SOLICITATION NOTICE
A -- Evaluation and Qualification of the MIMIC System - Package #1
- Notice Date
- 5/28/2013
- Notice Type
- Combined Synopsis/Solicitation
- NAICS
- 541711
— Research and Development in Biotechnology
- Contracting Office
- Department of Health and Human Services, Food and Drug Administration, Office of Acquisitions and Grants Services, 3900 NCTR Road, HFT-320, Bldg 50 | Rm 421, Jefferson, Arkansas, 72079, United States
- ZIP Code
- 72079
- Solicitation Number
- 1115909
- Archive Date
- 7/4/2013
- Point of Contact
- Marcia O Park, Phone: (870) 543-7405
- E-Mail Address
-
marcia.park@fda.hhs.gov
(marcia.park@fda.hhs.gov)
- Small Business Set-Aside
- Total Small Business
- Description
- Deliverable Attachment This is a combined synopsis/solicitation for commercial items prepared in accordance with the format in Subpart 12.6, as supplemented with additional information included in this notice. This announcement constitutes the only solicitation, proposals are being requested and a written solicitation will not be issued. The solicitation number is 1115909 and is issued as a request for quotation (RFQ). The solicitation document and incorporated provisions and clauses are those in effect through Federal Acquisition Circular (FAC) 2005-66 dated April 1, 2013. The appropriate NAICS code for this acquisition is 541711 - Research and Development in Biotechnology for which the small business size standard is 500 employees. This acquisition is 100% set aside for small businesses. Background Preclinical evaluation of immunogenicity of live and inactivated vaccines is conducted in a variety of animal models. They have an obvious limitation determined by species-specific differences in immune response to different antigens. Therefore the ultimate assessment of immunogenicity is possible only in human systems. There are a number of in vitro models that study antigenic structure of vaccines rather than its ability to induce specific protective antibodies. It would be highly desirable to assess and qualify an in vitro biomimetic system that would mimic immune responses that occur in humans after administration of protective antigens. Screening for synthetic immunogenic peptides that could potentially be used as vaccines is also done in animal models that suffer from the same limitations. The need to use animals also limits the number of peptides that may be screened. Use of a high-throughput system would significantly increase chances of finding the right immunogenic peptides. VaxDesign developed a system that is called MIMIC (Modular Immune In vitro Construct). The MIMIC system is comprised of isolated primary human immune cells integrated into engineered tissue constructs that are functionally equivalent to the physiological environment of the human immune system. By accurately representing the cellular synergy and communication kinetics that are critical for the induction of adaptive immunity in vivo, VaxDesign has shown the potential of the MIMIC model to support the sensitization of primary human B and T cell responses in an in vitro setting. The study currently being conducted by the Food and Drug Administration's Center for Biologic Evaluation and Research, Office of Biostatistics and Epidemiology (FDA/CBER/OBE) includes 50 donors immunized with Inactivated Polio Vaccine (IPV) (commercial vaccine). Both pre-vaccination and post-vaccination apheresis products have been collected. Various immunoassays were performed based on in vivo/serum, ex vivo, and in vitro/MIMIC assays. Immune response data with regard to serum antibody against polio serotypes 1, 2, and 3, T cell response measured by the enzyme-linked immuno sorbent spot (ELISPOT) and multiparameter flow cytometry, B cell response measured by polio serotype-specific antibody titers, as well as enzyme-linked immuno sorbent assay (ELISA) neutralization titers will be available for analysis. Project Objectives The goal of this Research Project is to Evaluate and Qualify the MIMIC System and functional immunoassays for Determining the Immunogenicity of Vaccines and Screening Synthetic Peptides as Vaccine Candidates. In addition to helping characterize the immunogenic properties of natural and synthetic peptides, the prospective contractor shall help determine whether the automated MIMIC system is a suitable tool for the high-throughput screening of large libraries of synthetic peptides for potential in vivo immunological activity. The use of fully synthetic peptides to induce protective immunity would have tremendous safety and cost reduction benefits. A major obstacle to realizing synthetic peptide vaccines has been the difficulty in screening synthetic peptides for immunogenic activity. This goal is consistent with FDA's Critical Path goals of bringing new technologies to the development, characterization and validation of the next generation of biological products. The MIMIC system provides a step-wise immunological progression of a vaccine in the biomimetic of the human immune system Broadly, this encompasses sera evaluations by novel functional assays, vaccine dosing/toxicity in immune cells, and examinations of vaccine inflammatory/reactogenicity potential in the PTE module and capacity to elicit cellular and humoral responses in the LTE module of the MIMIC system. In the current effort, we will qualify the MIMIC with inactivated poliovirus vaccines (IPV) as a model vaccine because of the ample structural and functional information about poliovirus antigens that is available in literature and at the FDA/CBER, as well as a number of comparable vaccine products with different clinical immunogenicity profile. Besides being a model system, development of a new generation of vaccines against polio is currently a high international public health priority. Therefore results of this study will be used to demonstrate feasibility of this in vitro biomimetic approach for other vaccines, e.g., vaccines against various biothreats, as well as to compare immunogenicity of different new IPV products currently under development. The study will include a statistically relevant number of donors immunized with IPV. The overarching objective is to demonstrate if the results generated in vitro in the MIMIC platform correlate with in vivo responses generated in the same donors immunized with the vaccines. The inherent advantage to this approach is that each donor ‘subject' serves as their own baseline control allowing a pair approach to analysis. Description of Work/Tasks The contractor shall provide statistical data analysis and reporting for this project to include: 1. Association/correlation between in vitro immune results obtained in culture and in the in vivo virus-specific responses A statistically relevant number of donors to be determined by the biostatistician at the FDA will be immunized with IPV and the pre-vaccination and post-vaccination apheresis collections from these individuals will be used to seed the MIMIC platform. The in vitro immune results obtained in culture will be correlated against the in vivo virus-specific responses in the following aspects:. Illustrate similar expansion of antigen-specific precursors/Th differentiation profiles with regard to CD4+T cell responses (quantity and functionality). Show comparable trends in magnitudes of antigen-specific responses B cell expansion. Demonstrate correlation between in vitro and in vivo trends; and between novel fluorescent adherence inhibition (fADA) and conventional functional assays such as ELISA and neutralization tests Statistical analyses are to be performed to address the following research objectives as a minimum: a. Agreement/correlation of the qualitative immune response measures between the in vitro and in vivo methods. The qualitative measures include: i. proportion of positive responses defined as that an antibody level is above a cut-off level considered as protection ii. Proportion of >/= 4-fold antibody increase at post-vaccination compared with baseline (pre-vaccination) b. Agreement/correlation of the quantitative antibody levels across the range of the typical response levels between the in vitro and the in vivo methods. Statistical techniques such as the error-in-variable regression models may be employed to explore the comparability of the in vitro and the in vivo results. c. Validity of using the measured in vitro immune responses to predict the in vivo immune responses. Validation of the MIMIC system and establishment of statistical metrics for the evaluation. The complexity of these validation results will require a significant contribution of a biostatistician to aid in defining statistical relevance and provide scientific validity to the measured responses. Correlations between in vivo (vaccination) and from and in vitro (MIMIC) polio-specific responses will be established by statistical evaluations including multiple regression models and analyses. The study will consider factors such as donor serostatus, assay endpoints, and correlation trends on an individual and population, where applicable. 2. Qualification of novel functional assays. While modern immunosorptive methods, such as ELISA, can provide tremendous sensitivity in evaluating the quantity of antibody against a particular antigen target, the lesser sensitive microneutralization and hemagglutination inhibition tests remain important because they provide readouts of the functionality of the humoral immune response that cannot be achieved by immunosorptive assays. Though these assays have a long history of use by many in the field and have well-defined correlates of immunity, they often lack sensitivity, interlaboratory reproducibility, and require the use of live pathogen that can be very cumbersome when dealing with a deadly organism. As an alternative, we have developed a suite of sensitive and cost-effective target-cell based functional assays that can be used to determine whether antibody in donor sera or MIMIC cultures is able to block or neutralize a pathogen of interest; in some cases, these assays can also be used to deduce the mode of inhibition. These techniques offer major advantages over current methods because they were designed to be used with killed organisms, have a high level of sensitivity and reproducibility, are rapid and cost-effective and can be performed in hours rather than days. They can be used to evaluate antibodies in sera samples from donors pre- and post-vaccination and/or following antigen encounter in the MIMIC system. For example, the fluorescent adherence inhibition (fADI) approach provides for a surrogate evaluation of antibody-mediated virus neutralization by measuring the binding of a fluorescently tagged virus or other antigen directly to a target cell population in the presence or absence of graded doses of a test antibody. In the absence of a neutralizing antibody, the fluorescent virus particles will bind the cells, generating a signal on the BioPlex (flow-based fluorescence) reader. In contrast, blocking antibody in sera or with the virus-cell interaction in a dose-dependent fashion. Since all the incubations and wash steps are performed at 4 degrees centigrade (which prevents virus engulfment), the readout of the response reflects exclusively the binding of virus to the cell membrane. The fADI assay will also be qualified in the proposed study with the FDA/CBER via comparison with WHO standard microneutralization assays. 3. Exploration of the impact of baseline characteristics of the donors on the validity of the in vitro results 4. Development of analysis modules for use in future research of the validity of the MIMIC system for other vaccines. Detailed Requirements 1. The contractor shall perform all analysis including innovative statistical approaches 2. This project shall have an analytic plan, deliverables, and a final deliverable including the final report; all programs shall be documented with references at the end of the projects. The final deliverable shall be submitted in a package which includes a hard copy of the final report and electronic copies of all the files and programs on a CD. 3. The contractor shall be responsible for maintaining clear and timely communication with the project leader at FDA/OBE at all times. 4. The contractor shall attend bi-weekly telemeetings and monthly progress reports; and additional meetings as required for clarifications or updated. 5. The Contractor shall present a final report approved by FDA/OBE staff that documents that all tasks were successfully completed and presents any information needed for future reference. 6. The contractor shall provide thorough documentation of the study. All computer program deliverables shall have sufficient documentation in the code so that a reasonably-knowledgeable programmer could understand and modify the code. All results shall be described in a manner that is reproducible given all the supported documentations. Deliverables for this work are outlined in attachment 1 to this notice. PRICE SCHEDULE QTY PRICE 1. Qualification of the MIMIC System 1 JOB _____________ Period of performance is 6 months after award of contract. FAR 52.212-1 Instruction to Offerors - Commercial Items (FEB 2012) applies to this solicitation. Period for acceptance of offerors: The offerors agree to hold prices firm through September 30, 2013. It is the offerors responsibility to monitor www.fbo.gov for the release of any amendments to this combined synopsis/solicitation. FAR 52.212.2 Evaluation - Commercial Items (JAN 1999) (a) The Government will award a contract resulting from this solicitation to the responsible offeror whose offer conforming to the solicitation will be most advantageous to the Government, price and other factors considered. The following factors listed in descending order of importance shall be used to evaluate offers: 1. Technical Capability of offeror to meet the Government's requirements: Indicate your approach for accomplishment of the Statement of Work; demonstrate recognition and ability to overcome potential difficulties in the performance of each component of the project; technical approach to the conduct of the study including overall research design, statistical methodology/approach, feasibility, and appropriateness of the proposed methods. Provide detailed description of data management, quality control and quality assurance; describe organizational experience and personnel who will be assigned to this project. Identify all proposed subcontractors, their specific roles and responsibilities, the proposed subcontract value expressed as a percentage of the total proposed price (do not include actual subcontract price for this effort or total proposed price information in this technical capability proposal). Please be advised that generic statements are not sufficient for effective evaluation of respondent's capability. Responses shall not exceed fifteen pages in length. 2. Past Performance Identify all ongoing and completed work (within the last 3 years from date of this solicitation) relevant to these requirements in terms of type, scope, complexity, and size. For each of these past performance references, provide a detailed description of the work, the period of performance, the dollar value of the work, your role and responsibilities as either a prime or subcontractor, the client name and address and client point of contact name, phone number, and email address. Provide this same information for any proposed subcontractor who will be performing a critical aspect of the required work or will otherwise be performing 15% of the total proposed price (do not include actual subcontract price for this effort or total proposed price information in this past performance proposal). Offeror shall also provide as part of this past performance proposal a list (in bibliography format) of contractor (and subcontractor who will be performing a critical aspect of the required work or will otherwise be performing 15% of the total proposed price) authored/co-authored articles (which were subjected to peer review) related to this work. 3. Price. Completed Pricing Schedule Technical and Past Performance, when combined are more important than Price. FAR 52.212-4 Contract Terms and Conditions - Commercial Items (FEB 2012) is incorporated by reference. The following addenda apply: FAR 52.204-4 Printed or Copied Double-sided on Recycled Paper (May 2011) FAR 52.227-17 Rights in Data Special Works (Dec 2007) HHSAR 352.202-1 Definitions (Jan 2006) HHSAR 352.203-70 Anti-Lobbying (Jan 2006) HHSAR 352.222-70 Contractor Cooperation in Equal Employment Investigations (Jan 2010) HHSAR 352.231-71 Pricing of Adjustments (Jan 2001) Invoice Submission A. The Contractor shall submit all invoices in accordance with the following instructions below (acceptable methods of delivery include email, mail and hand delivery); An original and two (2) copies shall be submitted to: Attn: Marcia Park, Contract Specialist Food and Drug Administration Jefferson Laboratories Complex National Center for Toxicological Research Office of Acquisitions & Grants Services, HFT-320 3900 NCTR Road, Bldg 50, Room 434 Jefferson, AR 72079-9502 Email: Marcia.park@fda.hhs.gov One copy of the invoice shall be submitted to the Project Officer/Contracting Officer's Representative, clearly marked "Courtesy Copy Only" to: (To be identified at time of award) B. Invoices submitted under this contract must comply with the requirements set forth in FAR Clause 52. 232.25 (Prompt Payment) and 52.232.33 (Payment by Electronic Funds Transfer - Central Contractor Registration) and/or other applicable FAR Clauses specified herein. To constitute a proper invoice, the invoice must be submitted on company letterhead and include each of the following: (i) name and address of the contractor; (ii) invoice date and invoice number; (iii) purchase order/award number; (a) period of performance for which costs are claimed; (b) itemized travel costs, including origin and destination; (c) any other supporting information necessary to clarify questionable expenditures; (iv) terms of any discount for prompt payment offered; (v) name and address of official to whom payment is to be sent (must be the same as that in the purchase order/award, or in a proper notice of assignment) (vi) name, title, and phone number of person to notify in event of defective invoice; (vii) taxpayer identification number (TIN); (viii) electronic funds transfer (EFT) banking information, including routing transit number of the financial institution receiving payment and the number of the account into which funds are to be deposited; (ix) name and telephone number of the FDA Project Officer/Contracting Officer's Representative or other program center/office point of contact, as referenced on the contract/order; and (x) any other documentation required by the contract/order. C. An electronic invoice is acceptable if submitted in adobe acrobat (pdf) format. All items listed in (i) through (x) of this clause must be included in the electronic invoice. Electronic invoices must be on company letterhead and must contain no ink changes and be legible for printing. D. Questions regarding invoice payments should be directed to the FDA payment office at: Food and Drug Administration Attn: Vendor Payments, OFS FDA 3900 NCTR Road, HFT-324 Building 50, Room 620 Jefferson, AR 72079-9502 nctrinvoices@fda.hhs.gov The clause at FAR 52.212.5, Contract Terms and Conditions Required to Implement Statutes or Executive Orders - Commercial Items (Jan 2013) is incorporated by reference. The following additional FAR 52.212-5 clauses are applicable: (b) 52.204-10, 52.209-6, 52.209-6, 52.219-8, 52.219-28, 52.222-3, 52.222-19, 52.222-21, 52.222-26, 52.222-35, 52-222-36, 52.222-37, and 52.223-18 FAR and HHSAR clauses and provisions incorporated by reference may be obtained by accessing https:www.acquision.gov/far/ and http://www.hhs.gov/policies/hhsar/subpart352.html. All responsible sources may submit a proposal, which if timely received, shall be considered. The proposal shall reference Solicitation number 1115909. Proposals are due in person, by postal mail or email to the point of contact listed below on or before 1:00 P.M. CST, June 19, 2013, Jefferson, AR, at the Food and Drug Administration, OO/OFBA/OAGS, Attn: Marcia E. Park, 3900 NCTR Road, HFT-320, Jefferson, AR 72079-9502. For information regarding this solicitation, please email Marcia Park at marcia.park@fda.hhs.gov.
- Web Link
-
FBO.gov Permalink
(https://www.fbo.gov/spg/HHS/FDA/NCTR/1115909/listing.html)
- Place of Performance
- Address: 1401 Rockville Pike, Rockville, Maryland, 20852, United States
- Zip Code: 20852
- Zip Code: 20852
- Record
- SN03072820-W 20130530/130528234710-b690194095e57afde1878e4433f4621d (fbodaily.com)
- Source
-
FedBizOpps Link to This Notice
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