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Federal Register / Vol. 86, No. 180 / Tuesday, September 21, 2021 / Rules and Regulations consumption. The Agency will use similar criteria as for the approval of NADAs in making its determinations, including any other information the Commissioner deems necessary to assure safe and effective use. See section 512d1D of the FD&C Act. Similarly, the Agency must ensure that a request for a particular import tolerance includes all the relevant information needed to make an appropriate human food safety determination. For example, the requester may not have submitted enough information for FDA to adequately assess the toxicity of the new animal drug or the requester may not have provided enough detail about the proposed analytical method. The information requested will not be ad hoc because it must be relevant to the criteria and review standards for human food safety, which are the same for approval of new animal drugs and establishment of import tolerances.
Comment 11 One comment asks whether the Agency employs analysts to verify the accuracy of translations of materials submitted in a foreign language.
Response 11 The Agency will rely on the requesters assertion that it is submitting a complete and accurate translation of any materials submitted in a foreign language. As provided for in 18 U.S.C. 1001, any person, in any matter within the jurisdiction of the Agency, who knowingly and willfully falsifies, conceals, or covers up by any trick, scheme, or device a material fact;
makes any materially false, fictitious, or fraudulent statement or representation;
or makes or uses any false writing or document knowing the same to contain any materially false, fictitious, or fraudulent statement or entry, may be subject to criminal fines or imprisonment.
Comment 12 One comment requests that electronic submission of import tolerance request dossiers be an option.
There should be no need for paper submissions.
Response 12 We agree that electronic submission of import tolerance requests should be an option and are providing for electronic submission of requests in 510.105b of this final rule. At present, the Center for Veterinary Medicine CVM Office of New Animal Drug Evaluation ONADE
can receive and process electronic submissions for import tolerance files.
Submissions to CVM can be made after first registering with FDAs Electronic Submissions Gateway ESG and CVMs Electronic Submission System.
Additional information and a user guide on eSubmitter can be obtained at either the CVM eSubmitter Resource Center
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website or the Getting Started with eSubmitter website. Contact ESGHelpDEsk@fda.hhs.gov for help with the ESG or cvmesubmitter@
fda.hhs.gov for help using CVMs eSubmitter tool.
Comment 13 Several comments question how FDA will evaluate an established acceptable daily intake ADI, especially considering different food consumption patterns of different countries. Comments also question whether FDA considers subpopulations, such as children and immunecompromised people who may be particularly sensitive to the effects of exposure to drug residues. Comments express concerns that safety standards are being loosened and unsafe residues will be allowed in foods.
Response 13 The ADI established for residues of an unapproved new animal drug in edible tissues of food-producing animals that is used in evaluating an import tolerance request is based on the same toxicity data and information as is used to establish an ADI for a domestically approved new animal drug and is evaluated using the same standards and methodology that is used for a domestic drug approval. The toxicity data that FDA uses to determine the ADI are described in guidances available on our website https
www.fda.gov/animal-veterinary/
guidance-industry/human-food-safetyguidances. The guidances for toxicology studies are documents that are internationally harmonized through the International Cooperation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products VICH
Expert Working Groups. The ADI, expressed in a micrograms or milligrams of the new animal drug per kilogram of body weight per day mg/kg bw/day or mg/kg bw/day, is the amount of drug residue that can be consumed on a daily basis for up to a lifetime without adverse effects or harm to the health of a consumer.
The ADI is meant to be applied to a general population, including sensitive subpopulations. The ADI determination uses conservative procedures to ensure that the final value is protective of a general population, such as application of a safety factor to account for human variability in sensitivity to the toxicity of the new animal drug, and tests for specific subpopulations if needed asthmatic persons, allergic persons, etc.. Additionally, the application of the ADI to safe concentrations of the drug residues in edible tissues uses a lower average human body weight 60
kg and conservative estimates of food consumption, such as a high milk
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consumption factor of 1.5 liter per day.
Therefore, the Agency believes using the same methodology to calculate ADI for import tolerances as U.S.-approved animal drugs is appropriate.
Comment 14 One comment states that the rule should explicitly prohibit the setting of import tolerances for residues of new animal drugs that induce cancer when ingested by humans or animals.
Response 14 We disagree that the rule should explicitly prohibit the Agency from considering new animal drugs of carcinogenic concern new animal drugs that induce cancer when ingested by people or animals. Section 512a6 of the FD&C Act provides FDA
the authority to consider requests to establish import tolerances using food safety criteria similar to those that are applied to the approval of new animal drugs. Under section 512d1I of the FD&C Act, the Agency may approve NADAs for drugs of carcinogenic concern as long as the compound does not adversely affect the animals and no residue of a carcinogenic compound will be found in food produced from those animals. Pursuant to section 512a6 of the FD&C Act, FDA will consider requests for import tolerances for animal drugs of carcinogenic concern using similar food safety criteria as it would for a new animal drug application for approval. Thus, if FDA determines that a new animal drug for which an import tolerance request has been submitted is a new animal drug of carcinogenic concern, the requester will be directed to comply with the no residue requirements of 500.80 through 500.92 21 CFR part 500, subpart E, Regulation of Carcinogenic Compounds Used in FoodProducing Animals. Any regulatory method for ascertaining the marker residue in the target tissue will be made publicly available pursuant to 510.207b of the final rule. We have revised 510.205e and 510.207b of the final rule and made conforming changes to 500.80, 500.82, 500.88, and 500.92 to clarify the process for evaluating a new animal drug of carcinogenic concern under these circumstances.
Comment 15 One comment states that the rule should specifically prohibit the setting of import tolerances for antimicrobial animal drugs that are in the same classes as drugs used in human medicine.
Response 15 We disagree. Rather than declining to establish import tolerances for residues of antimicrobial new animal drugs that are in the same classes as drugs used in human medicine, we intend to apply the same
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