The US Food and Drug Administration (FDA) released a new proposed regulation on Wednesday, 25 January that aims to provide a stable pathway for persons requesting the import of food items containing residues of animal drugs that are unapproved in the US.
The proposed regulation - Import Tolerances for Residues of Unapproved New Animal Drugs in Food - is the final outstanding action FDA needs to take to fully implement the Animal Drug Availability Act of 1996 (ADAA). The law stipulated that the Commissioner of the FDA may establish a tolerance for imported animal drug residues present in food products if the manufacturer has submitted sufficient data showing that the drug is safe.
Any drug residue found in a food product for a drug that has not been approved in the US is grounds for declaring the food product adulterated under the Food, Drug and Cosmetic Act (FD&C Act). Under the ADAA, residue is defined as "any compound present in edible tissues that results from the use of a drug, and includes the drug, its metabolites, and any other substance formed in or on food because of the drug's use."
It should be noted that establishing an import tolerance-"a tolerance for a residue of a new animal drug not approved or conditionally approved for use in the US, but present in any imported edible portion of any animal"-for the animal drug residue does not confer any legal protections for the use of the drug in the US. The drug must undergo the New Animal Drug Approval process in order to receive marketing access.
Currently, New Animal Drug tolerances are determined after a sponsor submits a New Animal Drug Application (NADA) and, after being shown to be safe and effective for its prescribed application, shows the drug product to be safe for consumption in humans if the drug is likely to be used in food animals.
To do this, FDA sets drug residue tolerances by requiring the applicant to furnish evidence "demonstrating that the residues of the new animal drug in the edible products of treated animals are safe." This involves conducting studies, including toxicity studies, residue chemistry studies and microbial studies, depending on the nature of the product.
Acceptable Daily Intake (ADI) levels should be determined by the toxicology studies, the maximum residue level (MRL) tolerance should be determined by the residue chemistry studies, and the effects (if any) of the drug on antimicrobial resistance should be assessed by the antimicrobial studies.
The proposed regulation establishes ways to submit, amend or revoke an import tolerance application.
Further, FDA is working to harmonize its import tolerances with the Codex Alimentatius Commisssion of the Joint Food and Agriculture Organization, World Health Organization and Food Standards Program.
If the product seeking an import tolerance has a permanent Codex MRL, the product is eligible to be reviewed by FDA, which will determine if the Codex MRL information is sufficient or if more information is necessary to determine the safety of the product for human consumption.
If the product does not have a permanent listing in the Codex Alimentatius, then FDA may require complete toxicology, residue chemistry and/or microbial studies. Data submitted to the regulatory authority that originally approved the drug in the food product's country of origin should also be included.
FDA will consider a variety of conditions when evaluating the safety of the residue, including dose, duration, formulation, uptake, metabolism and distribution of the residue.
Requesting an Import Tolerance
Any person may request that FDA establish or amend an import tolerance by using a form specific in proposed FDA&C Act section 510.205, and the Commissioner may act on his or her own accord to initiate such proceedings under 21 CFR 10.25(b).
The request must include the established name of the drug, all pertinent drug information, the properties of the drug (biological, chemical, physical, etc.), the route of administration, dosage, drug labeling, a list of which countries have approved the drug, the proposed import tolerances for the drug, human food safety information to support the proposed import tolerance(s) and the description of the validated method for measuring the residue level.
The application must show that the drug's proposed tolerance is safe. This may be done by adhering closely to existing criteria used under the New Animal Drug regulations present in FD&C Act section 512(b)(1).
If a Codex MRL has been established, then the applicant should include the Codex's monograph in the application.
Applications that fail to submit full reports required to establish the safety of the residue will be regarded as incomplete. Further, an applicant must obtain written approval if the applicant wishes to refer to nonpublic information that they do not have the right of reference to. Applications using material submitted to a foreign regulatory authority that were composed in a foreign language must submit both the original document and an accurately translated version to FDA.
Applicants are further required to sign and date the application and furnish an address of the applicant and/or an authorized agent that resides in the US.
Applicants are also required to submit an environmental assessment as described under 21 CFR 25.40 to show that the residue will have no discernable impact on the environment.
Revoking, Withdrawing or Delaying an Import Tolerance Application
An applicant may withdraw or amend the import tolerance application at any time in advance of FDA's public decision making. All information submitted to FDA-with the exception of proprietary information or trade secrets-shall be made available for public disclosure.
Import tolerances that are later found to be unsafe or exceeding the agreed-upon tolerance for food products may be revoked and the ground for revocation made public by FDA.
Applicants may petition FDA for reconsideration of the agency's action so long as the petition is received no more than 30 days after public notification of the decision. The application is also subject to petitions to stay or extend the effective date for the import tolerance.
FDA notes that the proposed rule "will provide a more efficient method for the submission of requests to establish import tolerances since the regulation would set forth the information required to be submitted in such a request."
Comments on the proposed rule must be received by 24 April, 2012.