6-STO_Biologics.pdf

Sample Statement of Work Technical Area: Drug Substance Development – Biologics

A. Background The Government is developing BIOL001, a human fusion protein, as a therapeutic candidate for a rare disease indication. NCATS requires support to develop an appropriate manufacturing process.

B. Scope and Objectives The overall scope of this Task Order (TO) is for the Contractor to conduct full Chemistry, Manufacturing and Controls (CMC) process development for BIOL001. The Government may exercise the option for the Contractor to generate cGMP drug substance to support GLP toxicity studies and proof-of-concept first-in-human clinical trials.

The objectives of this TO include:

Base Tasks

1. Lab scale expression and evaluation studies of BIOL001

2. Process development and engineering run

Optional Tasks

3. Manufacture of cGMP-grade bulk BIOL001 drug substance (DS)

C. Project Description and Technical Requirements

Base Tasks

Task 1: Lab scale expression and evaluation studies

• Coordinate technology transfer activities to access relevant starting materials.

• Generate a working 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.

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

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

Attachment 6

• 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.

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

Optional Tasks

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 Certificate of Analysis to confirm that bulk DS is ready for cGMP drug product manufacturing.

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.

D. 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 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

Attachment 6 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 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.

The following table contains a list of deliverables with notation of due dates. All days identified are intended to be normal business days unless otherwise specified. The Contractor may suggest an alternative due date for any or all deliverables in their offer. The final schedule will be agreed to by the COR and the Contractor based on the Contractor’s proposed delivery schedule.

E. Task Order Deliverables and Reporting Requirements

The below study deliverables and reports shall be submitted in accordance with the terms and conditions described in the parent IDIQ contract and this SOW. The Contractor shall propose delivery dates / timelines for the listed tasks. Final delivery schedules will be determined through negotiation between the Contractor and the Government.

In addition to specific acceptance criteria included with certain deliverables, the following general quality measures will be applied to each deliverable received from the Contractor under this Statement of Work:

• Accuracy – Deliverables shall be accurate in presentation, technical content, and adherence to accepted elements of style.

• Clarity – Deliverables shall be clear and concise. Any/all diagrams shall be easy to understand and be relevant to the supporting narrative.

• Consistency to Requirements – All deliverables must satisfy the requirements of this SOW.

• Timeliness – Deliverables shall be submitted on or before the due date specified in this SOW or submitted in accordance with a later scheduled date determined by the Government.

Reports submitted shall include the following:

• Contractor Name and Address

• Name of Person Submitting the Report

• Subcontract Number (if required)

• Report Date

• Period Covered by the Report

• A comprehensive Summary of Work performed during reporting period

Description Due Date

Base Task 1: Lab scale expression and evaluation studies

• Complete initial technology transfer

• Generate a working cell bank

• Complete lab-scale studies to confirm yield and functional activity of purified BIOL001 DS

TBD

Base Task 2: Process development and engineering run

• Produce research cell banks (20 each for the top 3 clones) and identify the best high-producing cell line

• Provide cell line generation report detailing host cell lineage, codon optimization, plasmid sequence verification, clonality confirmation, and TSE/BSE report

• Deliver 300 vials (minimum) of cGMP MCB for the best high-producing clone

• Provide CoA and manufacturing report for the MCB

• Provide Design of Experiments (DOE) plan

• Deliver 80 g (minimum) purified and tested non-GMP

BIOL001 DS

• Provide a summary report defining optimal process conditions and quality attributes, including qualification reports for all assays

• Develop a technology transfer document

Optional Task 3:

Manufacture cGMP-grade bulk DS

• Manufacture 1 kg of purified cGMP-grade BIOL001 DS

• Provide a data report on release assays (CoA for bulk DS)