Pharmacology Studies and Animal Model Development and Related Services for Drug Development
Related Notice: Request for Information, Notice ID 75N95023R00004, Pharmacology Studies and Animal Model Development and Related Services for Drug Development, published November 7, 2022.
PURPOSE OF NOTICE
This is a Research and Development (R&D) Sources Sought notice. This is NOT a solicitation for proposals, proposal abstracts, or quotations. The purpose of this notice is to obtain information regarding the availability and capability of all qualified sources to perform a potential R&D requirement.
This notice is issued to help determine the availability of qualified companies technically capable of meeting the Government requirement and to determine the method of acquisition. It is not to be construed as a commitment by the Government to issue a solicitation or ultimately award a contract. Responses will not be considered as proposals or quotes. No award will be made as a result of this notice. Responses will not be considered as proposals or quotes. The Government will NOT be responsible for any costs incurred by the respondents to this notice. This notice is strictly for research and information purposes only. The Government will not entertain questions regarding the results of this market research.
BACKGROUND
The Therapeutic Development Branch (TDB) within the Division of Preclinical Innovation (DPI) at the National Center for Advancing Translational Sciences (NCATS) within the National Institutes of Health (NIH) conducts translational research to support therapeutic development by moving small molecule and biologic drug candidates forward in the drug development pipeline. Upon reaching predetermined milestones, TDB hands off clinical candidates to external partners to bring these novel therapies to patients. In addition to developing new candidate drugs, TDB seeks to advance the entire field of drug discovery and development by encouraging scientific and technological innovations aimed at improving success rates in the crucial preclinical stage of drug development. The TDB model is to operate as a comprehensive small molecule and biologics drug development organization, moving therapeutic candidates through each phase of the preclinical development process until an Investigational New Drug (IND) application is filed with the US Food and Drug Administration (FDA). For certain drug development campaigns, TDB will support studies up to human Phase IIb. TDB conducts drug development through collaborations, with therapeutic candidates originating from academia, industry, non-profit foundations, or internally from NCATS and other NIH institutes. TDB’s operational strategy is to combine the capabilities of in-house staff and collaborative partners with complementary support from contract research organizations (CROs). Each development program operates in a multi-disciplinary matrix team environment, with NCATS responsible for overall planning and execution.
The NCATS has an existing single-award IDIQ contract for CRO Support for NCATS Efficacy and In Vivo Pharmacology Studies and Related Services. This potential procurement would be a re-competition of this existing contract with some technical and administrative updates. The incumbent is Lovelace Biomedical Research Institute, Contract No. 75N95019D00012.
PURPOSE AND OBJECTIVES
The purpose of this Sources Sought is to obtain information about vendor capabilities to support Pharmacology Studies and Animal Model Development and Related Services for Drug Development.
The objectives of this potential acquisition are to obtain information about the biological effects of test articles on cellular and organismal function during the drug discovery and development process; to provide expertise in designing, executing, interpreting, and reporting on such studies, including in support of regulatory filings; and to optimize or develop relevant in vivo animal models and/or in vitro / ex vivo animal model replacement systems that support preclinical drug development efforts. The test article/product formats may include small molecules, short oligomeric compounds, biological (large) molecules, quaternary molecular assemblies (homogenous or heterogenous), vectors for gene therapy, nanoparticles, and any of the above modified genetically, biologically, or chemically. Novel formats identified after this draft might also be needed. Formats could also include Devices or Combination Products.
ANTICIPATED PERIOD OF PERFORMANCE
The potential IDIQ contract(s) are expected to have a seven-year ordering period. Task orders issued under the IDIQ contract(s) will have their own periods of performance that are based on the specific requirement.
PROJECT REQUIREMENTS
The potential acquisition is anticipated to be a multiple-award Indefinite Delivery / Indefinite Quantity (IDIQ) contract. The anticipated IDIQ contract(s) would include one or more of three separate technical areas:
Technical Area 1: In Vivo Pharmacology Services and Model Development in Small Animals
Technical Area 2: In Vivo Pharmacology Services and Model Development in Large Animals
Technical Area 3: In Vitro Pharmacology Studies in Ex Vivo Tissue-, Cell-Based, or Other Relevant Animal Replacement Models
SEE ATTACHED SOURCES SOUGHT NOTICE FOR COMPLETE PROJECT REQUIREMENTS, RESPONSE INSTRUCTIONS, AND IMPORTANT NOTES.
75N95023R00004-SS Department of Health and Human Services National Institutes of Health National Institute on Drug Abuse
2/7/23, 9:48 AM Pharmacology Studies and Animal Model Development and Related Services for Drug Development
INTRODUCTION
PURSUANT TO FAR Subpart 5.2—Synopses of Proposed Contract Actions, THIS IS A PRE-SOLICITATION NOTICE OF A PROPOSED CONTRACT ACTION.
The National Institute on Drug Abuse (NIDA), Office of Acquistion (OA) on behalf of the National Center for Advancing Translational Sciences (NCATS) intends to award multiple indefinite-delivery, indefinite-quantity (IDIQ) type research and development (R&D) contracts for Pharmacology Studies and Animal Model Development and Related Services for Drug Development.
EXTENT OF COMPETITION
This acquisition is proposed to be solicited under full and open competition with no set-aside restrictions.
NORTH AMERICAN INDUSTRY CLASSIFICATION SYSTEM (NAICS) CODE and PRODUCT SERVICE CODE
The intended procurement is classified under NAICS Code 541714 - Research and Development in Biotechnology (except Nanobiotechnology); with a Size Standard of 1,000 employees.
The intended PSC Code is AN12 - Health R&D Services, Health care services, Applied Research.
REGULATORY AUTHORITY
The resultant contract will include all applicable provisions and clauses in effect through the Federal Acquisition Circular that is current at the time the solicitation is posted, which is currently (FAC) 2023-04 with effective date of June 2, 2023.
This acquisition is conducted under the procedures as prescribed in FAR Subpart 15—Contracting by Negotiation at an amount exceeding the simplified acquisition threshold.
DESCRIPTION OF REQUIREMENT
Project Description
The Division of Preclinical Innovation (DPI) at the National Center for Advancing Translational Sciences (NCATS) conducts translational research on human therapeutics development by moving small molecule and biologic drug candidates forward in the drug development pipeline. Upon reaching predetermined milestones, DPI hands off clinical candidates to external partners to bring these novel therapies to patients. In addition to developing new candidate drugs, DPI seeks to advance the entire field of drug discovery and development by encouraging scientific and technological innovations aimed at improving success rates in the crucial preclinical stage of drug development.
DPI’s model is to operate as a comprehensive small molecule and biologic drug development organization, moving therapeutic candidates through each phase of the preclinical development process until an Investigational New Drug (IND) application is filed with the US Food and Drug Administration (FDA). For certain drug development campaigns, DPI will support studies up to human Phase IIb. DPI conducts drug development through collaborations, with therapeutic candidates originating from academia, industry, non-profit foundations, or internally from NCATS and other NIH institutes. DPI’s operational strategy is to combine the capabilities of in-house staff and collaborative partners, who may be the drug originators, with complementary support from contract research organizations (CROs).
Purpose and Objectives
The purpose of this contract is to obtain pharmacology services related to the execution of in vivo and in vitro/ex vivo and related studies, including the optimization and/or development of animal models.
The objectives are to obtain information about the biological effects of test articles on cellular and organismal function during the drug discovery and development process; to provide expertise in designing, executing, interpreting, and reporting on such studies, including in support of regulatory filings; and to optimize or develop relevant in vivo animal models and/or in vitro / ex vivo animal model replacement systems that support preclinical drug development efforts.
The test article/product formats may include small molecules, short oligomeric compounds, biological (large) molecules, quaternary molecular assemblies (homogenous or heterogenous), vectors for gene therapy, nanoparticles, and any of the above modified genetically, biologically, or chemically. Novel formats identified after this draft might also be needed. Formats could also include Devices or Combination Products.
There are three technical areas: Technical Area 1, Technical Area 2, and Technical Area 3. Offerors may propose on one or more Technical Areas.
Project requirements
Technical Area 1: In Vivo Pharmacology Services and Model Development in Small Animals
The Contractor shall provide services related to the conduct of in vivo studies with therapeutics under development. The studies under this technical area will be conducted using small animal models to support demonstration / verification of efficacy and further drug development activities. The Contractor also shall provide services related to the optimization / refinement of existing animal models or the development of novel models, including characterizing and validating such models to support drug development activities.
Anticipated in vivo pharmacology services under this technical area include, but are not limited to:
1. Defining pharmacokinetic / pharmacodynamic (PK/PD) relationships from existing data or by independently establishing the PK parameters for therapeutic candidates.
2. Optimizing / refining or developing biomarkers and efficacy endpoints.
3. Determining correct route of administration (e.g., SC, IV, PO, IT, or ICV).
4. Determining appropriate dosing parameters.
5. Determining appropriate formulation(s) for administration.
6. Evaluating efficacy and biomarkers in response to treatment with test article.
7. Examination of preliminary toxicity and safety parameters.
Anticipated model refinement / development services under this technical area may include, but are not limited to:
1. Developing novel or similarly existing genetically modified animals that are organ system-specific or whole-body targeted for stable or conditional knock-ins, knock-outs, knock-downs, overexpression, etc. using appropriate genomic techniques such as, but not limited to:
a. Generating targeting constructs per model requirement, including, plasmid DNA vector, single-stranded oligodeoxynucleotides (ssODNs), and ribonucleic acid interference (RNAi) (e.g., silencing ribonucleic acid (siRNA) or short hairpin RNA (shRNA)).
b. Use of cre-lox or tetracycline-induced technology.
c. Use of random DNA transgenesis or optimization of other delivery / gene editing system (e.g., CRISPR/Cas9 or recombinant adeno-associated viruses (rAAVs)-mediated or other applicable technology).
d. Transfection or electroporation of appropriate cells (e.g., skin fibroblasts (somatic) or embryonic stem (ES) cells) with targeting construct with appropriate gene/editing delivery system(s).
e. Conducting somatic cell nuclear transfer (SCNT) into oocytes, transgene pronuclear microinjection or ES cell microinjection into fertilized eggs for uterine implantation to generate required fetuses / harvest appropriate cells for downstream procedures as necessary including genetic characterization.
f. Cryopreservation of embryos or sperm or harvested fibroblast for SCNT to resuscitate model as needed for future studies.
2. Chemically- or diet-induced models (e.g., CNS, respiratory or metabolic).
3. Physiologically- or procedure-induced models (e.g., anemic).
4. Mechanically-induced models.
5. Single or multiple genetic crossings / breeding.
6. Re-derivation, back-crossing, etc. as necessary to optimize or refine existing models, if feasible and cost-effective.
7. Production of live animals of the model.
8. Basic phenotypic characterization / validation of the model and/or definomg comprehensively the natural history of disease progression.
Technical Area 2: In Vivo Pharmacology Services and Model Development in Large Animals
The Contractor shall provide services related to the conduct of in vivo studies with therapeutics under development. The studies under this technical area will be conducted using large animal models, inclusive of non-human primates, to support demonstration / verification of efficacy and further drug development activities. The Contractor also shall provide services related to the optimization / refinement of existing animal models or the development of novel models, including characterizing and validating such models to support drug development activities.
Anticipated in vivo pharmacology services under this technical area include, but are not limited to:
1. Defining pharmacokinetic / pharmacodynamic (PK/PD) relationships from existing data or by independently establishing the PK parameters for therapeutic candidates.
2. Optimizing / refining or developing biomarkers and efficacy endpoints.
3. Determining correct route of administration (e.g., SC, IV, PO, IT, or ICV).
4. Determining appropriate dosing parameters.
5. Determining appropriate formulation(s) for administration.
6. Evaluating efficacy and biomarkers in response to treatment with test article.
7. Examination of preliminary toxicity and safety parameters.
Anticipated model refinement / development services under this technical area may include, but are not limited to:
1. Developing novel or similarly existing genetically modified animals that are organ system specific or whole-body targeted for stable or conditional knock-ins, knockouts, knock-downs, overexpression, etc. using appropriate genomic techniques such as, but not limited to:
a. Generating targeting constructs per model requirement (e.g., plasmid DNA vector, single-stranded oligodeoxynucleotides (ssODNs), and ribonucleic acid interference (RNAi) (e.g., silencing ribonucleic acid (siRNA) or short hairpin RNA (shRNA)).
b. Use of cre-lox or tetracycline-induced technology.
c. Use of random DNA transgenesis or optimization of other delivery / gene editing system (e.g., CRISPR/Cas9 or recombinant adeno-associated viruses (rAAVs)-mediated or other applicable technology).
d. Transfection or electroporation of appropriate cells (e.g., skin fibroblasts (somatic) or embryonic stem (ES) cells) with targeting construct with appropriate gene/editing delivery system(s).
e. Conducting somatic cell nuclear transfer (SCNT) into oocytes, transgene pronuclear microinjection or ES cell microinjection into fertilized eggs for uterine implantation to generate required fetuses / harvest appropriate cells for downstream procedures as necessary including genetic characterization.
f. Cryopreservation of embryos or sperm or harvested fibroblast for SCNT to resuscitate model as needed for future studies.
2. Chemically- or diet-induced models (e.g., CNS, respiratory or metabolic).
3. Physiologically- or procedure-induced models (e.g., anemic).
4. Mechanically-induced models.
5. Single or multiple genetic crossings / breeding.
6. Re-derivation, back-crossing etc. as necessary to optimize or refine existing models, if feasible and cost-effective.
7. Production of live animals of the model.
8. Basic phenotypic characterization / validation of the model and/or defining comprehensively the natural history of disease progression.
Technical Area 3: In Vitro Pharmacology Studies in Ex Vivo Tissue-, Cell-Based, or Other Relevant Animal Replacement Models
The Contractor shall conduct in vitro pharmacology studies to establish biomarkers and efficacy endpoints, and to test the efficacy and toxicity of therapeutics in existing, optimized / refined, or newly developed in vitro / ex vivo cell- or tissue-based models of disease or other relevant animal replacement models, including those derived from human samples.
The Contractor shall provide services related to the optimization / refinement of existing alternative animal replacement models or the development of such novel alternative animal replacement models. The Contractor shall characterize and validate such models to support drug development activities.
Anticipated in vitro / ex vivo models under this technical area include, but are not limited to:
1. Stably (immortalized) or transiently transfected genetically modified cell lines (e.g., knock-in, knock-down, knock-out, overexpressing transgene).
2. Unaffected or affected donor-derived cells (e.g., induced pluripotent stem cells (iPSCs) or progenitor or primary cells from human patients or animal models).
3. Tissue-chip technology (e.g., single or interconnected organ systems).
4. 3D cell- or tissue-based models (e.g., skin, liver, neuronal architecture).
5. Freshly harvested cells / tissues.
Anticipated in vitro / ex vivo study activities under this technical area include, but are not limited to:
1. Optimizing conditions / performing cell or tissue culture maintenance.
2. Optimizing / refining or developing biomarkers and efficacy endpoints.
3. Treatment with test articles, collection of samples (e.g., cells, tissues, fluids) and performance of relevant assays (e.g., protein concentration, imaging).
4. Performing relevant biomarker and/or efficacy assays.
5. Assessment of cell viability / toxicity.
Contractors shall also perform activities related to the overall administration of the contract including administrative reporting and deliverable requirements.
Mandatory Qualification Criteria
All offerors must acknowledge the terms and conditions of the Determination of Exceptional Circumstances by signing and including the RFP Attachment titled FAR Clause Deviation Acknowledgement Form as part of their proposal. In addition -
Technical Areas 1 and 2: Offerors proposing on Technical Area 1 and/or Technical Area 2 must have an approved Animal Welfare Assurance from the Office of Extramural Research (OER), Office of Laboratory Animal Welfare (OLAW) (https://olaw.nih.gov/home.htm), Office of the Director, NIH, as required by the Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals. There must be an approved Assurance for each contractor and subcontractor facility proposed to conduct work involving live vertebrate animals. Offerors and proposed subcontractors must also have an active accreditation by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC).
Period of Performance
The Government anticipates making multiple Indefinite Delivery, Indefinite Quantity (IDIQ) type contract awards with six-year ordering periods from July 1, 2024, through June 20, 2030, resulting under the future solicitation. Projects will then be performed by contractors under individual task orders awarded under these IDIQ contracts. The Government anticipates awards will be made on or around June 1, 2024.
Closing Statement
Solicitation No. 75N95023R00004 is anticipated to be issued on or about June 28, 2023. Proposals will be tentatively due within 45 days after the solicitation release date. This presolicitation notice does not commit the Government to award a contract.
75N95023R00004 Department of Health and Human Services National Institutes of Health
6/13/23, 3:04 PM Pharmacology Studies and Animal Model Development and Related Services for Drug Development
This is a REQUEST FOR INFORMATION (RFI). This RFI is for market research purposes only to formulate a procurement strategy. It does not constitute a Request for Proposal (RFP) or a promise to issue an RFP in the future.
Background
The Division of Preclinical Innovation (DPI) at the National Center for Advancing Translational Sciences (NCATS) within the National Institutes of Health (NIH) conducts translational research on human therapeutics development by moving small molecule and biologic drug candidates forward in the drug development pipeline. Upon reaching predetermined milestones, DPI hands off clinical candidates to external partners to bring these novel therapies to patients. In addition to developing new candidate drugs, DPI seeks to advance the entire field of drug discovery and development by encouraging scientific and technological innovations aimed at improving success rates in the crucial preclinical stage of drug development. DPI’s model is to operate as a comprehensive small molecule and biologics drug development organization, moving therapeutic candidates through each phase of the preclinical development process until an Investigational New Drug (IND) application is filed with the US Food and Drug Administration (FDA). For certain drug development campaigns, DPI will support studies up to human Phase IIb. DPI conducts drug development through collaborations, with therapeutic candidates originating from academia, industry, non-profit foundations, or internally from NCATS and other NIH institutes. DPI’s operational strategy is to combine the capabilities of in-house staff and collaborative partners, who may be the drug originators, with complementary support from contract research organizations (CROs). Each development program operates in a multi-disciplinary matrix team environment, with a DPI project officer (PO) responsible for overall planning, execution, and reporting.
Contract research organizations (CROs) and contract manufacturing organizations (CMOs) provide DPI with manufacturing, pharmacology, toxicology, regulatory, and clinical operations services to assist with drug development. Planning and execution of each individual drug development program includes identification of scientific areas best suited for utilization of CROs and CMOs to conduct some or all parts of a given drug development program.
Information Requested
The Government seeks to obtain information about industry capabilities to support the DPI drug development programs by providing pharmacology studies and animal model development and related services for drug development. This requires novel, re-developed, optimized, or use of existing, validated animal models to conduct in vivo pharmacology studies, often for rare disorders and neglected diseases. These models are not able to be pre-determined as needs change depending on the disease; as such, access to both small (e.g., mice, rat) and large (e.g., dog, cat, monkey, pig) models are needed. In addition, therapies can cover a wide range of modalities such as, small molecules, and biologics (e.g. antibody, proteins, and cell and gene therapy).
Specifically, the Government seeks to determine industry capability in the following five areas:
1. In Vivo Pharmacology Services in Small Animal Models
2. In Vivo Pharmacology Services in Large, Non-Traditional Animal Models Including Non-Human Primates
3. Small Animal Models—Acquisition, Optimization/Refinement, and Development
4. Large, Non-Traditional Animal Models—Acquisition, Optimization/Refinement, and Development
5. In Vitro Pharmacology Studies in Ex-Vivo Tissue, Cell-Based or Other Relevant Animal Replacement Models including Acquisition, Optimization/Refinement, or Development of Such Relevant Experimental Model Systems
The specific information requested is in the attached Word document titled “Vendor Response Form”. This document provides the required format for responses and is REQUIRED for all responses. Additional information may be provided along with this document if the respondent wishes to do so. There is no page limit on additional information but the Government may or may not review any or all of the additional information provided.
Submission Instructions
Submissions MUST include the attached document. Vendors may submit this document as a Word document or a PDF. This response document is intended to minimize the effort of the respondent and structure the responses for ease of review by the Government. Use of this document is REQUIRED for all responses.
Responses must be emailed to Kimberly Espinosa, Contracting Officer, at kimberly.espinosa@nih.gov. The Government will make every attempt to acknowledge receipt but is not obligated to do so.
Questions
Questions regarding this RFI shall be submitted via email to Kimberly Espinosa at kimberly.espinosa@nih.gov no later than 12:00pm Eastern Time on Monday, November 14, 2022. Verbal questions will not be accepted. The Government will attempt but does not guarantee to answer questions submitted. Any answers will be provided in writing.
Additional Information
This RFI is not a Request for Proposal (RFP) or an obligation on the part of the Federal Government and the NIH. The Government will not formally evaluate or provide feedback to responses received to this RFI. The Government does not intend to award a contract based on this RFI or to otherwise pay for the information solicited. All exchanges between the Government and outside entities, including responses to this RFI, may guide the NIH in drafting future solicitations at an undetermined time. There is no solicitation available at this time; no basis for claims against NIH shall arise as a result of this RFI, responses thereto, or the NIH’s use of such information as either part of its evaluation process or in developing specifications for any subsequent requirement.
Responses to this RFI are voluntary. This RFI is for planning purposes only and should not be construed as a solicitation for proposals or an obligation on the part of the Federal Government, the National Institutes of Health, or individual NIH Institutes or Centers. The Government will not pay for the preparation of any information submitted or for the Government’s use of that information.
The information provided will not be considered confidential. The NIH will use the information submitted in response to this RFI at its discretion; the submitted information will be reviewed by the NIH and shared with the NIH Institutes and Centers that have an interest in this matter. No proprietary, classified, confidential, or sensitive information should be included in your response. The Government reserves the right to use any non-proprietary technical information in any resultant solicitation(s), policies or procedures; responses to the RFI may be reflected in future funding opportunity announcements.
Any solicitation resulting from the review of information obtained from this notice will be announced to the public in the System for Award Management (SAM.gov), in accordance with the FAR Part 5. However, responses to this notice will not be considered adequate responses to any resulting solicitation.
75N95023R00004 Department of Health and Human Services National Institutes of Health National Institute on Drug Abuse
11/7/22, 9:43 AM