MOU 225-24-013
MEMORANDUM OF UNDERSTANDING
BETWEEN
U.S. Food and Drug Administration (FDA) – Center for Drug Evaluation and Research (CDER) – Office of Pharmaceutical Quality (OPQ) – Office of Pharmaceutical Quality Research (OPQR) AND
UNITED STATES ARMY
COMBAT CAPABILITIES DEVELOPMENT COMMAND (DEVCOM)CHEMICAL BIOLOGICAL CENTER (CBC)
FOR
Research Collaboration entitled, “The Manufacture of an Acetylcholinesterase Fusion Protein from a Cell Free Protein Synthesis Platform for Organophosphorus Biosensor Development” (Research Collaboration)
CBC Agreement Number: 2415G
FDA Agreement Number: 225-24-013
This is a new Memorandum of Understanding (MOU) between the Requesting Party, FDA-CDER, and the Servicing Party, U .S. Army Combat Capabilities Development Command (DEVCOM) Chemical Biological Center (CBC). When referred to collectively, the Requesting Party and DEVCOM CBC are referred to as the “Parties”.
1. PURPOSE
This MOU provides a general framework for the collaborative relationship between the Parties. The MOU delineates the roles and responsibilities of the Parties under the Research Collaboration. Under the terms of this MOU, CDER/OPQR and DEVCOM-CBC propose to collaboratively (i) establish an E. coli-based cell free protein synthesis (CFPS) manufacturing platform within OPQR at the FDA to assess cell lysate stability and critical process parameters that impact recombinant protein synthesis, (ii) perform a stability study using liquid and lyophilized acetylcholinesterase (AChE) fusion proteins, and (iii) develop a CFPS platform at DEVCOM-CBC to manufacture AChE fusion proteins for the development of novel biosensors that detect organophosphorus (OP) agent exposure.
2. BACKGROUND
FDA is authorized to enforce the Federal Food, Drug, and Cosmetic Act (the FD&C Act) as amended (21 U.S.C. §301 et seq). In fulfilling its responsibilities under the FD&C Act, FDA among other things, directs its activities toward promoting and protecting the public health by assuring the safety, efficacy, and security of drugs, veterinary products, medical devices and radiological products and the safety and security of foods and cosmetics.
DEVCOM CBC is the U.S. Army principal research and development center for chemical and biological (CB) defense technology, engineering, and services. DEVCOM CBC provides products and services to vital national programs such as technology development and integration of subject matter expertise, chemical analysis services, Weapons of Mass Destruction (WMD) training, and other related services in partnership with the U.S. military, other government agencies, academia, and industry.
3. UNDERSTANDINGS OF THE PARTIES:
3.1. The Requesting Party may:
3.1.1. Develop and scale-up an E.coli-based cell free protein synthesis (CFPS) system at the FDA using DEVCOM-CBC Materials as controls.
3.1.2. Investigate potential critical process parameters that impact physicochemical and biological properties of experimental therapeutic proteins, such as romiplostim.
3.1.3. Perform upstream and downstream processes to generate FDA Material from Chinese Hamster Ovary cell lines expressing the AChE fusion protein.
3.1.4. Provide DEVCOM-CBC with the FDA AChE fusion proteins with the purity results via SEC-UPLC and other relevant physicochemical property and biological activity data.
3.1.5. Characterize the stability of the liquid and lyophilized AChE fusion proteins under long storage, accelerated, and stress conditions.
3.1.6. Perform characterization studies that include but is not limited to the following: purity, enzymatic activity, isoelectric point, glycosylation, biological activity, carbamate and Fc receptor binding, process and product-related impurities, host cell DNA and protein impurities, blood brain barrier penetrance, and endotoxin levels.
Note: The Requesting Party will not conduct any experiments involving any OP simulants.
3.2. DEVCOM CBC may:
3.2.1. Develop a cell free protein synthesis (CFPS) system to manufacture AChE fusion proteins.
3.2.2. Develop a CFPS manufacturing platform for an FDA AChE fusion protein.
3.2.3. Investigate physicochemical and biological properties of the AChE fusion protein from the CFPS system.
3.2.4. Perform lyophilization studies to identify an appropriate formulation and lyophilization condition.
3.2.5. Perform long-term, accelerated, and stress stability studies using the lyophilized AChE fusion protein.
3.2.6. Perform in vitro assays, and cell-based assays using OP simulants that investigates the toxin neutralization potential of the anti-organophosphorus agents using cell-free and cell-based analytical methods that characterize potency and safety.
3.2.7. Complete the analysis of the studies and provide a verbal and/or written summary of the research to the FDA.
3.2.8. Provide the FDA with raw Research Data
3.2.8.1. Raw and summarized results obtained from studies that use the FDA AChE fusion proteins with OP simulants such as paraoxon, DFP, mipafox, NIMP, and NEMP.
3.3. The Parties may:
3.3.1. Qualify an AChE fusion protein lyophilization process using FDA- manufactured AChE fusion proteins manufactured from a Chinese Hamster Ovary production platform.
3.3.2. Design and perform accelerated and stress stability studies to investigate potential changes in the physicochemical and biological properties of the AChE fusion protein.
3.3.3. Test potency using FDA-manufactured AChE fusion proteins and OP simulants such as paraoxon, mipafox, diisopropyl fluorophosphate (DFP), NIMP, and/or NEMP.
3.3.4. Share and exchange research results and data. Any data disclosure outside of US Government entities will be in accordance with applicable regulation and with prior agreement of both parties.
3.3.5. Confer on research results.
3.3.6. Confer on analyses of the research data.
3.3.7. Confer on manuscript(s) for publication outside of US Government. Any publication will be in accordance with applicable regulation and with prior agreement of both parties.
3.3.8. Publish research findings in e.g., abstracts, posters and/or manuscripts.
3.3.9. Meet at least bi-annually via telecon or in-person to discuss the research plan and analysis of research data and findings.
4. Information Sharing:
The Parties will not, as a part of the activities covered by this MOU, share any non- public information, including “confidential commercial or financial information” (21 C.F.R 20.61) or trade secret information (21 U.S.C. 360j(c)) obtained by or provided directly to FDA from a third party. Access to non-public information shall be governed by separate Confidentiality Disclosure Agreements, to include the provisions of 21 C.F.R. 20.85.
5. PERSONNEL:
Each Party is responsible for supervision, management, and costs of its own personnel. Each Party will maintain sole and exclusive control over its personnel.
6. GENERAL PROVISIONS:
6.1. POINTS OF CONTACT (POC): The Parties will use the following POCs to communicate matters concerning this MOU. Each Party will provide notice to the other Party within 30 days of a POC change, as needed.
6.1.1. For Requesting Party:
6.1.1.1. Primary POCs
Name: Thomas G. Biel, Ph.D.
Position: Senior Research Scientist
Division of Pharmaceutical Quality Research III, Office of Pharmaceutical Quality Research, Office of
Pharmaceutical Quality
Phone: 240-402-4000
Email: Thomas.Biel@fda.hhs.gov
Name: Tongzhong Ju, M.D., Ph.D.
Position: Senior Staff Fellow
Phone: 240-402-7337
Email: tongzhong.ju@fda.hhs.gov
6.1.1.2. Alternate POC
Name: Gerald Feldman, Ph.D.
Position: Supervisory Biologist
Phone: 240-4029-521
Email: Gerald.Feldman@fda.hhs.gov
6.1.1.3. Agreements Office POC
Name: Gibbes Johnson, Ph.D.
Position: Supervisory Pharmacologist
Phone: 240-402-9611
Email: Gibbes.Johnson@fda.hhs.gov
6.1.2. For DEVCOM CBC:
6.1.2.1. Primary POC
Name: Stephanie Cole, Ph.D.
Position: Research Biologist
Phone: 410-417-3174
Email: stephanie.d.cole9.civ@army.mil
6.1.2.2. Alternate POC
Name: Matthew Lux, Ph.D.
Position: Research Biologist
Phone: 410-436-1448
Email: matthew.w.lux.civ@army.mil
6.1.2.3. Agreements Office POC
Name: Matt Jones
Position: Technology Transfer Specialist
Phone: 410-303-1967
Email: matthew.l.jones10.civ@army.mil
6.2. CORRESPONDENCE: All correspondence to be sent and notices to be given pursuant to this MOU will be addressed, if to:
6.2.1. For Requesting Party
ATTN: CDER Technology Transfer
Office of Translational Sciences – Immediate Office Center for Drug Evaluation and Research
U.S. Food and Drug Administration
White Oak, Bldg. 21, Room 2530
10903 New Hampshire Ave.
Silver Spring, MD 20993-0002
6.2.2. For DEVCOM CBC
ATTN: FCDD-CBD-S
8198 Blackhawk Road
Aberdeen Proving Ground, MD 21010-5424
6.3. FUNDS AND MANPOWER: This MOU neither documents nor provides for the exchange of funds or manpower between the Parties, nor does it make any commitment of funds or resources. No provision in this MOU will be interpreted to require obligation or payment of FUNDS.
6.4. MODIFICATION OF MOU: This MOU may only be modified by the written agreement of the Parties, duly signed by their authorized representatives. This MOU will be reviewed no less often than at the mid-point of its term and around the anniversary of its effective date in its entirety.
6.5. DISPUTES: Any disputes relating to this MOU will, subject to any applicable law, Executive order, or DoD issuances, be resolved by consultation between the Parties.
6.6. TERMINATION OF AGREEMENT: This MOU may be terminated in writing at will by either Party.
6.7. TRANSFERABILITY: This MOU is not transferable except with written consent of the Parties.
6.8. ENTIRE UNDERSTANDING: It is expressly understood and agreed that this MOU embodies the entire understanding between the Parties regarding the MOU’s subject matter, thereby superseding all prior understandings of the Parties with respect to such subject matter.
6.9. EFFECTIVE DATE: This MOU takes effect beginning on the day the last Party signs. The effective date is: 7/15/2024
5.10. EXPIRATION DATE: This MOU expires five 5 years after the effective date.
5.11. NO THIRD PARTY BENEFICIARIES: Nothing in this MOU, express or implied, is intended to give to, or will be construed to confer upon, any person or entity not a party any remedy or claim under or by reason of this MOU and this MOU will be for the sole and exclusive benefit of the Parties.
7. List of Attachments:
7.1. Attachment A: Documentation of Reviews
APPROVED:
For DEVCOM CBC
/s/
MICHAEL A. BAILEY
Director, U.S. Army Combat Capabilities Development Command Chemical Biological Center
Date: 7/3/24
For FDA
/s/
PATRIZIA CAVAZZONI, M.D.
Director Center for Drug Evaluation and Research (CDER)
Date: 7/15/2024
DOCUMENTATION OF REVIEWS FOR
MEMORANDUM OF UNDERSTANDING
BETWEEN
U.S. Food and Drug Administration (FDA) – Center for Drug Evaluation and Research (CDER) – Office of Pharmaceutical Quality (OPQ) – Office of Pharmaceutical Quality Research (OPQR)
AND
UNITED STATES ARMY
COMBAT CAPABILITIES DEVELOPMENT COMMAND (DEVCOM)
CHEMICAL BIOLOGICAL CENTER (CBC)
FOR
Research Collaboration entitled, “The Manufacture of an Acetylcholinesterase Fusion Protein from a Cell Free Protein Synthesis Platform for Organophosphorus Biosensor Development”
CBC Agreement Number: 2415G
FDA Agreement Number: 225-24-013
Annual Review Due Date: May 2025
Mid-Point Review Due Date: May 2027
Reviews will be documented and recorded as completed in accordance with the referenced MOU between the Parties.
Review Type | Party | Date Reviewer | Name | Signature |
Annual | ||||
Mid-Point |