A17_JA_-_Redacted_1.pdf

United States Department of the Interior

INTERIOR BUSINESS CENTER

Washington, DC 20240

SOLE SOURCE JUSTIFICATION

SIMPLIFIED PROCEDURES FOR CERTAIN COMMERCIAL ITEMS

AUTHORITY: FAR 13.501(a), 41 U.S.C. 1901

140D0425Q0704

1. Identification of the agency and the contracting activity, and specific identification of the document as a “Sole Source Justification.”

This document is a sole source justification for the Department of the Interior, Interior Business Center, Acquisition Services Directorate, National Institutes of Health (NIH), National Center for Advancing Translational Sciences (NCATS).

2. Nature and/or description of the action being approved.

This requisition is to manufacture a novel investigational drug 2R,6R- Hydroxynorketamine (a naturally occurring metabolite of ketamine) product and the drugs diluent for extended us in Phase 2 clinical trials. The order includes requalification of the drug substance, manufacture of the drug product and diluent, analytical testing and release for human use and a 24-month stability assessment program.

3. A description of supplies or services required to meet the agency’s needs (including the estimated value).

The order includes the following and the total estimated value is

1) The proper actions for drug substance requalification

a. Confirmation of identity (1H NMR, IR or Raman spectroscopy)

b. Characterization of predefined related substances (HPCL)

c. Measurement of water content (KF)

d. Measurement of residual solvents (GC)

e. Measurement of residue on ignition (sulphated ash)

f. Characterization of polymorphs (XPRD)

g. Confirmation of chiral purity

h. Measurement of microbial and bacterial endotoxin examination

i. Shipment of recertified drug substance to manufacturing site.

2) Production of Drug produced and diluent

a. Production of batches of 5 mg/mL (2R,6R)-Hydroxynorketamine investigational drug product (IDP) (not more than 700 vials)

b. Production of batches of 25 mM Phosphate / 0.9% w/v Saline pH 7 Buffer

(Diluent) (not more than 700 vials)

c. Compliance with cGMP productions (adhering to ICH Q2 and USP

140D0425Q0704

<1225>).

d. Labeling of all vials with client-approved labels.

e. Production, review and approval of the master batch records (MBR) and executed batch records (EBRs) for the IDP and Diluent.

f. Shipment to MRIGlobal and storage in a controlled (frozen) environment.

3) Analytical release of Investigational drug product (IDP) and diluent

a. Retention of an appropriate number of vials for release testing according to established specifications.

b. Release testing including

i. appearance

ii. QC (assay, impurities)

iii. pH

iv. osmolality

v. visible particulate matter

vi. subvisible particulate matter

vii. container content USP <697>

viii. sterility USP <71>

ix. endotoxin USP <85>

4) Stability and suitability of both IDP and diluent (24-month program)

a. This testing will involve twenty-four months of IDP and Diluent stability studies following ICH guidelines and stability protocols for vials stored at - 20°C/amb RH (recommended storage) and for six months at 2 to 8°C/amb RH (accelerated storage).

4. An identification of the statutory authority permitting sole source acquisition.

This is an acquisition conducted under the authority of the Simplified Procedures for Certain Commercial Items. The statutory authority permitting sole source acquisition is 41 U.S.C 1901 as implemented by FAR 13.501(a)(1)(ii).

5. A demonstration that the proposed contractor’s unique qualifications or the nature of the acquisition requires use of the authority cited.

This requisition is for the National Institutes of Health Intramural Research Program as it extends its efforts to define new therapy options for mental health disorders that are safe and free of misuse and addiction-related side effects (e.g. the opioid epidemic). The phase 2 studies are a culmination of ten plus years of effort to define the suitability of 2R,6R-Hydroxynorketamine as a novel therapy with significant preclinical validation and no significant side effects as determined in phase 1 studies

(NCT04711005).

The proper conduct of human clinical trials is multifaceted and governed by multiple regulations to protect the safety of the trial participants. Among the most important is the manufacture of the drug product using ‘Good Manufacturing Practices (GMP). At the root of our request to award this contract as a sole source to MRIGlobal are the established GMP methods to make the 2R,6R-Hydroxynorketamine drug product and diluent. MRIGlobal is the only manufacturing group to have made these products previously and are experts in the manufacturing, storage, QC and shipment requirements that are consistent with GMP and FDA regulations. In fact, this will be the fourth time MRIGlobal has conducted a GMP manufacture of these materials for human use.

In each of the previous 3 manufacturing runs, the outcomes were approved by the US FDA and human clinical studies were conducted without issue. Our requirement for consistent methods in the manufacture of this material is absolute and the time, cost and effort associated with any other contract manufacturing organization (CMO) to stand up and recreate the methods used by MRIGlobal would be substantial to the point of being overwhelming. Ultimately, the excess cost and delay would cause us to halt the existing study and severely impact our mission to finalize the phase 2 effort and determine if this novel therapy holds promise for the population of the U.S.

To provide a specific example, any new contract manufacturing organization (CMO) would be required to conduct an ‘engineering run’ prior to the actual GMP manufacture run. This is the equivalent of a trial run of item #2 above (i.e. the Production of Drug produced and diluent) with an additional price tag of >$500,000 and a delay of at least six months.

6. A description of efforts made to ensure that offers are solicited from as many potential sources as practicable, including whether a notice was or will be publicized as required by FAR Subpart 5.2 and, if not, which exception under FAR 5.202 applies.

The original contract award to MRIGlobal for this work (75N98019D00061) (2019) was part of a broader IDIQ award offered for drug manufacturing in support of NIH clinical studies. A broad effort was made at that time to ensure that suitable contract manufacturing organizations (CMOs) were aware of this opportunity and allowed to submit a competitive application. Notice will be publicized as required.

7. A determination by the contracting officer that the anticipated cost to the

Government will be fair and reasonable.

The NIH routinely works with contract manufacturing organizations (CMOs) and other entities in the private sector to manufacture and/or use drug products within investigational clinical trials at the NIH or at partnering institutions. As such, there is significant experience and expertise in the manufacturing processes of different drug products and their related costs. Unsurprisingly, different drug types often have vastly different manufacturing costs. Thus, the most appropriate way to judge if a specific drug products cost is fair and reasonable is to contrast with previous procurements of the same or related agents. In this instance, MRIGlobal has made the 2R,6R-Hydroxynorketamine drug product and diluent previously.

A determination will be made by the Contracting Officer at the time of award to determine the pricing fair and reasonable.

8. A description of the market research conducted (see Part 10) and the results or a statement of the reason market research was not conducted.

No other providers can perform this requirement. This requirement is for a specific drug going through trials. A different provider would not have familiarity with the drug substance such as salt form, polymorph, purity, related substances, solubility, pH, viscosity, microbial content testing, endotoxin testing, etc. In addition, a different provider would be required to produce an “engineering batch” which has already been accomplished by MRIGlobal. This data is reviewed by the FDA to assure stability of the process and new manufacturing sites. An engineering batch along would cost an estimated $700K and require an additional six months to complete. Our market research concludes that no other provider could match the cost and timeliness offered by MRIGlobal. In accordance with FAR Part 10 and DOI-AAAP-F010, market research must be conducted appropriate to the circumstances and simplifies the requirements for when market research must be conducted. The Contracting Officer has determined that no additional market research needs to be conducted at this time.

9. Any other facts supporting the use of other than full and open competition, such as:

The previous manufacturing experience of MRIGlobal is the primary reason for the sole source justification. However, another key fact involves the current knowledge of the MRIGlobal manufacturing team around our regulatory requirements for all reporting elements in support of the ongoing human clinical trials. MRIGlobals ability to quickly provide information on any requests from the FDA is a significant help to the program. This is particularly important for the annual Clinical Pharmacology Summary that is a required element of FDA reporting.

10. A listing of the sources, if any, that expressed, in writing, an interest in the acquisition.

N/A

11. A statement of the actions, if any, the agency may take to remove or overcome any barriers to competition before any subsequent acquisition for the supplies or services required.