Attachment 1 - SOW.pdf

Version 11-30-2016-1 FAR Part 11—Describing Agency Needs

STATEMENT OF WORK (SERVICES)

(SOW)

GENERAL INFORMATION

Title of Project: cGMP Mitragynine HCl Supplemental Stability & Analytical Activities

Statement of Need and Purpose: 1) To have contractor complete the long term stability studies on two cGMP batches of Mitragynine HCl started under previous contract; 2) To have contractor requalify cGMP reference standard of Mitragynine HCl annually for up to 3 years.

Background Information and Objective:

NCATS is conducting a preclinical development of Mitragynine (MG) to support its clinical evaluation, as part of the Helping to End Addiction Long-term initiative (HEAL). To support the systematic evaluation of the pharmacology, safety, and risk profile of MG in the clinic, TDB of NCATS has generated 5-Kg of cGMP MG as a HCl salt in 2 batches through a CDMO (Curia Global, Inc) using a R&D contract (Contract number: HHSN271201700005I, Task Order:

75N95019F00088). In this contract, Curia also developed and validated analytical methods, qualified a batch of reference standard of Mitragynine HCl, and performed long term stability studies in 2 proposed storage conditions and 1 accelerated condition for 6 months. The period of performance of this contract was from 09/01/2019 to 05/31/2024.

Preclinical safety evaluation of Mitragynine HCl is being performed, and NIDA (as a collaborator) will support the First-in-Human (FIH) trial afterwards. It is critical to keep the long term stability study on going to support both preclinical safety evaluation and FIH trial, and submitting results for Investigational New Drug (IND) application.

The Regulatory agency (FDA) also recommended NCATS to perform extra analytical tests (pesticide residual and Mycotoxin tests) on either starting material or final APIs. Since the quantity of retained starting material is not enough to support a GMP method development and testing, the Pesticide residual and Mycotoxin tests on 2 GMP batches will be the only choice.

Period of Performance: The estimated period of performance is 9/4/2024-9/3/2027 (3 years from award).

SCOPE OF WORK

General Requirements: The contractor shall perform the long term stability study in 2 conditions up to 36 months and requalify the reference standard annually. Independently and not as an agent of the Government, the Contractor shall furnish all the necessary services, qualified personnel, material, equipment, and facilities, not otherwise provided by the Government as needed to perform the Statement of Work below:

Specific Requirements:

1) The contractor shall perform the stability studies using qualified analytical methods along with validated assay and impurity method on both GMP Mitragynine HCl batches (lot #:13791-B-R0-01-19-01 and 13791-B-R0-02-19-01) on the following condition and time intervals, and provide the Interim and final Stability Study Reports:

5 °C at 9, 12, 18, 24, and 36 months;

25°C/60% relative humidity (RH) at 0, 3, 6, 9, 12, 18, 24, and 36 months Test: Appearance, Assay and impurities, water content, XRPD (12, 24, 36 M), Microbal (36 M).

2) The contractor shall requalify reference standard of Mitragynine HCl using developed and validated analytical methods annually for 2 times and generate COAs.

3) The contractor shall perform pesticide residual and Mycrotoxin tests on both cGMP baches of Mitragynine and report the results.

LEVEL OF EFFORT:

All work shall be performed under cGMP (analytical service). Quality assurance personnel shall be available.

GOVERNMENT RESPONSIBILITIES

Government will review all reports submitted by the contractor.

DELIVERY OR DELIVERABLES

Deliverable Delivery Method Due Date 1 Interim Stability Study Reports Electronically 1 month after each pull date 2 Final Stability Study Report Electronically 1.5 month after the final pull date 3 Updated COAs of reference standard Electronically 1 month after test date

4 Residue pesticide and Mycotoxin test reports

Electronically 1 month after the testing date

REPORTING REQUIREMENTS

N/A

OTHER CONSIDERATIONS

Travel: N/A

Key Personnel: Key personnel shall have demonstrated experience in the technical areas given above that are applicable to their role, perform successfully in the past in the role proposed, and have all skills needed to execute this project.

Information System Security Plan: N/A

Data Rights: FAR 52.227-14 Rights in Data-General (May 2014)

Section 508—Electronic and Information Technology Standards: N/A

Publications and Publicity: N/A

Confidentiality of Information: N/A