SSN_N01DA-21-8957.pdf

SOURCES SOUGHT NOTICE NUMBER: N01DA-21-8957

PROJECT TITLE: In Vitro Metabolism and Non-Clinical ADME Studies

THIS IS NOT A REQUEST FOR PROPOSALS, ABSTRACTS, OR QUOTATIONS. This notice is for information and planning purposes only and does not commit the Government to any contractual agreement. The Government does not intend to award a contract based on responses under this announcement nor otherwise pay for preparing any information sent for the Government's use. Any proprietary information should be so marked.

The purpose of this notice is to obtain information regarding:

1. The availability and capability of any qualified small business or other-than-small business sources;

2. Whether they are small businesses; HUBZone small businesses; service-disabled, veteran-owned small businesses; 8(a) small businesses; veteran-owned small businesses; woman-owned small businesses; small disadvantaged businesses; or other-than-small businesses; and

3. Their size classification relative to the North American Industry Classification System (NAICS) code for the proposed acquisition.

The established NAICS code is 541712 – Research and Development in the Physical, Engineering, and Life Sciences. Responses should clearly state whether the respondent is considered a small or other-than-small business under this NAICS code.

Your responses to the information requested will assist the Government in determining the appropriate acquisition method, including whether a set-aside is possible.

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.

Objectives for the Procurement:

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 requirement:

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:

o Estimation of toxicokinetic parameters and preparation of detailed reports.

o 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:

o 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.

Mandatory Criteria:

DEA RESEARCH REGISTRATION

In order to handle substances under the Controlled Substances Act of 1970, it is mandatory that offerors will possess a DEA Registration for Chemical Analysis or Research Registration for Schedules II to V and demonstrate the capability to obtain a DEA registration for Schedule I controlled substances.

ANIMAL WELFARE

All research involving live, vertebrate animals shall be conducted in accordance with the Public Health Service Policy on Humane Care and Use of Laboratory Animals (PHS Policy). The PHS Policy can be accessed at: http://grants1.nih.gov/grants/olaw/references/phspol.htm

Anticipated Period of Performance:

The anticipated period of performance is one-year base period and four (4) one-year option periods.

Capability Statement/Information Sought:

Information submitted should be relevant and specific in the technical area under consideration, on each of the following qualifications:

1) Experience: An outline of previous similar projects, specifically the techniques employed in the areas described above;

2) Personnel: Name, professional qualifications and specific experience in the work requested and knowledge of, and experience in, the field of research;

http://grants1.nih.gov/grants/olaw/references/phspol.htm

3) Facilities: Availability and description of the facilities and equipment required to conduct the types of work/studies discussed above.

4) Mandatory Qualifications: A clear outline of the offeror’s ability to meet the mandatory criteria detailed above.

Any other specific and relevant information about this particular area of procurement that would improve our consideration and evaluation of the information presented.

Interested organizations should demonstrate and document, in any capability statements submitted, extensive experience with and the ability to perform all of the above tasks.

Organizations should demonstrate capability to administer and coordinate interrelated tasks in an effective and timely manner. Documentation may include, but is not limited to, government and commercial contract the organization performed, references (i.e., names, titles, telephone numbers) and any other information serving to document the organization's capability (e.g., awards, commendations, etc.).

All capability statements must provide the following: 1) company name and address; 2) point of contact;

3) phone/email; 4) NAICS Code(s); 5) business size and status; 6) capability information in response to the requirement and qualifications identified in this notice; and 7) type of small business your organization classifies itself as, if applicable.

Capability statements must be submitted electronically via email to polina.klimenkova@nih.gov NO LATER THAN October 14, 2020 at 11:00 AM (EST). Electronic capability statements will be accepted in the form of a single PDF file with the subject line: “Capability Statement # N01DA-21-8957”.

THIS IS NOT A REQUEST FOR PROPOSALS. This notice does not obligate the Government to award a contract or otherwise pay for the information provided in 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.

After a review of the responses received, a pre-solicitation synopsis and solicitation may be published in beta.sam.gov. However, responses to this notice will not be considered adequate responses to a solicitation.