of both the Principal Investigator and the responsible business representative are to be included on the Form NIH-2043, "Proposal Summary and Data Record," contained in the NIH Gopher under the FORMS, FORMATS, AND ATTACHMENTS subdirectory found in C. RFP REFERENCES. If you have any additional questions regarding this RFP, please contact Cyndie Cotter at the internet electronic mail address cc41w@nih.gov, by phone at 301/402-0641, or by fax at 301/402-0972. Collect calls will NOT be accepted. Sincerely, \s\ Rosemary McCabe Hamill Chief, IAD Contract Section Contract Management Branch National Institute of Allergy and Infectious Diseases Attachments: 1 - 5 ***************************************************************** ***************************************************************** RFP-NIH-NIAID-DMID-96-13 I. STREAMLINED RFP ------------------- ATTACHMENT 1 11/29/95 INTRODUCTION ------------ Building on its broad research base, the development and testing of new vaccines and therapies has historically been a major focus of the research supported by the National Institute of Allergy and Infectious Diseases (NIAID) in the Division of Microbiology and Infectious Diseases (DMID). Through its network of Vaccine and Treatment Evaluation Units (VTEUs), the Division has supported the development and clinical testing (Phase I and Phase II testing) of a wide variety of vaccines including those designed to protect against pertussis, influenza, hepatitis, meningitis, pneumonia (e.g. Hib, pneumococcal, RSV), diarrhea (e.g. cholera and rotavirus), typhoid fever, and malaria, among others. Since many of the candidate vaccines used in such trials have been developed by vaccine companies, the capacity to develop a wide range of candidate vaccines that are not currently under development will enhance the ability of DMID to better fulfill its mission. In its initial effort to catalyze this process, in 1991, DMID awarded its first vaccine production contract to DynCorp/Program Resources, Inc. (N01-AI-15129) to develop and produce pilot lots of vaccines appropriate for Phase I and Phase II testing in human volunteers. WITH THE COMPLETION OF THIS INITIAL FIVE YEAR CONTRACT IN 1996, THIS REQUEST FOR PROPOSAL (RFP) REPRESENTS A RECOMPETITION OF THE VACCINE PRODUCTION CONTRACT AND DMID'S RENEWED COMMITMENT TO THIS ENDEAVOR. The principle objective of this contract is to accelerate the development of new and improved vaccines of public health importance by providing appropriate expertise and equipment at a facility capable of process development and pilot lot production of candidate vaccines. Where appropriate, this contract will also include safety testing, characterization, purity and potency testing, filling, labeling, storing and shipping of a broad range of vaccine candidates and vaccine-related products. It is anticipated that these products may include bacterial, viral, fungal, and parasitic preparations (or subfractions thereof) and may consist of, but will not be limited to: polysaccharides, nucleic acids, lipoproteins, purified proteins and/or synthetic peptides (either linear or variations of branched multiple antigen preparations) intended for evaluation in humans as experimental vaccines in Phase I, II and/or Phase III clinical trials. The preparation of challenge lots of bacteria and viruses for preclinical and clinical testing of candidate vaccines may also be supported under this contract. This contract consists of two work statements, described in detail below. The principle thrust of this contract (work statement Part A) is to produce pilot lots of promising vaccine candidates and/or vaccine-related materials, such as challenge lots of virus or bacteria for Phase I and Phase II vaccine trials, and to support a repository for serum specimens generated during DMID-supported clinical trials. A secondary goal of this contract (work statement Part B), will provide for the process development and pilot lot production of vaccines or vaccine-related products for use in large Phase II and/or Phase III clinical vaccine trials (i.e. produced under current Good Manufacturing Practices (cGMP) standards). This OPTION will require additional funding support and will be invoked by the Government if an appropriate candidate vaccine of high public health priority, but not under commercial development, is identified. All proposals will be evaluated on Part A and Part B separately. Award and exercise of the Optional Contract Activities (Part B) is solely at the discretion of the Government and will be based on need and the availability of funds during the five year period of performance. Offerors submitting a proposal under this solicitation must prepare a proposal which includes both the required work outlined in Part A and the Optional Contract Activities identified in Part B. PROPOSALS FOR PART A ALONE OR FOR PART B ALONE SHALL NOT BE ACCEPTED FOR REVIEW OR CONSIDERED FOR AWARD UNDER THIS SOLICITATION. It is anticipated that one contract will be awarded. Given the breadth and specialization required in the Work Statements, and in order to assemble the strongest proposal possible, the Contractor is encouraged to establish subcontracts (when appropriate) with other facilities and/or institutions as necessary, in order to produce and deliver required materials in an expeditious and cost- effective manner. ************************************************************** PART A - PILOT LOT PRODUCTION ----------------------------- BACKGROUND - PART A ------------------- While advances in immunology and molecular biology continue to offer an ever-expanding array of approaches towards the development of new candidate vaccines, the limited national capacity to move promising concepts through the development process--from the research bench to pilot lot production to scale-up--presents a substantial barrier to the full achievement of this potential. Toward this end, this contract provides the capability for pilot lot production of promising vaccine candidates and vaccine-related materials, such as challenge lots of bacteria and viruses, appropriate for Phase I and Phase II testing in human volunteers. In addition, this contract will also fulfill DMID's need for a central facility to systematically receive, label, store, track and transport clinical specimens, such as serum, generated in DMID- supported clinical trials. WORK STATEMENT - PART A ------------------------------------------------------------ Independently, and not as an agent of the Government, the Contractor shall furnish all the necessary services, qualified personnel, materials, equipment, facilities and methods, not otherwise provided by the Government under the terms of this contract as needed to perform the work set forth below. [NOTE TO OFFEROR: A. While it is the intent of this "Request for Proposal" (RFP) to award a single contract, because the tasks outlined in the Work Statement may require capabilities, expertise, and/or facilities that are beyond the scope of a single Contractor, it is anticipated that subcontracts may be proposed. Letters of agreement and pertinent information regarding the subcontractor's experience, expertise, personnel, and facilities should be included in the Offeror's proposal.] Specifically, the Contractor shall: 1. Develop, produce, characterize, test (safety, sterility, purity, potency, immunogenicity and other appropriate tests), formulate (including adjuvanting), vial, label, store and ship pilot lots of vaccines and vaccine-related products. These products shall be prepared in facilities and by methods that meet FDA standards for vaccines appropriate for Phase I and Phase II human clinical trials as described in the Code of Federal Regulations, Title 21, Chapter I, Parts 58, 210 & 211, and 600-640 [April 1994] and the Guidelines on Sterile Drug Products Produced by Aseptic Processing [June 1987]. At the direction of the Project Officer, prepare or acquire approximately 10 pilot lots of vaccine and/or vaccine-related products per year. These products shall be provided to the Project Officer, or to recipients specified by the Project Officer, for use in Phase I or Phase II human clinical trials. The types of vaccines and related products will be specified by the Project Officer and may include, but are not restricted to, vaccines against influenza viruses, parainfluenza viruses, rotaviruses, respiratory syncytial viruses, rhinoviruses, Group B Streptococcus, cholera, gonococcus, pneumococcus, Salmonella, meningococcus, Cryptococcus, and malaria. Seed strains will be provided by the Project Officer, as appropriate. [NOTES TO OFFEROR: B. The vaccine approaches and vaccine-related materials that may be requested to be produced during the course of this contract may include: i) Conjugated polysaccharide vaccines. Example: Group B Streptococcus (type II) polysaccharide-protein conjugate vaccine. ii) Subunit vaccines. Example: Purified rotavirus vaccine expressed in a baculovirus system. iii) Inactivated viral vaccine. Example: Formalin- inactivated Rhesus rotavirus vaccine. iv) Live attenuated viral vaccines produced in tissue culture. Example: Cold-adapted type A (H3N2) influenza virus vaccine. v) Challenge lots: live virus and/or live bacteria. Example: challenge lots of Vibrio cholerae, influenza, RSV, parainfluenza, or rotavirus. C. For evaluation and costing purposes, the offeror should provide sample production protocols, time lines and cost estimates, including proposed procedures for safety, sterility, purity and immunogenicity testing, purification, characterization, formulation, filling, labeling, storing; final container testing; other appropriate tests; and shipping for each of the following vaccine candidates. Each of the sample protocols should include thorough discussions of the potential problems that might arise at each stage of the project, and how these problems will be overcome. 1) VIRAL CHALLENGE LOT. Provide detailed description of production of 1000 doses of 10 to the 4.7th power pfu/ml titer Respiratory Syncytial Virus (RSV) for challenge testing in the ferret model of RSV infection. Assume production requirements of 2 lots per year. Assume that the Project Officer will provide a seed strain (isolated and passaged in AGMK cells, a single clone selected and purified after amplification in MRC5 cells and 3 serial passages in Vero cells). In addition to descriptions of safety testing, virus characterization, purity and potency testing, filling, labeling, storing and shipping, the description should include the production of the live virus pool, animal safety tests for adventitious agents and Mycobacterium tuberculosis. 2) BACTERIAL VACCINE PRODUCTION a. VIBRIO CHOLERAE: Provide a detailed description of production of a 10 liter batch for testing in humans as a frozen preparation containing 10 to the 9th power/ml viable V. cholerae. Assume production requirement of two (2) lots per year. Assume that the Project officer will provide a frozen master seed culture. Describe how you would prepare, by fermentation, a 10 liter batch of Vibrio cholerae by fermentation to be used in Phase I/II clinical studies. Optimize fermentation parameters in order to obtain maximum yield of viable organisms, to be harvested in the late logarithmic phase of the growth curve. Describe how you would produce, harvest, wash, quantify, and characterize the final product. Describe stabilization, filling, labeling, and storage operations you would employ to produce the product as frozen cells in cryovials each vial to contain 2 ml of 10 to the 9th power/ml viable V. cholerae. b. Purification of cholera toxin to produce one thousand (1,000) 50 ug doses. Assume production requirement of two (2) lots per year. Using the same strain of V. cholerae and fermentation conditions described above (C.2)a.), provide description for processing the cell paste obtained from a 10 liter fermentation to purify the toxin as a subunit vaccine candidate suitable for Phase I/II clinical trials. Describe methods for purification and detoxification of the protein, characterization and quantification of the product, and fill and label the vials to provide one thousand (1,000) 50 ug doses. c. Purification of lipopolysaccharide antigen. Assume production needs of one (1) lot per year. Using the same strain of V. cholerae and fermentation conditions described above (C.(2)a), provide a detailed description of how you would process the cell paste obtained from a 10 liter fermentation to purify the O-antigen lipopolysaccharide so that it could be detoxified and conjugated for use as a cholera vaccine in Phase I/II clinical trials. Describe how you would purify, characterize and quantify the product, and fill and label the vials to provide one thousand (1,000) 50 ug doses of a lyophilate product. 3) SYNTHETIC PEPTIDE VACCINE. Assume production needs of one (1) lot per year. Produce 100 mg of a well-characterized, alum- adsorbed, thirty amino acid peptide appropriate for a vaccine to be used in Phase I and Phase II human clinical trials filled in 50 ug/dose vials. Describe how you would characterize the peptide, adsorb to alum, fill and label 50 ug per dose vials. For purposes of this example, assume no sequence- specific problems or unusual amino acids. D. Award of a contract does not commit the Government to approve the protocols outlined in the proposal. The Project Officer will determine which studies are actually undertaken.] 2. Provide appropriate and qualified staff with documented expertise and experience to accomplish the tasks outlined in item 1. above, as well as access to required equipment and facilities. [NOTES TO OFFEROR: E. To fulfill the requirements of this contract, a well- trained team consisting of a Principal Investigator, research scientists, and technicians is required. In aggregate, the team should be experienced in vaccine development and pilot lot production, including filling, labeling, storing and shipping of vaccines suitable for testing in human clinical trials. The team should have composite expertise in, but not limited to, the following vaccine-related technologies: fermentation (including 500 liter fermenters), lyophilization, tissue culture systems, purification (protein and carbohydrate), bacterial or viral expression systems, and synthetic peptides as potential vaccine candidates. A two-page biosketch of each proposed professional and technical personnel, including those of proposed subcontractors, should be included in the proposal, as well as an organizational plan for coordinating the work of the contract. F. Documentation of available equipment and appropriate certification of the facilities, including those of proposed subcontractors, should be included in the proposal to fulfill the requirements of this work statement. This should include documentation of access to an AALAC, or equivalent facility and the capacity for testing the safety and immunogenicity of manufactured products.] 3. Provide final vaccine protocols appropriate for submission to the CBER, FDA for Investigational New Drug Application. [NOTE TO OFFEROR: G. Provide one sample vaccine protocol, either for a vaccine in Work Statement 1.C, or for another, in a format appropriate for submission to the FDA for IND.] 4. Receive, store, ship and track clinical specimens (primarily serum) generated from clinical trials of vaccines and vaccine- related products supported by DMID, including preparation of appropriate certification. [NOTE TO OFFEROR: H. For purposes of evaluation, describe plans, facilities, equipment, procedures, and budget for: a) receiving and storage, at -70 C, serum specimens. (It is estimated that approximately 2,000 serum specimens, 2 ml each, will be received per year.) b) shipping serum specimens. (During the course of this contract, it is estimated that approximately ten (10) shipments of serum specimens (200 specimens/shipment, 2 ml each) will be performed. Eight (8) shipments within the United States and two (2) shipments to Europe.)] 5. Prepare a transition plan for transfer of all products, documentation and samples to a new contractor or storage site at the end of the contract period. 6. Attend and participate in two 2-day meetings per year in Rockville, Maryland to discuss results and future plans, and/or review regulatory issues related to vaccine production. [NOTE TO OFFEROR: I. Travel, lodging and meal costs for the Principal Investigator and one other staff member should be included in the business proposal. The Project Officer will determine the schedule and need for attending meetings related to contract activities.] ********************************************************* PART B: OPTIONAL CONTRACT ACTIVITIES - cGMP PRODUCTION OF PILOT LOTS OF VACCINES FOR LARGE PHASE II AND/OR PHASE III TESTING AND CHALLENGE LOTS OF VIRUS AND/OR BACTERIA APPROPRIATE FOR TESTING IN HUMANS. BACKGROUND - PART B, OPTIONAL CONTRACT ACTIVITIES ------------------------------------------------- During the course of the contract the Contractor may be required to procure or provide a) scale-up and pilot lot production of vaccines or vaccine-related products in current Good Manufacturing Practices (cGMP) facilities for large phase II and/or Phase III clinical vaccine trials and/or b) challenge lots of virus and/or bacteria appropriate for testing in humans. This option will be invoked by the Government if an appropriate candidate vaccine, which is of high public health priority but does not meet industrial priorities, is identified, and assumes that additional funding support and lead time will be available. While the award and exercise of this Optional Contract Activities (Part B) is solely at the discretion of the Government and will be based on need and the availability of funds during the five year period of performance, Offerors submitting a proposal under this solicitation must prepare a proposal which includes both the required work outlined in Part A AND the Optional Contract Activities outlined in Part B. Proposals for Part A alone or for Part B alone shall not be accepted for review or considered for award under this solicitation. All proposals will be evaluated on Part A and Part B separately. WORK STATEMENT - PART B, OPTIONAL CONTRACT ACTIVITIES ----------------------------------------------------- Independently, and not as an agent of the Government, the Contractor shall furnish all the necessary services, qualified personnel, materials, equipment, facilities and methods, not otherwise provided by the Government under the terms of this contract as needed to perform the work set forth below. Specifically, the Contractor shall: 1. Produce and/or procure up to 50,000 doses of candidate vaccines (include characterization, testing [safety, sterility, purity, potency, immunogenicity and other appropriate tests], formulation [including adjuvanting], vialing, labeling, storing and shipping) for viral, bacterial, parasitic or fungal diseases for clinical evaluation in Phase II or Phase III trials. These products shall be prepared in cGMP facilities and by methods that meet FDA standards for vaccines appropriate for human clinical trials as described in the Code of Federal Regulations, Title 21, Chapter I, Parts 58, 210 & 211, and 600-640 [April 1994] and the Guidelines on Sterile Drug Products Produced by Aseptic Processing [June 1987]. [NOTE TO OFFEROR: A. For the purposes of evaluation, the offeror should demonstrate understanding of the approach and document capacity for production and scale-up under cGMP. Therefore, a detailed description of the differences in approach, preparation, production, and quality control and costs of the manufacture under cGMP (including safety, sterility, purity and potency, and immunogenicity testing), time lines and potential pitfalls (and their resolution) should be submitted for the following vaccine: A cholera toxin subunit vaccine, as described in Part A.[C(2)b] above, in a cGMP facility appropriate for clinical trials in humans. Produce 50,000 doses each containing 50 ug of lyophilized product appropriate for phase III trials.] 2. Produce and/or procure (including characterization, testing [safety, sterility, purity, potency, immunogenicity and other appropriate tests], formulation [including adjuvanting], vialing, labeling, storing and shipping) 1,000 doses of a viral or bacterial challenge lot appropriate for use in clinical trials in humans. These products shall be prepared in cGMP facilities and by methods that meet FDA standards appropriate for human clinical trials as described in the Code of Federal Regulations, Title 21, Chapter I, Parts 58, 210 & 211, and 600-640 [April 1994] and the Guidelines on Sterile Drug Products Produced by Aseptic Processing [June 1987]. [NOTES TO OFFEROR: B. For the purposes of evaluation, the offeror should demonstrate understanding of the approach for production of live organisms under cGMP for human challenge studies. Therefore, a detailed description of the differences in approach, preparation, production, and quality control and costs of the manufacture under cGMP (including safety, sterility, purity and potency, and immunogenicity testing), time lines and potential pitfalls (and their resolution) should be submitted for the following vaccines: An RSV challenge lot in cGMP facility appropriate for clinical trials in humans. Produce one thousand (1,000) doses of 10 to the 4.7th power pfu/ml titer RSV for challenge testing in human clinical trials. In contrast to RSV challenge lots prepared in Work Statement - Part A of this contract (above) intended for use in animal models, a viral challenge that may be used in human clinical trials will require preparation and production under cGMP conditions. Therefore, describe the differences in approach required for cGMP preparation, production, immunogenicity and safety testing and cost of producing one thousand (1000) doses (10 to the 4.7th power pfu/dose) of an RSV challenge appropriate for experiments in human subjects. C. Award of a contract does not commit the Government to approve the protocols outlined in the proposal. The Project Officer will determine which pilot lot production projects are actually undertaken.] 3. Provide appropriate and qualified staff with documented expertise and experience to accomplish the tasks outlined above, specifically under cGMP, as well as access to required equipment and facilities. [NOTES TO OFFEROR: D. To fulfill the requirements of this contract, a well trained team consisting of a Principal Investigator, research scientists, technicians, and appropriate Quality Assurance/Control personnel is required. Any differences in staffing from Work Statement - Part A should be described and justified. A two-page biosketch of each additional proposed professional and technical personnel, including those of proposed subcontractors, should be included in the proposal. E. Documentation of available equipment and appropriate certification as a GMP facility, including those of proposed subcontractors should be included in the proposal to fulfill the requirements of this work statement (see Attachment 3, item 3. MANDATORY QUALIFICATIONS FOR FACILITIES). This should also include documentation of access to an AALAC, or equivalent animal facility and the capacity for testing the safety and immunogenicity of manufactured products.] 4. Provide final vaccine protocol appropriate for submission to the CBER, FDA for Investigational New Drug Application. 5. Attend and participate in two 2 day meetings per year in Rockville, Maryland to discuss results and future plans, and/or review regulatory issues related to vaccine production. [NOTE TO OFFEROR: F. Travel, lodging and meal costs for the Principal Investigator and one other staff member should be included in the business proposal. The Project Officer will determine the schedule and need for attending meetings related to contract activities.] ******************************************************************* ******************************************************************* RFP-NIH-NIAID-DMID-96-13 ATTACHMENT 2 11/29/95 DELIVERABLES AND REPORTING REQUIREMENTS --------------------------------------- The Contractor shall submit to the Contracting Officer and Project Officer technical progress reports covering the work accomplished during each reporting period. These reports are subject to the technical inspection and request for clarification of the Project Officer. These reports shall be brief and factual and prepared in accordance with the following format: A. TECHNICAL REPORTS In addition to those reports required by SECTION I and other terms of this contract, the Contractor shall prepare and submit the following reports in the manner stated below: (1) Monthly Reports - by the first day of every month, the Contractor shall submit to the Project Officer seven (7) copies of a monthly report detailing project activities and inventory and shipping records. (2) Semi-Annual Technical Progress Reports - by the fifteenth working day of the month following the end of each six month period, the Contractor shall submit eight (8) copies of a semi-annual Technical Progress Report, comprising seven (7) copies to the Project Officer and one (1) copy to the Contracting Officer. Such reports shall include the following specific information: a. A cover page that lists the contract number and title, the period of performance being reported, the contractor's names and address, the author(s), and the date of submission; b. SECTION I - An introduction covering the purpose and scope of the contract effort; c. SECTION II - A description of overall progress plus a separate description for each task or other logical segment of work on which effort was expended during the report period. 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; d. SECTION III - Substantive performance; a description of current technical or substantive performance and any problems encountered and/or which may exist along with proposed corrective action. Each project should be reported separately according to the number assigned by the Project Officer. 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. An anticipated work plan for the subsequent six months. f. Preprints, reprints, and abstracts shall be submitted along with the report. Semi-annual Technical Progress Reports are not due for periods in which an Annual or Final Report is due. (3) Annual Reports - On the anniversary date of the contract, the Contractor shall submit eight (8) copies of an Annual Technical Progress Report, as above, comprising seven (7) copies to the Project Officer and one (1) copy to the Contracting Officer. Such reports shall detail, document, and summarize the results of the entire contract work for the period covered. These reports shall be in sufficient detail to explain comprehensively the results achieved. Also to be included in the report is a summary of work proposed for the next reporting period. Specific requirements, if any, are set forth in ARTICLE C.1., Work Statement. A one page summary of each ongoing and completed protocol shall be submitted at this time. An Annual Report will not be required for the period when the Final Report is due. Preprints and reprints of papers and abstracts not submitted in the semi-annual report shall be submitted. (4) Final Report - By the expiration date of the contract, the Contractor shall submit eight (8) copies of a comprehensive Final Report, as above, comprising seven (7) copies to the Project Officer and one (1) copy to the Contracting Officer. This final report shall detail, document and summarize the results of the entire contract work for the period covered. This report shall be in sufficient detail to explain comprehensively the results achieved. Additional specific requirements are set forth in ARTICLE C.1. Preprints and reprints not included previously shall be submitted. (5) Summary of Salient Results - With the Final Report the Contractor shall submit a summary (not to exceed 200 words) of salient results achieved during the performance of the contract. (6) Final Manufacturing and Safety Tests Protocols - The Contractor shall submit seven (7) copies of completed protocols to the Project Officer appropriate for submission to CBER, FDA in support of Investigational New Drug applications, at the end of each project, regardless of the calendar date of completion. B. If the Contractor becomes unable to deliver the reports specified hereunder within the period of performance because of unforeseen difficulties, notwithstanding the exercise of good faith and diligent efforts in performance of the work, the Contractor shall give the Contracting Officer immediate written notice of anticipated delays with reasons, therefore. C. Technical Report Distribution Copies of the technical reports shall be submitted as follows: Type of No. of Report Copies Addresses Due Dates Monthly 7 Project Officer *Monthly Semi-Annual 7 DMID, NIAID, NIH *Semi-Annually Annual 7 Solar Bldg. *Annually Final 7 6003 Exec. Blvd, MSC 7630 Completion date Bethesda, MD 20892-7630 Semi-Annual 1 Contracting Officer *Semi-Annually Annual 1 CMB, DEA, NIAID, NIH *Annually Final 1 Solar Bldg., Rm. 3C07 Completion date 6003 Exec. Blvd, MSC 7610 Bethesda, MD 20892-7610 Final Manuf. 7 Chief, Clinical and At end of & Safety Test Regulatory Affairs Branch each project Protocols DMID/NIAID Solar Building, Rm. 3A01 6003 Executive Blvd, MSC 7610 Bethesda, MD 20892-7610 * specific dates will be listed in the contract document ****************************************************************** ******************************************************************* RFP-NIH-NIAID-DMID-96-13 ATTACHMENT 3 11/29/95 EVALUATION FACTORS FOR AWARD ---------------------------- 1. GENERAL The technical proposal will receive paramount consideration in the selection of the contractor for this acquisition. The evaluation will be based on the demonstrated capabilities of the prospective contractors in relation to the needs of the project as set forth in the RFP. The merit of each proposal will be evaluated carefully, based on responsiveness to the RFP and thoroughness and feasibility of the technical approach taken. Offerors must submit information sufficient to evaluate their proposals based on the detailed criteria listed below. Failure to provide the information required to evaluate the proposal may result in rejection of that proposal without further consideration. While high competency is sought, capabilities that exceed those needed for successful performance of the contract work statement are not requested. 2. COMPARATIVE IMPORTANCE OF PROPOSALS You are advised that paramount consideration shall be given to the evaluation of the technical proposals, but not to the exclusion of cost considerations. In the event that the technical evaluation reveals that two or more offerors are approximately equal in technical ability, then the estimated cost of performance will become paramount. In any event, the Government reserves the right to make an award to the best advantage of the Government, cost and other factors considered. 3. MANDATORY QUALIFICATIONS FOR FACILITIES Listed below are mandatory qualification criteria. The mandatory qualification criteria establish conditions that MUST be met at the time of receipt of Best and Final Offers (BAFO) by the Contracting Officer in order for your proposal to be considered any further for award. o The offeror must provide documentation that they meet the requirements listed in the Code of Federal Regulations (Number 21, April 1, 1994) for an establishment engaged in the preparation of vaccines licensed for human use by the Center for Biologics Evaluation and Research (CBER). Please note that while it is expected that facilities used and procedures followed in Part A (Phase I and II trials) will approach, if not achieve cGMP standards, this will be REQUIRED for products produced under Part B of this contract (vaccines for large Phase II and Phase III clinical trials and bacterial and/or viral challenge lots appropriate for human clinical trials). Therefore, the Offeror may be subject to inspections under the "Good Laboratory Practices Act" and "Good Manufacturing Practices Act". 4. TECHNICAL EVALUATION CRITERIA (for Part A and Part B) Proposals submitted in response to this RFP will be evaluated based on the following factors which are listed and weighted in order of their relative importance. Proposals will be judged solely on the written material provided by the offeror. Part A and Part B will be evaluated separately. In order to be eligible for a contract award, both Part A and Part B must be determined to be technically acceptable. FOLLOWING EVALUATION OF BOTH PART A AND PART B, A FINAL SCORE FOR EACH TECHNICAL PROPOSAL WILL BE CALCULATED BY WEIGHTING AS FOLLOWS: 80% PART A AND 20% PART B. PART A ------ CRITERION ELEMENT WEIGHT ----------------- ------ 1. TECHNICAL APPROACH 60 Documented adequacy of the technical approach for preparing experimental vaccines and vaccine-related products, as requested in the Work Statement. Soundness of the sample protocols, including the adequacy of discussion of problems likely to occur and plans for addressing them. 2. PERSONNEL 30 Documented expertise and proficiency of the Principal Investigator, professional and technical staff in development and pilot lot production, including appropriate testing, according to standards set forth in the Code of Federal Regulations, of vaccines for use in human clinical trials, and in preparing final protocols to be submitted to the CBER, FDA for Investigational New Drug review. (20 points) Demonstration of coordination of the various components of the contract and distribution of senior investigators and technicians time for the performance of various phases of work described in the Work Statement. (10 points) 3. FACILITIES AND RESOURCES 10 Adequacy and availability of the facilities and resources to accomplish the work described in the Work Statement. ----- TOTAL 100 ******************************************************************* ******************************************************************* PART B ------ CRITERION ELEMENT WEIGHT ----------------- ------ 1. TECHNICAL APPROACH 60 Documented adequacy of the technical approach for preparing experimental vaccines and vaccine-related products under cGMP as requested in the Work Statement. Soundness of the sample protocols, including the adequacy of discussion of problems likely to occur and plans for addressing them. 2. PERSONNEL 30 Documented expertise and proficiency of the Principal Investigator, professional and technical staff in development and production, including appropriate testing, according to standards set forth in the Code of Federal Regulations, of vaccines for use in human clinical trials, and in preparing final protocols to be submitted to the CBER, FDA for Investigational New Drug review. (20 points) Demonstration of coordination of the various components of the contract and distribution of senior investigators and technicians time for the performance of various phases of work described in the Work Statement. (10 points) 3. FACILITIES AND RESOURCES 10 Adequacy and availability of the facilities and resources to accomplish the work described in the Work Statement. ------ TOTAL 100 5. EVALUATION OF OPTIONS It is anticipated that any contract(s) awarded from this solicitation will contain option provision(s) and period(s). In accordance with FAR Clause 52.217-5, Evaluation of Options (July 1990), the Government will evaluate offers for award purposes by adding the total price for all options to the total price for the basic requirement, except when it is determined in accordance with FAR 17.206(b) not to be in the Government's best interests. Evaluation of options will not obligate the Government to exercise the option(s). ******************************************************************* ******************************************************************* RFP-NIH-NIAID-DMID-96-13 ATTACHMENT 4 11/29/95 II. SPECIFIC RFP INSTRUCTIONS AND PROVISIONS --------------------------------------------- NOTICE TO OFFERORS: This attachment contains proposal instructions and information which are specifically related to this acquisition. The information provided below is only a portion of the instructions and notices required for the submission of a proposal. References to additional, more general, information and forms regarding proposal preparation are contained in Attachment 5, "Applicable RFP References." 1. SIC CODE AND SMALL BUSINESS SIZE STANDARD (NIH 3150) (JUN 1988) Note: The following information is to be used by the offeror in preparing its Representations and Certifications (see Attachment 5, item 4. of this RFP), specifically in completing the provision entitled, SMALL BUSINESS PROGRAM REPRESENTATIONS (OCT 1995), FAR 52.219-1: (a) The standard industrial classification (SIC) code for this acquisition is 8731. (b) (1) The small business size standard is 500 employees. (2) The small business size standard for a concern which submits an offer in its own name, other than on a construction or service contract, but which proposes to furnish a product which it did not itself manufacture, is 500 employees. (c) This requirement is NOT Set-Aside for Small Business. However, the Federal Acquisition Regulation (FAR) requires in every solicitation (except for foreign acquisitions) the inclusion of the Standard Industrial Classification (SIC) Code and corresponding size standard which best describes the nature of the requirement in the solicitation. 2. NUMBER AND TYPE OF AWARD(S) (NIH 2980) (APR 1984) It is anticipated that one (1) award will be made from this solicitation and that award will be made on or about September 30, 1996. It is anticipated that the award from this solicitation will be multiple-year cost reimbursement type completion contract with a period of performance of 5 years, and that incremental funding will be used [see paragraph (6) of Business Proposal Instructions, in the "Standard RFP Instructions and Provisions" of the Gopher RFP]. 3. ESTIMATE OF EFFORT (NIH 2985) (APR 1984) It is expected that a completion type contract will be awarded as a result of this RFP. To assist you in the preparation of your proposal, the Government considers the total effort to perform this contract to be approximately 2,000% for Part A and 600% for Part B (Option). This number is furnished for your information only and is not to be considered restrictive for proposal purposes. As further assistance, it is estimated that the above total labor effort is constituted as follows: PART A Percentages of Effort Labor 5 YR Category Yr1 Yr2 Yr3 Yr4 Yr5 :TOTAL -------- ----- ----- ----- ----- ----- :----- Prin. Investigator 25% 25% 25% 25% 25% : 125% Other Prof. (Inv. + QA/QC) 75% 75% 75% 75% 75% : 375% Technicians (Lab + Animal) 275% 275% 275% 275% 275% :1375% Administrative 25% 25% 25% 25% 25% : 125% ----- ----- ----- ----- ----- :----- TOTAL 400% 400% 400% 400% 400% :2000% PART B Percentages of Effort Labor 5 YR Category Yr1 Yr2 Yr3 Yr4 Yr5 :TOTAL -------- ----- ----- ----- ----- ----- :----- Prin. Investigator 10% 10% 10% 10% 10% : 50% Other Prof. (Inv. + QA/QC) 10% 10% 10% 10% 10% : 50% Other Support (Tech + Admin) 100% 100% 100% 100% 100% : 500% ----- ---- ----- ----- ----- :----- TOTAL 120% 120% 120% 120% 120% : 600% The above percentages are based on a twelve (12) month effort. 4. 52.233-2 SERVICE OF PROTEST (NOV 1988) (a) Protests, as defined in Section 33.101 of the Federal Acquisition Regulation, that are filed directly with an agency, and copies of any protests that are filed with the General Accounting Office (GAO) or the General Services Administration Board of Contract Appeals (GSBCA), shall be served on the Contracting Officer (addressed as follows) by obtaining written and dated acknowledgement of receipt from: Mr. Lewis Pollack Hand-Carried Address: NIH/NIAID Contract Management Branch Solar Building, Room 3C07 6003 Executive Boulevard Rockville, Maryland 20852 Mailing Address: NIH/NIAID Contract Management Branch Solar Building, Room 3C07 6003 Executive Boulevard MSC 7610 Bethesda, Maryland 20892-7610 (b) The copy of any protest shall be received in the office designated above on the same day a protest is filed with the GSBCA or within one day of filing a protest with the GAO. 5. PACKAGING AND DELIVERY OF THE PROPOSAL (NIH 2995) (JUL 1994) Shipment and marking shall be as indicated below: External Package Marking: _________________________ In addition to the address cited below, mark each package as follows: "RFP No. NIH-NIAID-DMID-96-13" "TO BE OPENED BY AUTHORIZED GOVERNMENT PERSONNEL ONLY" Number of Copies: ________________ TECHNICAL PROPOSAL: ORIGINAL AND 20 COPIES BUSINESS PROPOSAL: ORIGINAL AND 5 COPIES If hand delivered or delivery service ------------------------------------- Contract Specialist Contract Management Branch DEA, NIAID, NIH Solar Building, Room 3C07 6003 Executive Boulevard Rockville, Maryland 20852 If using U.S. Postal Service ---------------------------- Contract Specialist Contract Management Branch DEA, NIAID, NIH Solar Building, Room 3C07 6003 Executive Boulevard MSC 7610 Bethesda, Maryland 20892-7610 * THE ORIGINALS MUST BE READILY ACCESSIBLE FOR DATE STAMPING PURPOSES NOTE: The U.S. Postal Service's "Express Mail" does not deliver to the Rockville, Maryland address. Any package sent to the Rockville address via this service will be held at a local post office for pick-up. THE GOVERNMENT IS NOT RESPONSIBLE FOR PICKING UP ANY MAIL AT A LOCAL POST OFFICE. If a proposal is not received at the place, date, and time specified herein, it will be considered a "late proposal" and handled in accordance with PHSAR 352.215-10 LATE PROPOSALS, MODIFICATIONS OF PROPOSALS AND WITHDRAWALS OF PROPOSALS (NOV 1986). 6. PHS 352.223-70 SAFETY AND HEALTH (APRIL 1984) (a) In order to provide safety controls for protection to the life and health of employees and other persons; for prevention of damage to all property; and for avoidance of work interruptions in the performance of the contract; the Contractor will consult, comply with, and include in all applicable subcontracts, the following standards, as appropriate: (1) Biosafety in Microbiological and Biomedical Laboratories, U.S. Department of Health and Human Services, Centers for Disease Control (CDC) and the NIH, HHS Pub. No. (CDC) 88-8395. (2) Recommendations for Prevention of HIV Transmission in Health-Care Settings, Morbidity and Mortality Report, August 21, 1987, Vol. 35, No. 2S. (3) Update: Universal Precautions for Prevention of Transmission of Human Immunodeficiency Virus, Hepatitis B Virus, and Other Bloodborne Pathogens in Health-Care Settings. Morbidity and Mortality Weekly Report, June 24, 1988, Vol. 37, No. 24. (4) Agent Summary Statement for Human Immunodeficiency Viruses (HIV); Included are GTLV-III, LAV, HIV-1, and HIV-2. Morbidity and Mortality Weekly Report, April 1, 1988, Vol. 37, No. S4. (5) Recommendations for the Safe Handling of Parenteral Antineoplastic Drugs, NIH Publication No. 83-2621. (6) NIH Guidelines for the Laboratory Use of Chemical Carcinogens, NIH Publication No. 81-2385. The above, (1) - (6), may be obtained from: Division of Safety Office of Research Services National Institutes of Health Building 31, Room 1CO2 Bethesda, Maryland 20892 (7) Guidelines for Research Involving Recombinant DNA Molecules (49 FR 46266 or latest revision) and Administrative Practices Supplement. These may be obtained from: Office of Recombinant DNA Activities Office of Science Policy and Legislation National Institutes of Health Building 31, Room B1C34 Bethesda, Maryland 20892 (8) Procedures for the Domestic handling and Transport of Diagnostic Specimens and Etiologic Agents, National Committee for Clinical Laboratory Standards, July 17, 1985, Vol. 5. This may be obtained from National Committee for Clinical Laboratory Standards 771 East Lancaster Avenue Villanova, Pennsylvania 19085 Further, the Contractor shall take or cause to be taken such additional safety measures as the Contracting Officer may determine to be reasonably necessary; Provided, that if compliance with such additional safety measures results in a material increase in the cost or time of performance of the contract, an equitable adjustment will be made in accordance with the clause of this contract entitled "Changes." (b) Prior to commencement of work, the Contractor will submit in writing its plan for complying with the safety and health provisions of this contract, and will meet with the Contracting Officer or his/her designated representative to discuss and develop a mutual understanding relative to administration of the overall safety program. (c) During the performance of work under this contract, the Contractor shall comply with all procedures prescribed by the Contracting Officer for the control and safety of persons visiting the job site and will comply with such requirements to prevent accidents as may be prescribed by the Contracting Officer. (d) The Contractor will maintain an accurate record of, and report to the Contracting Officer in such manner as the Contracting Officer may prescribe, all accidents and incidents resulting in death, traumatic injury, occupational disease, and/or damage to all property incident to work performed under the contract. (e) The Contracting Officer shall notify (if otherwise, confirm in writing) the Contractor of any noncompliance with the provisions of this clause and corrective action to be taken. After receipt of such notice, the Contractor shall immediately take such corrective action. (Such notice, when delivered to the Contractor or its representative at the site of the work, shall be deemed sufficient for the purpose.) If the Contractor fails or refuses to comply promptly, the Contracting Officer may issue an order stopping all or part of the work until satisfactory corrective action has been taken. No part of the time lost due to any such stop order shall be the subject of claim for extension of time or for costs or damages by the Contractor. (f) The Contractor shall insert the substance of this clause in each subcontract involving the use of hazardous materials or operations. Compliance with the provisions of this clause by subcontractors will be the responsibility of the Contractor. 7. OPTIONAL CONTRACT ACTIVITIES PROVISION (a) Unless the Government exercises its option pursuant to paragraph (b) of this article, the contract consists only of Work Statement - Part A. Pursuant to the clause set forth in paragraph (b), below, the Government may, by unilateral contract modification, require the Contractor to perform the optional contract activities described in Work Statement - Part B. If the Government exercises this option, notice must be given 60 days prior to the effective date of the option period and the estimated cost of the contract will be increased at an amount consistent with the schedule stated in paragraph (b), below. (b) The Government may require the performance of the additional work, identified in the Work Statement - Part B as optional contract activities within the limits and at the estimated costs to be determined during contract negotiations. 8. 52.227-6 ROYALTY INFORMATION (APR 1984) (a) Cost or charges for royalties. When the response to this solicitation contains costs or charges for royalties totaling more than $250, the following information shall be included in the response relating to each separate item of royalty or license fee: (1) Name and address of licensor. (2) Date of license agreement. (3) Patent numbers, patent application serial numbers, or other basis on which the royalty is payable. (4) Brief description, including any part or model numbers of each contract item or component on which the royalty is payable. (5) Percentage or dollar rate of royalty per unit. (6) Unit price of contract item. (7) Number of units. (8) Total dollar amount of royalties. (b) Copies of current licenses. In addition, if specifically requested by the Contracting Officer before execution of the contract, the offeror shall furnish a copy of the current license agreement and an identification of applicable claims of specific patents. 9. FACILITIES CAPITAL COST OF MONEY (This is applicable if you are a commercial organization) Facilities capital cost of money (see FAR 15.904) will be an allowable cost under the contemplated contract, but only if the Contractor specifically identifies or proposes it in the cost proposal for the contract and elects to claim this cost by checking the appropriate box below. If the contractor does not specifically identify or propose facilities capital cost of money and does not elect to claim this cost, the contract will include the Waiver of Facilities Capital Cost of Money clause. _____ The prospective Contractor has specifically identified or proposed facilities capital cost of money in its cost proposal and elects to claim this cost as an allowable cost under the contract. Submit form CASB- CMF (see FAR 31.205-10). _____ The prospective Contractor has not specifically identified or proposed facilities capital cost of money in its proposal and elects not to claim it as an allowable cost under the contract. 10. TECHNICAL PROPOSAL TABLE OF CONTENTS (NOTE: INSTRUCTIONS TO OFFERORS ARE INDICATED IN PARENTHESES OR AS FOOTNOTES.) PAGE NUMBERS 1. Technical Proposal Cover Sheet..(Format in Section C of Gopher RFP:FORMS,FORMATS,ATTACHMENTS) ................. 1 2. Technical Proposal Table of Contents ..................... 2 3. Abstract *................................................ 3 4. Technical Plan (Refer to Technical Proposal Instructions, Section C.1., Standard RFP Instructions and Provisions, Gopher RFP) a. Statement of Work 1. Objectives ...............(Items a.1............... 4- 2. Approach ...........through a.4 are not............ ___ 3. Methods ...................to exceed............... ___ 4. Schedule .................. 100 pages**)........... ___ b. Personnel ***,**** 1. List of All Personnel on the Project, including Subcontractors, Consultants/Collaborators, by Name, Title, Department and Organization ................ ___ 2. Principal Investigator/Project Director ........... ___ 3. Other Investigators ............................... ___ 4. Additional Personnel .............................. ___ c. Resources and Environment ............................ ___ d. Other Considerations (use specifically titled subparagraphs, as applicable) ....................... ___ 5. Other Support (Refer to "Summary of Current and Proposed Activitiesþ in the FORMS, FORMATS, ATTACHMENTS Directory found in Section C, Gopher RFP) ........................... ___ 6. Human Subjects and Minority and Gender Issues Not Otherwise Addressed ..(if applicable)..................... ___ 7. Vertebrate Animals ..(if applicable)....................... ___ 8. Technical Proposal Cost Information (Format in Section C, Gopher RFP, FORMS,FORMATS,& ATTACHMENTS).................. ___ 9. Literature Cited ......................................... ___ 10. Appendices (Appendices, Literature citations, Protocols and 4b. through 8. above; list each Appendix. Appendices must be clear and legible.) * State the proposal's broad, long-term objectives and specific aims. Describe concisely the research design and methods for achieving these goals. DO NOT EXCEED one page in providing the abstract. Identify the RFP Number, Institution and Principal Investigator on the abstract. ** The front side of a page equals one page. The front and back of a page equals two pages. *** Type density and size must be 10 to 12 points. If constant spacing is used, there should be no more than 15 cpi, whereas proportional spacing should provide and average of no more than 15 cpi. There must be no more than six lines of text within a vertical inch. **** An individual biosketch should not exceed two pages. 11. PROPOSAL INTENT RESPONSE SHEET PROPOSAL INTENT --------------- RFP No.: NIH-NIAID-DMID-96-13 PLEASE REVIEW THE ATTACHED REQUEST FOR PROPOSAL. FURNISH THE INFORMATION REQUESTED BELOW AND RETURN THIS PAGE BY THE EARLIEST PRACTICABLE DATE. YOUR EXPRESSION OF INTENT IS NOT BINDING BUT WILL GREATLY ASSIST US IN PLANNING FOR PROPOSAL EVALUATION. __________________________________________________________________ [ ] DO INTEND TO SUBMIT A PROPOSAL FOR THE FOLLOWING: ____________________________________________________ ____________________________________________________ [ ] DO NOT INTEND TO SUBMIT A PROPOSAL FOR THE FOLLOWING REASONS: ____________________________________________________ TYPED NAME AND TITLE: ________________________________________ INSTITUTION: ________________________________________ SIGNATURE: ________________________________________ TELEPHONE NO.: ________________________________________ DATE: ________________________________________ - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - COLLABORATORS/CONSULTANTS - Provide name(s) and institution(s): (Continue list on reverse if necessary) ________________________________________________________________ ________________________________________________________________ RETURN TO: CMB, NIAID, NIH Solar Building, Room 3C07 6003 Executive Boulevard MSC 7610 Bethesda, Maryland 20892-7610 Attn: Cyndie Cotter RFP NIH-NIAID-DMID-96-13 Fax # 301/402-0972 PLEASE RETURN BY DECEMBER 19, 1995 *********************************************************** ******************************************************************* RFP-NIH-NIAID-DMID-96-13 ATTACHMENT 5 11/29/95 III. APPLICABLE RFP REFERENCES ------------------------------- This section identifies the items located in the Gopher directory "C. RFP REFERENCES" that are applicable to this RFP. 1. The entire file entitled "STANDARD RFP INSTRUCTIONS AND PROVISIONS" is applicable to this RFP, except as otherwise may be modified by the inclusion of an item from the "OPTIONAL RFP INSTRUCTIONS AND PROVISIONS". 2. The following items are applicable from the file entitled "OPTIONAL RFP INSTRUCTIONS AND PROVISIONS": (1) LATE PROPOSALS, MODIFICATIONS OF PROPOSAL, AND WITHDRAWALS OF PROPOSALS, PHS 352.215-10 (2) NOTICE TO OFFERORS OF REQUIREMENT FOR ADEQUATE ASSURANCE OF PROTECTION OF VERTEBRATE ANIMAL SUBJECTS (SEP 1985), PHSAR 352.280-2(a) (3) SMALL BUSINESS AND SMALL DISADVANTAGED BUSINESS SUBCONTRACTING PLAN [NOTE: A Subcontracting Plan is not due with the initial proposal. The Contracting Officer will notify offerors if a plan becomes due.] 3. The following items are applicable from the subdirectory entitled "FORMS, FORMATS, AND ATTACHMENTS": Applicable to Technical Proposal -------------------------------- (1) Technical Proposal Coversheet (2) Technical Proposal Cost Information, Dec 1988 (3) Summary of Current and Proposed Activities, July 1995 Applicable to Business Proposal ------------------------------- (4) Contract Pricing Proposal, SF-1411, July 1987 (5) Proposal Summary and Data record, NIH-2043 (Rev. 6/82) (6) Business Proposal Cost Information (7) Disclosure of Lobbying Activities, OMB SF-LLL To Become Contract Attachments ------------------------------ (8) Invoice/Financing Requests Instructions for NIH Cost- Reimbursement Type Contracts, NIH(RC)-1, JUN 1992 (9) Procurement of Certain Equipment, NIH(RC)-7 Other - to be submitted as directed by Contracting Officer ---------------------------------------------------------- (10) Certificate of Current Cost or Pricing Data, NIH-1397 (11) Subcontracting Plan Format 4. The Representations and Certifications are applicable. 5. The "Sample Contract Format-General" is applicable.