Inactive
Notice ID:75N95020R00020
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 mandat...
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. The objectives of this contract are to provide in vitro metabolism and permeability services to the medications development program of the National Institute on Drug Abuse (NIDA). The body generally eliminates drugs either by excretion of intact molecules or by biotransformation (metabolism) to more readily eliminated forms (metabolites). Because these metabolites may contribute to therapeutic efficacy or toxicity, it is important in the early stages of drug development to understand these metabolic processes. Of particular interest are the identification of the enzymes involved in metabolic pathways; individual variations in metabolic rates; and genetic polymorphisms in these enzymes that may alter their metabolic activity. All of these factors can significantly affect the safety and efficacy of drug candidates. One can characterize drug metabolism using simple, rapid, and low-cost in vitro methods to provide predictions of toxicity and efficacy which may significantly affect the design of preclinical in vivo studies and clinical evaluations. In vitro metabolism studies use liver fractions (e.g., hepatocytes, microsomes) and tissue slices from different species (e.g., human, mouse, dog, monkey) to investigate interspecies variations in biotransformations. This data is useful in determining relevant animal models for preclinical evaluations of drug candidates. Further, in vitro studies allow for the determination of metabolic pathways and the identification and characterization of major metabolites to aid in the prediction of drug-drug interactions and potential sources of drug toxicity. Another important concern in drug development is a compound’s ability to pass through biological membranes to reach the systemic circulation and therapeutic targets. Orally dosed drugs need to be absorbed by the gastrointestinal tract and pass through the intestinal wall to achieve sufficient bioavailability for therapeutic efficacy at target organs. Drugs intended to treat disorders of the central nervous system need to permeate the blood-brain barrier. In vitro permeability studies using relevant cell lines allow for the evaluation of a drug candidate’s ability to pass through biological membranes and to identify any transporters involved in its absorption across or efflux from the interior of these barriers. Together, in vitro metabolism and permeability studies allow for an evaluation of the pharmacokinetic properties of a drug and its active metabolites, which is critical for the understanding of its potential pharmacological effects. NIDA is soliciting proposals from qualified businesses to provide in vitro metabolism and permeability determinations for its medications development program. The in vitro metabolism studies for this contract typically include metabolite profiling for interspecies comparison using liver fractions (Phase I and Phase II metabolism), enzyme phenotyping reactions, and enzyme inhibition and/or induction studies. This contract will also include structure identification of major metabolites by mass spectrometry or nuclear magnetic resonance (NMR). Additional in vitro studies include determination of intestinal and blood-brain barrier permeability of new compounds. Objectives The objective of this contract is to carry out in vitro metabolis, including metabolite identification ane permeability studies to support the medications development program of the National Institute on Drug Abuse (NIDA). NIDA and NIDA sponsored investigators 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). Services to be Performed General Requirements 1. Independently, and not as an agent of the Government, the Contractor shall furnish all necessary labor, materials (except new compounds the Contractor will study), supplies, equipment, and services and perform the work set forth below. NIDA will provide new potential medications to the Contractor to study. 2. The Contractor will provide in vitro metabolism and permeability studies for the medications development program of the National Institute on Drug Abuse (NIDA). The Contractor must follow pertinent FDA guidance and regulations. New compounds from NIDA contractors, grantees, or pharmaceutical industry sources which show promise in initial pharmacological screening will be the subject of studies detailed in this contract. The in vitro metabolism services for this contract typically include metabolic stability and metabolite profiling for interspecies comparison using cellular and subcellular liver fractions (i.e., Phase I and Phase II metabolism), enzyme phenotyping reactions, and enzyme inhibition and induction studies. This contract will also provide structure identification of major metabolites by mass spectrometry or nuclear magnetic resonance (NMR). In addition, the in vitro studies include determination of permeability across biological membranes, such as the intestine and blood-brain barrier, of new compounds under development. The Contractor shall evaluate the permeabilities in the presence and absence of specific inhibitors of drug-transport systems. The Contracting Officer’s Representative (COR) must approve all reports and protocols, in content and format. NIDA and NIDA sponsored investigators will use the data for submissions to the FDA. The reports shall be adequate in format and substance for submission to the FDA in support of IND and NDA applications. The Contractor shall also establish electronic data files and keep all reports, protocols, raw data, and assay results in secure storage. For proposal purposes: the in vitro studies provided for in this contract typically include Tasks 1 through 7 as listed under Specific Requirements. For proposal purposes: approximately once a year and under an issued task order, the Contractor may be required to participate in a meeting or to meet with the COR at NIDA or at a scientific meeting. 3. The Government COR, whose position is defined in this contract, will monitor all work under this contract. Specific Requirements: Through issued task orders, the Contractor shall perform the following tasks: Task 1. Interspecies Comparison of In Vitro Metabolism Study in vitro metabolism of new compounds under development, typically by using hepatic microsomes or hepatocytes from a variety of species for interspecies metabolism comparison. Evaluate in vitro metabolism by other systems such as hepatic cytosol, hepatic mitochondrial fraction, or Phase II reactions Task 2. Metabolic Pathway Identification (Reaction Phenotyping) Perform in vitro metabolism studies to identify the enzymes involved in the metabolism of a new medication (CYP450s and/or others) Task 3. Enzyme Inhibition Perform studies to evaluate new compounds for their potential to inhibit hepatic CYP 450 and/or other metabolic enzymes Perform studies to determine if there are interactions between new 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 new compounds. Task 4. Enzyme Induction Perform studies to evaluate new compounds for their potential to induce human CYP 450 enzymes and/or other metabolic enzymes Task 5. 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). For proposal purposes, NIDA may not be able to provide reference standards of metabolites. Task 6. Metabolic Stability Perform in vitro metabolism of new compounds by hepatic cells or subcellular fractions from a variety of species for estimation of metabolic stability and intrinsic clearance 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 Evaluate the permeabilities in the presence and absence of specific inhibitors of drug-transport systems Determine the solubility of new compounds if such information is not available Task 8. Archival Maintenance of Records Place all data, including laboratory notebooks, hard copies of raw data, and databases of assay results on disk or tape in secure storage for 5 years. 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, all reference material, data files, etc. will be disposed of per instructions of the COR. Task 9. 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. A list of possible example deliverables follows: Annual Progress Reports; Final Contract Report w/ Summary of Salient Results; All data, etc. as directed by the COR; Annual Utilization Reports; Final Invention Statement (if applicable); Reporting of Financial Conflict of Interest (FCOI); Small Business Subcontracting Reports (if applicable); Roster of Employees Requiring Suitability Investigations; IT Security Plan; IT Risk Assessment (if applicable); FIPS 199 Assessment (if applicable); IT Security Certification and Accreditation (if applicable); Reports of New and Departing Employees; and Non-Disclosure Agreements. Mandatory Criteria: In order to handle substances under the Controlled Substances Act of 1970, it is mandatory that offerors possess a Drug Enforcement Administration (DEA) Research Registration for Schedules II to V and demonstrate the capability to obtain a DEA registration for Schedule I controlled substances. All offerors must be in compliance with the FDA's Good Laboratory Practices Program. Notice: NIDA anticipates that one (1) indefinite delivery, indefinite quantity (IDIQ), task order contract will be awarded for a period of performance of five (5) years. NIDA may award fixed price task orders under this contract. NIDA anticipates that at least one or more task orders will be awarded with the contract. Future funding will be made through issuances of task orders and will be dependent on NIDA programmatic needs and availability of funds. This RFP will be available electronically on or about February 10, 2020. You can access the RFP through the FedBizOpps (URL: https://beta.sam.gov/search?index=opp) or through the NIDA website: (URL: http://www.drugabuse.gov/funding/funding-opportunities/nida-requests-contract-proposals-rfps). 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 45 days from the release date. NIDA will consider proposals submitted by any responsible offeror. This advertisement does not commit the Government to award a contract. Based upon market research, the Government is not using the policies contained in Part 12, Acquisition of Commercial Items, in its solicitation for the described supplies or services. However, interested persons may identify to the Contracting Officer their interest and capability to satisfy the Government's requirement with a commercial item within 15 days of this notice.
