Compounding Animal Drugs From Bulk Drug Substances; Draft Guidance for Industry; Availability; Withdrawal of Compliance Policy Guide; Section 608.400 Compounding of Drugs for Use in Animals, 28624-28629 [2015-11982]

Download as PDF 28624 Federal Register / Vol. 80, No. 96 / Tuesday, May 19, 2015 / Notices tkelley on DSK3SPTVN1PROD with NOTICES condition(s) in the species that the drug compounded with the nominated substance is intended to address; • if there are FDA-approved or index listed drug products that address the same conditions in the same species, an explanation, supported by relevant veterinary literature, of why a compounded drug product is necessary (i.e., why the approved drug product is not suitable for a particular patient population); • a review of the veterinary literature to determine whether there are FDAapproved animal or human drugs that could be prescribed as an extra-label use under section 512(a)(4) and (a)(5) of the FD&C Act and part 530 to treat the condition(s) in the species that the drug compounded with the nominated substance is intended to address; • if the bulk drug substance is an active ingredient in an approved animal or human drug, an explanation, supported by appropriate scientific data, of why the animal drug product cannot be compounded from the approved drug under 21 CFR 530.13(b); • an explanation, supported by relevant veterinary literature, of why the animal drug product to be compounded with the nominated bulk drug substance must be available to the veterinarian for immediate treatment to avoid animal suffering or death. Nominations should include specific information documenting that animal suffering or death will result if treatment is delayed until a compounded animal drug can be obtained pursuant to a prescription for an individually identified animal; and • a discussion of any safety concerns associated with use of the nominated bulk drug substance or finished compounded product for the condition(s) in the species that the compounded drug is intended to address. If there are any safety concerns, an explanation, supported by veterinary literature, of why the concerns should not preclude inclusion of that bulk drug substance on Appendix A. D. Nomination Process For efficient consolidation and review of nominations, nominators are encouraged to submit their nominations in a format that explicitly addresses each item previously listed in the order that they appear. To consider a bulk drug substance for inclusion in Appendix A, FDA must receive adequate supporting data for the substance. FDA cannot guarantee that all drugs nominated during the nomination period will be considered for inclusion on Appendix A prior to its initial publication. Nominations that are not evaluated during this first phase VerDate Sep<11>2014 16:53 May 18, 2015 Jkt 235001 will receive consideration for later addition to Appendix A. Individuals and organization may petition FDA to make additional amendments to Appendix A after it is published, in accordance with § 10.30. Interested persons may submit either electronic nominations to https:// www.regulations.gov or written nominations to the Division of Dockets Management (see ADDRESSES). It is only necessary to send one set of nominations. Identify nominations with the docket number found in the brackets in the heading of this document. Received nominations may be seen in the Division of Dockets Management between 9 a.m. and 4 p.m., Monday through Friday, and will be posted to the docket at https:// www.regulations.gov. Dated: May 12, 2015. Leslie Kux, Associate Commissioner for Policy. [FR Doc. 2015–11983 Filed 5–18–15; 8:45 am] BILLING CODE 4164–01–P DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket Nos. FDA–2015–D–1176 and FDA– 2003–D–0202] Compounding Animal Drugs From Bulk Drug Substances; Draft Guidance for Industry; Availability; Withdrawal of Compliance Policy Guide; Section 608.400 Compounding of Drugs for Use in Animals AGENCY: Food and Drug Administration, HHS. ACTION: Notice; withdrawal. The Food and Drug Administration (FDA) is announcing the availability of a draft guidance for industry (GFI) #230 entitled ‘‘Compounding Animal Drugs from Bulk Drug Substances.’’ The draft guidance describes FDA’s policies with regard to compounding animal drugs from bulk drug substances. When final, the guidance will reflect FDA’s current thinking on the issues addressed by the guidance. FDA is also announcing the withdrawal of the compliance policy guide (CPG) entitled ‘‘Section 608.400 Compounding of Drugs for Use in Animals,’’ which was issued in July 2003. This 2003 CPG is being withdrawn because it is no longer consistent with FDA’s current thinking on the issues it addresses. DATES: Although you can comment on any guidance at any time (see 21 CFR SUMMARY: PO 00000 Frm 00046 Fmt 4703 Sfmt 4703 10.115(g)(5)), to ensure that FDA considers your comment on the draft guidance before it begins work on the final version of the guidance, submit either electronic or written comments on the draft guidance by August 17, 2015. Submit written or electronic comments on the proposed collection of information by August 17, 2015. ADDRESSES: Submit written requests for single copies of the draft guidance to the Policy and Regulations Staff (HFV–6), Center for Veterinary Medicine, Food and Drug Administration, 7519 Standish Pl., Rockville, MD 20855. Send one selfaddressed adhesive label to assist that office in processing your request. See the SUPPLEMENTARY INFORMATION section for electronic access to the draft guidance. Submit electronic comments on the draft guidance, including comments regarding the proposed collection of information, to https:// www.regulations.gov. Submit written comments on the draft guidance, including comments regarding the proposed collection of information, to the Division of Dockets Management (HFA–305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. FOR FURTHER INFORMATION CONTACT: With regard to this draft guidance: Division of Compliance, Center for Veterinary Medicine, Food and Drug Administration (HFV–230), 7519 Standish Pl., Rockville, MD 20855, 240– 402–7001, CVMCompliance@ fda.hhs.gov. With regard to the proposed collection of information: FDA PRA Staff, Office of Operations, Food and Drug Administration, 8455 Colesville Rd.; COLE–14526, Silver Spring, MD 20993– 0002; PRAStaff@fda.hhs.gov. SUPPLEMENTARY INFORMATION: I. Draft Guidance FDA is announcing the availability of a draft GFI #230 entitled ‘‘Compounding Animal Drugs from Bulk Drug Substances.’’ The draft guidance provides information to compounders of animal drugs and other interested stakeholders on FDA’s application of the Federal Food, Drug, and Cosmetic Act (the FD&C Act) with respect to the compounding of animal drugs from bulk drug substances.1 1 FDA regulations define ‘‘bulk drug substance’’ as ‘‘any substance that is represented for use in a drug and that, when used in the manufacturing, processing, or packaging of a drug, becomes an active ingredient or a finished dosage form of the drug, but the term does not include intermediates used in the synthesis of such substances.’’ 21 CFR 207.3(a)(4). ‘‘Active ingredient’’ is defined as ‘‘any component that is intended to furnish E:\FR\FM\19MYN1.SGM 19MYN1 Federal Register / Vol. 80, No. 96 / Tuesday, May 19, 2015 / Notices tkelley on DSK3SPTVN1PROD with NOTICES Sections 503A (21 U.S.C. 353a) and 503B (21 U.S.C. 353b) of the FD&C Act do not apply to the compounding of animal drugs. The FD&C Act does not distinguish between compounding animal drugs from bulk drug substances and any other manufacturing or processing of animal drugs. Except with respect to the limited exemption provided by the FD&C Act described in this document, statutory provisions applicable to manufactured animal drugs under the FD&C Act also apply to compounded animal drugs. Section 512(a)(4) and (5) of the FD&C Act (21 U.S.C. 360b(a)(4) and (5)), provide a limited exemption from certain requirements for use for compounded animal drugs made from already approved animal or human drugs. Such use is considered an extralabel use and the FD&C Act provides that a compounded drug is exempt from the approval requirements and requirements of section 502(f)(1) (21 U.S.C. 352(f)(1)) of the FD&C Act, if it meets the conditions set out in the statute and the extra-label use regulations at 21 CFR part 530. This draft guidance does not address the compounding of animal drugs from approved animal or human drugs pursuant to the extra-label provisions of the law, nor does it address the repackaging of approved animal drugs. FDA is considering whether guidance is needed on those issues, and if so, will publish separate guidances. In section III, FDA is asking for comment on specific questions about several issues including the practice of compounding from approved animal and human drugs and the repackaging of drugs for animal use to help determine whether additional guidance is necessary on these topics. This draft guidance describes conditions under which FDA does not generally intend to initiate enforcement action against State-licensed pharmacies, licensed veterinarians, and facilities registered as outsourcing facilities under section 503B of the FD&C Act (outsourcing facilities) that compound animal drugs from bulk drug substances. The draft guidance provides pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body of man or other animals. The term includes those components that may undergo chemical change in the manufacture of the drug product and be present in the drug product in a modified form intended to furnish the specified activity or effect.’’ 21 CFR 210.3(b)(7). Any component other than an active ingredient is an ‘‘inactive ingredient.’’ See 21 CFR 210.3(b)(8). Inactive ingredients used in compounded drug products commonly include flavorings, dyes, diluents, or other excipients. VerDate Sep<11>2014 16:53 May 18, 2015 Jkt 235001 that FDA does not generally intend to take action under sections 512(a), 501(a)(5) (21 U.S.C. 351(a)(5)), 501(a)(2)(B) (21 U.S.C. 351(a)(2)(B)), and 502(f)(1) of the FD&C Act if a Statelicensed pharmacy or a licensed veterinarian compounds drugs intended for use in animals from bulk drug substances in accordance with all of the applicable conditions set out in the guidance. In addition, the draft guidance provides that FDA does not generally intend to take action under sections 512(a), 501(a)(5), and 502(f)(1) of the FD&C Act if the drug product is compounded from a bulk drug substance by an outsourcing facility and that meets all of the applicable conditions set out in the guidance, and the drug product is compounded from a bulk drug substance that appears on Appendix A of the draft guidance. Importantly, the draft guidance provides that FDA generally intends to enforce all other adulteration and misbranding provisions of the FD&C Act against entities compounding animal drugs from bulk drug substances. To ensure FDA can timely identify and address safety issues related to animal drugs compounded from bulk drug substances, one of the conditions, if met, under which FDA does not generally intend to take action for violations of the provisions described previously is that State-licensed pharmacies and veterinarians report any product defect or serious adverse event associated with animal drugs they compound from a bulk drug substance to FDA, within 15 days of becoming aware of them, using Form FDA 1932a. FDA intends to use these adverse event reports to identify animal drugs compounded from bulk drug substances that present serious risks to animal health. Unlike for human drugs, there are no State Departments of Health or Federal Agencies, such as the Centers for Disease Control and Prevention (CDC), which are responsible for identifying and tracing the source of injury and/or disease in animals. Adverse event reporting regarding drugs compounded from bulk drug substances by compounding pharmacies and veterinarians will provide a mechanism for FDA to identify and possibly prevent adverse events associated with compounded animal drugs. This is another topic on which we are requesting specific comment in section III. Elsewhere in this issue of the Federal Register, FDA is publishing a notice soliciting nominations for bulk drug substances that should be included in Appendix A, ‘‘List of Bulk Drug Substances That May Be Used By an PO 00000 Frm 00047 Fmt 4703 Sfmt 4703 28625 Outsourcing Facility to Compound Drugs for Use in Animals.’’ The notice also describes the information that should be provided to the Agency in support of such nominations. II. Withdrawal of 2003 Compliance Policy Guide In a notice published in the Federal Register of July 14, 2003 (68 FR 41591), FDA announced the availability of CPG Section 608.400 of the Compliance Program Guidance Manual entitled, ‘‘Compounding of Drugs for Use in Animals.’’ This document is being withdrawn because it is no longer consistent with FDA’s current thinking on the issue it addresses. The current CPG does not focus on the three main concerns FDA has about animal drug compounding: compounding copies of approved animal or human drugs from bulk drug substances, compounding for food-producing animals from bulk drug substances, and compounding office stock from bulk drug substances. Because the CPG does not reflect FDA’s current thinking, to leave it in effect until this draft guidance is finalized may confuse stakeholders about FDA’s current enforcement priorities. Stakeholders should be aware that, until this draft guidance is finalized, FDA intends to look at the totality of the circumstances when determining whether to take enforcement action for unlawful animal drug compounding activities. III. Specific Topics for Comment In addition to comments on the draft guidance as written, we are specifically requesting comments on the following issues: • Should the final guidance address the issue of FDA-approved animal and human drugs that are in shortage or are otherwise unavailable (e.g., disruptions in the manufacture or supply chain; business decisions to stop marketing the drug; drug is subject to Agency action based on safety, effectiveness, or manufacturing concerns)? If so: Æ How should these situations be addressed in the final guidance? Æ How should the final guidance define the terms ‘‘shortage’’ and ‘‘unavailable’’? Æ What criteria should FDA use to determine if an approved animal or human drug is in shortage or otherwise unavailable? • Do United States Pharmacopeia and National Formulary (USP–NF) 2 2 Chapters <795> ‘‘Pharmaceutical Compounding—Nonsterile Preparations’’ and <797> ‘‘Pharmaceutical Compounding—Sterile Preparations’’ can be found in the combined United E:\FR\FM\19MYN1.SGM Continued 19MYN1 tkelley on DSK3SPTVN1PROD with NOTICES 28626 Federal Register / Vol. 80, No. 96 / Tuesday, May 19, 2015 / Notices chapters <795> and <797> provide suitable standards for animal drugs compounded by veterinarians, and if not, what standards of safety, purity, and quality should apply to animal drugs compounded by veterinarians? • Should licensed veterinarians be able to sell or transfer an animal drug compounded from bulk drug substances by a State-licensed pharmacy or an outsourcing facility to owners or caretakers of animals under the veterinarian’s care? • How should FDA apply the condition to identify an individual patient when it is not possible to identify an individual animal (e.g., koi in a koi pond)? • Should the final guidance include a condition on the amount or percentage of compounded animal drugs that a pharmacy or outsourcing facility can ship in interstate commerce? If so, what would a reasonable amount be? • Should facilities registered as outsourcing facilities under section 503B of the FD&C Act be able to compound animal drugs from bulk drug substances that do not appear on Appendix A for an individually identified animal patient under conditions similar to those applicable to state-licensed pharmacies (i.e., the conditions contained in section III.A. of the draft guidance)? • Is additional guidance needed to address the repackaging of drugs for animal use? Æ How widespread is the practice of repackaging drugs for animal use? Æ What types of drugs are repackaged for animal use, and why are they repackaged? Æ Have problems been identified with repackaged drugs for animal use? • Is additional guidance needed to address the compounding of animal drugs from approved animal or human drugs under section 512(a)(4) or (a)(5) of the FD&C Act and part 530? • Is additional guidance needed to address the compounding of animal drugs from bulk drug substances for food-producing animals? • As one condition under which FDA does not generally intend to take action for certain violations of the FD&C Act if this and the other conditions are followed, FDA is proposing that Statelicensed pharmacies and veterinarians report any product defect or serious adverse event associated with animal drugs they compound from bulk drug substances to FDA within 15 days of becoming aware of the product defect or serious adverse event. Outsourcing States Pharmacopeia and National Formulary (USP–NF), available at https://www.usp.org/. VerDate Sep<11>2014 16:53 May 18, 2015 Jkt 235001 facilities are required to report adverse events associated with the drugs they compound. FDA believes it is important to receive this information from Statelicensed pharmacies and veterinarians because there are no other State Departments of Health or Federal Agencies (e.g., the CDC) charged with identifying and tracing animal injuries or disease associated with an animal drug compounded by these entities. FDA has the following specific questions with respect to this proposed condition: Æ How many State-licensed pharmacies and veterinarians compound animal drugs from bulk drug substances and would potentially be reporting product defects and serious adverse events to FDA? Æ Are State-licensed pharmacies and veterinarians reporting the same or similar information to any State regulatory agency (e.g., State boards of pharmacy, State boards of veterinary medicine)? If so, how many reports on average does each State-licensed pharmacy and veterinarian submit to these State agencies each year? Æ For purposes of the guidance, how should FDA define the terms ‘‘product defect’’ and ‘‘serious adverse event’’? Æ Can FDA achieve the same objective of identifying and tracing the source of injuries or disease associated with an animal drug compounded from a bulk drug substance through means other than product defect and serious adverse event reporting, and if so, what other means? For example, would reports of product defects alone achieve the same objective? IV. Significance of Guidance This Level 1 draft guidance is being issued consistent with FDA’s good guidance practices regulation (21 CFR 10.115). The draft guidance, when finalized, will represent the current thinking of FDA on compounding animal drugs from bulk drug substances. It does not establish any rights for any person and is not binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations. V. Paperwork Reduction Act of 1995 This draft guidance contains proposed information collection provisions that are subject to review by the Office of Management and Budget (OMB) under the Paperwork Reduction Act of 1995 (the PRA) (44 U.S.C. 3501–3520). ‘‘Collection of information’’ is defined in 44 U.S.C. 3502(3) and 5 CFR 1320.3(c) and includes Agency requests or requirements that members of the PO 00000 Frm 00048 Fmt 4703 Sfmt 4703 public submit reports, keep records, or provide information to a third party. Section 3506(c)(2)(A) of the PRA, 44 U.S.C. 3506(c)(2)(A), requires Federal Agencies to provide a 60-day notice in the Federal Register for each proposed collection of information before submitting the collection to OMB for approval. To comply with this requirement, FDA is publishing this notice of the proposed collection of information set forth in this document. With respect to the collection of information associated with this draft guidance, we invite comments on these topics: (1) Whether the proposed collection of information is necessary for the proper performance of FDA’s functions, including whether the information will have practical utility; (2) the accuracy of FDA’s estimate of the burden of the proposed collection of information, including the validity of the methodology and assumptions used; (3) ways to enhance the quality, utility, and clarity of the information to be collected; and (4) ways to minimize the burden of the collection of information on respondents, including through the use of automated collection techniques, when appropriate, and other forms of information technology. Title: Compounding Animal Drugs from Bulk Drug Substances (OMB Control Number 0910–NEW) Description of Respondents: The proposed collection of information would affect State-licensed pharmacies, licensed veterinarians, and outsourcing facilities that compound animal drugs from bulk drug substances. Description: This draft guidance describes FDA’s current thinking regarding compounding animal drugs from bulk drug substances and describes the conditions under which FDA does not generally intend to take action for violations of the following sections of the FD&C Act: 512, 501(a)(5), 502(f)(1), and, where specified, 501(a)(2)(B), when a State-licensed pharmacy, licensed veterinarian, or an outsourcing facility compounds animal drugs from bulk drug substances. The draft guidance provides three sets of conditions, one for each entity: State-licensed pharmacies, licensed veterinarians, and outsourcing facilities. This draft guidance only addresses the compounding of animal drugs from bulk drug substances. It does not apply to the compounding of animal drugs from approved new animal or new human drugs. Such compounding can be conducted in accordance with the provisions of section 512(a)(4) and (5) of the FD&C Act and part 530. In addition, this guidance does not address the compounding of drugs intended for use E:\FR\FM\19MYN1.SGM 19MYN1 28627 Federal Register / Vol. 80, No. 96 / Tuesday, May 19, 2015 / Notices in humans, which is addressed in other guidances. FDA estimates the burden of this collection of information as follows: Reporting This draft guidance contains no new reporting provisions. This draft guidance refers to previously approved collections of information found in FDA regulations. These collections of information are subject to review by OMB under the PRA. The collections of information regarding voluntary reporting of adverse drug experiences or product/manufacturing defects on Form FDA 1932a, ‘‘Veterinary Adverse Drug Reaction, Lack of Effectiveness or Product Defect Report,’’ have been approved under OMB control number 0910–0284; the information collection provisions regarding establishment registration under section 510 of the FD&C Act (21 U.S.C. 360) have been approved under OMB control number 0910–0777. This draft guidance also refers to proposed collections of information regarding drugs made by an outsourcing facility during the previous 6-month period as described in FDA’s notice of November 24, 2014 (79 FR 69857), announcing the availability of a draft guidance entitled ‘‘Electronic Reporting for Human Drug Compounding Outsourcing Facilities.’’ The proposed collections of information in the draft guidance are subject to review by OMB under the PRA. As required by the PRA, FDA published an analysis of the information collection provisions of the draft guidance (79 FR 69857 at 69858) and intends to submit them for OMB approval. Recordkeeping Entities compounding animal drugs from bulk drug substances should keep adequate records to demonstrate that they are compounding such drugs in accordance with all of the applicable conditions described in the draft guidance. FDA tentatively concludes that it is usual and customary for Statelicensed pharmacies, veterinarians, and outsourcing facilities to keep such records, and that this draft guidance imposes no additional recordkeeping burden beyond those usual and customary for the respondents to this collection, with the exception of that described in section III.A.5. Nonetheless, table 1, row 1 provides a nominal estimate of potential recordkeeping burden that respondents may incur. FDA therefore specifically invites comment regarding whether these provisions impose any effort beyond that which would normally be incurred in absence of this draft guidance. A condition set forth in section III.A.5. is that, if there is an FDAapproved animal or human drug with the same active ingredient(s), the pharmacy determines that the compounded drug cannot be made from the FDA-approved drug(s), and documents that determination. TABLE 1—ESTIMATED ANNUAL RECORDKEEPING BURDEN 1 Number of recordkeepers Guidance section Number of records per recordkeeper III; general recordkeeping beyond usual & customary. III.A.5; documentation of determination that compound drug cannot be made from the FDAapproved drug(s). 138,551 75,000 Total ........................................ .............................. 1 There 1 Average burden per recordkeeping Total hours 138,551 0.01 (30 seconds) ..... 1,386 84.67 6,350,000 0.01 (30 seconds) ..... 63,500 ................................ .............................. .................................... 64,886 are no capital costs or operating and maintenance costs associated with this collection of information. For row 1, we base our burden estimates on the American Veterinary Medical Association’s Market Research Statistics for 2013 for the total number of veterinarians in practice minus those veterinarians in food animal exclusive practice (63,500), the National Pharmacy Market Summary SK&A of March 2010 for the total number of pharmacy sites (75,000), and the number of registered outsourcing facilities as of March 20, 2015 (51), for a total of 138,551 respondents.3 For row 2, we estimate that approximately 75,000 pharmacies will receive approximately 6,350,000 prescriptions for compounded animal tkelley on DSK3SPTVN1PROD with NOTICES Total annual records 3 The AVMA’s Market Research Statistics—U.S. Veterinarians—2013 can be found at this URL: (https://www.avma.org/KB/Resources/Statistics/ Pages/Market-research-statistics-USveterinarians.aspx); the National Pharmacy Market Summary SK&A (March 2010) can be found at this URL: https://www.skainfo.com/index.php; and the list of registered outsourcing facilities can be found at this URL: https://www.fda.gov/Drugs/ GuidanceComplianceRegulatoryInformation/ PharmacyCompounding/ucm378645.htm. VerDate Sep<11>2014 16:53 May 18, 2015 Jkt 235001 drugs annually, and we also estimate that it will take approximately 30 seconds (0.01 hours) to document that the compounded drug cannot be made from the FDA-approved drug(s) for a total of 63,500 hours recordkeeping burden. A condition set forth in section III.A.2. of the draft guidance is that State-licensed pharmacies can compound a drug in advance of receipt of a prescription in a quantity that does not exceed the amount of drug product that the State-licensed pharmacy compounded pursuant to patientspecific prescriptions based on a history of receipt of such patient-specific prescriptions for that drug product over any consecutive 14-day period within the previous 6 months. The records necessary for a State-licensed pharmacy to review to determine that its compounding practices are within the condition set forth in section III.A.2 of the draft guidance are records that Statelicensed pharmacies would already be PO 00000 Frm 00049 Fmt 4703 Sfmt 4703 keeping as part of usual and customary business practice; therefore, no burden has been estimated for the recordkeeping associated with this condition. This draft guidance also refers to proposed collections of information currently undergoing the process of OMB review under the PRA. Recordkeeping by outsourcing facilities, described in the draft guidance for industry, ‘‘Current Good Manufacturing Practice—Interim Guidance for Human Drug Compounding Outsourcing Facilities Under Section 503B of the FD&C Act’’ announced July 2, 2014 (79 FR 37743), will be reviewed by OMB in response to an information collection request associated with that guidance. Third-Party Disclosure Prescriptions or Orders for Drugs Compounded From Bulk This draft guidance contains new third-party disclosures as reported in table 2. Row 1 reflects a potential E:\FR\FM\19MYN1.SGM 19MYN1 28628 Federal Register / Vol. 80, No. 96 / Tuesday, May 19, 2015 / Notices burden associated with section III.C.9. regarding the following condition: The veterinarian’s prescription or order states, in addition to the species, the condition(s) for which the substance is listed in Appendix A. At this time, however, FDA has no data upon which to base an estimated number of prescriptions or orders to outsourcing facilities until the referenced list of bulk drugs (Draft Guidance; Appendix A) is finalized. For purposes of this analysis, however, we are providing an estimate of 1 as a placeholder. is a component of a marketed FDAapproved animal or human drug, the prescription or documentation accompanying the prescription contains a statement that the change between the compounded drug and the FDAapproved drug produces a clinical difference for the individual identified patient. For example, the veterinarian could state that, ‘‘This compounded drug is needed to treat [specifically identified patient] because the approved drug product(s) cannot be divided or diluted into the small dose required.’’ In section III.A.4., the draft guidance sets forth the following condition: If the drug contains a bulk drug substance that is a component of any marketed FDAapproved animal or human drug, there is a change between the compounded drug and the comparable FDA-approved animal or human drug made for an identified individual patient that produces a clinical difference for that identified individual patient, as determined by the veterinarian prescribing the compounded drug for his/her patient under his/her care. If the drug contains a bulk drug substance that TABLE 2—ESTIMATED ANNUAL THIRD-PARTY DISCLOSURE BURDEN 1 Number of disclosures per respondent Number of respondents Activity Total annual disclosures Average burden per disclosure Total hours III.C.9; documentation of condition to be treated. Statements on prescription (Section III.A.4 of the draft guidance). 1 1 1 0.017 (1 minute) ........ 63,500 100 6,350,000 0.017 (1 minute) ........ 107,950 Total ........................................ .............................. .............................. .............................. .................................... 107,950 tkelley on DSK3SPTVN1PROD with NOTICES 1 There 0.017 are no capital costs or operating and maintenance costs associated with this collection of information. For row 2, we estimate that approximately 63,500 veterinarians will, on average, each produce approximately 100 prescriptions for compounded animal drugs annually for a total of 6,350,000 prescriptions. We also estimate that it will take approximately 1 minute (0.017 hours) to include the statement discussed in section III.A.4 of the draft guidance on each prescription for a total of 107,950 hours third-party disclosure burden, as reported in table 1. It is usual and customary for licensed veterinarians to write prescriptions in the normal course of their activities. The conditions set forth in the guidance require veterinarians to include certain information on prescriptions for animals drugs compounded from bulk substances. It is usual and customary for veterinarians to include much of this information (except as noted previously); therefore, the time it would take to provide this information on prescriptions or documents accompanying prescriptions is not included in the burden estimate reported in table 2. Sections III.A.3 and III.A.6.b of the draft guidance set forth the conditions that the following statements appear verbatim on or with prescriptions for animal drugs compounded from bulk drug substances: • ‘‘This patient is not a foodproducing animal.’’ (Section III.A.3). • ‘‘There are no FDA-approved animal or human drugs that can be used VerDate Sep<11>2014 16:53 May 18, 2015 Jkt 235001 as labeled or in an extra-label manner under section 512(a)(4) and (5) and 21 CFR part 530 to appropriately treat the disease, symptom, or condition for which this drug is being prescribed.’’ (Section III.A.6.b). In addition, section III.C.3 of the draft guidance sets forth the condition that the following statement appears verbatim on or with prescriptions or orders for animal drugs compounded by outsourcing facilities from bulk drug substances listed on Appendix A: • ‘‘This drug will not be dispensed for or administered to food-producing animals.’’ (Section III.C.3). We tentatively conclude that these statements are ‘‘public disclosures of information originally supplied by the Federal Government to the recipient for the purpose of disclosure to the public’’ (5 CFR 1320.3(c)(2)) and are therefore not subject to review by OMB under the PRA. Thus, the time it would take to provide this information is not included in the burden estimate reported in table 2. Labeling of Drugs Compounded From Bulk Drug Substances The draft guidance sets forth conditions for the labeling of animal drugs compounded from bulk drug substances. The draft guidance indicates in sections III.A.11 and III.B.9 that, to meet the conditions of the guidance, State-licensed pharmacies and licensed veterinarians include on the label of any compounded drug: The species of the PO 00000 Frm 00050 Fmt 4703 Sfmt 4703 intended animal patient, the name of the animal patient, and the name of the owner or caretaker of the animal patient. It is usual and customary for Statelicensed pharmacies and licensed veterinarians to include such information on the labels of compounded drugs in the normal course of their activities; thus, the time it would take to provide this information is not included in the burden estimate reported in table 2. In addition, the draft guidance indicates in section III.C.10. that, to meet the conditions of the guidance, outsourcing facilities include on the label of any compounded animal drug pursuant to a specific prescription or order: The active ingredient; the dosage form, strength, and flavoring, if any; direction for use, as provided by the veterinarian prescribing or ordering the drug; the quantity or volume, whichever is appropriate; the lot or batch number of the drug; special storage and handling instructions; the date the drug was compounded; the beyond use date of the drug; the name of the veterinarian prescribing or ordering the drug; the inactive ingredients; and the address and phone number of the outsourcing facility that compounded the drug. It is usual and customary for outsourcing facilities to include such information on the labels of compounded drugs in the normal course of their activities; thus, the time it would take to provide this information is not included in the burden estimate reported in table 2. E:\FR\FM\19MYN1.SGM 19MYN1 Federal Register / Vol. 80, No. 96 / Tuesday, May 19, 2015 / Notices tkelley on DSK3SPTVN1PROD with NOTICES The draft guidance indicates in section III.C.10 that, to meet the conditions of the guidance, outsourcing facilities compounding animal drug from bulk drug substances for office use in veterinary practices include on the label of any compounded drug these four statements: • ‘‘Not for resale.’’ • ‘‘For use only in [fill in species and any associated condition or limitation listed in Appendix A].’’ • ‘‘Compounded by [name of outsourcing facility].’’ • ‘‘Adverse events associated with this compounded drug should be reported to FDA on a Form FDA 1932a.’’ We tentatively conclude that these four label statements are ‘‘public disclosures of information originally supplied by the Federal Government to the recipient for the purpose of disclosure to the public’’ (5 CFR 1320.3(c)(2)) and are therefore not subject to review by OMB under the PRA. Thus, the time it would take to provide this information is not included in the burden estimate reported in table 2. This draft guidance also refers to previously approved collections of information. A condition set forth in sections III.A.7., III.B.6, and III.C.5 is that any bulk drug substance used is manufactured by an establishment that is registered under section 510 of the FD&C Act (including a foreign establishment that is registered under section 360(i) of the FD&C Act) and is accompanied by a valid certificate of analysis. The information collection related to the disclosure of the certificate of analysis is approved under OMB control number 0910–0139. Before the proposed information collection provisions contained in this draft guidance become effective, we will publish a notice in the Federal Register announcing OMB’s decision to approve, modify, or disapprove the proposed information collection provisions. An Agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB control number. VI. Comments Interested persons may submit either electronic comments regarding this draft guidance to https://www.regulations.gov or written comments to the Division of Dockets Management (see ADDRESSES). It is only necessary to send one set of comments. Identify comments with Docket No. FDA–2015–D–1176. Received comments may be seen in the Division of Dockets Management between 9 a.m. and 4 p.m., Monday VerDate Sep<11>2014 16:53 May 18, 2015 Jkt 235001 through Friday, and will be posted to the docket at https:// www.regulations.gov. VII. Electronic Access Persons with access to the Internet may obtain the draft guidance at either https://www.fda.gov/AnimalVeterinary/ GuidanceComplianceEnforcement/ GuidanceforIndustry/ucm042450.htm or https://www.regulations.gov. Dated: May 12, 2015. Leslie Kux, Associate Commissioner for Policy. [FR Doc. 2015–11982 Filed 5–18–15; 8:45 am] BILLING CODE 4164–01–P DEPARTMENT OF HEALTH AND HUMAN SERVICES National Committee on Vital and Health Statistics: Meeting Pursuant to the Federal Advisory Committee Act, the Department of Health and Human Services (HHS) announces the following advisory committee meeting. Name: National Committee on Vital and Health Statistics (NCVHS) Review Committee, pursuant to Section 1104(i) of the Patient Protection and Affordable Care Act (ACA). Time and Date: June 16, 2015, 9:00 a.m.– 5:00 p.m. EST; June 17, 2015, 8:00 a.m.–5:15 p.m. EST. Place: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics, 3311 Toledo Road, Auditorium B and C, Hyattsville, Maryland 20782, (301) 458–4524. Status: Open. Purpose: The purpose of this hearing is to obtain information from the health care industry on the currently adopted standards, operating rules, code sets and identifiers used in administrative simplification transactions. The objectives of this hearing are as follows: (1) Review currently adopted standards, operating rules, code sets and identifiers used in each of the HIPAA-named administrative simplification transactions and evaluate the degree to which they meet current industry business needs; and (2) Identify transactions, standards, operating rules, code sets and identifiers used in administrative simplification that require changes, deletions or new versions in order to meet industry needs. We invite the public to prepare and submit written testimony on any and all areas covered by this hearing. We also invite testifiers to prepare and submit more extensive written testimony, in addition to the oral testimony they will be providing during the hearing. Written testimonies should be sent to Marietta Squire, Committee Management Specialist, Centers for Disease Control and Prevention, National Center for Health Statistics, email msquire@cdc.gov. PO 00000 Frm 00051 Fmt 4703 Sfmt 4703 28629 Background on the Review Committee, including the Review Committee’s Charter can be accessed at https://www.ncvhs.hhs.gov/ subcommittees-work-groups/subcommitteeon-standards/review-committee/. Contact Person for More Information: Debbie M. Jackson, Acting Executive Secretary, NCVHS, National Center for Health Statistics, Centers for Disease Control and Prevention, 3311 Toledo Road, Room 2339, Hyattsville, Maryland 20782, telephone (301) 458–4614 or Terri Deutsch, Centers for Medicare and Medicaid Services, Office of EHealth Standards and Services, 7500 Security Boulevard, Baltimore, Maryland 21244, telephone (410) 786–9462. Program information as well as summaries of meetings and a roster of committee members are available on the NCVHS home page of the HHS Web site: https://ncvhs.us/, where further information including an agenda will be posted when available. Should you require reasonable accommodation, please contact the CDC Office of Equal Employment Opportunity on (301) 458–4EEO (4336) as soon as possible. Dated: May 13, 2015. James Scanlon, Deputy Assistant Secretary for Planning and Evaluation Science and Data Policy, Office of the Assistant Secretary for Planning and Evaluation. [FR Doc. 2015–12106 Filed 5–18–15; 8:45 am] BILLING CODE 4151–05–P DEPARTMENT OF HEALTH AND HUMAN SERVICES Meetings of the Advisory Group on Prevention, Health Promotion, and Integrative and Public Health Office of the Surgeon General of the United States Public Health Service, Office of the Assistant Secretary for Health, Office of the Secretary, Department of Health and Human Services. ACTION: Notice. AGENCY: In accordance with Section 10(a) of the Federal Advisory Committee Act, Public Law 92–463, as amended (5 U.S.C. App.), notice is hereby given that two meetings are scheduled for the Advisory Group on Prevention, Health Promotion, and Integrative and Public Health (the ‘‘Advisory Group’’). The meetings will be open to the public. Information about the Advisory Group and the agendas for these meetings can be obtained by accessing the following Web site: https:// www.surgeongeneral.gov/initiatives/ prevention/advisorygrp/. DATES: The first meeting will be held on June 11, 2015, from 11:30 a.m. to 2:30 p.m. EST. The second meeting will be held on August 31 from 9:00 a.m. to SUMMARY: E:\FR\FM\19MYN1.SGM 19MYN1

Agencies

[Federal Register Volume 80, Number 96 (Tuesday, May 19, 2015)]
[Notices]
[Pages 28624-28629]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-11982]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket Nos. FDA-2015-D-1176 and FDA-2003-D-0202]


Compounding Animal Drugs From Bulk Drug Substances; Draft 
Guidance for Industry; Availability; Withdrawal of Compliance Policy 
Guide; Section 608.400 Compounding of Drugs for Use in Animals

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice; withdrawal.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA) is announcing the 
availability of a draft guidance for industry (GFI) #230 entitled 
``Compounding Animal Drugs from Bulk Drug Substances.'' The draft 
guidance describes FDA's policies with regard to compounding animal 
drugs from bulk drug substances. When final, the guidance will reflect 
FDA's current thinking on the issues addressed by the guidance.
    FDA is also announcing the withdrawal of the compliance policy 
guide (CPG) entitled ``Section 608.400 Compounding of Drugs for Use in 
Animals,'' which was issued in July 2003. This 2003 CPG is being 
withdrawn because it is no longer consistent with FDA's current 
thinking on the issues it addresses.

DATES: Although you can comment on any guidance at any time (see 21 CFR 
10.115(g)(5)), to ensure that FDA considers your comment on the draft 
guidance before it begins work on the final version of the guidance, 
submit either electronic or written comments on the draft guidance by 
August 17, 2015. Submit written or electronic comments on the proposed 
collection of information by August 17, 2015.

ADDRESSES: Submit written requests for single copies of the draft 
guidance to the Policy and Regulations Staff (HFV-6), Center for 
Veterinary Medicine, Food and Drug Administration, 7519 Standish Pl., 
Rockville, MD 20855. Send one self-addressed adhesive label to assist 
that office in processing your request. See the SUPPLEMENTARY 
INFORMATION section for electronic access to the draft guidance.
    Submit electronic comments on the draft guidance, including 
comments regarding the proposed collection of information, to https://www.regulations.gov. Submit written comments on the draft guidance, 
including comments regarding the proposed collection of information, to 
the Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: With regard to this draft guidance: 
Division of Compliance, Center for Veterinary Medicine, Food and Drug 
Administration (HFV-230), 7519 Standish Pl., Rockville, MD 20855, 240-
402-7001, CVMCompliance@fda.hhs.gov.
    With regard to the proposed collection of information: FDA PRA 
Staff, Office of Operations, Food and Drug Administration, 8455 
Colesville Rd.; COLE-14526, Silver Spring, MD 20993-0002; 
PRAStaff@fda.hhs.gov.

SUPPLEMENTARY INFORMATION: 

I. Draft Guidance

    FDA is announcing the availability of a draft GFI #230 entitled 
``Compounding Animal Drugs from Bulk Drug Substances.'' The draft 
guidance provides information to compounders of animal drugs and other 
interested stakeholders on FDA's application of the Federal Food, Drug, 
and Cosmetic Act (the FD&C Act) with respect to the compounding of 
animal drugs from bulk drug substances.\1\
---------------------------------------------------------------------------

    \1\ FDA regulations define ``bulk drug substance'' as ``any 
substance that is represented for use in a drug and that, when used 
in the manufacturing, processing, or packaging of a drug, becomes an 
active ingredient or a finished dosage form of the drug, but the 
term does not include intermediates used in the synthesis of such 
substances.'' 21 CFR 207.3(a)(4). ``Active ingredient'' is defined 
as ``any component that is intended to furnish pharmacological 
activity or other direct effect in the diagnosis, cure, mitigation, 
treatment, or prevention of disease, or to affect the structure or 
any function of the body of man or other animals. The term includes 
those components that may undergo chemical change in the manufacture 
of the drug product and be present in the drug product in a modified 
form intended to furnish the specified activity or effect.'' 21 CFR 
210.3(b)(7). Any component other than an active ingredient is an 
``inactive ingredient.'' See 21 CFR 210.3(b)(8). Inactive 
ingredients used in compounded drug products commonly include 
flavorings, dyes, diluents, or other excipients.

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[[Page 28625]]

    Sections 503A (21 U.S.C. 353a) and 503B (21 U.S.C. 353b) of the 
FD&C Act do not apply to the compounding of animal drugs. The FD&C Act 
does not distinguish between compounding animal drugs from bulk drug 
substances and any other manufacturing or processing of animal drugs. 
Except with respect to the limited exemption provided by the FD&C Act 
described in this document, statutory provisions applicable to 
manufactured animal drugs under the FD&C Act also apply to compounded 
animal drugs.
    Section 512(a)(4) and (5) of the FD&C Act (21 U.S.C. 360b(a)(4) and 
(5)), provide a limited exemption from certain requirements for use for 
compounded animal drugs made from already approved animal or human 
drugs. Such use is considered an extra-label use and the FD&C Act 
provides that a compounded drug is exempt from the approval 
requirements and requirements of section 502(f)(1) (21 U.S.C. 
352(f)(1)) of the FD&C Act, if it meets the conditions set out in the 
statute and the extra-label use regulations at 21 CFR part 530.
    This draft guidance does not address the compounding of animal 
drugs from approved animal or human drugs pursuant to the extra-label 
provisions of the law, nor does it address the repackaging of approved 
animal drugs. FDA is considering whether guidance is needed on those 
issues, and if so, will publish separate guidances. In section III, FDA 
is asking for comment on specific questions about several issues 
including the practice of compounding from approved animal and human 
drugs and the repackaging of drugs for animal use to help determine 
whether additional guidance is necessary on these topics.
    This draft guidance describes conditions under which FDA does not 
generally intend to initiate enforcement action against State-licensed 
pharmacies, licensed veterinarians, and facilities registered as 
outsourcing facilities under section 503B of the FD&C Act (outsourcing 
facilities) that compound animal drugs from bulk drug substances. The 
draft guidance provides that FDA does not generally intend to take 
action under sections 512(a), 501(a)(5) (21 U.S.C. 351(a)(5)), 
501(a)(2)(B) (21 U.S.C. 351(a)(2)(B)), and 502(f)(1) of the FD&C Act if 
a State-licensed pharmacy or a licensed veterinarian compounds drugs 
intended for use in animals from bulk drug substances in accordance 
with all of the applicable conditions set out in the guidance. In 
addition, the draft guidance provides that FDA does not generally 
intend to take action under sections 512(a), 501(a)(5), and 502(f)(1) 
of the FD&C Act if the drug product is compounded from a bulk drug 
substance by an outsourcing facility and that meets all of the 
applicable conditions set out in the guidance, and the drug product is 
compounded from a bulk drug substance that appears on Appendix A of the 
draft guidance.
    Importantly, the draft guidance provides that FDA generally intends 
to enforce all other adulteration and misbranding provisions of the 
FD&C Act against entities compounding animal drugs from bulk drug 
substances.
    To ensure FDA can timely identify and address safety issues related 
to animal drugs compounded from bulk drug substances, one of the 
conditions, if met, under which FDA does not generally intend to take 
action for violations of the provisions described previously is that 
State-licensed pharmacies and veterinarians report any product defect 
or serious adverse event associated with animal drugs they compound 
from a bulk drug substance to FDA, within 15 days of becoming aware of 
them, using Form FDA 1932a. FDA intends to use these adverse event 
reports to identify animal drugs compounded from bulk drug substances 
that present serious risks to animal health. Unlike for human drugs, 
there are no State Departments of Health or Federal Agencies, such as 
the Centers for Disease Control and Prevention (CDC), which are 
responsible for identifying and tracing the source of injury and/or 
disease in animals. Adverse event reporting regarding drugs compounded 
from bulk drug substances by compounding pharmacies and veterinarians 
will provide a mechanism for FDA to identify and possibly prevent 
adverse events associated with compounded animal drugs. This is another 
topic on which we are requesting specific comment in section III.
    Elsewhere in this issue of the Federal Register, FDA is publishing 
a notice soliciting nominations for bulk drug substances that should be 
included in Appendix A, ``List of Bulk Drug Substances That May Be Used 
By an Outsourcing Facility to Compound Drugs for Use in Animals.'' The 
notice also describes the information that should be provided to the 
Agency in support of such nominations.

II. Withdrawal of 2003 Compliance Policy Guide

    In a notice published in the Federal Register of July 14, 2003 (68 
FR 41591), FDA announced the availability of CPG Section 608.400 of the 
Compliance Program Guidance Manual entitled, ``Compounding of Drugs for 
Use in Animals.'' This document is being withdrawn because it is no 
longer consistent with FDA's current thinking on the issue it 
addresses. The current CPG does not focus on the three main concerns 
FDA has about animal drug compounding: compounding copies of approved 
animal or human drugs from bulk drug substances, compounding for food-
producing animals from bulk drug substances, and compounding office 
stock from bulk drug substances. Because the CPG does not reflect FDA's 
current thinking, to leave it in effect until this draft guidance is 
finalized may confuse stakeholders about FDA's current enforcement 
priorities. Stakeholders should be aware that, until this draft 
guidance is finalized, FDA intends to look at the totality of the 
circumstances when determining whether to take enforcement action for 
unlawful animal drug compounding activities.

III. Specific Topics for Comment

    In addition to comments on the draft guidance as written, we are 
specifically requesting comments on the following issues:
     Should the final guidance address the issue of FDA-
approved animal and human drugs that are in shortage or are otherwise 
unavailable (e.g., disruptions in the manufacture or supply chain; 
business decisions to stop marketing the drug; drug is subject to 
Agency action based on safety, effectiveness, or manufacturing 
concerns)? If so:
    [cir] How should these situations be addressed in the final 
guidance?
    [cir] How should the final guidance define the terms ``shortage'' 
and ``unavailable''?
    [cir] What criteria should FDA use to determine if an approved 
animal or human drug is in shortage or otherwise unavailable?
     Do United States Pharmacopeia and National Formulary (USP-
NF) \2\

[[Page 28626]]

chapters <795> and <797> provide suitable standards for animal drugs 
compounded by veterinarians, and if not, what standards of safety, 
purity, and quality should apply to animal drugs compounded by 
veterinarians?
---------------------------------------------------------------------------

    \2\ Chapters <795> ``Pharmaceutical Compounding--Nonsterile 
Preparations'' and <797> ``Pharmaceutical Compounding--Sterile 
Preparations'' can be found in the combined United States 
Pharmacopeia and National Formulary (USP-NF), available at https://www.usp.org/.
---------------------------------------------------------------------------

     Should licensed veterinarians be able to sell or transfer 
an animal drug compounded from bulk drug substances by a State-licensed 
pharmacy or an outsourcing facility to owners or caretakers of animals 
under the veterinarian's care?
     How should FDA apply the condition to identify an 
individual patient when it is not possible to identify an individual 
animal (e.g., koi in a koi pond)?
     Should the final guidance include a condition on the 
amount or percentage of compounded animal drugs that a pharmacy or 
outsourcing facility can ship in interstate commerce? If so, what would 
a reasonable amount be?
     Should facilities registered as outsourcing facilities 
under section 503B of the FD&C Act be able to compound animal drugs 
from bulk drug substances that do not appear on Appendix A for an 
individually identified animal patient under conditions similar to 
those applicable to state-licensed pharmacies (i.e., the conditions 
contained in section III.A. of the draft guidance)?
     Is additional guidance needed to address the repackaging 
of drugs for animal use?
    [cir] How widespread is the practice of repackaging drugs for 
animal use?
    [cir] What types of drugs are repackaged for animal use, and why 
are they repackaged?
    [cir] Have problems been identified with repackaged drugs for 
animal use?
     Is additional guidance needed to address the compounding 
of animal drugs from approved animal or human drugs under section 
512(a)(4) or (a)(5) of the FD&C Act and part 530?
     Is additional guidance needed to address the compounding 
of animal drugs from bulk drug substances for food-producing animals?
     As one condition under which FDA does not generally intend 
to take action for certain violations of the FD&C Act if this and the 
other conditions are followed, FDA is proposing that State-licensed 
pharmacies and veterinarians report any product defect or serious 
adverse event associated with animal drugs they compound from bulk drug 
substances to FDA within 15 days of becoming aware of the product 
defect or serious adverse event. Outsourcing facilities are required to 
report adverse events associated with the drugs they compound. FDA 
believes it is important to receive this information from State-
licensed pharmacies and veterinarians because there are no other State 
Departments of Health or Federal Agencies (e.g., the CDC) charged with 
identifying and tracing animal injuries or disease associated with an 
animal drug compounded by these entities. FDA has the following 
specific questions with respect to this proposed condition:
    [cir] How many State-licensed pharmacies and veterinarians compound 
animal drugs from bulk drug substances and would potentially be 
reporting product defects and serious adverse events to FDA?
    [cir] Are State-licensed pharmacies and veterinarians reporting the 
same or similar information to any State regulatory agency (e.g., State 
boards of pharmacy, State boards of veterinary medicine)? If so, how 
many reports on average does each State-licensed pharmacy and 
veterinarian submit to these State agencies each year?
    [cir] For purposes of the guidance, how should FDA define the terms 
``product defect'' and ``serious adverse event''?
    [cir] Can FDA achieve the same objective of identifying and tracing 
the source of injuries or disease associated with an animal drug 
compounded from a bulk drug substance through means other than product 
defect and serious adverse event reporting, and if so, what other 
means? For example, would reports of product defects alone achieve the 
same objective?

IV. Significance of Guidance

    This Level 1 draft guidance is being issued consistent with FDA's 
good guidance practices regulation (21 CFR 10.115). The draft guidance, 
when finalized, will represent the current thinking of FDA on 
compounding animal drugs from bulk drug substances. It does not 
establish any rights for any person and is not binding on FDA or the 
public. You can use an alternative approach if it satisfies the 
requirements of the applicable statutes and regulations.

V. Paperwork Reduction Act of 1995

    This draft guidance contains proposed information collection 
provisions that are subject to review by the Office of Management and 
Budget (OMB) under the Paperwork Reduction Act of 1995 (the PRA) (44 
U.S.C. 3501-3520). ``Collection of information'' is defined in 44 
U.S.C. 3502(3) and 5 CFR 1320.3(c) and includes Agency requests or 
requirements that members of the public submit reports, keep records, 
or provide information to a third party. Section 3506(c)(2)(A) of the 
PRA, 44 U.S.C. 3506(c)(2)(A), requires Federal Agencies to provide a 
60-day notice in the Federal Register for each proposed collection of 
information before submitting the collection to OMB for approval. To 
comply with this requirement, FDA is publishing this notice of the 
proposed collection of information set forth in this document.
    With respect to the collection of information associated with this 
draft guidance, we invite comments on these topics: (1) Whether the 
proposed collection of information is necessary for the proper 
performance of FDA's functions, including whether the information will 
have practical utility; (2) the accuracy of FDA's estimate of the 
burden of the proposed collection of information, including the 
validity of the methodology and assumptions used; (3) ways to enhance 
the quality, utility, and clarity of the information to be collected; 
and (4) ways to minimize the burden of the collection of information on 
respondents, including through the use of automated collection 
techniques, when appropriate, and other forms of information 
technology.
    Title: Compounding Animal Drugs from Bulk Drug Substances (OMB 
Control Number 0910-NEW)
    Description of Respondents: The proposed collection of information 
would affect State-licensed pharmacies, licensed veterinarians, and 
outsourcing facilities that compound animal drugs from bulk drug 
substances.
    Description: This draft guidance describes FDA's current thinking 
regarding compounding animal drugs from bulk drug substances and 
describes the conditions under which FDA does not generally intend to 
take action for violations of the following sections of the FD&C Act: 
512, 501(a)(5), 502(f)(1), and, where specified, 501(a)(2)(B), when a 
State-licensed pharmacy, licensed veterinarian, or an outsourcing 
facility compounds animal drugs from bulk drug substances. The draft 
guidance provides three sets of conditions, one for each entity: State-
licensed pharmacies, licensed veterinarians, and outsourcing 
facilities.
    This draft guidance only addresses the compounding of animal drugs 
from bulk drug substances. It does not apply to the compounding of 
animal drugs from approved new animal or new human drugs. Such 
compounding can be conducted in accordance with the provisions of 
section 512(a)(4) and (5) of the FD&C Act and part 530. In addition, 
this guidance does not address the compounding of drugs intended for 
use

[[Page 28627]]

in humans, which is addressed in other guidances.
    FDA estimates the burden of this collection of information as 
follows:

Reporting

    This draft guidance contains no new reporting provisions. This 
draft guidance refers to previously approved collections of information 
found in FDA regulations. These collections of information are subject 
to review by OMB under the PRA. The collections of information 
regarding voluntary reporting of adverse drug experiences or product/
manufacturing defects on Form FDA 1932a, ``Veterinary Adverse Drug 
Reaction, Lack of Effectiveness or Product Defect Report,'' have been 
approved under OMB control number 0910-0284; the information collection 
provisions regarding establishment registration under section 510 of 
the FD&C Act (21 U.S.C. 360) have been approved under OMB control 
number 0910-0777. This draft guidance also refers to proposed 
collections of information regarding drugs made by an outsourcing 
facility during the previous 6-month period as described in FDA's 
notice of November 24, 2014 (79 FR 69857), announcing the availability 
of a draft guidance entitled ``Electronic Reporting for Human Drug 
Compounding Outsourcing Facilities.'' The proposed collections of 
information in the draft guidance are subject to review by OMB under 
the PRA. As required by the PRA, FDA published an analysis of the 
information collection provisions of the draft guidance (79 FR 69857 at 
69858) and intends to submit them for OMB approval.

Recordkeeping

    Entities compounding animal drugs from bulk drug substances should 
keep adequate records to demonstrate that they are compounding such 
drugs in accordance with all of the applicable conditions described in 
the draft guidance. FDA tentatively concludes that it is usual and 
customary for State-licensed pharmacies, veterinarians, and outsourcing 
facilities to keep such records, and that this draft guidance imposes 
no additional recordkeeping burden beyond those usual and customary for 
the respondents to this collection, with the exception of that 
described in section III.A.5. Nonetheless, table 1, row 1 provides a 
nominal estimate of potential recordkeeping burden that respondents may 
incur. FDA therefore specifically invites comment regarding whether 
these provisions impose any effort beyond that which would normally be 
incurred in absence of this draft guidance.
    A condition set forth in section III.A.5. is that, if there is an 
FDA-approved animal or human drug with the same active ingredient(s), 
the pharmacy determines that the compounded drug cannot be made from 
the FDA-approved drug(s), and documents that determination.

                                                   Table 1--Estimated Annual Recordkeeping Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                            Number of       Number of records     Total annual
           Guidance section               recordkeepers     per recordkeeper        records         Average burden per recordkeeping      Total hours
--------------------------------------------------------------------------------------------------------------------------------------------------------
III; general recordkeeping beyond                 138,551                1               138,551  0.01 (30 seconds)..................              1,386
 usual & customary.
III.A.5; documentation of                          75,000               84.67          6,350,000  0.01 (30 seconds)..................             63,500
 determination that compound drug
 cannot be made from the FDA-approved
 drug(s).
                                       ----------------------------------------------------------                                     ------------------
    Total.............................  .................  ..................  .................  ...................................             64,886
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.

    For row 1, we base our burden estimates on the American Veterinary 
Medical Association's Market Research Statistics for 2013 for the total 
number of veterinarians in practice minus those veterinarians in food 
animal exclusive practice (63,500), the National Pharmacy Market 
Summary SK&A of March 2010 for the total number of pharmacy sites 
(75,000), and the number of registered outsourcing facilities as of 
March 20, 2015 (51), for a total of 138,551 respondents.\3\
---------------------------------------------------------------------------

    \3\ The AVMA's Market Research Statistics--U.S. Veterinarians--
2013 can be found at this URL: (https://www.avma.org/KB/Resources/Statistics/Pages/Market-research-statistics-US-veterinarians.aspx); 
the National Pharmacy Market Summary SK&A (March 2010) can be found 
at this URL: https://www.skainfo.com/index.php; and the list of 
registered outsourcing facilities can be found at this URL: https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/ucm378645.htm.
---------------------------------------------------------------------------

    For row 2, we estimate that approximately 75,000 pharmacies will 
receive approximately 6,350,000 prescriptions for compounded animal 
drugs annually, and we also estimate that it will take approximately 30 
seconds (0.01 hours) to document that the compounded drug cannot be 
made from the FDA-approved drug(s) for a total of 63,500 hours 
recordkeeping burden.
    A condition set forth in section III.A.2. of the draft guidance is 
that State-licensed pharmacies can compound a drug in advance of 
receipt of a prescription in a quantity that does not exceed the amount 
of drug product that the State-licensed pharmacy compounded pursuant to 
patient-specific prescriptions based on a history of receipt of such 
patient-specific prescriptions for that drug product over any 
consecutive 14-day period within the previous 6 months. The records 
necessary for a State-licensed pharmacy to review to determine that its 
compounding practices are within the condition set forth in section 
III.A.2 of the draft guidance are records that State-licensed 
pharmacies would already be keeping as part of usual and customary 
business practice; therefore, no burden has been estimated for the 
recordkeeping associated with this condition.
    This draft guidance also refers to proposed collections of 
information currently undergoing the process of OMB review under the 
PRA. Recordkeeping by outsourcing facilities, described in the draft 
guidance for industry, ``Current Good Manufacturing Practice--Interim 
Guidance for Human Drug Compounding Outsourcing Facilities Under 
Section 503B of the FD&C Act'' announced July 2, 2014 (79 FR 37743), 
will be reviewed by OMB in response to an information collection 
request associated with that guidance.

Third-Party Disclosure

Prescriptions or Orders for Drugs Compounded From Bulk
    This draft guidance contains new third-party disclosures as 
reported in table 2. Row 1 reflects a potential

[[Page 28628]]

burden associated with section III.C.9. regarding the following 
condition: The veterinarian's prescription or order states, in addition 
to the species, the condition(s) for which the substance is listed in 
Appendix A. At this time, however, FDA has no data upon which to base 
an estimated number of prescriptions or orders to outsourcing 
facilities until the referenced list of bulk drugs (Draft Guidance; 
Appendix A) is finalized. For purposes of this analysis, however, we 
are providing an estimate of 1 as a placeholder.
    In section III.A.4., the draft guidance sets forth the following 
condition: If the drug contains a bulk drug substance that is a 
component of any marketed FDA-approved animal or human drug, there is a 
change between the compounded drug and the comparable FDA-approved 
animal or human drug made for an identified individual patient that 
produces a clinical difference for that identified individual patient, 
as determined by the veterinarian prescribing the compounded drug for 
his/her patient under his/her care. If the drug contains a bulk drug 
substance that is a component of a marketed FDA-approved animal or 
human drug, the prescription or documentation accompanying the 
prescription contains a statement that the change between the 
compounded drug and the FDA-approved drug produces a clinical 
difference for the individual identified patient. For example, the 
veterinarian could state that, ``This compounded drug is needed to 
treat [specifically identified patient] because the approved drug 
product(s) cannot be divided or diluted into the small dose required.''

                                               Table 2--Estimated Annual Third-Party Disclosure Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                               Number of
               Activity                     Number of       disclosures per      Total annual       Average burden per disclosure         Total hours
                                           respondents         respondent        disclosures
--------------------------------------------------------------------------------------------------------------------------------------------------------
III.C.9; documentation of condition to                  1                  1                  1  0.017 (1 minute)...................               0.017
 be treated.
Statements on prescription (Section                63,500                100          6,350,000  0.017 (1 minute)...................         107,950
 III.A.4 of the draft guidance).
                                       ---------------------------------------------------------                                     -------------------
    Total.............................  .................  .................  .................  ...................................         107,950
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.

    For row 2, we estimate that approximately 63,500 veterinarians 
will, on average, each produce approximately 100 prescriptions for 
compounded animal drugs annually for a total of 6,350,000 
prescriptions. We also estimate that it will take approximately 1 
minute (0.017 hours) to include the statement discussed in section 
III.A.4 of the draft guidance on each prescription for a total of 
107,950 hours third-party disclosure burden, as reported in table 1.
    It is usual and customary for licensed veterinarians to write 
prescriptions in the normal course of their activities. The conditions 
set forth in the guidance require veterinarians to include certain 
information on prescriptions for animals drugs compounded from bulk 
substances. It is usual and customary for veterinarians to include much 
of this information (except as noted previously); therefore, the time 
it would take to provide this information on prescriptions or documents 
accompanying prescriptions is not included in the burden estimate 
reported in table 2.
    Sections III.A.3 and III.A.6.b of the draft guidance set forth the 
conditions that the following statements appear verbatim on or with 
prescriptions for animal drugs compounded from bulk drug substances:
     ``This patient is not a food-producing animal.'' (Section 
III.A.3).
     ``There are no FDA-approved animal or human drugs that can 
be used as labeled or in an extra-label manner under section 512(a)(4) 
and (5) and 21 CFR part 530 to appropriately treat the disease, 
symptom, or condition for which this drug is being prescribed.'' 
(Section III.A.6.b).
    In addition, section III.C.3 of the draft guidance sets forth the 
condition that the following statement appears verbatim on or with 
prescriptions or orders for animal drugs compounded by outsourcing 
facilities from bulk drug substances listed on Appendix A:
     ``This drug will not be dispensed for or administered to 
food-producing animals.'' (Section III.C.3).
    We tentatively conclude that these statements are ``public 
disclosures of information originally supplied by the Federal 
Government to the recipient for the purpose of disclosure to the 
public'' (5 CFR 1320.3(c)(2)) and are therefore not subject to review 
by OMB under the PRA. Thus, the time it would take to provide this 
information is not included in the burden estimate reported in table 2.
Labeling of Drugs Compounded From Bulk Drug Substances
    The draft guidance sets forth conditions for the labeling of animal 
drugs compounded from bulk drug substances. The draft guidance 
indicates in sections III.A.11 and III.B.9 that, to meet the conditions 
of the guidance, State-licensed pharmacies and licensed veterinarians 
include on the label of any compounded drug: The species of the 
intended animal patient, the name of the animal patient, and the name 
of the owner or caretaker of the animal patient. It is usual and 
customary for State-licensed pharmacies and licensed veterinarians to 
include such information on the labels of compounded drugs in the 
normal course of their activities; thus, the time it would take to 
provide this information is not included in the burden estimate 
reported in table 2.
    In addition, the draft guidance indicates in section III.C.10. 
that, to meet the conditions of the guidance, outsourcing facilities 
include on the label of any compounded animal drug pursuant to a 
specific prescription or order: The active ingredient; the dosage form, 
strength, and flavoring, if any; direction for use, as provided by the 
veterinarian prescribing or ordering the drug; the quantity or volume, 
whichever is appropriate; the lot or batch number of the drug; special 
storage and handling instructions; the date the drug was compounded; 
the beyond use date of the drug; the name of the veterinarian 
prescribing or ordering the drug; the inactive ingredients; and the 
address and phone number of the outsourcing facility that compounded 
the drug. It is usual and customary for outsourcing facilities to 
include such information on the labels of compounded drugs in the 
normal course of their activities; thus, the time it would take to 
provide this information is not included in the burden estimate 
reported in table 2.

[[Page 28629]]

    The draft guidance indicates in section III.C.10 that, to meet the 
conditions of the guidance, outsourcing facilities compounding animal 
drug from bulk drug substances for office use in veterinary practices 
include on the label of any compounded drug these four statements:
     ``Not for resale.''
     ``For use only in [fill in species and any associated 
condition or limitation listed in Appendix A].''
     ``Compounded by [name of outsourcing facility].''
     ``Adverse events associated with this compounded drug 
should be reported to FDA on a Form FDA 1932a.''
    We tentatively conclude that these four label statements are 
``public disclosures of information originally supplied by the Federal 
Government to the recipient for the purpose of disclosure to the 
public'' (5 CFR 1320.3(c)(2)) and are therefore not subject to review 
by OMB under the PRA. Thus, the time it would take to provide this 
information is not included in the burden estimate reported in table 2.
    This draft guidance also refers to previously approved collections 
of information. A condition set forth in sections III.A.7., III.B.6, 
and III.C.5 is that any bulk drug substance used is manufactured by an 
establishment that is registered under section 510 of the FD&C Act 
(including a foreign establishment that is registered under section 
360(i) of the FD&C Act) and is accompanied by a valid certificate of 
analysis. The information collection related to the disclosure of the 
certificate of analysis is approved under OMB control number 0910-0139.
    Before the proposed information collection provisions contained in 
this draft guidance become effective, we will publish a notice in the 
Federal Register announcing OMB's decision to approve, modify, or 
disapprove the proposed information collection provisions. An Agency 
may not conduct or sponsor, and a person is not required to respond to, 
a collection of information unless it displays a currently valid OMB 
control number.

VI. Comments

    Interested persons may submit either electronic comments regarding 
this draft guidance to https://www.regulations.gov or written comments 
to the Division of Dockets Management (see ADDRESSES). It is only 
necessary to send one set of comments. Identify comments with Docket 
No. FDA-2015-D-1176. Received comments may be seen in the Division of 
Dockets Management between 9 a.m. and 4 p.m., Monday through Friday, 
and will be posted to the docket at https://www.regulations.gov.

VII. Electronic Access

    Persons with access to the Internet may obtain the draft guidance 
at either https://www.fda.gov/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/ucm042450.htm or 
https://www.regulations.gov.

    Dated: May 12, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-11982 Filed 5-18-15; 8:45 am]
 BILLING CODE 4164-01-P

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