PRN 96-1: Tolerance Enforcement Methods - Independent Laboratory Validation by Petitioner
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: Tolerance 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.
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.
- When An Independent Laboratory Validation (ILV) Trial Is Required:
Results of an ILV study must accompany the following types of submissions:
- 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.
- 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.
- When An Independent Laboratory Validation (ILV) Trial Is Not Required:
- 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.
- 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.
- 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.
- 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.
- Information to be Reported To The Agency
If the ILV trial is successful, the following should be submitted by the petitioner.
- Address and contact person for the independent laboratory.
- Description of the analytical method.
- All recovery and control values for all commodities that were obtained during all ILV trials.
- Representative chromatograms for all ILV trials performed.
- Description of the instruments used and operating parameters.
- Description of any problems encountered.
- Any steps considered critical, i.e., steps where little variation is allowable or directions must be precisely followed.
- The number of person-hours required to complete one set of samples.
- The number of calendar days required for one set of samples.
- 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).
- 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.
- When An Independent Laboratory Validation (ILV) Trial Is Required:
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.
For Further Information
Persons wishing further information on this notice may contact:
U.S. Environmental Protection Agency
Analytical Chemistry Branch
701 Maples Rd.
Ft. Meade, MD 20755
Telephone Number: (410) 305-2636