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U.S. Department of Health and Human Services

Animal & Veterinary

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Leveraging Examples in CVM – Part V: Interagency Agreements

by David B. Batson, Ph.D.
FDA Veterinarian Newsletter May/June 2003 Volume XVIII, No 3

Introduction

This is the fifth in a series of articles on leveraging activities in FDA’s Center for Veterinary Medicine (CVM). This article will define interagency agreements, when they can be used and how these agreements can be used as leveraging tools for addressing important research/regulatory questions facing the Center.

The purpose of an interagency agreement is to provide a mechanism for project collaboration and the transfer of funds between two Federal agencies. This agreement involves collaboration to eliminate duplication of effort and extend overall consumer protection through use of the collective resources. It could also involve sharing knowledge, personnel, property, facilities and equipment that would strengthen programs of mutual concern in the public interest. If FDA receives funds from and provides services to another agency this collaborative arrangement is referred to as a reimbursable interagency agreement. Before an agreement is signed by FDA, it may have to be cleared, depending on the subject matter, through (1) the Research Involving Human Subjects Committee, (2) the Associate Commissioner for Regulatory Affairs, (3) the Office of Resources Information Management, (4) the Office of Planning and Evaluation, (5) the Office of Human Resources and Management Services and/or the Institutional Animal Care and Use Committee. The clearances are the responsibility of the sponsoring FDA office. The sponsoring office is also responsible for the scientific peer review of the data from these scientific research efforts.

The FDA has been involved in highly successful interagency agreements with agencies such as the United States Department of Agriculture (USDA), the Centers for Disease Control and Prevention (CDC), the Veterans Administration, the U. S. Army, and the U.S. Geological Survey. Examples of these agreements are described below.

National Antimicrobial Resistance Monitoring System

The National Antimicrobial Resistance Monitoring System (NARMS) was established in 1996 as a collaborative effort among three Federal agencies, FDA, USDA, and CDC. The NARMS program monitors changes in susceptibilities of human and animal enteric bacteria to 17 antimicrobial drugs.

Bacterial isolates are collected from human and animal clinical specimens, from healthy farm animals, and from the raw products of food-producing animals. The objectives of the program include: (1) provide descriptive data on the extent and temporal trends of antimicrobial susceptibility in Salmonella and other enteric organisms from human and animal populations, (2) facilitate the identification of resistance in humans and animals as it arises, and (3) provide timely information to veterinarians and physicians. The ultimate goal of this program is to prolong the lifespan of approved drugs by promoting prudent and judicious use of antimicrobial drugs and to identify areas for more detailed investigation.

NARMS is composed of two separate components for testing the susceptibility of animal and human isolates. These isolates are submitted by 17 State and local Departments of Health to either CDC or USDA. Isolates derived from human patients are submitted for testing to CDC, Atlanta, Georgia. Bacterial isolates of animal parts are submitted for testing to USDA, Athens, Georgia. Animal and human isolates currently monitored in NARMS are non-typhoid Salmonella, Campylobacter, E. coli, and Enterococci. In addition, human isolates are monitored for Salmonella typhi, Shigella Spp., Listeria monocytogenes and Vibrio Spp. Additional information on the NARMS program is available.

Use of Tissue Fluid Correlations to Predict Drug Residue Levels in Edible Tissues from Food Producing Animals

In 2001 FDA entered into a reimbursable interagency agreement with USDA’s Food Safety and Inspection Service (FSIS) (1) to investigate the correlation of drug levels in biologic fluids such as urine, saliva or blood, with residues that are present in edible tissues, e.g., meat, liver or kidney, (2) to develop and validate physiologic models to enable food safety personnel to accurately predict, prior to slaughter, whether a particular animal has tissue drug residues which are violative of the approved tolerances, and (3) to develop these models by correlating drug levels in some easily sampled biologic fluids, e.g., urine, saliva or blood, with drug residues that are present in edible tissues. These models may also be useful for back extrapolating an estimate of the dose administered and the time of administration based on a measured concentration in tissue.

The testing for drug residues in tissues from food producing animals normally occurs after slaughter. As a result, edible tissues with residues that exceed tolerance are declared adulterated and must be destroyed. The analytical methods used to measure these residues in tissues are time-consuming to perform and less than 1% of the slaughtered animals are monitored for drug residues. This approach is inefficient and economically costly for both consumers and producers, and does not provide assurance of optimal food safety. The use of rapid, inexpensive preslaughter screening tests, similar to those used for milk, based on detection of drug residues in some easily obtainable biological fluid (saliva, plasma or urine) would enable monitoring of more animals and help ensure greater food safety. Preslaughter testing also allows animals with violative residues to be held back until such time as drug residues deplete to safe levels by normal routes of excretion.

The pharmacokinetics of a number of agents are characterized by tissue distribution studies and subsequent physiologically based modeling. These models are useful in predicting tissue levels at certain times after initial or multiple dosages. By evaluating the relationship between drug administration, tissue uptake, and, more importantly, tissue elimination, one can better predict if an animal is likely to have tissue residues which exceed tolerances. The investigators will assess the tissue exposure by developing physiologically based pharmacokinetic flow models characterizing tissue distribution and elimination of the test agents. In addition to providing insight on tissue distribution and disposition, these physiological flow models can also assist in extrapolating results in one animal species to another. For additional information on this study please contact Keesla Moulton, Ph. (301) 827-8054.

Real-Time Monitoring for Toxicity Caused by Harmful Algal Blooms and Other Water Quality Perturbations

FDA entered into a reimbursable interagency agreement with the U.S. Army at Fort Detrick, MD, in collaboration with the University of Maryland, in 1999 to provide the public and public officials with real-time information on developing toxic conditions in ambient water that may be caused by harmful algal blooms or other sources of water quality degradation. Such information is quite valuable for protecting the public from direct exposure to toxins in the water as well as an early warning system for bioaccumulation of toxin. The objective was accomplished through the use of an automated biomonitoring system that tracks the ventilatory and movement patterns of fish.

Harmful algal blooms, including those associated with toxicity, have been increasing in frequency, intensity, and severity in U.S. coastal areas. Recently, the Mid-Atlantic region has experienced blooms of Pfiesteria and Pfiesteria-like organisms leading to fish kills that have damaged local fisheries and to concerns about potential effects on people exposed while engaged in sport or commercial fishing, swimming, or other water-related recreational activities. The risks of consuming exposed fish are currently unknown but are of concern due to the fact that numerous other dinoflagellate toxins accumulate in the food chain. Unfortunately, the public and environmental decision-makers may not learn that an algae-related fish kill is underway until large numbers of dead or dying fish are observed, so the availability of early warning information on developing toxic conditions in susceptible waters is critical. The information generated by this project was beneficial to FDA by providing insight into the monitoring for algal blooms. Since many of these cause foodborne toxicity, such a monitoring system is quite valuable. In addition, the data benefits commercial fisheries, recreation industries, and the general public. Health and environment officials can use these data, in real time, to advise these sectors on the safety of waters in terms of potential exposures to harmful algal blooms. Additional information may be obtained by contacting Dr. Renate Reimschuessel (Ph. 301-827-8025).

Concluding Comments

The collaborations formed through these projects allowed the Center to leverage and expand its on-going program by partnering with outside organizations, including other Federal agencies. These collaborations permit the Center to utilize outside scientific expertise, facilities, and equipment to address regulatory and research questions before the Center. Although these particular projects were between FDA and other government agencies, it is possible for individuals and organizations outside of the government to submit proposals based upon projects consistent with the mission of CVM. Therefore, if you have questions on any of the Center’s interagency agreement projects, leveraging in general, or if you have an interest in initiating a collaboration with FDA’s Center for Veterinary Medicine please contact David Batson at (301) 827-8021 or David Lynch at (301) 827-5337.

The next and final installment in this series will be titled “Where Do We Go From Here?” This final article will provide suggestions on the development of collaborative research ideas and subsequent steps for initiating new leveraging opportunities with the FDA.

Dr. Batson is a Health Scientist Administrator in CVM’s Office of Research.

CVM Warns of Dioxin in Mineral Mixes

FDA is alerting firms manufacturing mineral mixes and mineral premixes for use in animal feed that minerals that are by-products or co-products of industrial metal production may contain dioxin.

Recently, FDA found that some of these by-products or co-products contained high levels of dioxin. In March 2002, FDA requested a recall of chelated minerals and mineral premixes because of high levels of dioxin. In the 2002 case, the source of the dioxins was related to the high temperature process used in making the chelated minerals. The Agency believes that in the current case the process used to produce brass resulted in the dioxin contamination of zinc oxide. FDA will be actively checking these and similar products for dioxin.

Dioxins are ubiquitous, low level environmental contaminants. With cumulative exposure, they are potential carcinogens and may cause reproductive or developmental health problems. Environmental sources of dioxin pollution have been markedly reduced over the past decade. The result has been a significant reduction in overall dioxin exposure to the public. Presently, the primary source of human exposure to dioxins is through food.

Earlier this year, FDA’s food and feed surveillance programs detected elevated levels of dioxin in a feed and traced the dioxin to a mineral component of that feed. The implicated zinc oxide and zinc oxide premixes that were used in livestock, aquaculture, and poultry feed contained extremely high levels of dioxin. A recall of these products and feed containing the zinc oxide has been implemented. An additional mineral component (copper oxide) is also being investigated as a possible source of dioxin. Both mineral components currently under investigation are reclamation products from industrial metal production.

FDA’s public health objective is to reduce the level of exposure to dioxin in the animal and human foods by finding and stopping sources of added dioxin from entering the food supply. To further reduce public exposure to dioxins, FDA will continue its food and feed surveillance programs, and continue investigating whether other products from industrial metal production that are used as feed ingredients are a source of dioxin.

Firms or individuals that have questions about this subject may contact Ms. Gloria Dunnavan, Division of Compliance, Center for Veterinary Medicine at 301-827-1168.