MOU 225-17-014

MEMORANDUM OF UNDERSTANDING
CLINICAL PROTEOGENOMICS CANCER RESEARCH
BETWEEN THE NATIONAL CANCER INSTITUTE, NATIONAL INSTITUTES OF HEALTH, U.S.
DEPARTMENT OF HEALTH AND HUMAN SERVICES
AND FOOD AND DRUG ADMINISTRATION
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES

I. Preamble

The National Cancer Institute (NCI) and the U.S. Food and Drug Administration (FDA) both as part of the Department of Health and Human Services (DHHS), and hereinafter referred to as "Federal partners," agree to work together to facilitate cooperative activities in understanding the molecular biology of cancer as it relates to diagnostic measurements, product development, and therapeutic treatment in accordance with their respective individual missions. The Federal partners find that the collaborative activities under this Memorandum of Understanding (MOU) are in their best interests to continue the partnership that was initiated under previous MOUs that leveraged each Federal partner's expertise and resources to advance public health in the area of clinical proteogenomics cancer research.

II. Purpose

The purpose of this MOU is to engage in scientific and programmatic collaborations in clinical proteogenomics cancer research, such as statistical experimental design, instrument/technology validation, informatics, biological sample preparation, diagnostics, discovery, and validation of biomarkers for cancer development, treatment, and response. This MOU sets forth the basic principles and guidelines under which the Federal partners intend to foster partnership in: research and education; the exchange of ideas, information, and data; the development, and validation of proteogenomic technologies in clinical applications; mutual collaborations with industrial, non-profit, academic, and other government institutions and agencies; and other efforts to further the advancement and application of proteogenomic technologies and pipelines to improve patient response to treatment, reduce the pain and suffering of cancer and improve the standard of living and quality of life.

Ill. Background

FDA and NIH are agencies within the DHHS and NCI is an institute of the NIH. Since achievements in science and technology require a high level of integration, particularly in the development of interdisciplinary research teams, the programmatic strengths of the NCI and FDA in the areas of molecular biology, technology development and standardization, protein chemistry, analytical validation and clinical trials designs offer a great opportunity for synergy that will accelerate clinical proteogenomics cancer research and its application in clinical settings. Although with a different emphasis, each institution already has existing programs and resources for facilitating technology development and application.

FDA is a regulatory agency responsible for protecting the public health through the regulation of food, cosmetics, and medical products, including drugs, biological products, animal drugs, and medical devices. FDA also has responsibility for regulating the manufacturing, marketing and distribution of tobacco products to protect the public health and to reduce tobacco use by minors. FDA administers the Federal Food, Drug and Cosmetic Act (see 21 U.S.C. 321) and relevant sections of the Public Health Service Act (See 42 U.S.C. 262), among other statutes. Among its duties, FDA approves pre-market applications, conducts inspections of manufacturing facilities, and monitors post-marketing adverse events. FDA also recommends civil and criminal litigation to enforce applicable laws and regulations. FDA's role is to regulate medical products and develop new policies to allow commercial marketing and distribution of safe and effective technologies and products.

The FDA's Office of In Vitro Diagnostics in the Center for Devices and Radiological Health (CDRH) was created to handle all aspects of in vitro diagnostic approval, post-market surveillance and compliance to ensure that approved devices are based on valid scientific evidence of safety and that they provide evidence for effectiveness and clinical utility. With the emergence of novel genomic and proteomic technologies, the FDA needs to prepare for new regulatory challenges while continuing to apply scientific evidence-based oversight.

The FDA Oncology Center of Excellence (OCE) leverages the combined skills of regulatory scientists and reviewers with expertise in drugs, biologics, and devices (including diagnostics) .The OCE will help expedite the development of oncology and hematology medical products and support an integrated approach in the clinical evaluation of drugs, biologics, and devices for the treatment of cancer. The development of appropriate evaluation methods, standard protocols, and analysis methods is essential for faster, more predictable regulatory approval of safe and effective innovative medical products and the translation and integration of new technologies and molecular-based diagnostics that can enhance public health.

The NCI is the Federal government's principal agency for the conduct and support of research, training, health information dissemination, and other programs related to the cause, prevention, diagnosis, and treatment of cancer; cancer survivorship; and the continuing care of cancer patients and their families, as authorized under Section 410 of the Public Health Service Act (42
U.S.C. 285). The NCI's Office of Cancer Clinical Proteomics Research (OCCPR) supports research, training, data collections and analysis, technology assessment and standardization, regulatory science and other programs including the NCI Clinical Proteomic Tumor Analysis Consortium (CPTAC) to improve proteogenomic technological capabilities to accelerate the understanding of cancer biology for early detection, diagnostics, prevention, therapeutic monitoring, and treatment of cancer. These OCCPR programs help advance the field of proteomics/proteogenomics by providing high quality data with accompanying assays and protocols to the public, which will serve as the main conduit for exchange of information between these two agencies pursuant to this MOU.

This MOU provides a framework that will enable and encourage the sharing of knowledge and support the formation of research teams to solve complex problems in the area of each agency's mission. Specifically, the Federal partners agree to collaborate through working groups and partnerships to develop strategic plans, set priorities, and leverage resources and expertise from multiple sources, including the private sector. Both organizations will adhere to all appropriate protocols and procedures to ensure there are no conflict-of-interest issues existing in these initiatives, toward the goals of facilitating the development of proteogenomic technologies in clinical research and applications that constitute novel tools, more effective diagnostics, better characterization of novel products and molecularly-based personalized cancer therapeutics. This will be done, in part, by establishing a framework for effective assessment and evaluation of existing and emerging proteogenomic technologies and informatics. This MOU sets forth the framework for collaboration among the Federal partners and for pursuing specific collaborative projects that may involve additional partners and will be implemented through separate agreements. The Federal partners anticipate that concepts developed and activities undertaken under the auspices of this MOU may lead to partnerships that will be implemented through separate agreements.

IV. Authority

FDA has authority to enter into this MOU pursuant to sections 1003(b) and (c) of the Federal Food, Drug, and Cosmetic Act. NCI has the authority to enter into this MOU in accordance with Section 301 of the Public Health Service Act, which authorizes NIH to cooperate with public authorities and scientific institutions.

V. Substance of Agreement

This MOU records the intent of the Federal partners to continue to collaborate in areas including, but not limited to, the following aspects of clinical proteogenomics cancer research: statistical study design, sample collection, preparation, storage and processing, bioinformatics and data analysis/integration, diagnostic assay development, discovery, and validation of biomarkers and surrogate biomarkers of cancer development and drug response, including standardization among technology platforms and assay standards development . Both Federal partners will depend on the reproducibility of results and correct statistical experimental design of studies to ensure accurate clinical applications. In order for the field of proteogenomics to move forward, both agencies would benefit from a mutual understanding of analytical, product characteristics, and clinical validation of proteogenomic technologies, proteogenomic data submission requirements, and the subsequent results and interpretations of such data.

By capitalizing on the core strengths of each Federal partner, this collaboration will benefit the NCI in improving its transfer of science, technology ,and engineering discoveries from its funded institutions involving clinical proteogenomics cancer research to the marketplace and public through collaboration with the analytical, product characterization and clinical validation expertise at the FDA, and will benefit the FDA by extending outreach to medical device manufacturers early in the development of those products, as well as clinicians and drug manufacturers who are utilizing proteogenomics approaches in their development programs. This will enhance FDA's knowledge and technical expertise in proteogenomics as it is applied to medical devices and oncology drug development, and will facilitate the review of such medical devices and therapies when they are submitted to FDA. The Federal partners intend for this close collaboration to help promote the accomplishment of the goals of both agencies as summarized in their respective strategic platforms.

a. Cooperation may include, but is not limited to, the specific areas identified below:

i. Development of guidelines for necessary requirements for data submission and analysis for proteogenomic data repositories that is mutually beneficial to the NCI and the FDA. These requirements will be intended to meet the needs of the NCI for the purposes of technology assessment and standardization, validation, and experimental reproducibility and the needs of the FDA for the purposes of diagnostic and drug submissions.

ii. Development of joint educational materials and programs in which the NCI and FDA detail the most current standards and practices for proteogenomic technologies and applications.

iii. Formation of NCI, FDA, academic, industry and other government agency partnerships to improve proteogenomics standard operating procedures and data policies.

iv. Mutual use of facilities, software, algorithms, and data repositories and collaboration on development of new facilities, as appropriate.

v. Cooperation through the exchange of agency personnel, expertise, scientific and technical information, data, and publications.

vi. Mutual assistance in program planning, and in the review of research development projects and proposals.

vii. Inclusion of representatives from each agency in workshops, working groups, seminars, and other related activities.

b. To pursue the collaboration described above the Federal partners intend to use the following framework for implementing collaborations:

i. Both the NCI and FDA will identify coordinators to implement and manage this MOU. The Director of the NCI's OCCPR, the Director of the FDA's Office of In Vitro Diagnostics in CDRH, and the Director of OCE or their designees, will be the primary representatives to coordinate the activities from their respective agencies for the purposes of this MOU. The coordinators intend to meet on a regular basis to discuss activities conducted under the MOU, review all aspects of implementation, and plan future directions of programmatic interaction and cooperation, and report to signatories annually.

ii. Concepts or ideas for developing collaborations or activities involving joint projects or integrated approaches to conducting science or technology development and standardization will be formally presented by submission of concepts to the coordinators of the MOU.

iii. Industry and scientific organizations' representatives for relevant proteomic technologies may interact with the Federal partners through guidelines established and accepted by each agency's representative. The guidelines will be established in keeping with the applicable laws, regulations, and policies for both organizations.

VI. Data Sharing Guidelines

FDA and NCI agree that the following principles and procedures will govern the exchange of data and non-public information between the two agencies. Although there is no legal requirement that FDA and NCI exchange information in all cases, FDA and NCI agree that there should be a presumption in favor of full and free sharing of information between FDA and NCI. As public health agencies within DHHS, there are no legal prohibitions that preclude FDA or NCI from sharing with each other most information in the possession of either agency. Both Federal partners recognize and acknowledge, however, that all non-public information shared between FDA and NCI whether in writing or orally, must be protected from any disclosure not authorized by law or regulation. See, e.g., 18 U.S.C. § 1905; 5 U.S.C. § 552 and 552a; 21 U.S.C. § 331(j); 21CFR Parts 20 and 21; 42 U.S.C. § 241(d) 45 CFR Parts 5 and 5b. Safeguards are needed to protect shared non-public information, such as trade secrets and confidential commercial information; identities of study participants and other personal privacy information; privileged and/or pre-decisional agency information; research proposals, progress reports, and/or unpublished data; or national security information. Such safeguards also help ensure compliance by FDA and NCI with other applicable laws and regulations.

To facilitate the sharing of non-public information, FDA and NCI expect to implement procedures to ensure that such sharing is appropriate and in accordance with applicable law, and that the recipient Federal partner will guard the confidentiality of all non-public information received. Both Federal partners are committed to responding to requests for information in a complete and timely manner, consistent with budgetary and resource constraints, and in accordance with applicable laws, regulations, and agency policy and practice. The Federal partner receiving shared non-public information (requesting Federal partner) will be responsible for protecting that information from any unauthorized disclosure. The provisions for sharing of non-public information in accordance with applicable laws, regulations, and agency policy and practice are set out below:

The requesting Federal partner will comply with the following conditions:

a. The requesting Federal partner will limit the dissemination of shared nonpublic information it receives to internal Federal partner offices and/or employees that have been identified in its written request. If the requesting Federal partner determines that employees other than those identified in the original request have a need to know the requested information, then an update to the request letter will be supplied to the sharing Federal partner before the requesting Federal partner distributes the information to those employees. The Federal partner official who signs the request letter will be responsible for ensuring that there are no inappropriate recipients of the information.

b. The requesting Federal partner will agree in writing, by using the model request letter (or a reasonable, mutually agreed upon variation), not to disclose any shared non-public information in any manner not authorized by law or regulation, including disclosure in publications and public meetings. If the requesting Federal partner wishes to disclose shared information that the sharing Federal partner has designated as non-public, the requesting Federal partner will ask the sharing Federal partner whether the information's non-public status has changed, and if so, will first obtain written confirmation and permission from the sharing Federal partner before disclosing that information. If the requesting Federal partner receives a FOIA request for shared information, the requesting Federal partner will: (a) refer the FOIA request to the information-sharing contact person or designee for the sharing Federal partner to respond directly to the FOIA requester regarding the release of the information, and (b) notify the FOIA requester of the referral and that a response will issue directly from the sharing Federal partner. The requesting Federal partner will leave all final disclosure decisions up to the sharing Federal partner, including decisions on whether the records are responsive and whether they must be disclosed. Accordingly, the requesting Federal partner will not indicate to the FOIA requester whether the sharing Federal partner has responsive records or releasable records.

c. The sharing Federal partner will include a transmittal letter along with any agency information shared. The transmittal letter will indicate the type of information (e.g. confidential commercial information, personal privacy, pre-decisional, etc.). A model transmittal letter is attached. The shared documents containing non-public information should be stamped "Do not disclose without permission of [FDA or NCI]", with the name in the brackets being that of the sharing Federal partner.

d. The requesting Federal partner will promptly notify the contact person or designee of the sharing Federal partner of any attempt by a third party to obtain shared non-public information by compulsory process, including, but not limited to, a FOIA request, subpoena, discovery request, or litigation complaint or motion.

e. The requesting Federal partner will notify the sharing Federal partner before complying with any judicial order that compels the release of shared nonpublic information, so that the Federal partners may determine the appropriate measures to take, including, where appropriate, legal action.

VII. General Provisions

a. This MOU represents the broad outline of the Federal partners' intent to engage in collaborative efforts related to clinical proteogenomics cancer research, which is of mutual interest to FDA and NCI. All activities undertaken pursuant to the MOU are subject to the availability of personnel, resources, and funds.

b. This MOU does not affect or supersede any existing or future agreements or arrangements among the Federal partners and does not affect the ability of the Federal partners to enter into other agreements or arrangements related to this MOU.

c. This MOU and all associated agreements will be subject to the applicable policies, rules, regulations, and statutes under which FDA and NCI operate.

VIII. Liaison Officers

Food and Drug Administration

Douglas Jeffery, Ph.D. (FDA CDRH Liaison)
Acting Branch Chief
Immunology and Flow Cytometry Branch
Division of Immunology and Hematology Devices

Office of In Vitro Diagnostics and Radiological Health

Center for Devices and Radiological Health
Food and Drug Administration 10903
New Hampshire Avenue Silver Spring, MD 20993, USA
(240) 402-6648

Gideon Blumenthal, M.D. (FDA OCE Liaison)

Associate Director Precision Therapeutics

Office of Hematology Oncology Products Office of New Drugs
Center for Drug Evaluation and Research
Food and Drug Administration 10903
New Hampshire Avenue Silver Spring, MD 20993, USA
(301) 796-5369

National Cancer Institute

Henry Rodriguez, Ph.D., M.B.A.
Director, Office of Cancer Clinical Proteomics Research
Office of the Director
National Cancer Institute
National Institutes of Health
31 Center Drive, MSC 2580
Bethesda, MD 20892,
USA Telephone: (301) 451-8883

IX. Term, Termination, and Modification

This MOU, when accepted by all participating Federal partners, will have an effective period of performance from the date of the latest signature for five years and may be modified or terminated by mutual written consent by both Federal partners or may be terminated by either Federal partner upon a 90-day advance written notice to the other.

APPROVED AND ACCEPTED BY
FOOD AND DRUG ADMINISTRATION

Scott Gottlieb, M.D.
Commissioner
U.S. Food and Drug Administration

May 23, 2017

APPROVED AND ACCEPTED BY
NATIONAL CANCER INSTITUTE

NATIONAL INSTITUTES OF HEALTH

Douglas R. Lowry, M.D.
Acting Director
National Cancer Institute
National Institutes of Health

May 23, 2017

Appendix A:

Model Language for Information Request

Reference: MOU No. 225-17-014

The National Cancer Institute (NCI) has requested the following information from the FDA for the following purposes: [Identify information and purpose]

NCI hereby requests the following information from FDA for the following purposes

:
[Identify information and purpose]

NCI agrees that it will not publicly disclose any such information that FDA shares without prior written permission from FDA and that it will comply with the principles and procedures set forth in the Memorandum of Understanding on information sharing between NCI and FDA. Applicable laws and regulations may prohibit the disclosure of such information. See, e.g., 21 U.S.C. sec. 331(j): 18 U.S.C. sec. 1905, 21 C.F.R. Parts 20 and 21, 45 C.F.R. Parts 5 and 5b and 42 U.S.C. sec. 241(d).

NCI will limit dissemination of any shared information to the following NCI offices and/or employees: [Identify office(s) and/or employee(s)]

_________________________________________________________________________

Name Date

Model Language for Information Request

Reference: MOU No. 225-17-014

The Food and Drug Administration (FDA) has requested the following information from the NCI for the following purposes: [Identify information and purpose]

FDA hereby requests the following information from NCI for the following purposes:

[Identify information and purpose]

FDA agrees that it will not publicly disclose any such information that NCI shares without prior written permission from NCI and that it will comply with the principles and procedures set forth in the Memorandum of Understanding on information sharing between NCI and FDA. Applicable laws and regulations may prohibit the disclosure of such information. See, e.g., 21 U.S.C. sec. 331(j): 18 U.S.C. sec.1905, 21 C.F.R .Parts 20 and 21, 45 C.F.R. Parts 5 and 5b and 42 U.S.C. sec. 241(d).

FDA will limit dissemination of any shared information to the following FDA offices and/or employees: [Identify office(s) and/or employee(s)]

___________________________________________________________________________
Name Date

Model Transmittal Letter from NCI to FDA

Reference: MOU No. 225-17-014

This letter accompanies agency records that the NCI is sharing with the Food and Drug Administration (FDA) in response to FDA's request, dated__________.

These agency records contain one or more of the following categories of non-public information, including information the public disclosure of which may be prohibited by law;

[NCI checks applicable items below]

___Trade secrets;
___Confidential commercial or financial information
___Information the disclosure of which would constitute a clearly unwarranted invasion of personal privacy;
___Information subject to the Privacy Act;

___Intra-agency records;
___Records or information compiled for law enforcement purposes;

___Information protected for national security reasons; or
___Other.

FDA shall notify the appropriate office of NCI if there are any attempts to obtain shared information by compulsory process, including but not limited to, Freedom of Information Act requests, subpoenas, discovery requests, and litigation complaints or motions. FDA shall notify NCI before complying with any judicial order that compels the release of such information so that NCI and/or FDA may take appropriate measures, including filing a motion with the court or an appeal. FDA has agreed, by this letter or e-mail and by a signed request letter dated ______________________, not to publically disclose the above-described information without prior written permission of NCI. FDA acknowledges that applicable laws and regulations may prohibit the disclosure of such information. See, e.g., 21 U.S.C. section 331(j); 18 U.S.C. section 1905, 21 C.F.R. Parts 20 and 21, 45 CF.R. Parts 5 and 5b and 42 U.S.C. Section 241(d).

______________________________________________________________________________
Name Date

Model Transmittal Letter from FDA to NCI

Reference: MOU No. 225-17-014

This letter accompanies agency records that the FDA is sharing with NCI in response to NCI's request, dated _______________. These agency records contain one or more of the following categories of non-public information, including information the public disclosure of which may be prohibited by law;

[FDA checks applicable items below]

___Information protected for national security reasons; or
___Other.

NCI shall notify the appropriate office of FDA if there are any attempts to obtain shared information by compulsory process, including but not limited to, Freedom of Information Act requests, subpoenas, discovery requests, and litigation complaints or motions. NCI shall notify FDA before complying with any judicial order that compels the release of such information so that FDA and/or NCI may take appropriate measures, including filing a motion with the court or an appeal. NCI has agreed, by this letter or e-mail and by a signed request letter dated _________________,
not to publically disclose the above-described information without prior written permission of FDA. NCI acknowledges that applicable laws and regulations may prohibit the disclosure of such information. See, e.g., 21 U.S.C. section 331(j); 18 U.S.C. section 1905, 21 C.F.R. Parts 20 and 21, 45 CF.R. Parts 5 and 5b and 42 U.S.C. Section 241(d).

_________________________________________________________________________________
Name Date