RFP No. NIH-NIAID-DMID-98-11 Title: "IN VITRO ANTIVIRAL SCREENS" 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: OCTOBER 16, 1997 PROPOSAL DATE DUE: JANUARY 16, 1998, 4:00 P.M. (EST) Ladies and Gentlemen: You are invited to submit a proposal in accordance with the requirements of this RFP (NIH-NIAID-DMID-98-11) entitled "In Vitro Antiviral Screens." The Government contemplates making up to four awards of five (5) year, cost-reimbursement, completion type contracts as a result of this RFP. The documents included with this electronic RFP package are as follows: I. Streamlined RFP a. Background, Introduction, and Work Statement, dated October 16, 1997 (Attachment 1) b. Deliverables and Reporting Requirements, dated October 16, 1997 (Attachment 2) c. Evaluation Factors for Award, dated October 16, 1997 (Attachment 3) II. Specific RFP Instructions and Provisions, dated October 16, 1997 (Attachment 4) III. Applicable RFP References, dated October 16, 1997 (Attachment 5) IV. Proposed Deviation for Determination of Exceptional Circumstances (DEC), FAR 52.227-14 and FAR 52.227-11 (Attachment 6) In addition to the directory which you are currently in (i.e., the streamlined RFP), there are five other subdirectories in the Gopher System (gopher://gopher.nih.gov/11/res/rd-rfp/rfpref.c) under RFP REFERENCES which must be retrieved, in whole or in part, in order to submit a proposal. The applicable portions are explained in Attachment 5, Applicable RFP References. The Subdirectories are: STANDARD RFP INSTRUCTIONS AND PROVISIONS OPTIONAL RFP INSTRUCTIONS AND PROVISIONS FORMS, FORMATS, AND ATTACHMENTS REPRESENTATIONS AND CERTIFICATIONS SAMPLE CONTRACT FORMAT - GENERAL If you are unable to download any of these documents, please contact Cyndie Cotter, Contracting Officer, by phone, fax, or Internet at the numbers/addresses listed at the end of this letter. The attachments/documents 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 who comprise the competitive range. The Business and Technical Proposals must be separate from one another in the proposal package as the peer review panel will only receive the Technical Proposal. The Business Proposal must be signed by an authorized official of your organization and must contain a detailed breakdown of costs by year, for each cost category/element. See STANDARD RFP INSTRUCTIONS AND PROVISIONS, in the Gopher System, for more details on the Business Proposal requirements. With the Business Proposal, please submit Form NIH-2043, "Proposal Summary and Data Record," contained in the NIH Gopher under the FORMS, FORMATS, AND ATTACHMENTS subdirectory. 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. 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. 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. BE ADVISED THAT PORTIONS OF YOUR TECHNICAL PROPOSAL ARE SUBJECT TO PAGE LIMITATIONS. The format and content of your Technical Proposal along with page limitation information is detailed in the "Technical Proposal Table of Contents/Format", Attachment 4, Item 8. Please note that the Representations and Certifications MUST be submitted with the offeror's proposal. This form can be found in the Gopher System under the REPRESENTATIONS AND CERTIFICATIONS subdirectory. 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 16, 1998, at 4:00 p.m. local time at the address listed in Attachment 4, Item 5. Your attention is further directed to the "Proposal Intent" form contained in Attachment 4, item 9. Please complete this form and return it to this office on or before November 28, 1997. This will allow us to expedite preparations for the peer review of proposals. If you intend to submit a proposal in response to this RFP, IT IS ESSENTIAL THAT YOU IMMEDIATELY NOTIFY CYNDIE COTTER, CONTRACTING OFFICER, OF THE NIAID CONTRACTING OFFICE AT THE INTERNET ADDRESS LISTED BELOW. IF YOU FAIL TO NOTIFY THE CONTRACTING OFFICE OF YOUR INTEREST, YOU WILL NOT RECEIVE NOTIFICATION OF AMENDMENTS WHICH MAY BE ISSUED FOR THIS RFP, AND THIS COULD IMPACT YOUR PROPOSAL PREPARATION. HOWEVER, PLEASE NOTE THAT ALL AMENDMENTS WILL BE POSTED ON THE NIH GOPHER AND THE NIAID CONTRACT MANAGEMENT BRANCH (CMB) HOME PAGE. Questions concerning any areas of uncertainty which, in your opinion, require clarification or correction, must be furnished in writing to Cyndie Cotter. Your questions should be received no later than December 16, 1997, at the address indicated in Attachment 4, Item 5 (Fax or E-mail is also acceptable) and marked "Offeror's Questions, RFP-NIH-NIAID-DMID-98-11." 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, NIH Attachments: 1 - 6 ***************************************************************** ***************************************************************** RFP-NIH-NIAID-DMID-98-11 I. STREAMLINED RFP ATTACHMENT 1 10/16/97 BACKGROUND ---------- This initiative intends to consolidate the two previous DMID in vitro screening solicitations into one solicitation with multiple awards. The first solicitation resulted in the award of two contracts: one for the identification of novel experimental compounds with activity against herpesviruses (herpes simplex virus- 1 and -2, varicella zoster virus, cytomegalovirus, and Epstein-Barr virus) and the other for respiratory viruses (influenza A and B, respiratory syncytial virus, parainfluenza-3, measles, and adenovirus-5). The second solicitation resulted in the award of one contract to evaluate compounds for activity against hepatitis B virus. The current contractors are: University of Alabama at Birmingham (herpesviruses; N01-AI-35177; PI, Earl Kern), Utah State University (respiratory viruses; N01-AI-35178; PI, Robert Sidwell), and Georgetown University (HBV; N01-AI-45195; PI, Brent Korba). All three contracts are now managed by the Antiviral Research and Antimicrobial Chemistry Program Officer. Because these contracts share many common resources, a unified initiative will result in significant savings of staff time and review associated expenses. The majority of viral infections are impossible to treat effectively and many are serious health concerns. Currently, only fifteen antiviral drugs (idoxuridine, trifluridine, acyclovir, valacyclovir, famciclovir, vidarabine, ganciclovir, foscarnet, cidofovir, podofilox, amantadine, rimantadine, ribavirin, RSVIGIV, and interferon) have been approved by the FDA for the treatment of a small number of non-HIV viral diseases. However, in many cases, their utility is limited by toxicity or the emergence of resistant mutants. Because many of these drugs have the same mechanism of action, a simple mutation can result in cross-resistance to a whole family of the drugs. For example, emergence of thymidine kinase deficient mutants of herpes simplex virus in immunocompromised patients renders the three acyclic nucleosides for herpes simplex infections ineffective for the treatment of these patients. Amantadine and rimantadine share a common mechanism of action and influenza virus quickly develops resistance to both drugs even in immunocompetent patients. In addition to development of viral resistance, cidofovir, ganciclovir and foscarnet, the three drugs approved for CMV retinitis in AIDS patients, have significant toxicity. Therefore, the development of clinically effective and safe antiviral agents is essential for the control of viral infections. To date most of the licensed as well as experimental antivirals have been discovered by screening. It is also possible to design drugs based on knowledge of steps in the viral life cycle or pathogenesis. Yet due to the lack of this information for most viruses, it is certain that many more clinically important drugs will be identified through antiviral screens. Large pharmaceutical firms usually have adequate facilities to test and screen their developmental compounds for antiviral efficacy. However, many investigators at universities and small pharmaceutical firms who design and synthesize novel compounds, or who select, isolate and characterize new natural products do not have sufficient facilities and/or expertise to set up antiviral screens. In recognition of this need, NIAID awarded two contracts, in September of 1988, which established a screening project providing in vitro evaluation of potential antiviral agents for inhibitory activity against viral diseases caused by herpes and respiratory viruses. This project was re-competed and two contracts were awarded to the University of Alabama at Birmingham (infection- based herpes screen) and Utah State University (infection-based respiratory viruses screen) in September of 1993. In October 1993, Georgetown University, in response to another RFP, was awarded a contract to evaluate compounds for activity against hepatitis B virus (transfection-based screen). This new initiative is intended to re-compete the contracts currently awarded to University of Alabama (N01-AI-35177), Utah State University (N01-AI-35178), and Georgetown University (N01-AI- 45195) WITH AN EXPANSION OF RESEARCH INTO HEPATITIS C VIRUS. Viruses included in the current contracts will continue. These are herpes simplex viruses type 1 and type 2, varicella zoster virus, cytomegalovirus, Epstein-Barr virus, influenza viruses A and B, respiratory syncytial virus, parainfluenza virus type 3, measles, and hepatitis B virus. Because hepatitis C virus (HCV) is the major cause of non-A, non-B hepatitis, this initiative will include HCV as a new principal virus. HCV was first cloned in 1988. The viral genome is a positive strand linear RNA. The annual incidence of HCV has decreased in recent years. However, the current estimate is that 3.9 million Americans are chronically infected with HCV (1.8% of the population). The yearly medical cost includes approximately 10,000 deaths and 1,000 liver transplantations as a consequence of HCV infection. These numbers are predicted to rise 3.8-fold by 2010. Several observations lessen the likelihood of the imminent development of an effective vaccine. First, 50-80% of those infected become chronic carriers which suggests that the host immune response has minimal capability to provide protection. This is in contrast to infections with viruses such as the DNA-containing hepatitis B and cytomegalovirus which also cause persistent infections but generally only in individuals with impaired or immature immune systems. Like the human immune deficiency virus, HCV mutates readily leading to a high degree of viral heterogeneity and the emergence of variant viruses in individual patients. Although blood transfusions were the major source of transmission in the United States before the development of specific detection systems, injection drug use is now the dominant means of transmission. Health workers are also at risk from needle sticks and other means of inadvertent blood exchange. Although most cases are asymptomatic and progression to full-brown liver disease may take many years, chronic carriers are at high risk for cirrhosis and liver hepatocellular carcinoma. A recombinant alpha interferon has been approved as a therapy for chronic HCV. However, it is effective in less than half of treated patients and the disease recurs in the majority of patients when treatment is discontinued. Other viruses that may also be included are: human herpes virus types 6, 7, and 8, vaccinia virus, hantavirus, adenoviruses, and picornaviruses. Chemical substances selected for evaluation are based on a rationale for expectation of antiviral potential or as representatives of new chemical classes. The objective of these in vitro screens is multi-faceted: (1) therapeutic indices of potential antiviral compounds are determined to guide the selection and prioritization of compounds for evaluations in animal models; (2) active compounds are further evaluated against several virus strains including clinical and resistant isolates to explore their clinical potential; (3) when appropriate, studies on mechanisms of action and drug combinations are conducted to better understand compounds' pharmacological properties, as well as potential utilization and limitations (e.g., virustatic vs. virucidal activity, systemic vs. topical treatment, synergistic vs. antagonistic drug interaction); and (4) research also is conducted to improve the current screening systems and to develop automated high-capacity screening systems. The in vitro screening program is an integral part of the antiviral drug discovery and development activities of both the Virology Branch and the Enteric and Hepatic Diseases Branch. The investigators are members of the Collaborative Antiviral Testing Group (CATG). Currently, the CATG consists of seven contractors who evaluate promising new antivirals in experimental animal models, three contractors who conduct in vitro screens, and two investigators who engage in the development of new cell-based screening systems for human papillomavirus. The CATG meets annually to review progress and discuss strategies for future research. The CATG also interacts with investigators of USAMRIID Filovirus Screening Program and of NIAID-supported programs of NCDDG-OI, Targeted Antiviral Drug Design, and Topical Microbicides. Investigators in the antiviral research community have enthusiastically utilized the in vitro screening program. This program has helped identify and prioritize compounds for further studies in NIAID-supported animal models. A number of them are progressing in different stages of preclinical development. In addition, the data obtained from the screens have supported the IND applications for several compounds. Until antiviral therapies have been clinically proven to be safe and effective for each of the serious viral infections which afflict mankind, it is clear that continued efforts to identify antiviral substances by screening are needed. This recompetition is planned to assure the continuation of this vital resource for the identification of antiviral agents. INTRODUCTION ------------ The purpose of this solicitation is to obtain in vitro screening systems for the Government for the evaluation of the antiviral potential of experimental agents for the treatment of human viral infectious diseases. The delineation of mechanism of action and activity in drug combinations are of additional, but secondary, interest. Screening for retrovirus and human papillomavirus infections will NOT be considered for award since these are subjects of other initiatives or are already being supported. There are four PRINCIPAL VIRAL CATEGORIES covered under this Work Statement: (1) herpesviruses, (2) respiratory viruses, (3) hepatitis B virus, and (4) hepatitis C virus. Viruses other than these, unless specifically excluded (retrovirus and human papillomavirus), may also be proposed by the Offeror as an adjunct to the proposed principal viral category. A single Offeror may submit a proposal which includes one or more of the four principal viral categories. Each viral category within the Technical Proposal should be clearly marked so as to facilitate the technical review of that category. Each principal viral category will be scored separately and a competitive range will be determined for each. It is anticipated that up to one award will be made for each principal viral category, dependent upon the availability of funds and programmatic priorities. If more than one principal viral category is proposed, the business proposal should include a separate cost estimate for each viral category as well as a cost estimate which combines all proposed principal viral categories. [GENERAL NOTE TO OFFEROR: THE BASIC DATA SHALL REMAIN WITH THE CONTRACTOR; THE INFORMATION REQUIRED BY THE GOVERNMENT WILL BE OBTAINED THROUGH THE REQUIRED REPORTS. PATENT RIGHTS TO COMPOUNDS EVALUATED IN THE SCREENING PROGRAM WILL REMAIN WITH THE DRUG SPONSOR WHO PROVIDED THE DRUG FOR STUDY. NIAID INTENDS TO OBTAIN A DETERMINATION OF EXCEPTIONAL CIRCUMSTANCES (DEC) WHICH WILL STATE THAT POTENTIAL DRUG SPONSORS SHALL RETAIN ALL PRE-EXISTING RIGHTS TO THOSE COMPOUNDS OR PRODUCTS IN WHICH THE DRUG SPONSOR HAS A PROPRIETARY INTEREST. INTELLECTUAL PROPERTY RIGHTS FOR UNANTICIPATED DISCOVERIES, I.E., FOR BIOLOGICAL ACTIVITIES OTHER THAN (1) ANTIVIRAL EFFICACY AGAINST DRUG SENSITIVE AND DRUG RESISTANT VIRUS STRAINS AND AGAINST LABORATORY STRAINS AND CLINICAL ISOLATES; (2) CELL TOXICITY; AND (3) ACTIVITY IN COMBINATION WITH OTHER DRUGS ARE THE PROPERTY OF THE CONTRACTOR. THE CONTRACTOR IS ENCOURAGED TO COOPERATE WITH THE DRUG SPONSOR TO ENTER AN AGREEMENT REGARDING THE DISPOSITION OF THESE RIGHTS.] WORK STATEMENT -------------- Independently, and not as an agent of the Government, the Contractor shall furnish all the necessary services, qualified professional and technical personnel, material, equipment, and facilities 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) Conduct in vitro testing on experimental compounds for cell toxicity and their antiviral activity by using proven in vitro screening methods for herpes, respiratory viruses, and/or hepatitis viruses. The herpesvirus screen shall include herpes simplex viruses type 1 and type 2, human cytomegalovirus, varicella zoster virus, and Epstein-Barr virus. The respiratory viruses screen shall include human influenza A and B, respiratory syncytial virus, parainfluenza type 3, and measles. The hepatic viruses shall be hepatitis B virus or hepatitis C virus. Other viruses may include, but are not limited to: human herpes virus types 6, 7, and 8, vaccinia virus, hantavirus, adenoviruses, and picornaviruses. Each submitted compound provided by the Government shall be tested against all the viruses included in the contract, unless otherwise directed by the Project Officer. [NOTE TO OFFEROR (i): THE OFFEROR SHALL PROVIDE SCREENING FACILITIES FOR ALL OF THE DESIGNATED VIRUSES WITHIN THE CATEGORY(IES) SELECTED. METHODS OF SCREENING PROPOSED SHALL BE APPROPRIATE FOR THE SPECIFIC VIRUSES PROPOSED AND MAY INCLUDE PLAQUE REDUCTION, YIELD REDUCTION, INHIBITION OF CYTOPATHIC EFFECT, INHIBITION OF ENZYME ACTIVITY OR OTHER VIRUS-SPECIFIC ASSAYS. OFFERORS SHALL JUSTIFY THE CHOICE OF METHOD(S) PROPOSED.] (2) Maintain and store frozen stocks of compounds in a sterile manner. When data on solubility are not available, the Contractor shall select a vehicle and perform semi-qualitative solubility estimations in solvent and medium/solvent systems to solubilize the compound. [NOTE TO OFFEROR (ii): IT IS EXPECTED THAT 200 COMPOUNDS PER VIRUS WILL BE EVALUATED ANNUALLY. THESE COMPOUNDS WILL BE SUPPLIED BY THE DRUG SPONSORS AFTER RECEIVING APPROVAL FROM THE PROJECT OFFICER. COMPOUND ACQUISITION RESULTS FROM NIAID STAFF CONTACTS WITH DRUG SPONSORS OR CONTRACTORS' CONTACTS WITH DRUG SPONSORS. THESE COMPOUNDS MAY BE IRRITATING, TOXIC, AND/OR POTENTIALLY CARCINOGENIC OR HAZARDOUS.] (3) Maintain a master list of compounds received for testing, freezer location, usage, and other pertinent information. [NOTE TO OFFEROR (iii): THE TECHNICAL PROPOSAL SHALL PROVIDE DETAILED INFORMATOIN ABOUT HOW THIS WILL BE DONE AND IDENTIFY OTHER FACTORS THOUGHT TO BE PERTINENT.] (4) Maintain all confidential data in files accessible only by the Principal Investigator and involved staff. [NOTE TO OFFEROR (iv): THE TECHNICAL PROPOSAL SHALL SPECIFY PROCEDURES TO SAFEGUARD PROPRIETARY INFORMATION.] (5) Determine antiviral activity and cytotoxicity at various compound concentrations for all tested compounds. Calculate the 50% and/or 90% effective and cytotoxic concentrations. (6) Calculate the selective index for all tested compounds. (7) Determine antiviral activity against other virus strains (e.g., clinical isolates, resistant strains) in appropriate cell lines, as determined by the Project Officer, for compounds with reasonable separation between antiviral activity and cytotoxicity. Drug-resistant strains shall be included, if they are available. (8) Perform special studies as directed by the Project Officer which shall include, but are not restricted to, combination drug testing, mechanism of action studies targeting specific steps in viral replication, and other more detailed testing. [NOTE TO OFFEROR (v): MORE DETAILED TESTING WILL GENERALLY BE REQUIRED WHEN THE INITIAL SCREENING SHOWS THAT AN AGENT HAS A SUBSTANTIAL AMOUNT OF ANTIVIRAL ACTIVITY. THE TECHNICAL PROPOSAL SHALL DESCRIBE PRELIMINARY SCREENING PROCEDURES, THE CRITERIA USED TO SELECT COMPOUNDS RECOMMENDED FOR FURTHER EVALUATION, AND PROCEDURES FOR THE SPECIAL STUDIES. IT IS EXPECTED THAT SPECIAL STUDIES WILL BE PERFORMED ON NO MORE THAN 5 COMPOUNDS PER YEAR. OFFERORS MAY PROPOSE SUBCONTRACTORS FOR SPECIAL STUDIES. ] (9) Provide a screening report for each compound tested in accordance with the Technical Reporting Requirements contained in the contract (AS DESCRIBED IN ATTACHMENT 2 TO THIS RFP). The screening report shall contain the Contractor's recommendations and explanations as to a) whether or not a compound warrants further studies and, if applicable, b) specific additional studies to be performed. [NOTE TO OFFEROR (vi): THE PROJECT OFFICER WILL REVIEW THE SCREENING REPORT AND FORWARD IT TO THE COMPOUND SPONSOR. THE TECHNICAL PROPOSAL SHALL INCLUDE THE PROPOSED SCREENING REPORT.] (10) Participate in the annual meeting of NIAID contractors (Collaborative Antiviral Testing Group [CATG]) engaged in in vitro and in vivo pre-clinical evaluations of antiviral agents. [NOTE TO OFFEROR (vii): COSTS TO SUPPORT THIS TRAVEL FOR THE PRINCIPAL INVESTIGATOR, OR A DESIGNATED CO-INVESTIGATOR, SHOULD BE INCLUDED IN THE PROPOSED COST ESTIMATE. FOR ESTIMATING PURPOSES ASSUME THAT THE CATG MEETING WILL BE HELD FOR THREE FULL DAYS IN THE WASHINGTON, D.C. METROPOLITAN AREA.] (11) Evaluate and develop new in vitro testing systems at the direction of the Project Officer. [NOTE TO OFFEROR (viii): IT IS EXPECTED THAT NO MORE THAN 5% EFFORT OF THE PROPOSED PROFESSIONAL STAFF WILL BE UTILIZED PER YEAR TO PERFORM THESE EVALUATIONS.] ******************************************************************* ******************************************************************* RFP-NIH-NIAID-DMID-98-11 ATTACHMENT 2 10/16/97 DELIVERABLES AND REPORTING REQUIREMENTS --------------------------------------- The Contractor shall submit to the Contracting Officer and to the Project Officer technical progress reports covering the work accomplished during each reporting period. These reports are subject to technical inspection and requests for clarification by the Project Officer. A. TECHNICAL REPORTS In addition to those reports required by SECTION I and other terms of the contract, the Contractor shall prepare and submit the following reports in the manner stated below: (1) MONTHLY TECHNICAL PROGRESS REPORT - The Contractor shall submit four (4) copies, 7 calendar days following the end of each month. Each monthly report shall consist of: (a) A cover page containing: - Contract number and title - Period of performance being reported - Contractor's name and address - Author(s) - Date of submission (b) Screening reports for all compounds tested during the month. (c) An updated list of received compounds including NIAID's codes, compound names, compound sponsor names and institutions. (d) A summary sheet containing discussion and recommendations on any specific compounds to facilitate planning or for reporting to the compound sponsor. (e) A high density floppy disk containing all information recorded on the monthly screening report [(1)(b) above]. The stored information shall be retrievable by using the Microsoft Excel spreadsheet program. (2) SEMI-ANNUAL TECHNICAL PROGRESS REPORT - The Contractor shall submit three (3) copies of the semi-annual report 30 calendar days following the end of each sixth month period. In addition to the cover page described in A.(1)(a) above, each report shall include: (a) SECTION I - An introduction covering the purpose and scope of the contract effort. (b) SECTION II - A description of overall progress plus a separate description of each task or other logical segment of work on which effort was expended during the report period. Descriptions shall include pertinent data and graphs in sufficient detail to explain any significant results achieved and a scientific evaluation of the data accumulated to date under the contract. (c) 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. 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. (d) An anticipated work plan for the next reporting period. Semi-annual Technical Progress Reports are not due for periods in which an Annual or Final Report is due. (3) ANNUAL/FINAL REPORTS - The Contractor shall submit three copies of the annual and final reports, as outlined in item B. below, which 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. Annual reports shall be submitted 30 calendar days following the anniversary date of the contract. The final report shall be submitted by the completion date of the contract. An annual report is not required for the period when the final report is due. (4) 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. B. TECHNICAL REPORT DISTRIBUTION Copies of the technical reports shall be submitted as follows: Type of No. of Report Copies Addressee Due Dates ------- -------- ------------- ------------ Monthly 3 Project Officer Monthly* Progress DMID, NIAID, NIH Solar Bldg. 6003 Executive Blvd. Bethesda, MD 20892 Monthly 1 Contracting Officer Same Progress CMB, NIAID, NIH as Solar Bldg., Room 3C07 above 6003 Executive Blvd. Bethesda, MD 20892 Semi-Annual 2 Same as P.O. above Semi-Annually* Semi-Annual 1 Same as C.O. above Same as above Annual 2 Same as P.O. above Annually* Annual 1 Same as C.O. above Same as above Final 2 Same as P.O. above By completion date Final 1 Same as C.O. above Same as above * specific dates will be listed in the contract document C. 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. ****************************************************************** ******************************************************************* RFP-NIH-NIAID-DMID-98-11 ATTACHMENT 3 10/16/97 EVALUATION FACTORS FOR AWARD ---------------------------- 1. GENERAL Selection of an offeror for contract award will be based on an evaluation of proposals against two factors. The factors in order of importance are technical and cost. Although technical factors are of paramount consideration in the award of the contract, cost/price is also important to the overall contract award decision. The technical factor is significantly more important than cost or price. Offerors are advised that award will be made to that offeror whose proposal provides the best overall value to the Government. 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 merits of each proposal will be evaluated carefully. Each proposal must document the feasibility of successful implementation of the requirements of the RFP. Offerors must submit information sufficient to evaluate their proposals based on the detailed criteria listed below. 2. TECHNICAL EVALUATION CRITERIA Listed below are the technical evaluation criteria. The evaluation criteria are used by the technical evaluation group when reviewing the technical proposals. Proposals will be judged solely on the written material provided by the offeror. SEPARATE COMPETITIVE RANGES WILL BE DETERMINED FOR EACH OF THE FOUR PRINCIPAL VIRAL CATEGORIES: (1) HERPESVIRUSES, (2) RESPIRATORY VIRUSES, (3) HEPATITIS B VIRUS, AND (4) HEPATITIS C VIRUS. The criteria below are listed in the order of relative importance with weights assigned for evaluation purposes. CRITERION ELEMENT WEIGHT ------------------------------- ------ A. Technical Approach 55 1. Documented adequacy and suitability of the proposed methods and procedures for screening compounds for antiviral activity and evaluating cytotoxicity. (40) 2. Relevance and completeness of the proposed methods and approaches for performing special studies as specified in the Work Statement. (15) B. Personnel 25 Documented evidence of the relevance and suitability of expertise, experience and training of the Principal Investigator and other professional and support staff for performing all of the requirements of the Work Statement. C. Logistic Adequacy 10 Documented adequacy of the proposed plan for ensuring timely and efficient testing of compounds, recording and reporting data, and storing compounds. Adequacy of projected staffing and balance of professional and support staff to accomplish all of the tasks in the Work Statement. D. Facilities and Equipment 10 Documented adequacy and suitability of facilities and equipment for performing all of the requirements of the Work Statement. ---- TOTAL 100 ******************************************************************* ******************************************************************* RFP-NIH-NIAID-DMID-98-11 ATTACHMENT 4 10/16/97 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 Note: The following information is to be used by the offeror in preparing its Representations and Certifications (see Section C.4. of the Gopher RFP), specifically in completing the provision entitled, SMALL BUSINESS PROGRAM REPRESENTATIONS (JAN 1997), FAR 52.219-1: (a) The standard industrial classification (SIC) code for this acquisition is 8733. (b) (1) The small business size standard is $5M. (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 $5M. (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) It is anticipated that up to four (4) awards will be made from this solicitation and that these awards will be made on or about September 30, 1998. It is anticipated that the awards from this solicitation will be multiple-year cost reimbursement type completion contracts with a period of performance of 5 years, and that incremental funding will be used [see paragraph g.(6) of Business Proposal Instructions, in the "Standard RFP Instructions and Provisions" of the Gopher RFP]. 3. ESTIMATE OF EFFORT It is expected that multiple completion type contracts 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 EACH VIRAL CATEGORY to be approximately 1,675% (335%/year). This estimate 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: Percentages of Effort* Labor Annual 5 YR Category Effort TOTAL -------- ------ ----- Professional Staff 85% 425% Support Staff 250% 1,250% ----- ------ TOTAL 335% 1,675% * Effort in the above chart was based on 100% effort = 2,080 hours per year, which includes holidays and other paid absences. If you are using a different base, please state the work year used in your proposal. The above level of effort is the Government's estimate of the effort that will be necessary to satisfactorily accomplish the objectives of the Work Statement, and it will be used as a basis for negotiations. However, you can propose deviations from this estimated level of effort, with justification. 4. 52.233-2 SERVICE OF PROTEST (AUG 1996) (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) shall be served on the Contracting Officer (addressed as follows) by obtaining written and dated acknowledgment 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 within one day of filing a protest with the GAO. 5. PACKAGING AND DELIVERY OF THE PROPOSAL (NIH 2995) (JUL 1994) Your proposal shall be organized as specified in Section C.1., "Standard RFP Instructions and Provisions". 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-98-11" "TO BE OPENED BY AUTHORIZED GOVERNMENT PERSONNEL ONLY" Number of Copies: ________________ The number of copies required of each part of your proposal are as specified below: 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 ORIGINAL PROPOSAL MUST BE READILY ACCESSIBLE FOR DATE STAMPING 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. GOVERNMENT NOTICE FOR HANDLING PROPOSALS AN OFFEROR SHALL PLACE THIS NOTICE ON TOP OF EACH COPY OF ITS TECHNICAL PROPOSAL. This proposal shall be used and disclosed for evaluation purposes only, and a copy of this Government notice shall be applied to any reproduction or abstract thereof. Any authorized restrictive notices which the submitter places on this proposal shall also be strictly complied with. (For information regarding authorized restrictive notices, offerors should refer to the "Confidentiality of Proposals" section of the STANDARD RFP INSTRUCTIONS AND PROVISIONS subdirectory of the RFP REFERENCES directory of the Gopher RFP.) 7. PHSAR Clause 352.223-70, SAFETY AND HEALTH (AUG 1997) (a) In order to help ensure the protection of the life and health of all persons, as well as to help prevent damage to property, the Contractor shall comply with all Federal, State, and local laws and regulations applicable to the work being performed under the contract. These laws are implemented and/or enforced by the Environmental Protection Agency, Occupational Safety and Health Administration, and other agencies at the Federal, State, and local levels (Federal, State, and local regulatory/enforcement agencies). (b) Further, the Contractor shall take or cause to be taken such additional safety measures as the Contracting Officer, in conjunction with the project or other appropriate officers, determines to be reasonably necessary. If compliance with such additional safety measures results in an increase or decrease in the cost or time required of performance of any part of work under this contract, an equitable adjustment will be made in accordance with whichever applicable "Changes" Clause as set forth in this contract (FAR 52.243-1, Changes-Fixed Price; FAR 52.243-2, Changes-Cost- Reimbursement; or FAR 52.243-3, Changes-Time and Materials or Labor-Hours). (c) The Contractor shall maintain an accurate record of, and promptly report to the Contracting Officer, all accidents or incidents resulting in the exposure of persons to toxic substances, hazardous materials or hazardous operations; the injury or death of any person; and/or damage to property incidental to work performed under the contact and all violations for which the Contractor has been cited by any Federal, State, or local regulatory/enforcement agency. The report shall include a copy of the notice of violation and the findings of any inquiry or inspection, and an analysis addressing the impact these violations may have on the work remaining to be performed. The report shall also state the required action(s), if any, to be taken to correct any violation(s) noted by the Federal, State, or local regulatory/enforcement agency and the time frame allowed by the agency to accomplish the necessary corrective action. (d) If the Contractor fails or refuses to comply promptly with the Federal, State, or local regulatory/enforcement agency's directive(s) regarding any violation(s) and prescribed corrective action(s), the Contracting Officer may issue an order stopping all or part of the work until satisfactory corrective action (as approved by the Federal, State, or local regulatory/enforcement agencies) has been taken and documented to the Contracting Officer. No part of the time lost due to any such stop work order shall be subject to a claim for extension of time or costs or damages by the Contractor. (e) The Contractor shall insert the substance of this clause in each subcontract involving toxic substances, hazardous materials, or hazardous operations. Compliance with the provisions of this clause by subcontractors will be the responsibility of the Contractor. 8. TECHNICAL PROPOSAL TABLE OF CONTENTS/FORMAT (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, FORMAT & ATTACHMENTS)...............1 2. TECHNICAL PROPOSAL TABLE OF CONTENTS ..................... 2 3. SUMMARY OF OBJECTIVES AND METHODS (Abstract)* ............ 3 4. TECHNICAL PLAN (Refer to Technical Proposal Instructions, located in the Gopher RFP, STANDARD RFP INSTRUCTIONS AND PROVISIONS, for more details) a. STATEMENT OF WORK** 1. Objectives ........................................ 4- 2. Approach .......................................... ___ 3. Methods ........................................... ___ 4. Schedule .......................................... ___ b. PERSONNEL (List by name, title, department and organization, and detail each person's qualifications and role in the Project; provide narrative for: 1. Principal Investigator/Project Director ........... ___ 2. Other Investigators ............................... ___ 3. Additional Personnel e.g. technical support/ subcontractors/consultants) ...................... ___ [Note: For personnel, include 2 page biosketch/resume and the form entitled "Summary of Current and Proposed Activities" under Items 5. and 6. below.] c. FACILITIES/RESOURCES AND DIRECT COSTS (list/describe all equipment, facilities and other resources available for this project; attach "Technical Proposal Cost Information" form, and marked laboratory floor plan in Item 6. below) ............................................... ___ d. OTHER CONSIDERATIONS (provide brief narrative of any unique arrangements, safety procedures in place, animal welfare issues, human subject and minority and gender issues, etc.) ........................................ ___ 5. APPENDICES (protocols, literature citations, resumes/biosketches, policy manuals, etc. for above Technical Plan); list each Appendix; Appendices must be clear and legible, and easily located ............................... ___ 6. OTHER ATTACHMENTS: a. "Summary of Current and Proposed Activities" (All Key Personnel must be listed on this form; it is located in the FORMS, FORMATS, ATTACHMENTS subdirectory found in the Gopher RFP)......................................... ___ b. "Technical Proposal Cost Information" form (located in the Gopher RFP, FORMS, FORMATS, & ATTACHMENTS).......... ___ c. Laboratory Design and Floor Plan (clearly indicate the space available for this Project) ............................ ___ * 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. ** Item 4.a. above MUST NOT EXCEED 50 PAGES. Pages submitted in excess of this limit will be deleted and will not be reviewed. Please number each page. The front side of a page equals one page (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 an average of no more than 15 cpi. There must be no more than six lines of text within a vertical inch. 9. PROPOSAL INTENT RESPONSE SHEET PROPOSAL INTENT --------------- RFP No.: NIH-NIAID-DMID-98-11 IN VITRO ANTIVIRAL SCREENING PLEASE REVIEW THE ATTACHED REQUEST FOR PROPOSAL. FURNISH THE INFORMATION REQUESTED BELOW AND RETURN THIS PAGE BY NOVEMBER 28, 1997. YOUR EXPRESSION OF INTENT IS NOT BINDING BUT WILL GREATLY ASSIST US IN PLANNING FOR PROPOSAL EVALUATION. __________________________________________________________________ [ ] DO INTEND TO SUBMIT A PROPOSAL [ ] DO NOT INTEND TO SUBMIT A PROPOSAL FOR THE FOLLOWING REASONS: ____________________________________________________ TYPED NAME AND TITLE: ________________________________________ COMPANY/INSTITUTION: ________________________________________ ADDRESS: ________________________________________ NAME: ________________________________________ TITLE: ________________________________________ TELEPHONE NO.: ________________________________________ E-MAIL ADDRESS: ________________________________________ DATE: ________________________________________ - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - NAMES OF COLLABORATING INSTITUTIONS AND INVESTIGATORS (include Subcontractors and Consultants): (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-98-11 Fax # 301/402-0972 PLEASE RETURN BY NOVEMBER 28, 1997 ************************************************************ ****************************************************************** RFP-NIH-NIAID-DMID-98-11 ATTACHMENT 5 10/16/97 III. APPLICABLE RFP REFERENCES This section identifies the items located in the Gopher directory "RFP REFERENCES" that are applicable to this RFP. 1. The entire subdirectory 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" (below). 2. The following items are applicable from the subdirectory entitled "OPTIONAL RFP INSTRUCTIONS AND PROVISIONS": (a) LATE PROPOSALS, MODIFICATIONS OF PROPOSAL, AND WITHDRAWALS OF PROPOSALS, PHS 352.215-10 (b) SMALL, SMALL DISADVANTAGED, AND WOMEN-OWNED SMALL BUSINESS SUBCONTRACTING PLAN, FAR 52.219-9 [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 -------------------------------- (a) Technical Proposal Cover Sheet (b) Technical Proposal Cost Information, Dec 1988 (c) Summary of Current and Proposed Activities, July 1995 Applicable to Business Proposal ------------------------------- (d) Contract Pricing Proposal, SF-1411 (Rev. 10/95) (e) Proposal Summary and Data record, NIH-2043 (Rev. 6/82) (f) Business Proposal Cost Information (g) Disclosure of Lobbying Activities, OMB SF-LLL To Become Contract Attachments ------------------------------ (h) Invoice Instructions for Cost-Reimbursement Type Contracts, NIH(RC)-1, MAY 1997 (i) Instructions for Completing Form NIH 2706 (Financial Report) (j) Procurement of Certain Equipment, NIH(RC)-7 Other - to be submitted as directed by Contracting Officer ---------------------------------------------------------- (k) Certificate of Current Cost or Pricing Data, NIH-1397 (l) Small, Small Disadvantaged and Women-Owned Small Business Model Subcontracting Plan 4. The Representations and Certifications are applicable and a completed copy must be submitted with the offeror's Business Proposal. 5. The "Sample Contract Format-General" is applicable. ******************************************************************** ****************************************************************** RFP-NIH-NIAID-DMID-98-11 ATTACHMENT 6 10/16/97 IV. PROPOSED DEVIATION FOR DETERMINATION OF EXCEPTIONAL CIRCUMSTANCES, FAR 52.227-14 AND FAR 52.227-11 These contracts represent one segment of the drug discovery and development program within the Division of Microbiology and Infectious Diseases (DMID), NIAID. This project complements pharmaceutical efforts since NIAID's emphasis is on the discovery and development of drugs for viral infections, such as rare diseases, which are not being actively pursued by the pharmaceutical industry. This project is intended to accelerate development of new therapies for non-HIV viral diseases by encouraging owners of promising proprietary compositions to submit them for evaluation under the contracts. NIAID also intends to shepherd certain compositions (or processes) to the point of commercial development, where it could offer a commercial collaborator an attractive package of intellectual property rights which would give the collaborator the incentive to undertake the substantial investment needed to commercialize the composition or process and make it widely available to the public in the shortest practicable time. The NIAID seeks to attract suppliers having highly promising compositions for evaluation by making available standardized, validated efficacy testing systems such as will be provided by these contracts. These contracts will make available testing systems for evaluating candidate antiviral agents against certain viral infections and require specialized procedures, biosafety precautions, and technical expertise not usually available to academic, government, and pharmaceutical industry chemists. By providing information on biological activity developed under these contracts to suppliers of candidate compositions, the NIAID seeks to stimulate research and development in all sectors of the scientific community. In addition, newly discovered antiviral activity may require further testing and preclinical development within other components of the NIAID drug development program. Information on biological activity, physicochemical properties, and chemical structure must be protected in order to safeguard the rights of collaborating parties and thus to facilitate commercialization of new antiviral therapeutics. Because the goal of the NIAID drug discovery/development program is to promote the availability of new drugs, it will be necessary to restrict certain rights of the contractor providing the standardized testing to either attract suppliers of proprietary compositions or enable NIAID to offer a package of intellectual property rights to a collaborator for commercialization. It is anticipated that the great majority of compounds submitted to the NIAID for testing will be proprietary, and our experience has demonstrated that suppliers are reluctant to provide new chemical compositions or processes without complete assurance that their intellectual property rights are protected. In addition to the need to protect third party suppliers' proprietary rights, it is also necessary to consolidate into a single package the intellectual property rights that may arise in the performance of multiple contracts within the NIAID drug discovery program. This packaging of rights is much more likely to attract the large capital investment by pharmaceutical companies that is required to bring candidate drugs to market. Furthermore, in order to protect the intellectual property rights, the timing of data publication will need to be restricted in order for patent applications to be filed on inventions arising from the contracts. Thus, the NIAID intends to to seek a deviation from FAR clause 52.227-11, Patent Rights-Retention by the Contractor (Short Form) (June 1989) and from FAR clause 52.227-14, Rights in Data-General (June 1987). Pursuant to a Determination of Exceptional Circumstances (DEC) as required by FAR 27.303, the clause at FAR 52.227-11, Patent Rights- Retention by the Contractor (Short Form) (June 1989) will be modified to restrict the contractor's rights to subject inventions arising under the contract. Specifically, the contractor will be required to assign to the Government or, if deemed appropriate by the NIAID and subject to certain rights reserved to the Government, to a collaborating party designated by the Government the entire right, title and interest throughout the world to each subject invention, except to the extent that rights are retained by the Contractor under the Greater Rights Determination provision of the clause. The contractor may request greater rights to an identified invention, and the NIH will consider whether granting the requested rights will interfere with rights of the Government or any collaborating party or otherwise impede the ability of the Government or others to develop and commercialize new therapies to improve the treatment of viral infections in a rapid, efficient and cost effective manner. Contractors are encouraged to request greater rights where inventions relate to technology outside NIAID's program and where the contractor has negotiated with a supplier of a proprietary composition for the disposition of patent rights concerning a subject invention related to the composition. Although NIAID encourages the publication of articles on research results, FAR 52.227-14 Rights in Data-General (June 1987) will be narrowly modified to restrict the Contractor's right to use, release to others, reproduce, distribute, and publish data produced or used by the contractor in the performance of this contract in order to protect the supplier's proprietary rights, to protect data that will be submitted as part of a regulatory filing, and to delay the publication of data as necessary to obtain patent protection. NIAID will reserve the right to coordinate the timing of data publication with the supplier so that appropriate domestic and international invention applications may be filed. In general, a reasonable delay in publishing is expected to be less than six months. ******************************************************************* End of Document