ADME_PreSol_Notice.pdf

SOLICITATION NUMBER: N01DA-21-8957

PRE-SOLICITATION NOTICE INFORMATION

Title: In Vitro Metabolism and Non-Clinical ADME Studies

Introduction:

This is a Pre-Solicitation Notice of Intent. This is NOT a solicitation for proposals, proposal abstracts, or quotations. A solicitation will be issued on a later date.

The purpose of this pre-solicitation notice is to notify potential offerors that the National Institute on Drug Abuse (NIDA) intends to solicit proposals for In Vitro Metabolism and Non-Clinical ADME Studies services from qualified contractors having the capability to perform the tasks identified in this pre-solicitation notice.

This acquisition is a re-competition of the similar requirement Non-Clinical ADME Studies contract (N01DA-16-8931) for the NIDA the Division of Therapeutics and Medical Consequences (DTMC) that was awarded in 2016 to SRI International.

Requirement Background Information:

A major mission of the National Institute on Drug Abuse (NIDA) is the development of safe and effective medications for the treatment of drug addiction. In 1989, Congress mandated the establishment of the Pharmacotherapies Development Program within NIDA. As a result of this mandate, in 1990 NIDA created the Medications Development Division, now the Division of Therapeutics and Medical Consequences (DTMC), to operationalize the goals of the program. The program supports every aspect of the medications development efforts including syntheses, bioanalytical chemistry, pharmacology, toxicology, pharmacokinetics/metabolism, and clinical evaluations of potential treatment medications through grants and contracts.

Purpose and Objectives for the Requirement:

The objectives of this contract are to provide in vitro metabolism and permeability services and in vivo absorption, distribution, metabolism, and elimination (ADME) studies to support the medications development program of the National Institute on Drug Abuse. NIDA will use the data obtained for submissions to the Food and Drug Administration (FDA) in support of Investigational New Drugs (INDs) and New Drug Applications (NDAs).

Project Tasks/Requirements:

The NIDA DTMC requires the following tasks to be performed:

Task 1. Metabolic Stability

• Perform in vitro metabolism of new compounds by hepatic cells or subcellular fractions from variety of species for estimation of metabolic stability and intrinsic clearance.

Task 2. Interspecies Comparison of In Vitro Metabolism

• Perform in vitro metabolism of submitted compounds using hepatocytes or subcellular fractions from a variety of species for estimation and interspecies comparison of metabolic stability and intrinsic clearance.

Task 3. Metabolic Pathway Identification (Reaction Phenotyping)

• Perform in vitro metabolism studies to identify the enzymes (CYP450s and/or others) involved in the metabolism of submitted compounds.

Task 4. Enzyme Inhibition

• Perform studies to evaluate submitted compounds for their potential to inhibit hepatic CYP450 and/or other metabolic enzymes.

• Perform studies to determine if there are interactions between submitted compounds with drugs commonly abused by the target population, such as methamphetamine.

These studies involve determination of ki (inhibitory constant) and IC50 (the concentration required to inhibit enzyme activity by 50%) values for submitted compounds.

Task 5. Enzyme Induction

• Perform studies to evaluate submitted compounds for their potential to induce human CYP 450 enzymes and/or other metabolic enzymes.

Task 6. Metabolite Identification

• Identify the structure of major metabolite(s) produced either by in vitro studies or in vivo systems (from biological samples obtained in other NIDA sponsored studies) by mass spectrometry and/or nuclear magnetic resonance (NMR).

Task 7. In Vitro Permeability Studies

• Determine the intestinal permeability of new compounds in order to assess oral absorption using Caco-2 cells or other appropriate systems.

• Use appropriate cell-line to assess blood-brain barrier permeability of new compounds.

• Different concentrations of submitted compounds will be tested.

• Determine the solubility of new compounds if such information is not available.

Task 8. Assay Development and Validation

•Develop and validate sensitive assay methods (ng/mL or pg/mL) to quantify the study compound and its metabolite(s), as indicated, in biological matrices (e.g., plasma, urine) using LC-MS/MS or GC-MS/MS.

•Assay methods must be validated for precision, accuracy, selectivity, recovery, sensitivity, stability (short and/or long-term), and effect of hemolysis according to the FDA guidance.

•Provide services for handling of radioactive samples, when required.

Task 9. Bioavailability/Pharmacokinetics (PK) Studies

• Conduct bioavailability/PK studies in animal species (e.g., rats, dogs, monkeys) according to the specific guidelines.

• Conduct other PK studies (e.g., interaction studies and sub-chronic studies) as designated by the COR, in animal species (e.g., rats, dogs, monkeys) according to the specific guidelines.

Task 10. Absorption, Distribution, Metabolism, and Excretion Studies

• Conduct PK studies using radiolabeled study compound via IV or other designated route of administration to evaluate its absorption, distribution, metabolism and excretion.

Task 11. Toxicokinetic Analysis

• Perform toxicokinetic analysis of the data generated under NIDA toxicology program:

- Estimation of toxicokinetic parameters and preparation of detailed reports.

- Reports shall be suitable for submission to the FDA as part of IND or NDA submissions.

Task 12. Quantification of Study Compounds and Metabolites

• Perform quantitative assays (using a validated assay method as described under Task

7) of a study compound and its metabolite(s) in biological samples submitted by other investigators authorized by the COR:

- Most submissions will be blood, plasma, or urine samples from toxicology studies in rats, dogs, monkeys, or humans.

Task 13. Protein Binding Studies

• Determine the percent of study compound bound to plasma protein by performing plasma protein binding studies such as equilibrium dialysis or ultrafiltration with LC- MS/MS detection.

• Samples may be from an in vivo bioavailability study.

• Radioactive study compounds with scintillation counting may be used in the assay.

• Plasma from different species (mouse, rat, dog, monkey, and human) shall be used to evaluate protein binding across species.

• Three different concentrations of the study compound will be used, depending on the sensitivity of the assay method.

Task 14. Archival Maintenance of Records

• At the end of the contract period (when all analytical work is completed), all data, including laboratory notebooks, hard copies of raw data, and databases of assay results on disk or tape shall be placed in secure storage for a period of up to 5 years in case a GLP audit is required by FDA in connection with an IND or NDA submission. During this period, the contractor will be responsible for the integrity and organization of the material and its confidentiality. At the end of this period (or the Option below, if exercised), all reference material, data files, etc. will be disposed of per instructions of the COR.

Task 15. Administrative Support

• Perform additional support services related to contract administration. The support services may include, but are not limited to, preparing deliverables as required by the contract (e.g., monthly/annual progress reports), meeting contract requirements, invoicing, monthly/annual progress reports, preparing monthly invoices, and general contract meetings.

Set-Aside Status:

The services will be acquired through unrestricted full and open competitive procedures under NAICS Code 541715 - Research and Development in the Physical, Engineering, and Life Sciences (except Nanotechnology and Biotechnology)

Anticipated Period of Performance:

The anticipated period of performance is a period of five years.

Anticipated Contract Type:

The NIDA anticipates the award of one (1) contract. It is anticipated that the contract type shall be an Indefinite Delivery, Indefinite Quantity (IDIQ) using task orders.

Request for Proposal Release Information:

Request for Proposal (RFP) No. N01DA-21-8957 will be available electronically on or about January 30, 2021. The RFP shall be accessible through beta.sam.gov. All information required for the submission of a proposal will be contained in or accessible through the RFP package. Responses to the RFP will be due on or about 30 days following RFP release. Offerors must submit a proposal for all Task Areas in order to be considered for award. WE ENCOURAGE ALL RESPONSIBLE SOURCES TO SUBMIT

A PROPOSAL WHICH WILL BE CONSIDERED BY THE AGENCY.

Notes: It is the Offeror’s responsibility to monitor the above-mentioned site for the release of the solicitation and any amendments.

This notice does not obligate the Government to award a contract or otherwise pay for the information provided in the response. No proprietary, classified, confidential, or sensitive information should be included in your response. The Government reserves the right to use information provided by respondents for any purpose deemed necessary and legally appropriate. Any organization responding to this notice should ensure that its response is complete and sufficiently detailed to allow the Government to determine the organization’s qualifications to perform the work. Respondents are advised that the Government is under no obligation to acknowledge receipt of the information received or provide feedback to respondents with respect to any information submitted.