Attachment6-SampleTO_Area3.pdf

1 | P a g e Department of Health and Human Services Acquisition Plan (AP)

Sample Task Order Request for CMC- Biologic Drug Substance

Contractor: TBD STO Title: Process development, manufacture and analysis of BIOL001, a human fusion protein therapeutic candidate

Contract No.: TBD

NCATS Ref. No.: Contracted Technical Area(s): Technical Area 3

TO Originator: NCATS COR TO Type: Cost plus Fixed Fee or Firm Fixed Price

(Completion/Non-Severable)

STO 3 – Part I: Task Order Request for Proposals (TORP)

A. Period of Performance: 48 months

B. Task Leader: COR

C. Deliverables: The Contractor must submit reports and deliverables in accordance with Contract Articles C.2.

Reporting Requirements and F.2. Deliveries.

D. Proposal Instructions: See Part II Contractor’s Response to TORP.

E. Task Description: The following study involves work described in Technical Area 3 of the Statement of Work.

The Government is developing BIOL001, a human fusion protein, as a therapeutic candidate for a rare disease indication. The overall scope of this Task Order (TO) is for the Contractor to conduct full Chemistry, Manufacturing and Controls (CMC) process development for BIOL001, including manufacture of cGMP drug substance to support GLP toxicity studies and proof-of-concept first-in-human clinical trials. A comprehensive CMC report will be required in the Common Technical Document (CTD) format sufficient for use in a regulatory submission to FDA.

Task 1. Lab scale expression and evaluation studies

• Coordinate technology transfer activities to access relevant starting materials.

• Generate a research cell bank. Perform limited testing to ensure that the cell line meets regulatory requirements for cGMP Master Cell Banking.

• Carry out a sufficient number of lab scale studies, preferably in 250 mL or 1 L process-controlled bioreactors, to confirm BIOL001 expression yields.

• Incorporate a basic purification step to generate sufficient purified material for quality assessment and functional assays.

Task 2. Process development and engineering run

• Develop a high-producing (2 to 5 g/L) cell line suitable for manufacturing cGMP bulk drug substance (DS).

• Develop a scalable production and purification process for high titer bioreactor production using only animal component-free, chemically-defined media, whether proprietary or commercially sourced.

2 | P a g e

• Demonstrate scalability by performing at least two pilot scale (50 L or 100 L) engineering runs with subsequent purification.

• Develop downstream chromatography steps, including all collection criteria, to meet pre-defined quality specifications, and develop all auxiliary purification steps.

• Generate master specifications and assay profile (MS/AP) for the bulk BIOL001 DS.

• Generate and qualify a BIOL001 Master Cell Bank (MCB) to current FDA regulatory standards, providing a minimum of 300 vials of cGMP MCB for the best high-producing clone.

• Produce a minimum of 80 g purified and tested non-GMP BIOL001 DS.

• Review and approve all master batch records for manufacturing of the MCB, including release assay data for readiness of the MCB for DS manufacturing and cGMP storage of MCB.

• Develop all assays that demonstrate the Identity, Safety, Purity, Potency and Quality of BIOL001 DS.

Generate SOPs for analytical methods to determine critical quality attributes (CQA) and qualify the methods for release of cGMP DS.

• Generate reference standard of BIOL001 DS (>300 vials), and test reference standard using the developed assay methods.

Task 3. Manufacture of cGMP-grade bulk drug substance (DS)

• Manufacture 1 kg of cGMP-grade BIOL001 DS.

• Perform relevant release assays and provide a QA-approved Certificate of Analysis to confirm that bulk DS is ready for cGMP drug product manufacturing.

• Provide CMC report in CTD format.

Assumptions, Constraints, Clarifications and Qualifications

1. The technology transfer package from the Government and/or its Collaborator includes upstream and downstream process description documents and analytical methods with appropriate reference materials and/or analytical controls. The Government or its Collaborator will transfer research cell banks of the expression cell line and documentation describing derivation of research cell banks and genetic constructs, including a list of raw materials and complete genetic sequences used to generate the research banks. The research cell banks are assumed to be suitable for further development and use in cGMP manufacturing.

2. For purification process, the Government anticipates a need to incorporate additional chromatographic steps to improve the yield and meet the critical quality attributes.

F. Conformance and Compliance: Where specified, all materials manufactured under this subcontract shall adhere to cGMP under the current United States Code of Federal Regulations, 21 CFR Part 210 & 211, as well as the European Community Directive European Directive 2003/94/EC in relation to medicinal products for human use

3 | P a g e and investigational medicinal products for human use, as interpreted by ICH Harmonized Tripartite Guideline.

The Contractor will agree to enter into a Quality Agreement and will comply with all local and national laws and regulations and will conform to GMP as defined by provisions of the Federal Food, Drug and Cosmetic Act when engaged in the manufacture of biological products; said GMP provisions are available at:

https://www.fda.gov/drugs/pharmaceutical-quality-resources/current-good-manufacturing-practice-cgmp-regulations.

The Contractor shall permit appropriately skilled representatives of the Government, at the inspecting party’s expense, to have access during the Contractor’s normal business hours to inspect Contractor’s records and facilities as may be necessary to verify that the products manufactured by the Contractor are in accordance with cGMP requirements and conform to the specifications outlined in this Subcontract. These audits/inspections shall be conducted as deemed required by the Government and will last approximately 2-5 business days each, depending on the type of audit/inspection, the availability of required data, and the quantity of data to be reviewed. A successful audit outcome will be required prior to GMP activities.

https://www.fda.gov/drugs/pharmaceutical-quality-resources/current-good-manufacturing-practice-cgmp-regulations https://www.fda.gov/drugs/pharmaceutical-quality-resources/current-good-manufacturing-practice-cgmp-regulations