RFI-SSN Immunotox.pdf

SOURCES SOUGHT/REQUEST FOR INFORMATION (RFI):

NIEHS Assessment of Immunotoxicity – In Vitro and In Vivo Assessment of Immune Function

Notice ID: Immunotox_RFI‐SSN_NIEHS_2023

1 INTRODUCTION

THIS IS A COMBINED REQUEST FOR INFORMATION (RFI)/SOURCES SOUGHT NOTICE ONLY. This Request for Information (“RFI”) is issued by the National Institutes of Health’s (“NIH”) National Institute of Environmental Health Sciences (“NIEHS” or “the Government”) in accordance with FAR Part 15.201(e) ‐ Exchanges with Industry. It is solely issued for market research information and planning purposes. It does not constitute a Request for Proposal (RFP) or a promise to issue an RFP in the future. This RFI does not commit the Government to contract for any supply or service whatsoever. Further, NIEHS is not at this time seeking proposals and will not accept unsolicited proposals. Responders are advised that NIEHS will not pay for any information or administrative costs incurred in response to this RFI; all costs associated with responding to this RFI will be solely at the interested party’s expense. Not responding to this RFI does not preclude participation in any future RFP, if any is issued. If a solicitation is released, it may be synopsized on the SAM.gov website or issued through any number of existing Government contract vehicles determined by the Government to be the best procurement approach (e.g., GSA Federal Supply Schedule (FSS), Government Wide Acquisition Vehicles (GWACs), etc.). It is the responsibility of the potential offerors to monitor any related solicitation sites used by the Government for additional information pertaining to this requirement.

2 BACKGROUND

The Division of Translational Toxicology (DTT) is an intramural division of NIEHS within the National Institutes of Health (NIH). DTT uses traditional and cutting‐edge approaches to better understand how factors in our environment may impact human health. Such approaches include the conduct of immunotoxicology studies on chemical, physical, and biological agents, as well as non‐chemical stressors, using in vitro and in vivo models of health and disease. Specific research tasks include:

1) The development and establishment of methods with predictive value for potentially immunotoxic chemicals and drugs.

2) Examination of selected agents employing a defined panel of immune function tests and observational measures.

3) Mechanistic studies to define the cellular and molecular events associated with immunotoxicity.

Immunotoxicity is used to describe the potential of an agent to alter the normal structure and/or function of the immune system as determined by established immunological techniques. In cases of immunomodulation, a chemical or physical agent may alter hematopoietic or immunological function in humans and animals, resulting in changes in the ability to recognize and eliminate threats such as self‐ reactive or cancerous cells. When immune responses are suppressed, increased rates of infection and neoplasia may occur. Conversely, when the immune response is stimulated and uncontrolled, chronic inflammation or autoimmune disease may manifest. In cases of hypersensitivity, the immune system responds to chemically modified ("non‐self") compounds (haptens) as part of a "specific" immune response. The most likely health consequences include respiratory tract allergies (e.g., asthma, rhinitis) or allergic contact dermatitis.

With the increasing awareness of the need for translational toxicology and to reduce the use of animals, the use of in vitro methods to assess immune function will be main objectives in DTT’s research efforts to assess altered immunity. The focus of this requirement will be to provide DTT with a mechanism to evaluate chemical induced immunotoxicity by determining: 1) whether chemical or therapeutic agents can modulate the immune response using a battery of in vitro tests to measure immune suppression or stimulation in response to relevant antigens; 2) whether chemical agents have the potential to induce allergic responses using in chemico and in vitro OECD guideline test methods for skin sensitization as part of an integrated panel of tests and; 3) evaluate the potential of a test agent to modulate the immune system using a comprehensive in vivo immune testing panel that evaluates the major components of the immune system in the developing rat and/or adult mice or rats.

NAICS Code and Size Standard In the event that a Request for Proposal (RFP) is issued, North American Industry Classification System (NAICS) code 541990 – All Other Professional, Scientific, and Technical Services.

Anticipated Period of Performance The anticipated Period of Performance is (8) years with an estimated start date of March 2026.

Contract Type and Contractor’s Accounting System It is anticipated that the resultant contract will be a cost reimbursement type contract. Therefore, to be considered for an award under the resultant solicitation, the offeror’s accounting system and practices must be adequate and suitable for accumulating costs under government contracts. The offeror must further certify that the accounting system is currently in full operation. The Government will consider

Fixed‐Price options for research studies under Task Areas 1 and 3 described in the Statement of Work.

2.1 CAPABILITIES SOUGHT

The NIEHS seeks information on contract support to provide evaluation of the effects of chemicals on immune function (hypersensitivity, humoral, cell‐mediated, and innate immunity) using in vitro and in vivo test methods to predict the potential for human health effects as detailed in the Draft Statement of

Work (Attachment 1). Award of a cost‐reimbursement, cost‐plus‐fixed‐fee level of effort type contract is contemplated with the anticipated period of performance for eight (8) years. The total estimated level of effort is anticipated to be between 8,000 to 12,000 labor hours per year, including options, depending on the needs of the NIEHS.

In brief, the NIEHS is interested in acquiring the capability to assess chemical modulation of immune function. This is to be accomplished in primary human cells such as those obtained from donor human peripheral blood using in vitro screening methods in a panel of assays that provide information on humoral, cell‐mediated, and innate immune function. When assay appropriate, the test system shall include an assessment of antigen‐specific responses using human relevant antigens as stimulatory factors. The assay panel should include quantitative information on endpoints such as cell proliferation, cytokine production, lymphocyte subpopulations and cytotoxicity.

The DTT/NIEHS also is interested in acquiring the capability to evaluate test articles for their potential to produce dermal hypersensitivity using OECD test guideline in vitro/in chemico methods. Such methods may include but are not limited to: 1) The Direct Peptide Reactivity Assay (DPRA), an in chemico assay validated for examination of Key Event 1 in the Skin Sensitization Adverse Outcome Pathway (AOP) that evaluates the potential for chemical haptenization of proteins; 2 ) the KeratinoSens™ assay and similar me‐too methods that are in vitro cell‐based reporter gene assays validated for examination of Key Event

2 in the Skin Sensitization AOP and evaluate chemical induced keratinocyte activation and; 3) the Human

Cell Line Activation Test (h‐CLAT) which is validated for examination of Key Event 3 in the Skin

Sensitization AOP and represents a surrogate assay to test for chemical induced activation of dendritic cells. As no individual assay is considered sufficient as a stand‐alone method to draw conclusions on the skin sensitization potential of chemicals, data generated with these in chemico and in vitro methods addressing multiple key events of the skin sensitization AOP shall be used together to define sensitization potential. In addition, information sources such as in silico and read‐across predictions from chemical analogues should be considered using integrated approaches to testing and assessment

(IATA) or defined approaches (DAs). Contract laboratories that conduct the methods described above or other validated methods used to assess sensitization potential shall integrate the results from multiple information sources or data streams using established models for data interpretation.

The DTT/NIEHS also seeks the ability to conduct in vivo assessments of the potential to induce immunotoxicity in rodents, using adult or perinatal exposures. A comprehensive in vivo testing panel that evaluates the major components of the immune system in the developing rat and/or adult mice or rats has been employed by the DTT (Luster et al., 1992) and includes routine toxicology endpoints such as clinical observations, food and water consumption, body and organ weights and clinical pathology

(hematology and leukocyte differential), as well as specific assays to quantitate antigen‐specific antibody responses, cytotoxic T lymphocytes activity, identification of spleen cell populations and non‐specific immunity (i.e. natural killer cell activity or macrophage phagocytosis) and should serve as the template for these studies.

3 REQUESTED INFORMATION/RESPONSES

All interested parties are hereby invited to submit a capability statement in accordance with the following constraints:

Maximum of 15 pages in length submitted in Adobe Portable Document Format (.pdf), using the numbered format below (Items 1‐8).

Times New Roman font no smaller than 12‐point with one‐inch margins.

Electronic file submissions must be less than 30 megabytes in size.

Additionally, the Government will review each capability statement based on the interested party's demonstrated qualifications, capabilities, expertise, experience and past performance in each of the areas. More specifically, capability statements should provide the following information and address the following questions as appropriate and as applicable:

1. Company Information:

Company Name:

Point of Contact:

Address:

Phone #:

E‐mail address:

Cage Code:

UEI:

NAICS Code:

Small Business Status: (“8(a)” Program, Women‐Owned Small Business concern (WOSB), Economically Disadvantaged Women‐Owned Small Business concern (EDWOSB), HUBZone Small Business concern (HUBZoneSB), Veteran‐Owned Small Business concern (VOSB), Service‐ Disabled Veteran‐Owned Small Business concern (SDVOSB), Small Business, Large Business, Other)

2. Is your company currently capable of providing 100% of the requirements and objectives of the subject requirement? (Explain)

3. Please describe capabilities and experience in the following areas:

1) Demonstrated abilities and experience in planning, conducting, and reporting studies of immune system perturbation following in vitro and in vivo exposure to a test article, including evaluation of immunosuppression and immunostimulation.

2) Demonstrated capability and experience in the investigation of mechanisms of immunotoxicology.

3) Demonstration of performance for developing and validating in vitro and alternative methods used in immunotoxicology screening.

4) Integration of in vitro and in vivo toxicology data for use in translation to human health.

5) Familiarity of activities associated with OECD Test Guidelines Programme, and the

Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM).

6) Adequacy of experience in managing the conduct and reporting of toxicology studies and in the management and coordination of work projects.

4. What is the feasibility of solutions to accomplish the requirements detailed in the draft SOW?

Identify any barrier(s) that exist(s). Please include only items that are related to the requirement as described in the DRAFT SOW documents.

5. Describe your experience in a complex scientific research environment with respect to working together as a team, ability to conduct multiple tests for immune suppression or sensitization with the same test article, problem‐solving and working with various stakeholders, such as federal agency partners or test developers.

6. Provide up to three examples of projects of similar scope, and complexity to the NIEHS requirement described herein—preferably with the Federal Government. Briefly describe the scope of work, solutions designed/implemented, project management methodology, and best practices/lessons learned. Please be sure to describe any commercial business practices that are unique to your industry (i.e. capability to operate under Good Laboratory Practice (GLP) Regulations established by the FDA for Non‐clinical Laboratory Studies).

7. Vendors are invited to submit comments on the Draft Statement of Work (SOW). The comments should identify any gaps in the SOW including areas requiring clarification, missing or ambiguous requirements, staffing considerations and any other general comments or concerns. Vendors may also provide specific comments and suggestions for refining the SOW to reflect clear guidance to industry and industry best practices, as well as provide additional information that they think is relevant for developing the acquisition strategy for this requirement. Vendors are also invited to discuss commercial availability of sources.

8. Vendors are invited to submit comments on the anticipated NAICS code, period of performance and anticipated contract type.

Standard product brochures will not be considered a sufficient response to this RFI. Any additional comments that are not responsive to a particular RFI requirement/question should be separated labeled as “Additional Comments” and included at the end of the response.

NIEHS reserves the right to use any and all information submitted by, or obtained from, an interested party in any manner NIEHS determines is appropriate including, but not limited to, the creation of a competitive solicitation. An interested party should avoid including any business confidential and/or proprietary information in its response. However, if an interested party must submit such information, the information must be clearly marked accordingly, and the interested party must provide enough justification as to why such information is business confidential and/or proprietary.

NIEHS will review said information and safeguard it appropriately.

4 RESPONSE SUBMISSION INSTRUCTIONS

All capability statements/responses shall be submitted electronically no later than 2:00 p.m. Eastern Time (ET) on August 9, 2023 to Erica Walker, Contracting Officer, at the following e‐mail address:

erica.kitzmiller@nih.gov.

All questions in regards to this notice should be directed to Erica Kitzmiller at erica.kitzmiller@nih.gov.

NIEHS personnel may contact firms responding to this RFI/SSN to clarify a Responder’s capabilities and other matters as part of this market research process.

Respondents are advised that the Government is under no obligation to acknowledge receipt of the information received or provide feedback to Responders with respect to any information submitted.

THIS IS A REQUEST FOR INFORMATION (RFI) / SOURCES SOUGHT NOTICE (SSN) ONLY to identify sources that can provide the services described herein. The information provided in the RFI/SSN is subject to change and is not binding on the Government.

NIEHS has not made a commitment to procure any of the equipment, commodities, and services listed herein, and release of this RFI/SSN shall not be construed as such a commitment or as authorization to incur cost for which reimbursement would be required or sought. All submissions become Government property and will not be returned.