Memorandum of Understanding
The AOAC Research Institute
The United States Department of Health and Human Services
Food and Drug Administration
Center for Veterinary Medicine
The purpose of this memorandum of understanding (MOU) is to provide for cooperation between the AOAC Research Institute (Institute) and the Center for Veterinary Medicine (CVM), Food and Drug Administration (FDA) in evaluating test kits for detecting animal drug residues in milk. Test kits provide the means for State and federal regulatory agencies and milk processors to screen economically and efficiently large quantities of milk for a wide range of drug residues. In addition, the use of test kits by the veterinarian or milk producer provides the means of preclude unsafe milk from the individual treated cow from entering the food chain. However, if the use of these test kits is to provide credible results, the kits must perform reliably and accurately.
The cooperation between the Institute and CVM/FDA specified in this MOU is designed to result in test kits that are evaluated by the Institute and acceptable to CVM/FDA. These kits that are acceptable to CVM/FDA will then be recommended by CVM/FDA to the Milk Safety Branch, Center for Food Safety and Applied Nutrition (CFSAN), FDA, for subsequent recommendation to State regulatory agencies to monitor for animal drug residues in grade A milk as specified in the Pasteurized Milk Ordinance (PMO). These kits will also be recommended for use in monitoring programs by State regulatory agencies for "manufacturing" grade milk. In addition, test kits intended for use by the kit manufacturer on milk from the individual cow will also be evaluated under this program. Kits that are acceptable to CVM/FDA will be available for use by veterinarians and milk producers in monitoring milk from individually treated cows.
FDA's responsibilities under the Federal Food, Drug, and Cosmetic Act include the regulation of milk shipped in interstate commerce. FDA's milk safety program was initiated in 1946 at the request of the Conference of State and Territorial Health Officers. Since that time, that organization had evolved into the National Conference on Interstate Milk Shipments (NCIMS). The NCIMS is a voluntary organization directed and controlled by the member states. In order for the milk industry to ship milk interstate, the State where the milk originates must participate in this conference and pass laws or regulations which enact the provisions of the PMO. The PMO sets out standards, requirements and procedures that must be followed to ensure the safety of milk. All fifty States and Puerto Rico have chosen to participate in the PMO. FDA collaborates with the NCIMS to provide a system of regulation in the milk industry.
The PMO includes specific provisions regarding the monitoring of milk for animal drug residues. The PMO requires that each dairy farm be represented in a sampling program and tested for drug residues at least four times in each six month period. These tests are conducted by the Sates. This is in addition to the requirement that the industry test each bulk milk tanker of milk for beta lactams before it is processed. Positive results from these tests result in direct regulatory action by the State against the farm involved. FDA coordinates with the NCIMS on the implementation of State monitoring programs for other drugs.
The PMO also provides for the use by the States of "methods which have been evaluated by AOAC and/or accepted by FDA" as one method for monitoring milk for animal drug residues. In this regard the PMO provides that "FDA shall review the AOAC evaluation for each test kit and make a determination as to the acceptability of the use of the method in accordance with all applicable sections of the [PMO]." A similar arrangement between the States and the United States Department of Agriculture prescribes for use of AOAC evaluated and/or "manufacturing" grade milk.
Since the PMO specifies that all milk test kits must be accepted by FDA before use in State monitoring programs, the Institute and CVM/FDA are entering into this MOU. The Institute recognizes, as does CVM/FDA, the importance of the timely evaluation of milk screening tests. This timely review and final acceptance of the test kits by FDA is the impetus for the cooperation described in this MOU. This cooperation as specified in this MOU will provide for CVM/FDA to determine whether a milk test kits evaluated by the Institute is acceptable to FDA.
The AOAC Research Institute is a non-profit subsidiary of AOAC International (AOAC). The Institute has recently announced its intention to evaluate test kits through a test kit performance testing program. The purpose of this program is to provide an independent third-party review of manufacturers' performance claims for analytical test kits including those intended to detect or measure animal drug residues in milk. This MOU applies only to evaluation of test kits for analyzing for animal drug residues in milk.
As for test kits, AOAC Research Institute is establishing a new procedure for the evaluation of test kits' performance that is separate from the official AOAC collaborative study procedure. AOAC is recognized internationally as the organization which provides the mechanism for the collaborative study, validation and publication of reliable, official methods of analysis. FDA accepts and utilizes AOAC methods for regulatory enforcement as specified in 21 CFR 2.19. The PMO also provides for the use of official AOAC methods by the States for monitoring milk for animal drug residues. The Institute's test kit evaluation program, however, will not qualify tests as AOAC Official Methods, rather the procedure will certify the performance characteristics specified by the manufacturer for the test kit.
Under the Institute's program, manufacturers who elect to participate in the program will submit data to the Institute to support the labeled performance claims on the specific test kit. The Institute will select expert scientists to evaluate those data to determine whether the kit meets specific performance criteria for the intended use. These expert scientists will be selected worldwide from academia, industry, and government based on the scientist's individual recognition in the scientific community for his/her expertise in the specific area of science. The Institute will also select independent testing laboratories to conduct tests of each test kit and provide the results to the expert reviewers for evaluation. The Institute will grant a "PERFORMANCE TESTED" status to test kits it determines meet specific performance criteria.
To integrate CVM/FDA acceptance of test kits as specified in the PMO with the Institute's evaluation of the test kits, the Institute will provide the manufacturers' data and the laboratory testing data to CVM/FDA scientist for evaluation. In addition, the Institute and CVM/FDA will jointly develop protocols for laboratory testing of the test kits. The Institute will advise manufacturers of the results of the evaluation.
CVM/FDA is particularly interested in the performance of those kits which claim to detect animal drug residues in milk. This MOU provides one means for the milk test kits to be evaluated by CVM/FDA such that they could be recommended to the states, by the Milk Safety Branch, CFSAN/FDA, for regulatory purposes. Test kits intended by the kit manufacturer to detect animal drug residues in the milk of individually treated cows which are evaluated in the Institute's program and accepted by CVM/FDA will be available to the veterinarian and milk producer.
III. SUBSTANCE OF THE AGREEMENT
A. AOAC Research Institute agrees to:
1. Provide data submitted to the Institute by test kit manufacturers and data resulting from laboratory testing for CVM/FDA's evaluation of the test kit to CVM/FDA scientists.
2. Provide for CVM/FDA participation in the development of test protocols.
3. Ensure that laboratory testing is conducted in accordance with CVM/FDA accepted protocols.
4. Coordinate the CVM/FDA test kit evaluations with the evaluations of the Institute expert scientists.
5. Provide for CVM/FDA participation in meetings convened of Institute expert scientists.
6. Advise test kit manufacturers of the progress and results of the CVM/FDA evaluation.
B. The CVM/FDA agrees to:
1. Appoint a scientist to represent FDA for each announced Institute test kit review under the AOAC Research Institute Test Kit Performance Testing Program. This scientist will represent the Agency in all discussions with the Institute regarding test kits for specific drugs(s). In addition, this scientist will be supported by other Agency scientists in the review of data and for the development of protocols for the evaluation of test kits for monitoring drug residues in milk submitted to the AOAC Research Institute. FDA scientists will perform their reviews as part of their normal duties at their FDA work locations.
2. Provide the Institute with parameters and criteria necessary to CVM/FDA in the evaluation of test kits for monitoring drug residues in milk.
3. If requested by the Institute to provide incurred drug residues in milk for chemical analysis of milk test samples to be used for laboratory testing of test kits by AOAC Research Institute, a minimum of ninety days notice shall be required for CVM/FDA to provide such samples. The request for incurred drug reside samples in milk must include the date required, levels of residue in milk as outlined in the protocol, number of samples of each level, and any other information which may be a part of the protocol.
4. If the label claims of a test kit are such that the test kit is not intended to meet CVM/FDA levels of residue concern, then CVM/FDA would decline to participate in the review and evaluation of that test kit. Such test kits evaluated by the Institute would not be subject to CVM/FDA review under this MOU.
5. CVM/FDA agrees to provide AOAC Research Institute:
a. "Memorandum of Initial Review"
This memorandum is a review of kit performance claims as submitted by the manufacturer and is not a review of any data. This review is to review what the test is claimed to detect and that it does so at the tolerance or safe level set by CVM/FDA for drug residues in milk. Possible responses by CVM/FDA include "unqualified acceptance," "acceptance contingent on changes in labeling reflecting accuracy of information and adequate directions for use," "acceptance but with FDA explaining limitations to the expected user (States, milk processor, veterinarian, or milk producer)," and "non-acceptance by CVM/FDA" with reasons provided.
b. "Memorandum of Acceptance"
This memorandum would follow the complete CVM/FDA review and analysis of the application package, data submission, and Institute testing. Possible responses could be those in 5.a. above or "based on the CVM/FDA review of the labeling, directions for use, data submitted by the kit sponsor, and data from Institute testing, CVM/FDA recommends the test kit for use by the (States and milk processors) for monitoring milk for (name of drug)."
C. It is mutually agreed that:
1. This agreement is limited to the evaluation of test kits intended to detect animal drug residues in milk.
2. CVM/FDA does not take any position on any aspect of the Institute's program. The Institute decisions regarding its program are the independent decisions without CVM/FDA involvement.
3. CVM/FDA is not bound by any position the Institute may take as a result of the Institute's evaluation of a test kit. CVM/FDA decisions are independent decisions with the information provided by the Institute as specified in this MOU being considered.
4. The Institute is not bound by any positions CVM/FDA may take as a result of CVM/FDA's evaluation of a test kit. This Institute's decisions are independent with the CVM/FDA input being considered as specified in this MOU.
5. The Institute's granting a test kit a "PERFORMANCE TESTED" status reflects only the Institute's acceptance of the kit. CVM/FDA's acceptance of a test kit is separate and apart from the "PERFORMANCE TESTED" status granted by the Institute.
6. Either party on their own initiative may conduct additional research as it deems appropriate on drug residue test kits for milk. Following a determination that a drug residue test kit for drug residues in milk is not performing in an acceptable manner or if changes are needed in labeling, such will be communicated to the other party for nay action it deems appropriate. CVM/FDA, on its own, may take any action deemed appropriate as to the status of any test kit claimed to detect drug residues in milk.
IV. NAME AND ADDRESSES OF PARTICIPATING AGENCIES
A. AOAC Research Institute
2200 Wilson Boulevard
Arlington, VA 22201-3301
B. Center for Veterinary Medicine
Food and Drug Administration
7500 Standish Place
Rockville, MD 20855
V. LIAISON OFFICERS
A. Liaison Officer for AOAC Research Institute:
Mr. Scott G. Coates
AOAC Research Institute
2200 Wilson Boulevard
Arlington, VA 22201-3301
B. Liaison Officer for Center for Veterinary Medicine:
Dr. Joseph A. Settepani
Center for Veterinary Medicine
Food & Drug Administration
Agricultural Research Center
Beltsville, MD 20705
VI. PERIOD OF AGREEMENT
This agreement becomes effective upon acceptance by both parties and will continue indefinitely. It may be modified by mutual written consent at any time. It may be terminated by either party upon a 30-day advance written notice to the other party at the address listed in Section IV.
Approved and Accepted
Signed by: Scott G. Coates, Manager
Approved and Accepted
Signed by: Ronald G. Chesemore
Date: October 22, 1992