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Pesticide Registration (PR) Notice 96-1: Tolereance Enforcement Methods - Independent Laboratory Validation by Petitioner
Resources
February 7, 1996
Notice To: Manufacturers, Producers, Formulators, and Registrants of Pesticide Products
Attention: Persons Responsible for Federal Registration of Pesticides or Submission of Petitions for Tolerances or Exemptions from Tolerances for Pesticides
Subject: Tolereance Enforcement Methods - Independent Laboratory Validation by Petitioner
Since the issuance of PR Notice 88-5 (7/15/88), EPA scientists have reviewed many Independent Laboratory Validation (ILV) trials and provided guidance on conducting these trials to registrants of pesticide products. This notice is intended to clarify the requirements for submission of an Independent Laboratory Validation to accompany new pesticide analytical methods and does not contain additional data requirements. This notice supersedes PR Notice 88-5.
I. BACKGROUND
The Federal Insecticide, Fungicide, and Rodenticide Act
(FIFRA) requires the registration of all pesticides. If a
proposed use of a pesticide results in residues in or on raw
agricultural commodities or processed foods/feeds, a tolerance
(or an exemption from a tolerance) is required under the Federal
Food, Drug, and Cosmetic Act (FFDCA). Any organization seeking a
tolerance must petition the Agency to establish the tolerance.
EPA regulations in 40 CFR 158.240, 180.7 and 180.34 require
petitioners for pesticide tolerances to furnish adequate residue
analytical methods to determine the total toxic residue for
pesticides in or on raw agricultural commodities, and as
appropriate, in processed foods/feeds. The total toxic residue
includes the parent pesticide and its degradation products,
metabolites (free or bound), and impurities which are of
toxicological concern. These methods enable the Agency to
establish tolerances after determining the maximum pesticide
residues of concern which could be present in or on treated raw
agricultural commodities or processed foods/feeds. The
analytical methods are subsequently used by the Food and Drug
Administration, U.S. Department of Agriculture and individual
States for tolerance enforcement. Guidance on analytical method
data requirements is provided in the Pesticide Assessment
Guidelines (Subdivision O, Reference 171-4). EPA's review of
pesticide petitions for tolerances includes validation of new
methods in EPA laboratories to ensure their suitability for
enforcement purposes. An enforcement method must be suitable for
use in Federal and State laboratories throughout the country.
Moreover, sufficient information must be submitted about the
analytical method to permit a competent analyst to apply it
successfully.
Prior to the issuance of PR Notice 88-5, EPA method
validation trials were often impeded by poorly written and
incomplete descriptions of the analytical procedures submitted by
petitioners. This created delays in evaluating petitions and
unnecessarily tied up Agency laboratory resources while the
methods were rewritten and consultations occurred between EPA
representatives and the method developers. Since the issuance of
PR Notice 88-5, residue analytical methods submitted to the
Agency which require Agency method validation have dramatically
improved. However, the Agency recognizes that some clarification
of the Independent Laboratory Validation trial data requirements
is needed. The intent of this notice is to clarify the
requirements for submission of an Independent Laboratory
Validation trial to accompany new pesticide analytical methods.
II. DISCUSSION
A. When An Independent Laboratory Validation (ILV) Trial Is
Required:
Results of an ILV study must accompany the following types
of submissions:
1. The first tolerance petition (including those for
temporary tolerances) for residues of a pesticide in/on
a raw agricultural commodity, or a processed food/feed.
2. Any new tolerance for residues of a pesticide with
previously established tolerances if a new method is
proposed for enforcement or if the previously approved
enforcement method has been significantly modified to
accommodate the new commodity. If the registrant is
uncertain whether a method change is "significant", the
Agency should be consulted.
B. When An Independent Laboratory Validation (ILV) Trial Is Not
Required:
1. Results of an ILV trial are usually not required for an
enforcement analytical method which the Agency deems
superior to the currently accepted enforcement method.
2. An ILV trial is not normally required for confirmatory
methods. However, at the discretion of the Agency, an
ILV trial may be required for these methods on a case-
by-case basis.
C. Criteria for Selection of Independent Laboratory
The registrant should select an independent laboratory based
on the same performance standards as for any other scientific
project. The laboratory facility chosen to conduct the ILV trial
may be a State enforcement agency laboratory, a university
laboratory, or a privately owned laboratory which may include one
in the registrant's organization. In order to provide an
unbiased evaluation the laboratory chosen to conduct the ILV
trial must not have participated in the development of the
original method and must not use the same equipment, instruments
and supplies. Furthermore, personnel conducting the ILV trial
should not report to a study director who was involved in
development, validation or subsequent use of the method.
D. Requirements for Independent Laboratory Validation Trial
The Independent Laboratory Validation trials must be
conducted under FIFRA Good Laboratory Practice standards as
specified in 40 CFR 160. The method must be performed as
written with no significant modifications. A successful ILV
trial will require adequate results for the total toxic residue
on at least one set of samples. The laboratory conducting the
ILV will be allowed to test up to three sets of samples by the
method on a given commodity. The number of sets is limited to
three in order to provide an impartial evaluation by an analyst
inexperienced with this particular method. If additional
commodities are analyzed by the same method, they will be
considered to be separate ILV trials.
A set of samples consists of two control samples, two control
samples fortified at the proposed tolerance, and two control
samples fortified at the Limit of Quantitation (LOQ). If the
tolerance is proposed at the LOQ, the second fortification level
should be twice the LOQ. At the discretion of the registrant,
one additional fortification at another level may be included in
the set of samples.
The laboratory conducting the ILV trial may contact the
developers or previous users of the method prior to running the
first set of samples; however, all communications must be logged
and reported to EPA. Under no circumstances should personnel
familiar with the method visit the independent laboratory to
observe or offer help. If minor changes are made to the original
method resulting in improved performance as a result of the ILV
trial, a new trial for the amended method will not be necessary.
Any subsequent additions or modifications to the original method
shall be incorporated into the method write-up that is sent to
the EPA for validation.
If tolerances for several commodities are proposed, and one
method is to be used for all of the commodities a rationale for
the selection of the test commodity should be provided. If the
same method is used for both plant and animal commodities, then
separate ILV trials should be run on both plant and animal
matrices. If after three sets, the validation is not successful,
a new method must be submitted for another ILV trial.
An ILV trial will be considered successful if the results of
the study satisfy the requirements in Subdivision O of the
Residue Chemistry Guidelines, i.e., the recovery rates should be
70-120% and interference should be negligible compared to the
proposed tolerance level.
E. Information to be Reported to the Agency
If the ILV trial is successful, the following should be
submitted by the petitioner.
1. Address and contact person for the independent
laboratory.
2. Description of the analytical method.
3. All recovery and control values for all commodities
that were obtained during all ILV trials.
4. Representative chromatograms for all ILV trials
performed.
5. Description of the instruments used and operating
parameters.
6. Description of any problems encountered.
7. Any steps considered critical, i.e., steps where little
variation is allowable or directions must be precisely
followed.
8. The number of person-hours required to complete one set
of samples.
9. The number of calendar days required for one set of
samples.
10. Any contact between the independent laboratory and the
method developers or others familiar with the method,
including the reasons for the contact, any changes in
the method that resulted, and the time of this
communication with respect to the progress of the ILV
trial (i.e. after the first set, during the second set,
etc).
F. The Agency will Continue to Conduct Method Validation
If the Agency determines that the petitioner has submitted a
successful ILV trial, the method will be validated by the Agency.
III. Effective Date
All submissions received by the Agency after 2/7/97 must
include the results of an Independent Laboratory Validation trial
conducted according to this Notice. Submissions received prior
to that date need to adhere to the requirements set forth in PR
Notice 88-5.
IV. For Further Information
Persons wishing further information on this notice may
contact:
Dallas P. Wright, Jr.
U.S. Environmental Protection Agency
Analytical Chemistry Laboratory
Building 306, Room 113, ARC-East
Beltsville, MD 20705
Telephone Number: 301-504-8225
OR
Francis D. Griffith, Jr.
U.S. Environmental Protection Agency
Health Effects Division (7509C)
401 M Street, S.W.
Washington, DC 20460
Telephone Number: 703-305-5826
__________, Director
Office of Pesticide Programs