Blood stability and Pharmacokinetics of Antiviral Molecules

This is a combined synopsis/solicitation for commercial items prepared in accordance with the format in FAR 12.6 as supplemented with additional information included in this notice.  This announcement constitutes the only solicitation, and a separate written solicitation will not be issued.  This solicitation number is NICHD-22-206 and is issued as a Request for Quotation (RFQ).  The solicitation/contract will include all applicable provisions and clauses in effect through Federal Acquisition Circular NICHD-22-206.  The North American Industry Classification (NAICS) Code is 541380 and the business size standard is $15.0M.  This solicitation is not set aside for small business.  This acquisition is being conducted using Simplified Acquisition Procedures in accordance with FAR Part 13.  Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) has a requirement for a contractor to provide Blood stability and Pharmacokinetics of Antiviral Molecules.

OBJECTIVE

The objective of this contract is to provide research to advance the testing of a new class of antiviral molecules.  Results from each set of tests done are added to the file that will eventually be submitted as the Investigative New Drug Application.  The continuity of the project is enhanced by the use of as few CRO’s as possible. 

REQUIRED FEATURES AND SPECIFICATIONS

The Contractor must carefully follow confidential protocols from the NIDDK lab and provide written documentation of all deviations from established protocols. Experience in studying drug metabolism and compliance with FDA requirements and drug development protocols is required. Final reports must be delivered with all data and protocols clearly written and summarized. Obtaining this service will allow the NIDDK lab to pursue advanced experiments without needing to continually repeat established protocols over and over again.  The Contractor shall perform:

•           Blood stability studies on 2 small molecules with antiviral (HIV) activity

•           Rat PK studies with 2 small molecules with antiviral activity against HIV

•           Mouse PK studies with 2 small molecules with antiviral activity against HIV

•           Hepatocyte stability and metabolism studies with two lead small molecules with antiviral activity against HIV

Task Areas:

Task Area 1 – NIDDK will provide antiviral molecules under confidentiality for the proposed blood stability and hepatocyte metabolism studies and also for the pharmacokinetic studies.  It is anticipated that the Contractor will use the provided molecules for these studies.

Task Area 2 - Perform blood stability and hepatocyte metabolism studies, then pharmacokinetic studies, followed by delivery of final report.

Blood Stability Studies on 2 Small Molecules

The Contractor shall perform in vitro stability of 2 compounds in the presence of rat, monkey, and human whole blood (pooled 3 donors)

•           Perform incubations of these compounds (and MTS-IV-39 as the control) in whole blood from rats, monkeys, and humans for up to 4 hrs

•           Substrate concentration at 1 μM added to blood (fresh if possible) and the

degradation of the compounds monitored using LC/MS/MS (operated in the MRM mode)

The half-lives of each compound will be obtained and compared against MTS-IV-39 Tabulated data (as needed)

Data in excel file (includes experimental details, results, and summary).

Rat PK Studies with Two Small Molecules with Antiviral Activity against HIV

The Contractor shall perform two discrete IV/PO studies in SD rats

•           Male SD rats (weighing 275-350 g) will be administered IV and PO doses of two NIH test small molecules and blood samples collected at different time points for

analyses. N=4 rats/dose group. Doses: IV (1 mg/kg) and PO (5 mg/kg) will be

administered after preparing suitable formulations.

Tier 2 non-GLP bioanalytical method to quantify and measure the concentrations of

the analytes in rat plasma (collected serially)

Pharmacokinetic parameters of the analyte using WinNonlin (Phoenix software,

Pharsight)

Data initially in excel file

Mouse PK Studies with Two Small Molecules with Antiviral Activity against HIV

The Contractor shall perform two discrete IV/PO studies in CD-1 mice

Male CD-1 mice (weighing 20-30 g) will be administered IV and PO doses of two NIH compounds and blood samples collected at different time points for analyses. N=4 mice/dose group. Doses: IV (1 mg/kg) and PO (5 mg/kg) will be administered after preparing suitable formulations.

Tier 2 non-GLP bioanalytical method to quantify and measure the concentrations of

the analyte in mice blood (collected serially)

Pharmacokinetic parameters of the analyte using WinNonlin (Phoenix software,

Pharsight)

Data initially in excel file

In Vitro Stability and Metabolism of Two Small Molecules in Liver Microsomes and Hepatocytes from Rats, Monkeys and Humans (3 species)

The Contractor shall perform rat, monkey, and human liver microsomal incubations with the compounds under different conditions (+/- NADPH). Phase 1, Phase 2 and possibly nonenzymatic pathways investigated.

•           The Contractor shall conduct in vitro metabolism studies with the compounds in the presence of cryopreserved hepatocytes from male rats, monkeys and pooled (mixed gender) humans

Substrate concentration at 10 μM (so LC/UV and LC/MS profiles can be obtained,

Metabolite ID of most significant metabolites – MS/MS data, interpretation of

fragmentation pathways, and assignment of fragment ions).

Determine P450 and non-P450 mediated metabolism of the 2 compounds

Tentative assignment of structures of metabolites and determining the metabolic soft

spots.

Metabolism scheme in each species

Conduct stability tests of the two compounds (1 μM) in LM and hepatocytes of the

three species. Monitor the disappearance of the compounds in LM and hepatocytes

using LC/MS/MS peak area ratios. Calculate half lives and obtain intrinsic clearance

values of both compounds to predict in vivo clearance values. 

Data in power point

The offeror must include a completed copy of the following provision’s along with their quote:  FAR Clause 52.212-3, Offeror Representations and Certifications – Commercial Items; FAR Clause 52.204-24, Representation Regarding Certain Telecommunication and Video Surveillance Services or Equipment; FAR Clause 52.204-25, Prohibition on Contracting for Certain Telecommunications and Video Surveillance Services or Equipment.

The provisions of FAR Clause 52.212-1 Instructions to Offerors – Commercial Items; FAR Clause 52.212-2, Evaluation – Commercial Items: Evaluation Factors (1) technical capability to provide all services/consumables, etc.; (2) price; and (3) past performance. Technical capability and past performance, when combined, are significantly more important than cost/price; FAR Clause 52.212-4, Contract Terms and Conditions – Commercial Items; and FAR 52.212-5, Contract Terms and Conditions Required to Implement Statutes or Executive Orders – Commercial Items – Deviation for Simplified Acquisitions applies to this acquisition, apply to this acquisition.  The offeror must include their Unique Entity ID: (UEI), the Taxpayer Identification Number (TIN), and the certification of business size.  The clauses are available in full text at http://www.arnet.gov/far.  Interested vendors capable of providing the Government with the services specified in this synopsis should submit their quotation to the below address.  Quotations will be due ten (10) calendar days from the publication date of this synopsis or August 10, 2022 at 11:00 AM.  The quotation must reference “Solicitation number” NICHD-22-206.  All responsible sources may submit a quotation, which if timely received, shall be considered by the agency.  Quotations must be submitted by email to Verne Griffin at verne.griffin@nih.gov.   

Faxed copies will not be accepted