Notice2022-08092
Compounding Animal Drugs From Bulk Drug Substances; Guidance for Industry; Availability
Primary source
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Published
April 14, 2022
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA, Agency, or we) is announcing the availability of a final guidance for industry (GFI) #256 entitled "Compounding Animal Drugs from Bulk Drug Substances." This guidance describes FDA's current thinking about compounding animal drugs from bulk drug substances, identifies our enforcement priorities with respect to drugs compounded from bulk drug substances, and describes circumstances under which FDA generally does not intend to take action against veterinarians or pharmacists in either State- licensed pharmacies or Federal facilities, who compound animal drugs from bulk drug substances. We are also announcing that a proposed collection of information has been submitted to the Office of Management and Budget (OMB) for review and clearance under the Paperwork Reduction Act of 1995 (PRA).
Full Text
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<title>Federal Register, Volume 87 Issue 72 (Thursday, April 14, 2022)</title>
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[Federal Register Volume 87, Number 72 (Thursday, April 14, 2022)]
[Notices]
[Pages 22212-22215]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2022-08092]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2018-D-4533]
Compounding Animal Drugs From Bulk Drug Substances; Guidance for
Industry; Availability
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice of availability.
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SUMMARY: The Food and Drug Administration (FDA, Agency, or we) is
announcing the availability of a final guidance for industry (GFI) #256
entitled ``Compounding Animal Drugs from Bulk Drug Substances.'' This
guidance describes FDA's current thinking about compounding animal
drugs from bulk drug substances, identifies our enforcement priorities
with respect to drugs compounded from bulk drug substances, and
describes circumstances under which FDA generally does not intend to
take action against veterinarians or pharmacists in either State-
licensed pharmacies or Federal facilities, who compound animal drugs
from bulk drug substances. We are also announcing that a proposed
collection of information has been submitted to the Office of
Management and Budget (OMB) for review and clearance under the
Paperwork Reduction Act of 1995 (PRA).
DATES: The announcement of the guidance is published in the Federal
Register on April 14, 2022. Submit written comments (including
recommendations) on the collection of information by May 16, 2022.
ADDRESSES: To ensure that comments on the information collection are
received, OMB recommends that written comments be submitted to <a href="https://www.reginfo.gov/public/do/PRAMain">https://www.reginfo.gov/public/do/PRAMain</a>. Find this particular information
collection by selecting ``Currently under Review--Open for Public
Comments'' or by using the search function. The OMB control number for
this information collection is 0910-NEW. Also include the FDA docket
number found in brackets in the heading of this document.
You may submit either electronic or written comments on Agency
guidances at any time as follows:
Electronic Submissions
Submit electronic comments in the following way:
<bullet> Federal eRulemaking Portal: <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to <a href="https://www.regulations.gov">https://www.regulations.gov</a>
will be posted to the docket unchanged. Because your comment will be
made public, you are solely responsible for ensuring that your comment
does not include any confidential information that you or a third party
may not wish to be posted, such as medical information, your or anyone
else's Social Security number, or confidential business information,
such as a manufacturing process. Please note that if you include your
name, contact information, or other information that identifies you in
the body of your comments, that information will be posted on <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
<bullet> If you want to submit a comment with confidential
information that you do not wish to be made available to the public,
submit the comment as a written/paper submission and in the manner
detailed (see ``Written/Paper Submissions'' and ``Instructions'').
Written/Paper Submissions
Submit written/paper submissions as follows:
<bullet> Mail/Hand Delivery/Courier (for written/paper
submissions): Dockets Management Staff (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
<bullet> For written/paper comments submitted to the Dockets
Management Staff, FDA will post your comment, as well as any
attachments, except for information submitted, marked and identified,
as confidential, if submitted as detailed in ``Instructions.''
Instructions: All submissions received must include the Docket No.
FDA-2018-D-4533 for ``Compounding Animal Drugs from Bulk Drug
Substances.'' Received comments will be placed in the docket and,
except for those submitted as ``Confidential Submissions,'' publicly
viewable at <a href="https://www.regulations.gov">https://www.regulations.gov</a> or at the Dockets Management
Staff between 9 a.m. and 4 p.m., Monday through Friday, 240-402-7500.
[[Page 22213]]
<bullet> Confidential Submissions--To submit a comment with
confidential information that you do not wish to be made publicly
available, submit your comments only as a written/paper submission. You
should submit two copies total. One copy will include the information
you claim to be confidential with a heading or cover note that states
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will
review this copy, including the claimed confidential information, in
its consideration of comments. The second copy, which will have the
claimed confidential information redacted/blacked out, will be
available for public viewing and posted on <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Submit both copies to the Dockets Management Staff. If you do not wish
your name and contact information to be made publicly available, you
can provide this information on the cover sheet and not in the body of
your comments and you must identify this information as
``confidential.'' Any information marked as ``confidential'' will not
be disclosed except in accordance with 21 CFR 10.20 and other
applicable disclosure law. For more information about FDA's posting of
comments to public dockets, see 80 FR 56469, September 18, 2015, or
access the information at: <a href="https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf">https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf</a>.
Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to <a href="https://www.regulations.gov">https://www.regulations.gov</a> and insert the docket number, found in brackets in
the heading of this document, into the ``Search'' box and follow the
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852, 240-402-7500.
You may submit comments on any guidance at any time (see 21 CFR
10.115(g)(5)).
Submit written requests for single copies of the guidance to the
Policy and Regulations Staff (HFV-6), Center for Veterinary Medicine,
Food and Drug Administration, 7500 Standish Pl., Rockville, MD 20855.
Send one self-addressed adhesive label to assist that office in
processing your requests. See the SUPPLEMENTARY INFORMATION section for
electronic access to the guidance document.
FOR FURTHER INFORMATION CONTACT: Cindy Burnsteel, Office of
Surveillance and Compliance (HFV-200), Food and Drug Administration,
7519 Standish Pl., Rockville, MD 20855, 240-402-7011.
Regarding the proposed collection of information: Domini Bean,
Office of Operations, Food and Drug Administration, Three White Flint
North, 10A-12M, 11601 Landsdown St., North Bethesda, MD 20852, 301-796-
5733, <a href="/cdn-cgi/l/email-protection#a9f9fbe8faddc8cfcfe9cfcdc887c1c1da87cec6df"><span class="__cf_email__" data-cfemail="8ddddfccdef9ecebebcdebe9eca3e5e5fea3eae2fb">[email protected]</span></a>.
SUPPLEMENTARY INFORMATION:
I. Background
In the Federal Register of November 20, 2019 (84 FR 64085), FDA
published the notice of availability for draft GFI #256 entitled
``Compounding Animal Drugs from Bulk Drug Substances'' with a 90-day
comment period. In response to requests from interested parties, we
extended the comment period to July 17, 2020, and then to October 15,
2020. We requested comments on the draft guidance with respect to
animal drug compounding from bulk drug substances under certain
circumstances when no other medically appropriate treatment option
exists. This final GFI #256 describes FDA's current thinking about
compounding animal drugs from bulk drug substances, identifies our
enforcement priorities with respect to drugs compounded from bulk drug
substances, and describes circumstances under which FDA generally does
not intend to take action against veterinarians or pharmacists in
either State-licensed pharmacies or Federal facilities, who compound
animal drugs from bulk drug substances. FDA does not intend to take
action under sections 501(a)(2)(B) and (a)(5), 502(f), and 512(a) of
the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 351(a)(2)(B) and
(a)(5), 352(f), and 360(b)) under the circumstances described in GFI
#256.
FDA received numerous comments on the draft guidance, which were
considered as the guidance was finalized. Changes made in response to
comments include identifying compliance with relevant State and local
laws as the standard for compounding methods and eliminating references
to United States Pharmacopeia and National Formulary Chapters <795>
``Pharmaceutical Compounding--Nonsterile Preparations'' and <797>
``Pharmaceutical Compounding--Sterile Preparations.'' We also revised
the recommended label statement regarding reporting of adverse events
to include reporting to the pharmacy as well as FDA.
We also made a number of changes related to recommendations for
copies of approved products. We simplified the definition of ``copy''
used in the guidance and clarified that ``clinical difference''
includes issues affecting patient compliance and the safety of these
who administer the drug, but excludes cost differences between approved
and compounded products. The final guidance includes examples of how to
briefly describe the medical rationale for making a copy, such as the
compounding pharmacist contacting the prescribing veterinarian to
obtain the rationale and noting it in the compounding records as an
alternative to the veterinarian noting the rationale on the
prescription. It also provides examples of rationales to explain why an
approved drug cannot be used in a legal extralabel manner to compound a
drug with the same active moiety.
We also made changes to lists of bulk drug substances for
compounding office stock for nonfood-producing animals or antidotes for
food-producing animals. As outlined in the Appendix to the final
guidance,\1\ we streamlined the nomination process for these bulk drug
substances, reducing the information requested by FDA to support a
nomination. The list of bulk substances to compound drugs for use in
food-producing animals has been expanded to encompass nominations of
sedatives or anesthetics for free-ranging wildlife species.
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\1\ Elsewhere in this issue of the Federal Register, FDA is
requesting nominations or renominations for bulk drug substances to
be included on the ``Lists of Bulk Drug Substances for Compounding
Office Stock Drugs for Use in Nonfood-Producing Animals or Drugs for
Use in Food-Producing Animals or Free-Ranging Wildlife Species'' for
inclusion on a list of bulk drug substances for compounding certain
animal drugs without a patient specific prescription (i.e., office
stock) for use in nonfood-producing animals or for inclusion on a
list of compounded drugs for use as antidotes for food-producing
animals or for use as sedatives or anesthetics for free-ranging
wildlife species as described in GFI #256. That Federal Register
notice describes information requested by FDA to evaluate
nominations and explains when FDA will include bulk drug substances
on a list. Such nominations will be collected in a separate docket.
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In addition, editorial changes were made to improve clarity in the
final guidance. The guidance announced in this notice finalizes the
draft guidance dated November 2019. However, as explained in section II
of this notice, the information collection recommendations footnoted
with an asterisk are subject to OMB review and approval and are not for
current implementation.
This level 1 guidance is being issued consistent with FDA's good
guidance practices regulation (21 CFR 10.115). The guidance represents
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.
[[Page 22214]]
II. Paperwork Reduction Act of 1995
In compliance with 44 U.S.C. 3507, FDA has submitted the following
proposed collection of information to OMB for review and clearance. FDA
is issuing this guidance as final, footnoting with an asterisk
recommendation that include information collection subject to review
and approval by OMB under the PRA. FDA will implement the information
collection recommendations if OMB approves them. At that time, FDA will
announce OMB approval in the Federal Register and update the guidance
to reflect this approval.
Title: Compounding Animal Drugs from Bulk Drug Substances (OMB
Control Number 0910-NEW).
Description of Respondents: The respondents to the information
collection are pharmacists in either State-licensed pharmacies or
Federal facilities, or veterinarians who compound animal drugs from
bulk drug substances.
Description: The Center for Veterinary Medicine has developed GFI
#256 to address a need for Agency guidance in its work with the animal
health industry. The guidance describes FDA's current thinking, based
on our current understanding of the risks of animal drugs compounded
from bulk drug substances, and describes the circumstances under which
FDA generally does not intend to take enforcement action against
pharmacists and veterinarians who compound animal drugs from bulk drug
substances.
In the Federal Register of November 20, 2019 (84 FR 64085), we
published a notice of availability announcing draft guidance GFI #256,
including an analysis under the PRA, and solicited public comment on
the proposed collection of information. Comments regarding the
information collection included concerns that the guidance document
will impose requirements not placed on other prescribers. In any other
setting, the comments suggested, the prescription itself serves as
documentation of the veterinarian's determination of clinical need. We
disagree with these comments suggesting that a prescription serves the
same purpose as the medical rationale documentation recommended in GFI
#256. The documentation of the medical rationale by the compounding
pharmacist is recommended for copies of approved products because a
prescription demonstrates an animal's need for a prescription drug but
does not explain why an approved product could not be used legally to
treat the animal. The medical rationale addresses the clinical need for
an animal drug compounded from a bulk drug substance when there is an
approved product available.
Our exercise of discretion is dependent upon our ability to assess
whether the circumstances under which FDA intends to exercise such
discretion, as described in the guidance, exist. FDA staff may use
pharmacy and veterinary records, among other things, to determine the
circumstances surrounding the compounding activity. Except with regard
to the recommendations that compounders document rationales for
prescribing a compounded product from a bulk drug substance, routine
business records kept by pharmacists who compound animal drugs from
bulk drug substances and veterinarians who compound animal drugs from
bulk drug substances, as well as veterinarians prescribing compounded
animal drugs within a valid veterinarian-client-patient relationship,
should be adequate to demonstrate that the circumstances described in
the guidance exist. While we believe it is usual and customary business
practice for veterinarians to document medical rationales for
prescribing a compounded product as recommended in the guidance, we
acknowledge that documenting this information by the pharmacist
compounder, as well as documenting the rationale for using a bulk drug
substance as the source of the active ingredient by the veterinarian/
pharmacist compounder, may not be usual and customary practice. We have
therefore included an estimate for recordkeeping to account for burden
beyond that which may be usual and customary for respondents who follow
the recommended documentation of rationales for compounding the drug
product from bulk drug substance as discussed in the guidance.
We estimate the burden of the information collection as follows:
Table 1--Estimated Annual Recordkeeping Burden \1\
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Number of
Number of records per Total annual
Activity recordkeepers recordkeeper records Average burden per recordkeeping Total hours
\2\
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Documenting rationales by licensed 7,500 1,134 8,505,000 0.017 (1 minute)........................ 144,585
veterinarian/pharmacist compounder.
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of information.
\2\ Rounded to the nearest whole number.
We have revised figures from our 60-day notice to reflect a more
recent review of our experience with the information collection.
Sections III.A.5 and III.A.6 of the guidance describe circumstances
under which FDA recommends veterinarian and pharmacist compounders
document the prescribing veterinarian's medical rationale and the
reason that a bulk drug substance is being used as the source of the
active ingredient. Based on our evaluation, we believe it is usual and
customary business practice for veterinarians to document the medical
rationale, as recommended in the guidance. However, we believe
pharmacist compounders may not document the information recommended in
the guidance as a usual and customary business practice. According to
the American Pharmacists Association, of the approximately 56,000
community-based pharmacies in the United States, about 7,500 pharmacies
specialize in compounding services.\2\ We assume 11,339,400
prescriptions will be written for compounded animal drugs annually.
Based on our experience with the regulation of compounded animal drugs,
we assume 50 to 75 percent of these prescriptions will result in
documenting rationales as discussed in the guidance. Using the upper-
bound estimate of 75 percent, approximately 8,504,550 prescriptions
(0.75 x
[[Page 22215]]
11,339,400 prescriptions) will necessitate documenting rationales.
Averaging this figure equally among 7,500 compounding pharmacies, 1,134
(rounded to the nearest whole number) rationales will be documented
annually, for a total of 8,505,000 records. We estimate it will take 1
minute (0.017 hours) to document the rationales described in the
guidance, for a total of 144,585 hours, as reported in table 1.
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\2\ American Pharmacists Association, ``Frequently Asked
Questions About Pharmaceutical Compounding,'' n.d., <a href="https://www.pharmacist.com/Practice/Patient-Care-Services/Compounding/Compounding-FAQs">https://www.pharmacist.com/Practice/Patient-Care-Services/Compounding/Compounding-FAQs</a> (accessed September 15, 2021). We currently have no
data on the number of veterinarians who compound drugs for
individual patients, specifically, compound drugs from bulk drug
substances for individual patients; therefore, we are including this
class of respondents in our burden estimate.
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Under 5 CFR 1320.3(b)(2), the time, effort, and financial resources
necessary to comply with a collection of information are excluded from
the burden estimate if the reporting, recordkeeping, or disclosure
activities needed to comply are usual and customary because they would
occur in the normal course of activities. If the compounded drug is
compounded for use as an antidote for food-producing animals or for use
as a sedative or anesthetic for free-ranging wildlife species, section
III.C.3 of the guidance recommends that the veterinarian establishes
and documents a scientifically based withdrawal time that ensures
residues of the: (1) Antidote and the underlying toxin or (2) sedative
or anesthetic are not present in the animal at the time of slaughter or
harvest or the veterinarian ensures the animal does not enter the food
supply. We believe that it is usual and customary for veterinarians to
establish and document a scientifically based withdrawal time as a
matter of maintaining an adequate medical record in routine practice
and, therefore, estimate no burden for the time it would take for a
veterinarian to make this record. See 5 CFR 1320.3(b)(2).
In addition, the guidance makes a number of recommendations
regarding the labeling of animal drugs compounded from bulk drug
substances. In sections III.A.8, III.B.6, and III.C.6, the guidance
recommends basic information that pharmacists and veterinarians should
include on the label of the compounded drug, such as the name and
strength of the drug and the name, address, and contact information for
the compounding pharmacy or compounding veterinarian. We believe that
it is usual and customary for pharmacists and veterinarians to include
such information on the labels of compounded animal drugs in the normal
course of their activities, and therefore, estimate no burden for the
time it would take to prepare such labeling. See 5 CFR 1320.3(b)(2).
Sections III.A.8, III.B.6, and III.C.6 of the guidance also recommend
compounders (pharmacists and veterinarians) include several specific
statements on the label of animal drugs compounded from bulk drug
substances (e.g., ``This is a compounded drug. Not an FDA approved or
indexed drug.''). Because these recommended labeling statements are
public disclosure 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)), they are exempt from OMB review and approval
under the PRA.
III. Electronic Access
Persons with access to the internet may obtain the guidance at
<a href="https://www.fda.gov/animal-veterinary/guidance-regulations/guidance-industry">https://www.fda.gov/animal-veterinary/guidance-regulations/guidance-industry</a>, <a href="https://www.fda.gov/regulatory-information/search-fda-guidance-documents">https://www.fda.gov/regulatory-information/search-fda-guidance-documents</a>, or <a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Dated: April 11, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-08092 Filed 4-13-22; 8:45 am]
BILLING CODE 4164-01-P
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