NOI_75N91024Q00182.pdf

NOI No.: 75N91024Q00182

NOTICE OF INTENT TO SOLE SOURCE

Title: Acquisition of Services for the Production and Stability Testing of Clinical

Grade Lentiviral Vector Notice ID: 75N91024Q00182 Posted Date: 9/24/24 Response Date: 9/27/24 Classification Code: 6505 (Drugs and Biologicals) NAICS Code: 325414 (Biological Product (except Diagnostic) Manufacturing)

1.0 DESCRIPTION

The Department of Health and Human Services (HHS), National Institutes of Health (NIH), National Cancer Institute (NCI), Office of Acquisitions (OA) intends to procure services, on a sole source basis, from Vector Biomed, Inc., 910 Clopper RD STE 200S, Gaithersburg, Maryland 20878-1361.

This notice is being publicized in accordance with Federal Acquisition Regulation (FAR) Subpart 5.2. This acquisition will be processed under FAR Part 12 - Acquisition for Commercial Items and will be made pursuant to the authority in FAR Part 13.501(a); and is exempt from the requirements of FAR Part 6. The North American Industry Classification System code is 325414 and the business size standard is 1,250 employees.

2.0 BACKGROUND

The U.S Department of Health and Human Services (HHS), National Cancer Institute (NCI), National Institutes of Health (NIH), Center for Cancer Research (CCR), Pediatric Oncology Branch (POB) requires services for the production and subsequent stability testing of Good Manufacturing Practice (GMP), i.e., clinical grade lentiviral (LV) vector. Ultimately, this product will be used in a phase I clinical trial at NIH under protocol IRB002091, entitled IL-12 Genetically Engineered Myeloid Cells in participants with relapsed, refractory solid tumors. POB developed and utilizes a platform to generate genetically engineered myeloid cells (GEMys) to locally deliver anti-tumor factors to the tumor and metastatic microenvironment. Previous studies have focused primarily on the immune-activating cytokine IL-12 and harnessed the innate homing capacity of myeloid cells to accumulate in tumor and metastatic sites to locally deliver IL-12 to promote anti-tumor immunity. Based on promising preclinical studies, POB proposed a first in human Phase I trial for adults with solid tumor malignancies. As metastasis is the number one cause of cancer-related mortality in solid organ cancers in adults and pediatric populations, therapies that prevent or limit this process will have a profound impact on quality of life and outcome for these patients. The protocol is being submitted to the Office of Sponsor and Regulatory Oversight (OSRO) for review and in preparation for the Investigational New Drug Application (IND) package for submission to the Federal Drug Administration (FDA).

3.0 SCOPE

This acquisition includes services to prepare GMP clinical grade transfer plasmid; to produce and deliver purified, GMP clinical grade lentiviral vector, 400 ml in total; to perform stability studies on the lentiviral vector product; and to receive cross-referenced information on vector manufacturing and production facilities in support of the IND.

4.0 PURCHASE ORDER REQUIREMENTS /TASKS

The Contractor shall perform the following tasks:

4.1 TASK 1: PRODUCTION OF CLINICAL GRADE TRANSFER PLASMID

4.1.1 The Contractor shall produce a minimum of 50 mg GMP/clinical grade transfer plasmid from the IL12-GEMy plasmid. The amount shall be sufficient for the production of the lentiviral vector.

4.1.2 The turnaround time for the production of the GMP transfer plasmid shall be no more than eleven (11) weeks from the date of award.

4.1.3 The Contractor shall notify the NCI Technical Point of Contact (TPOC) and the Contracting Officer’s Representative (COR) upon completion and provide a Certificate of Analysis for the GMP-grade transfer plasmid to the TPOC and COR via email.

4.2 TASK 2: LENTIVIRAL VECTOR PRODUCTION

4.2.1 The Contractor shall produce the required GMP clinical grade products in full compliance with the U.S. Food and Drug (FDA) GMP regulations.

4.2.2 The Contractor shall construct the GMP transfer plasmid with the backbone of the proprietary transfer plasmid.

4.2.3 The Contractor shall produce a minimum of 400 ml of concentrated, GMP grade lentiviral vector from the GMP-grade transfer plasmid.

4.2.4 The Contractor shall inform the COR and the TPOC via email within one (1) business day on issues that arise with any aspect of product production or changes to the production protocols.

4.2.5 The Contractor shall record any incidents that occurred during manufacturing in a Deviation Report.

4.2.6 Upon completion, the Contractor shall notify the Contracting Officer’s Representative (COR) and the NCI Technical Point of Contact (TPOC).

4.2.7 The Contractor shall store a minimum of two aliquots of the production cell bank in liquid nitrogen for the full duration of the award, for potential future use in the event of catastrophic failure.

4.2.8 As applicable, the Contractor shall send back residual IL12-GEMy plasmid to the Government.

4.2.9 As applicable, the Contractor shall provide details required for IND filing including details of the backbone of the proprietary transfer plasmid.

4.3 TASK 3: PRODUCT TESTING

4.3.1 The Contractor shall test the LV product for GMP compliance and generate a Certificate of Analysis.

4.3.2 The completion of the Certificate of Analysis to confirm the product meets GMP standards shall not exceed fifteen (15) weeks from the time of manufacture completion.

4.3.3 The Certificate of Analysis for the released LV product shall include:

Test

Method

Sequence identification / integrity

Sanger sequencing and/or PCR followed by restriction digest electrophoresis

Appearance Inspection for visible particulates

Sterility US Pharmacopeia (USP) sterility test procedure number 71 (USP 71)

Mycoplasma USP mycoplasma test procedure number 63 (USP 63) Bacteriostasis, Fungiostasis Spike assay (non-inhibitory)

Endotoxin USP mycoplasma test procedure number 85 (USP 85;

to be <10 EU/ml)

Replication-Competent Lentivirus (RCL)

Cell based amplification of cells and supernatant (to be negative)

In vitro adventitious virus Cell based amplification (to be negative)

Host cell protein (HCP) HEK293 HCP measurement by enzyme-linked immunosorbent assay (ELISA)

Total DNA Picogreen Genomic DNA T Antigen PCR Endonuclease ELISA (to be < 10 ng/ml) Physical titer

(lentiviral coat protein p24) ELISA

Functional titer PCR Residual plasmid DNA Vesicular Stomatitis Virus G (VSVg) PCR pH pH measurement (to be between pH 7.0-7.5) Bovine serum albumin (BSA) Immunoassay (report results)

Residual benzonase Immunoassay (<100 ng/mL) Conductivity Report results

4.4 TASK 4: PRODUCT SHIPMENT

4.4.1 The turnaround time for the GMP lentiviral product shall be no more than six (6) months from the date of award.

4.4.2 The Contractor shall ship the concentrated GMP grade lentiviral product in separate portions to avoid potential catastrophe. A total of three (3) separate shipments of approximately equal quantities is anticipated.

4.4.3 The Contractor shall provide to the COR, TPOC, and onsite shipping point of contact (SPOC) an estimated delivery timeframe for the final GMP grade lentiviral product and tracking information to anticipate delivery to the best extent possible. The Contractor shall provide immediate notice upon setbacks that may impact this timeframe.

4.4.4 The Contractor shall ship the product as three hundred (300) 1 ml and one hundred (100) 0.5 mL aliquots, on dry ice, to the address provided in Section 8 below.

4.4.5 The Contractor shall include the Certificate of Analysis and the Deviation Report as printed versions in the first product shipment.

4.4.6 The Contractor shall send electronic pdf versions of the Certificate of Analysis and the Deviation Report to the NCI COR and the NCI TPOC via email.

4.5 TASK 5: LV PRODUCT STORAGE AND STABILITY TESTING

4.5.1 The Contractor shall store a sufficient amount of the lentiviral product at -80°C for long-term stability tests. Storage freezers shall be monitored with Quality Control oversight.

4.5.2 Stability testing shall be in accordance with the Guidance for Industry, “Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs)”, published by the FDA in January 2020; or most up to date guidance on product or stability testing by FDA or other accrediting bodies.

4.5.3 Stability testing shall follow the guidelines published by Jadlowsky et. al. (Long-term stability of clinical-grade lentiviral vectors for cell therapy. Molecular therapy - Methods & Clinical Development, 32(1), 101186); or most up to date guidance on product or stability testing by FDA or other accrediting bodies.

4.5.4 Testing shall include environmental factors (temperature, humidity, light) and product-related factors (packaging materials, container, expidients).

4.5.5 Storage and testing shall be performed under GMP conditions.

4.5.6 The Contractor shall conduct product stability testing at the following time points after product release:

3 months, 6 months, 9 months, 12 months, 18 months, 24 months, and 36 months.

4.5.7 At each time point, the Contractor shall test the product for visual appearance, sterility, endotoxins, functional titer (potency), pH, p24 physical titer by ELISA, conductivity, and product identity; or most up to date guidance on product or stability testing by FDA or other accrediting bodies.

4.5.8 At months 18 and 36, the Contractor shall additionally test the lentiviral product for sterility, to include mycoplasma and endotoxin.

4.5.9 The Contractor shall send the respective stability testing plan and reports as PDF files by email to the COR and the TPOC within one month of each test conducted.

Each test report shall include storage conditions, test methods, all test results, deviations from the protocol, unexpected results, and bilateral amendments to the protocol.

4.6 TASK 6: INVESTIGATIONAL NEW DRUG (IND) QUALITY INFORMATION

4.6.1 The Contractor shall provide the Government with a Statement of Right of Reference for vector manufacturing and facilities information. The cross-referenced submission shall remain active for the duration of the Government Investigational New Drug (IND) being active.

4.6.2 The Contractor shall amend their cross-referenced submission in response to FDA requests for information in a timely manner to prevent the Government IND from being put on Clinical Hold. If the response cannot be provided in that time frame, the Contractor shall notify the Government and a mutually agreed upon timeline for response shall be utilized.

4.6.3 The Contractor shall be available to assist the Government in case of FDA requests for cross-referenced materials, quality information during the initial Government IND submission, and at any time during the time the Government IND is active.

4.6.4 When requested by the Government, the Contractor shall provide information for qualification activities of their quality system and manufacturing facilities.

The Contractor shall provide access and information for audits of the cross-referenced materials, quality system and manufacturing facilities.

5.0 TYPE OF ORDER

This is a firm fixed price purchase order.

6.0 PERIOD OF PERFORMANCE

The anticipated period of performance shall be four years from the date of award.

7.0 PLACE OF PERFORMANCE

All work shall be performed at the Contractor’s facilities.

8.0 DELIVERABLES AND DELIVERY SCHEDULE

The final GMP grade lentiviral product, together with a printed version of the Certificate of Analysis, shall be delivered to the following NIH facility:

Onsite Shipment Point of Contact (SPOC): TBD at award Center for Cellular Engineering Department of Transfusion Medicine NIH Clinical Center Bldg. 10, Rm. 1-6XX (TBD at award) 10 Center Dr.

Bethesda, MD 20892 Phone: TBD

Delivery of items provided under this contract shall be accomplished between Monday through Friday unless changed by mutual agreement between the COR and the Contractor. No deliveries shall be made on Saturdays, Sundays, and days of Government closure or Federal legal holidays found at: http://www.opm.gov/operating_status_schedules.

All written drafts and final deliverable products shall be submitted as an electronic copy in draft format for review, comment, and approval by the COR and the TPOC. Final copies of approved drafts shall be delivered to the COR and the TPOC within 3 business days after receipt of the Government’s comments. If requested, final deliverable products shall be submitted in an electronic format. Other quantities and formats may be submitted after prior approval from the TPOC. All deliverables shall be sent electronically as Microsoft Excel 2013, Microsoft Excel, or Adobe Portable Document Format (PFD), unless otherwise approved by the COR or the TPOC.

Deliverables shall be provided in accordance with the following deliverables schedule:

Deliverable

Deliverable Description, Format Requirements

Due Date

Certificate of Analysis for GMP transfer plasmid

To be delivered by email as electronic PDF file to the COR and the TPOC.

Within 11 weeks of award

Production Issue Notification

To include a short description of the issue, its effect on the estimated production, and/or production protocols. To be delivered by email to the COR and the TPOC.

Within one (1) business day of issue identified

Production Completion Notification

To be delivered by email to the COR and the

TPOC.

Within six (6) months of award; to be delivered within one

(1) business day of production completion http://www.opm.gov/operating_status_schedules

GMP grade vector supernatant

To be delivered on dry ice to the Center for Cellular Engineering at the NIH Clinical Center as 1 ml aliquots and 0.5 mL aliquots. To include tracking information.

Within fifteen (15) weeks from the time of production completion;

subsequent shipments within ten (10) business days of request

Certificate of Analysis for GMP grade vector supernatant

(i) To be delivered by email as electronic PDF file to the COR and the TPOC.

(ii) To be delivered as printed version to the Center for Cellular Engineering.

Within fifteen (15) weeks from the time of production completion

Deviation Record

Record of all incidents that occurred during manufacturing.

(i) To be delivered by email as electronic PDF file to the COR and the TPOC.

(ii) To be delivered as printed version to the Center for Cellular Engineering.

At the time of the first shipment.

LV stability test result #1

T=3M GMP Lentivirus Stability Test Result.

To be delivered by email as electronic PDF file to the COR and the TPOC.

Within four (4) months of GMP LV product release

LV stability test result #2

T=6M GMP Lentivirus Stability Test Result.

To be delivered by email as electronic PDF file to the COR and the TPOC.

Within seven (7) months of GMP LV product release

LV stability test result #3

T=9M GMP Lentivirus Stability Test Result.

To be delivered by email as electronic PDF file to the COR and the TPOC.

Within ten (10) months of GMP LV product release

LV stability test result #4

T=12M GMP Lentivirus Stability Test Result.

To be delivered by email as electronic PDF file to the COR and the TPOC.

Within thirteen (13) months of GMP LV product release

LV stability test result #5

T=18M GMP Lentivirus Stability Test Result.

To be delivered by email as electronic PDF file to the COR and the TPOC.

Within nineteen (19) months GMP of LV product release

LV stability test result #6

T=24M GMP Lentivirus Stability Test Result.

To be delivered by email as electronic PDF file to the COR and the TPOC.

Within twenty-five

(25) months of GMP LV product release

LV stability test result #7

T=36M GMP Lentivirus Stability Test Result.

To be delivered by email as electronic PDF file to the COR and the TPOC.

Within thirty-seven

(37) months of GMP LV product release

Statement of Right of Reference

Statement of Right of Reference for vector manufacturing and facilities information. To be delivered by email as electronic PDF file to the COR and the TPOC.

Within ten (10) business days of request by the COR or the TPOC.

Answers to FDA inquiries

Amendment to cross-referenced submission in response to FDA inquiries.

Within one (1) business day of

To be delivered by email as electronic PDF file to the COR and the TPOC.

request by the COR or the TPOC.

Qualification Activities

Information for qualification activities of the quality system and manufacturing facilities;

and access and information for audits of the qualify system and manufacturing facilities.

To be delivered by email as electronic PDF file to the COR and the TPOC.

Within ten (10) business days of request by the COR or the TPOC.

9.0 UNIQUE QUALIFICATIONS OF THE CONTRACTOR

This acquisition includes services for the production of purified, clinical grade lentiviral vector.

Ultimately, this product will be used in a phase I clinical trial for adults with solid tumor malignancies. In this trial, genetically engineered myeloid cells (GEMys) will be examined for their ability to locally deliver anti-tumor factors to the tumor and metastatic microenvironment.

For clinical development, infectious particle concentration (titer) is one of the most important product quality attributes of a lentiviral vector. The proposed source, Vector Biomed, utilizes a robust propriety system optimized to produce consistently high titer vector product. This system relies on the interplay of the molecular design of the vector construct, an optimized cell production process, and an efficient purification and formulation process.

Vector Biomed previously provided NCI/CCR/POB with research-grade lentiviral vector, as well as preclinical-grade lentiviral vector supernatant. To ensure continuity in service and scientific comparison of data previously obtained from the research-grade and the preclinical-grade lentiviral vector, POB requires the clinical-grade vector to be produced using the same techniques, the same production system, and the same transfer plasmid containing tEGFR-IL12 needed to make IL12 GEMys. The transfer plasmid backbone design is proprietary and essential to the overall vector design platform. Therefore, clinical vector manufacturing must be performed by Vector Biomed. An award to a different vendor would be detrimental to the integration of the new clinical data into POB’s existing research data on this vector. A different vendor would be required to design a new transfer plasmid, which would in turn lead to a different product with untested myeloid cell transformation efficiency, thereby jeopardizing the conduct POB’s studies.

10.0 RESPONSE INSTRUCTIONS

This notice is not a request for competitive quotations. However, if any interested party believes it can meet the above requirements, it may submit a proposal/quote/capability statement for the Government to consider. The response and any other information furnished must be in writing and must contain material in sufficient detail to allow NCI to determine if the party can perform the requirement. All responses must be sent via email to Contracting Officer, Megan Kisamore, at megan.kisamore@nih.gov by no later than 3:00 PM EST, on Friday, September 27, 2024 (9/27/24). A determination by the Government not to compete this proposed requirement based upon responses to this notice is solely within the discretion of the mailto:megan.kisamore@nih.gov

Government. Information received will be considered solely for the purpose of determining whether to conduct a competitive procurement. In order to receive an award, Contractors must be registered and have an active certification for “all awards” in SAM.gov. Reference 75N91024Q00182 on all correspondence.