Source: http://www.govpulse.us/entries/2007/12/06/E7-23580/index-of-legally-marketed-unapproved-new-animal-drugs-for-minor-species
Timestamp: 2015-02-27 21:08:40
Document Index: 723862938

Matched Legal Cases: ['§ 516', '§ 516', 'art 25', 'art 25', '§ 25', '§ 25', '§ 25', 'art 207', 'art 207', '§ 207', 'art 207', '§ 207', '§ 207', '§ 516', '§ 516', '§ 516', '§ 516', 'art 12', '§ 516', 'art 12', '§ 516', 'art 16', '§ 516', '§ 516', 'arts 201', 'arts 201', 'art 201', 'art 201', '§ 201', '§ 201', '§ 201', 'art 202', '§ 202', 'art 207', 'art 207', 'art 207', '§ 207', 'art 207', 'art 510', 'art 510', '§ 510', '§ 510', '§ 510', '§ 516', '§ 516', '§ 530', 'art 530', '§ 201', '§ 202', '§ 558', '§ 558']

govpulse | Index of Legally Marketed Unapproved New Animal Drugs for Minor Species
The Minor Use and Minor Species Animal Health Act of 2004 (MUMS act) amended the Federal Food, Drug, and Cosmetic Act (the act) to authorize the U.S. Food and Drug Administration (FDA, the agency) to establish new regulatory procedures that provide incentives intended to make more drugs legally available to veterinarians and animal owners for the treatment of minor animal species and uncommon diseases in major animal species. At this time, FDA is issuing final regulations to implement section 572 of the act entitled “Index of Legally Marketed Unapproved New Animal Drugs for Minor Species.” These regulations establish administrative procedures and criteria for index listing a new animal drug for use in a minor species. Such indexing provides a basis for legally marketing an unapproved new animal drug intended for use in a minor species.
II. Major Changes to the Proposed Rule
IV. Conforming Changes
B. Comments on Proposed Rule
E. Costs to Government
F. Regulatory Flexibility Analysis
1. Small Business Impacts
This rule is effective February 19, 2008.
Bernadette Dunham, Center for Veterinary Medicine (HFV-50), Food and Drug Administration, 7519 Standish Pl., Rockville, MD 20855, 240-276-9090, e-mail:Bernadette.Dunham@fda.hhs.gov.
In enacting the MUMS act (Pub. L. 108-282), Congress sought to encourage the development of animal drugs that are currently unavailable to minor species (species other than cattle, horses, swine, chickens, turkeys, dogs, and cats) in the United States or to major species afflicted with uncommon diseases or conditions (minor use). Congress recognized that the markets for drugs intended to treat these species, diseases, or conditions are so small that there are often insufficient economic incentives to motivate sponsors to develop data to support approvals. Further, Congress recognized that some minor species populations are too small or their management systems too diverse to make it practical to conduct traditional studies to demonstrate safety and effectiveness of animal drugs for such uses. As a result of these limitations, sponsors have generally not been willing or able to collect data to support legal marketing of drugs for these species, diseases, or conditions. Consequently, Congress enacted the MUMS act, which amended the Federal Food, Drug, and Cosmetic Act to provide incentives to develop new animal drugs for minor species and minor use, while still ensuring appropriate safeguards for animal and human health.
The major incentives of the MUMS act include the following:
(1) Designation, established by section 573 of the act (21 U.S.C. 360ccc-2), which provides for eligibility for grants and contracts to defray the costs of qualified safety and effectiveness testing expenses and manufacturing expenses incurred in the development of designated new animal drugs. Designation also provides for eligibility for a 7-year period of exclusive marketing rights to enable sponsors to recover costs of drug development without competition. FDA published final regulations implementing the designation provision of the act on July 26, 2007 (72 FR 41010) (the designation final rule).
(2) Conditional approval, established by section 571 of the act (21 U.S.C. 360ccc), which provides for animal drug marketing after all safety and manufacturing components of a new animal drug approval have met the standards of section 512 of the act (21 U.S.C. 360b). For the effectiveness component, a reasonable expectation of effectiveness must be established, after which sponsors have up to 5 years to complete the demonstration of effectiveness by the standards of section 512 of the act and achieve a full approval. Regulations to implement the conditional approval provision will be proposed in the future.
(3) Indexing, established under section 572 of the act (21 U.S.C. 360ccc-1), which provides for the legal marketing of unapproved new animal drugs intended for use in a minor species through an integrated process of agency and expert panel review.
At this time, FDA is issuing final regulations implementing the indexing provisions of the MUMS act. These regulations establish procedures and criteria for index listing a new animal drug for use in a minor species. They describe a process whereby the agency makes a determination regarding the following: (1) The eligibility of a new animal drug, (2) the selection of a qualified expert panel, and (3) the findings of the qualified expert panel.
In the Federal Register of August 22, 2006 (71 FR 48840), FDA issued proposed regulations to implement section 572 of the act (21 U.S.C. 360ccc-1). The proposed rule initially provided for a 90-day public comment period during which the agency received several comments asserting that 90 days was not an adequate amount of time to prepare and submit meaningful comments. In response to this, in the Federal Register of October 2, 2006 (71 FR 57892), FDA extended the comment period allowing an additional 30 days of public comment.
II. Major Changes to the Proposed Rule ↑
After considering public comments FDA has made the following changes to the proposed rule:
In § 516.123, paragraph (b) has been revised to read: “The written notice will include information for scheduling the informal conference and state that a written request for a conference must be made within 60 days of the date FDA sends its notice.” Also, paragraph (c) has been revised to read: “Within 45 days of receiving a request for an informal conference, FDA will schedule and hold the informal conference at a time agreeable to both FDA and the person making the request.”
In § 516.123, proposed paragraphs (j) and (l)(3) have been deleted and paragraph (k) has been revised to read: “The presiding officer will prepare a written report regarding the subject of the informal conference that states and describes the basis for his or her findings. Whenever time permits, the parties to the informal conference will have 30 days to review and comment on the report.”
In section 516.141, paragraph (b)(1) has been revised to read: “A qualified expert panel member must be an expert qualified by training and experience to evaluate a significant aspect of target animal safety or effectiveness of the new animal drug under consideration.”
In addition, FDA has made two technical corrections to the proposed rule. The first one is in part 25 (21 CFR part 25). An amendment to § 25.33 was proposed as a conforming change to add index listed drugs to the list of actions for animal drugs which may be categorically excluded from the preparation of an environmental assessment. However, the agency neglected to propose a corresponding amendment to § 25.20 to also add indexlisted drugs to the list of actions requiring preparation of an environmental assessment. Therefore, this final rule contains a conforming change to § 25.20(m) to correct this omission. The second technical correction is in part 207 (21 CFR part 207). Amendments to §§ 207.21 and 207.35 were proposed as conforming changes to include index listed drugs under the drug registration and listing provisions of part 207. However, the agency neglected to propose a corresponding amendment to § 207.20(c) which describes who must register and submit a drug list. Therefore, this final rule contains a conforming change to § 207.20(c) to correct this omission.
III. Comments ↑
The agency received comments from six organizations on the August 22, 2006, proposal. Comments were received from a trade organization representing new animal drug manufacturers, a trade organization representing pet product manufacturers, an animal feed manufacturer, a professional association representing veterinarians, an aquaculture trade association, and a U.S. Government agency.
All of the comments supported the purpose of the proposed regulations. Four comments generally supported the structure and scope of the proposed regulations. Four comments expressed concern regarding the apparent complexity of the proposed regulations and encouraged the agency to demonstrate considerable flexibility in their implementation. The issue of greatest concern in these four comments involved the formation and functioning of the qualified expert panels proposed in the regulations—particularly the application of the conflict of interest provisions to potential panel members.
The agency understands the time and effort involved in providing comments on the proposed regulations and greatly appreciates this effort. The general issues noted previously, as well as a number of more specific issues raised in the comments, are addressed as follows:
(Comment 1) As noted, four comments expressed considerable concern over the apparent complexity of the process described in the proposed regulations. While most apparently accepted the need for this complexity as a direct consequence of the statutory requirements of section 572 of the statute, these comments uniformly expressed a desire that the agency be as flexible as possible in implementing the potentially more burdensome aspects of the regulations and encouraged the agency to provide as much guidance as possible to potential sponsors regarding their implementation.
(Response) The agency agrees that it should be flexible, to the extent allowable under the law, in implementing the indexing program. In order to further clarify the indexing process and assist requestors and potential requestors, the agency intends to develop guidance documents regarding various parts of the process as soon after finalization of implementing regulations as resources permit.
(Comment 2) One comment stated that the proposed indexing process is overly complex and too similar to the new animal drug approval process. This comment suggested that the proposed process be discarded and replaced with an alternative process that would emphasize general compounds rather than specific drug products.
(Response) The indexing process established by the MUMS act is for drug products rather than general compounds. For example, section 572(c)(1) of the act describes how to make a request for a determination of whether “a new animal drug” may be eligible for indexing. Moreover, that provision requires that the requestor submit information specific to a new animal drug, rather than for general compounds, such as information regarding the components and composition of the new animal drug and a description of the methods, facilities, and controls used for manufacturing the new animal drug. A request for addition to the index under section 572(d)(1) of the act is made “with respect to a new animal drug for which [FDA] has a made a determination of eligibility.” Additionally, in considering a request for eligibility for indexing, the statute requires that the request not involve the same drug in the same dosage form for the same intended use as a drug that is already approved or conditionally approved.
Based on this and similar language in the statute, the agency believes, with respect to the indexing of new animal drugs, that indexing should follow the product-specific model of new animal drug approval.
However, the agency notes that this basic statutory construction does not necessarily preclude information supporting the indexing of one product from being used to support the indexing of other products, provided the information is relevant to such products, and provided the party or parties gathering the information allow its use for that purpose if such information is proprietary.
(Comment 3) Four comments expressed concern about the formation and operation of qualified expert panels and, in particular, the application of the conflict of interest provisions of the regulations.
(Response) The agency is aware of the potential scarcity of experts to serve on some expert panels. It also wants to assure the integrity of this fundamental part of the indexing process, so that the agency can have confidence in the information and recommendations it receives from the expert panel and the public can trust the agency's decisions based on that information and recommendations.
The purpose of obtaining information regarding potential experts is to enable the agency to make an informed judgment, on a case-by-case basis, regarding whether a financial or other interest could impair the person's objectivity in serving on the panel or could create an unfair competitive advantage for a person or organization. Under the proposal, and not changed in the final rule, even if there is an otherwise disqualifying financial interest, FDA has discretion to nonetheless allow the person to serve as a member of the expert panel.
In making its determinations on the subject of conflicts of interest, the agency will be cognizant of both the need to assure the integrity of the expert panel process and the need to attract qualified experts to serve on these panels.
(Comment 4) Three comments suggested that the agency needs to consider the expertise of the entire panel as a whole, and not each panelist individually, when implementing the requirement that a panel be composed of “experts qualified by training and experience to evaluate the safety and effectiveness of the new animal drug under consideration.”
(Response) It is the intention of the agency to consider the expertise of the entire panel as a whole, as suggested in the comment. Proposed § 516.141(b)(5) says that the “panel, as a whole, is qualified by training and experience to evaluate the safety and effectiveness of the new animal drug under consideration.” However, paragraph (b)(1) of the same regulation could be read as requiring that each individual member of a panel must meet this requirement, that is, each member of an expert panel is expected to be qualified to independently assess all aspects of a particular product's target animal safety and effectiveness. This was not the agency's intention and, therefore, the language of § 516.141(b)(1) has been revised to read: “A qualified expertpanel member must be an expert qualified by training and experience to evaluate a significant aspect of target animal safety or effectiveness of the new animal drug under consideration.”
(Comment 5) Two comments suggested that the scope of review of the expert panel might be expanded to include elements of food safety and/or environmental safety.
(Response) The MUMS act clearly established several distinct steps in the review process for indexing new animal drugs. One step is the determination of eligibility for indexing, which involves an evaluation of most of the indexing criteria, including food, user and occupational safety and environmental impacts. This evaluation is to be performed by the agency prior to the formation of a qualified expert panel. After the agency makes its determination regarding eligibility, a subsequent step is the formation and operation of a qualified expert panel. The responsibilities of the expert panel are set forth in section 572(d)(2) of the act: Evaluate and make findings regarding target animal safety and effectiveness; provide information from which labeling can be written; and recommend whether the new animal drug should be over the counter, prescription, or veterinary feed directive.
Given this statutory construction, it would not be feasible or appropriate for the qualified expert panel to review or to comment upon aspects of product safety outside the scope of target animal safety and effectiveness. However, sponsors are free to involve experts, not serving in the capacity of qualified expert panel members, in the preparation of information submitted to the agency in support of a determination of eligibility for indexing.
(Comment 6) Several comments stated that 30 days is not a sufficient amount of time for a sponsor to submit a written response to the denial of a request for determination of eligibility for indexing or a denial of a request for indexing and indicated that this time period should be extended to 90 days.
(Response) While the agency agrees that 30 days may not be an adequate period for a written response to a denial, the agency also notes that the proposed regulation did not explicitly limit a sponsor to 30 days for a written response. Instead, it proposed that a sponsor must inform the agency within 30 days that it wishes to avail itself of the opportunity for an informal conference. Within 30 days of receipt of such a request, the agency would schedule such a conference at a time agreeable to both the agency and the sponsor, and the sponsor would be required to submit a written response at least two weeks prior to the scheduled meeting.
The agency continues to believe that it is appropriate to have a two-step process for scheduling an informal conference. This would involve an initial period of time during which a sponsor must signify their desire to have an informal conference followed by a second period of time during which the conference will actually be scheduled. The agency also continues to believe that it needs to receive the written response from a sponsor a minimum of two weeks prior to an informal conference.
However, the agency has extended the initial period during which sponsors must request an informal conference from 30 days to 60 days to permit sponsors additional time to consider the need for such a conference. The agency has also extended the second period of time during which the agency will schedule a requested informal conference from 30 days to 45 days. With these revisions, a sponsor may take as long as 60 days to request an informal conference, may request that the conference not be held until 45 days after such a request and need not submit the written response in support of the conference until two weeks before the conference. This process will generally permit sponsors to have as much as 90 days to prepare a written response, if they feel they need it.
Accordingly, the language of § 516.123(b) and (c) is revised to read as follows:
(Comment 7) Two comments stated that the language of § 516.123 indicated that informal conferences were, in fact, rather formal and one commentor asked for clarification of the reason for using the term “informal” in this context.
(Response) The statute and the proposed and final regulation use the phrase “informal conference.” The agency believes that the purpose of the statutory use of the term “conference” in section 572 of the act is to be distinct from the term “hearing” which is used in the context of similar denial or withdrawal decisions regarding products involved in the new animal drug approval process under section 512 of the act. The hearing referred to in section 512 of the act has been clarified by regulation to be a formal evidentiary hearing under 21 CFR part 12. The agency believes that the purpose of the statutory use of the word “informal” in section 572 of the act is to draw a further distinction between the formal evidentiary hearing under 512 of the act and the informal conference under section 572.
FDA believes that the process for the informal conference set forth in § 516.123 is appropriately tailored. While much less formal than the part 12 hearings, it still ensures that there is a meaningful opportunity for parties to express their views, a neutral decision maker, and an administrative record for judicial review if the final agency decision is challenged in court. Moreover, by describing the process in a regulation, the parties in the informal conference will have a common understanding of how it will operate, fostering an orderly operation and reducing the potential for disagreements over the process.
(Comment 8) One comment questioned the inclusion of the requirement for an estimation of annual product distribution in proposed § 516.129(c)(6).
(Response) In accordance with section 572(c)(1)(A) of the act, the request for determination of eligibility for indexing must include the anticipated annual distribution of the new animal drug. This information would be useful, for example, in estimating the extent of environmental and user exposure in the process of determining environmental and user safety.
(Comment 9) One comment suggested that requestors of an informal conference have an opportunity to read and respond to the minutes of an informal conference within 30 days.
(Response) This comment raises two issues which the agency needs to address and clarify in the final regulation. The first issue relates to whether the person requesting an informal conference should have the opportunity to review and comment on a summary of the informal conference. The agency believes that the requestor should have such an opportunity. In framing the comment in the context of the “minutes of an informal conference,” the comment also raises an issue regarding what sort of a summary of the informal conference the person requesting an informal conference should have an opportunity to review and comment on. In this context, the agency has reconsidered the requirement in the proposed regulation for the preparation of both a “written summary” of the conference and a“written report” of the conference. The latter was intended to parallel the written report associated with a 21 CFR part 16 informal hearing, and was intended to be more comprehensive than simply a “written summary of the conference” or the “minutes of an informal conference” as expressed in the comment. The agency believes that the requestor of an informal conference should have an opportunity to review and comment on the written report of the informal conference. We have revised § 516.123(k) to provide for such a review whenever time permits. That being the case, the agency believes that a written summary of the informal conference is superfluous and this requirement, which was proposed by means of §§ 516.123(j) and 516.123(l)(3), has been removed from the final regulation.
(Comment 10) Two comments requested clarification of different aspects of the early, non-food life-stage provision of the proposed regulations.
(Response) As stated in the preamble to the proposed regulations, the early, non-food life-stage provision of the statute and implementing regulations will be applicable only in limited circumstances, and the safety of food eventually derived from such animals will be determined in accordance with the safety standards of 512(d) of the act.
The agency has currently identified only early, non-food life stages of some aquatic species, such as certain fish eggs and mollusc larvae, as likely to be able to meet this standard. There is no explicit statutory restriction of this provision to aquatic minor species, although the statutory restriction to products intended only for use in a hatchery, tank, pond or other similar contained man-made structure tends to exclude terrestrial species. The agency has yet to identify a terrestrial species that it feels is likely to qualify under this provision of the statute, but has not ruled out the possibility that some terrestrial minor species could qualify.
The agency is unable at this time to establish any general criteria regarding ages, sizes, amount of time between early, non-food life stages and later food life stages, or biological developmental processes that can predict the applicability of this provision of the act. Nor is the agency able to make any general statements regarding how much information of what sort will be necessary to meet the requirements of 512(d) of the statute. These issues depend upon the drug and the minor species involved in each particular case.
(Comment 11) One comment asserted that the revenue to be expected from some segments of the minor species market may not justify the estimated administrative costs for indexing cited in the proposed rule. The comment is concerned with needed medicated feeds, especially for zoo and laboratory animals. The comment proposes that an “exemption” should be provided in cases where sales will not offset these costs. Specifically, the comment suggests that a threshold sales level should be set ($100,000 is recommended) above which indexing would be required, but below which an expanded policy of regulatory discretion would be provided.
The comment also notes that the inability to alter the nutrition and physical form of an approved medicated feed to suit use in a minor species limits the utility of the existing regulatory discretion policy (Compliance Policy Guide (CPG) 615.115) for the extra-label use of medicated feed in minor species. Therefore, it is suggested that a new policy of regulatory discretion based on customer formulated feeds be incorporated into the MUMS indexing rule for the intended uses that fall below the proposed sales threshold.
(Response) The lack of medicated feeds legally available to minor species is recognized by the agency. The Animal Medicinal Drug Use Clarification Act of 1994 (AMDUCA) (Pub. L. 103-396) provides for certain extra-label uses of new animal drugs by veterinarians, but specifically prohibits extra-label use of medicated feeds. The CPG is intended to be a limited exercise of regulatory discretion regarding access to needed medicated feeds for some minor species. The indexing provision was included in the MUMS act partly to address this concern. It is intended to provide legal means for sponsors to provide these much-needed formulations to non-food minor species animals, like the zoo species cited in this comment. The agency recognizes that indexing will not provide for the legal availability of drugs for minor species under all circumstances. However, the exercise of regulatory discretion does not provide legal access under any circumstances.
The administrative cost of indexing, as cited in the proposed rule, is an estimate of the average cost of indexing a new animal drug. The enormous variety of species and products will be reflected in the range of complexity of indexing these products. Variables such as the number of species to be included in the intended use, the availability of scientific literature and experts, whether or not the drug has already been approved in other species or formulations, etc. will have a significant effect on the cost of completing a request for indexing. Simple requests for indexing can be expected to require less time to prepare and, therefore, will be less costly than the estimate, while others may be more involved and will require more time.
The agency will nonetheless continue to consider the exercise of regulatory discretion under appropriate circumstances and, as it gains experience with the indexing process, will consider whether it should make any changes to CPG 615.115.
(Comment 12) One comment was received in regard to the proposed conforming changes to parts 201 and 202 (21 CFR parts 201 and 202). This comment stated that the addition of indexing references to these parts of 21 CFR will add very specific requirements to the labeling and advertising process for an unapproved drug.
(Response) Part 201 pertains to drug labeling. The proposed conforming changes to part 201 are in subpart D which is entitled “Exemptions for Adequate Directions for Use.” The regulations in this subpart describe situations where new drug and new animal drug labeling would be exempt from the misbranding requirements of section 502(f)(1) of the act or provide clear descriptions of specific labeling information required to avoid misbranding under section 502(f)(1) of the act. Specifically, § 201.105 describes what information must appear on prescription new animal drug labeling and § 201.122 describes what information must appear on drugs for processing, packing, or manufacturing. The agency believes these same exemptions and clear descriptions should be available for index listed drugs and does not believe that the specific labeling requirements described in this subpart for approved new animal drugs are overly burdensome for index listed drugs. Furthermore, the labeling requirements for prescription new animal drugs described in § 201.105 are necessary for the safe and effective use of such drugs whether they are approved or index listed.
Part 202 pertains to prescription drug advertising. The conforming change to § 202.1 will require that prescription drug advertising for index listed drugs shall not recommend or suggest any use that is not in the labeling accepted in such index listing and that the advertisement shall present information from labeling granted in the listing relating to each specific side effect and contraindication in such labeling that relates to the uses of the advertised drug dosage form(s). Section 202.1 currently contains this same provision for new animal drugs that are approved under section 512 of the act and for new drugsthat are approved under section 505 of the act. We do not believe this conformation to current regulations is unreasonable.
(Comment 13) One comment expressed confusion regarding whether unapproved index listed products that are drug listed under the provisions of part 207 (21 CFR part 207) are subject to product user fees under Animal Drug User Fee Act of 2003 (ADUFA).
(Response) Unapproved new animal drugs that are index listed under section 572 of the act are not subject to product user fees under ADUFA (Pub. L. 108-130). Unless specifically exempted, all new animal drugs that are in commercial distribution, whether approved or not, are subject to the drug listing requirements of part 207 (see § 207.20). However, to be subject to a product user fee, an animal drug product must not only be subject to the drug listing requirements of part 207, but also approved as either an animal drug application or supplemental animal drug application (see section 740(a)(2) of the act). As defined under ADUFA, these applications do not include drugs that are index listed under section 572 of the act (see section 739(1) and (2) of the act).
(Comment 14) One comment asked for clarification on why certain conforming changes to the regulations in part 510 for approved drugs were proposed to apply to index listed drugs.
(Response) Three sections in part 510 contain conforming changes. Those sections apply to new animal drugs, which means they apply to index listed drugs because they are new animal drugs. The conforming changes are needed so it is clear how these provisions apply in the context of index listed drugs. For example, § 510.301 describes the reporting and recordkeeping requirements for licensed medicated feed mills concerning experience with new animal drugs when used in or on animal feeds. Previously, the regulation said the records and report must be appropriately identified with the new animal drug application(s) to which they relate. The conforming amendment adds “or index listing(s)” to which they relate. Similarly, one of the items to be reported is any failure of the drug to meet specifications established for it in the new animal drug application. This is being amended to include specifications established in the request for determination of eligibility for indexing. Conforming amendments are also made in § 510.305, which requires licensed medicated feed mill operators to maintain approved labeling for each Type B and/or Type C feed being manufactured on the premises of the manufacturing establishment or the facility where the feed labels are generated, and § 510.455, which describes the requirements for manufacturing a free-choice medicated animal feed.
(Comment 15) One comment stated that due to the prohibitive cost of production of small quantities of separately labeled product, the requirement for labeling indexed drugs separately from approved drugs could be a deterrent for indexing useful drugs that are already approved in major species. The comment suggested that adequate distinction could be required on existing labeling to provide the indexed claims as well as information on the approved labeling.
(Response) New animal drug labeling that contains information derived from both an application approved under section 512(b) of the act and from an index listing granted under section 572 of the act (572 index listing) would be misbranded under section 502(w)(2) of the act and would cause the new animal drug to be unsafe under section 512(a)(1)(A) and (C) of the act. Simply put, in this situation, the labeling information derived from the 512(b) approval does not conform with the 572 index listing, and the labeling information derived from the 572 index listing does not conform with the 512(b) approval. For example, under section 572(h) of the act, the labeling of an index listed drug must include the statement “NOT APPROVED BY FDA.—Legally marketed as an FDA indexed product.” Such a statement would be false on the labeling of a product approved under section 512(b) of the act because that product has been approved by FDA.
(Comment 16) One comment requested clarification on the statement in proposed § 516.155 to the effect that a product cannot be utilized in an extra-label manner once it is indexed. The comment said that this could be prohibitive to the veterinarian's ability to utilize an approved medication off label when needed if it has also been indexed.
(Response) Under § 516.155, the label of an indexed drug must state that extra-label use is prohibited. This statement is based on section 572(h) of the act. However, this statement prohibiting extra-label use of new animal drugs indexed under section 572 of the act does not impose any restrictions, beyond those that already existed, on the extra-label use of new animal drugs approved under section 512(b) of the act.
The extra-label use of an approved new animal drug is not permitted when “the labeling of another animal drug that contains the same active ingredient which is in the same dosage form and concentration” provides for the same use as a contemplated extra-label use (section 512(a)(4)(A) of the act). We believe that the reference to “another animal drug” in this provision means a new animal drug that, like the drug to be used in an extra-label manner, has been approved under section 512(b) of the act, and that it does not include a new animal drug that has been indexed under section 572 of the act. The regulations implementing the extra-label use provisions of section 512 of the act provide that one of the conditions for the extra-label use of an approved new animal drug is that “there is no approved new animal drug that is labeled for such use and that contains the same active ingredient which is in the required dosage form and concentration” (§§ 530.20(a)(1) (emphasis added) and 530.30(a)). Based on our interpretation of the act, we do not believe the condition in this regulation should be broadened to reference indexed drugs along with approved drugs. Thus, if a new animal drug is index listed for intended use A, for example, and the same active ingredient in the same dosage form is approved for intended use B, then the approved drug may be used in an extra-label manner for intended use A, as long as all other provisions of 21 CFR part 530 have been met.
(Comment 17) One comment noted that the preamble failed to explicitly state that indexed drugs may fall into one of three categories: Over-the-counter, prescription, and veterinary feed directive (VFD).
(Response) We agree that index listed drugs may fall into one of these three categories. Prescription status for index listed drugs is provided for in section 503(f)(1)(A)(ii) of the act and VFD status is provided for in section 504(a)(1) of the act. The current regulations in title 21 of the CFR have been revised accordingly by conforming change in this rulemaking at § 201.105, § 202.1, § 558.3, and § 558.6.
(Comment 18) One comment stated that it appears that there can be a number of holders of the same product listed in the i