Animal & Veterinary
FDA Issues Drug “Indexing” Proposal Under MUMS
FDA Veterinarian Newsletter 2006 Volume XXI, No III
The Food and Drug Administration (FDA) has proposed a rule for placing drugs for minor species in an “index” that allows companies to legally market new animal drugs without developing a standard new animal drug application.
FDA proposed the rule under the Minor Use and Minor Species Animal Health Act of 2004. In passing the legislation, Congress recognized a need for limited-demand drugs that was not being met because animal drug sponsors could not expect returns from the market sufficient to pay the cost of the application process.
The indexing proposal would permit drug companies to legally market unapproved new animal drugs. The drug requestor and FDA would use a panel of outside experts for advice in determining whether a product is safe and effective for its intended uses.
The indexing rule would apply to drugs for non-food minor species, except in some cases in which a drug could be used for early life stages of food animals (e.g., fish eggs, oyster spat). Drugs for minor uses in major species cannot be included in the index. (Major species are dogs, cats, horses, cattle, pigs, turkeys and chickens.)
The rule will primarily help drug manufacturers legally market drugs sold in pet stores and drugs intended for use in wildlife and zoo animals.
Under the proposed rule, a drug sponsor would ask FDA to determine if a drug is eligible for addition to the index. The drug sponsor (requestor) would provide information about the intended use of the drug, the species to be treated, and conditions of use—dosage, route of administration, warnings, contraindications, or other significant limitations.
The requestor would be required to supply information on the need for the drug, and provide an estimate of expected annual distribution. The statute requires that the labeling of a new animal drug that is the subject of an index listing state: “NOT APPROVED BY FDA Legally marketed as an FDA indexed product. Extra-label use is prohibited.”
FDA will not accept index requests for products contained in, or that are the product of, transgenic animals. And FDA will not accept an index request for the same drug, dosage form, and intended use as a product that is already approved or conditionally approved.
The request for a determination of eligibility for indexing must include information to establish that the intended use of the product will pose no food safety hazard as well as information supporting either an environmental assessment or a categorical exclusion from an assessment.
Under the indexing proposal, FDA would ease the requirements for information about a drug’s chemistry and manufacturing processes. With a traditional application, the drug sponsor must provide a “full description” of the production process. Under the indexing proposal, the requestor would submit only a comprehensive summary of the manufacturing process that demonstrates that the requestor understands current Good Manufacturing Practice requirements and has established appropriate manufacturing specifications.
FDA is required to respond to requests for determination of eligibility for indexing within 90 days for drugs for non-food species, and within 180 days for requests for early-life-stage food-producing animals.
Expert panel review
If FDA determines that a product is eligible for indexing, the next step is an evaluation by an external panel of experts of the requestor’s target animal safety and effectiveness information to determine if that information is sufficient to permit the product to be added to the index list.
The requestor would propose individuals to serve on the panel, who have appropriate scientific training and experience to review safety and effectiveness information about the drug submitted for inclusion in the index. FDA would review the qualifications of the proposed panel members and could accept, reject proposed or suggest alternative members.
The panel members must be free of any conflict of interest or even the appearance of one.
The panel will draft a report evaluating the drug’s target animal safety and effectiveness, and stating the panel’s opinion regarding whether the benefit of allowing the drug on the market outweighs the potential risk to the target animal, taking into account the harm associated with not permitting legal access to the drug.
If the panel supports the drug’s inclusion in the index, the panel will either provide draft labeling for the product, including all conditions of use that the experts think are needed to assure that the product’s benefit outweighs the risk, or provide narrative information about what the requestor should put on the label.
FDA will decide, after reviewing the report, whether to add the product to the index.
If FDA decides not to index the drug based on deficiencies in the panel report or product labeling, the requestor can submit a second request addressing any shortcomings FDA cited in the initial request, using acceptable information from the first request. Alternatively, the requestor can ask FDA for an informal conference to have the Agency reconsider its denial based on the evidence already available. If FDA’s decision is still to deny the request, that denial constitutes the Agency’s final action in the matter pending the submission of further information from the requestor.
Once a product has been added to the index, the holder of an index listing can modify labeling to add cautionary information. Also, if FDA agrees, the holder can request modification to the Index or the label, to add new intended uses or species, or change the active ingredients or concentration of the active ingredient.
The holder of an index listing must report serious product defects to the Agency within three days, and serious and unexpected adverse drug reactions within 15 days. A holder must also file annual reports that describe the amounts of drug marketed, identify minor changes to the formulation or manufacturing process, and describe adverse drug experiences not already reported.
FDA can suspend an index listing if it identifies a reasonable probability of health risk to humans or animals. FDA also can partially remove a listing if, for instance, the drug creates problems for some of the species originally included on the label.