U. S. Food and Drug Administration
Center for Food Safety and Applied Nutrition
FDA Prime Connection

Milk Monitoring with Antimicrobial Drug Screening Tests
 
 
         MILK MONITORING WITH ANTIMICROBIAL
                DRUG SCREENING TESTS
 
 
 
Under the Public Health Service Act, the Food and Drug Administration
(FDA) and the States administer the Interstate Milk Shippers Program,
a voluntary Federal/State program established to ensure the safety and
wholesomeness of fresh milk in the United States.  Under this program,
the FDA publishes the Grade A Pasteurized Milk Ordinance (PMO), a
model regulation used in voluntary, cooperative interstate milk safety
programs in which all 50 States, the District of Columbia, and Puerto
Rico participate.  The PMO specifically requires that all bulk milk
pickup tankers be tested for the presence of beta-lactam drug residues.
 
Prior to 1991, the PMO recognized only one official test method for
detecting drug residues in milk, the Bacillus stearothermophilus Disc
Assay (BSDA).  Changes to the PMO in 1991 required intensified testing
 of milk for beta-lactam residues and created the need for additional
rapid, reliable screening tests that "have been evaluated through AOAC
and accepted by FDA."  (AOAC International, formerly known as the
Association of Official Analytical Chemists, is a scientific organization
whose primary objective is to validate and improve analytical methods.)
As a result of this change to the PMO, 17 screening tests for beta-lactam
antibiotics, one test for chloramphenicol, and one test for sulfonamide
drugs have been evaluated and accepted by FDA.  These tests are accepted
for the monitoring of truck tanker loads of raw, commingled, bovine milk
in accordance with Appendix N of the PMO and from bulk tank producer
samples in accordance with Section 6 of the PMO.
 
The reliability of these tests to monitor the nation's milk supply has
been questioned by some individuals.  This CVM UPDATE addresses
these issues and clarifies the role of screening tests for monitoring raw
milk.
 
The accepted screening tests have met a standard for a low incidence of
false positive and false negative findings.  Combined with these standards,
there are important principals of use which must be considered.  These
are:
 
     1.   A positive result from a screening test is a presumptive
          indication that an analyte is present in the milk sample.
 
     2    The screening test does not necessarily identify the specific
          analyte causing the test to be positive nor does it measure the
          quantity.
     3.   All the accepted tests may produce a positive result when the
          drug concentration is below the tolerance/safe level.  This is a
          false violative result, not a false positive result.
 
     4.   A chemical analysis is required to determine whether or not a
          given milk sample contains antimicrobial drug residues above the
          tolerance/safe level (violative).
 
     5.   Despite their limitations, the accepted tests represent the
          "state of the art" in rapid detection of drug residues in milk.
 
The percentage of truck tankers found positive in 1994 (National Milk
Drug Residue Third Party Data Base) was 0.063 percent.  This low
incidence of positive truck tankers supports our standard for selectivity
(false positive test result).  Further, this low incidence also demonstrates
that the majority of the milk producers are using drugs in a responsible
manner.  The FDA has found no evidence which would indicate that the
use of approved beta-lactam drugs in accordance with label directions will
cause a violative or non-violative residue in a truck tanker.  The FDA has
concluded that despite the inherent limitations of screening  tests, the issue
remains one of proper drug use.  The FDA believes the use of the
accepted tests under the provisions of Appendix N, PMO, has reduced the
amount of positive milk entering the food supply.
 
The FDA recognizes the economic losses to the milk producer which
would result from false violative and false positive test results.  With this
issue in mind, the NCIMS and the FDA agreed to retest all original
positive truck tanker samples using the same test when the initial test is
conducted  by an industry analyst.  Only after the results from retesting
indicate a positive finding is a truck tanker rejected.  Retesting increases
the probability of acceptance of a non-violative milk tanker and decreases
the number of non-violative truck tanker rejections.  The FDA must also
be concerned with the incidence of false negative results to ensure the
public health.
 
The low incidence of positive truck tanker results do not appear to be
caused by unreliable tests.  Based on reports from the States, the FDA
has concluded that misuse of animal drugs is the cause of most positive
test results from truck tanker testing even when residue concentrations are
below the tolerance/safe level.  The FDA has found no evidence which
indicates that treating lactating cows in accordance with labeled directions
will cause a positive truck tanker.  The follow-up by the State regulatory
agencies on positive truck tankers indicates that the positive test results are
primarily the result of misuse of animal drugs.
 
It has been suggested by some individuals that testing under the
provisions of Appendix N, PMO, with the FDA and NCIMS accepted
screening tests be discontinued.  The FDA takes the position that
discontinuing tanker truck testing is not consistent with a commitment to a
safe milk supply, and therefore would be unacceptable to the Agency.
Prior to the implementation of Appendix N, PMO, the Government
accounting Office concluded that there was no comprehensive strategy to
ensure the safety of the milk supply.  The State regulatory agencies and
FDA are committed to maintaining  a safe milk supply and have
developed a comprehensive strategy for ensuring a safe milk supply.  The
strategy adopted by FDA and NCIMS includes monitoring of truck tankers
in accordance with Appendix N, PMO, monitoring producer bulk tanks in
accordance with Section 6, PMO, participation in the ten point Milk and
Dairy Beef Quality Assurance Program in the event of a violation,
monitoring the use and labeling of drugs through the PMO Farm
Inspection Program, and individual cow testing.
 
Although research indicates that some screening tests may produce false
positive test results in milk from individual cows, the FDA is not aware of
any data which supports the conclusion that unique factors in the milk
from individual cows produce false positive findings in truck tanker milk
samples.  The FDA maintains the view that the misuse of animal drugs
causes a majority of screening test  positives at the truck tanker.  Despite
the inherent limitations of screening tests, the issue remains one of proper
drug use.
 
No screening test has been evaluated by the Center for Veterinary
Medicine or the AOAC International Research Institute for use on milk
from individual cows.  Nine of the currently accepted tests for testing
truck tanker milk are being evaluated for this use.
 
FDA has prepared a document entitled "Evaluation and Use of Milk and
Antimicrobial Drug Screening Tests" which provides a detailed discussion
of the evaluation and use of the screening tests as well as related issues
regarding the monitoring for animal drug residues in milk.  Copies of this
document  are available by calling CVM's Communications and Education
Branch on (301) 594-1755 or by writing to Communications and
Education Branch, HFV-12, CVM/FDA, 7500 Standish Place, Rockville,
MD 20855.  Comments or questions on this issue may be addressed to
Dr. Norris E. Alderson, HFV-500, CVM/FDA, 7500 Standish Place,
Rockville, MD  20855.  Phone 301-594-1702; email
alderson@a1.cvm.fda.gov.