Notice2022-08018
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; Request for Nominations
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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, the Agency, or we) is announcing updated information for interested parties to nominate bulk drug substances or renominate bulk drug substances that were previously nominated without adequate supporting information, 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 the guidance for industry #256 entitled "Compounding Animal Drugs from Bulk Drug Substances." Individuals may also comment on bulk drug substances that have been reviewed by FDA and added to these lists, or nominations that are currently under FDA review.
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 22222-22225]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2022-08018]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2018-N-4626]
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; Request for Nominations
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice; request for nominations.
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SUMMARY: The Food and Drug Administration (FDA, the Agency, or we) is
announcing updated information for interested parties to nominate bulk
drug substances or renominate bulk drug substances that were previously
nominated without adequate supporting information, 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 the guidance for industry #256 entitled ``Compounding
Animal Drugs from Bulk Drug Substances.'' Individuals may also comment
on bulk drug substances that have been reviewed by FDA and added to
these lists, or nominations that are currently under FDA review.
DATES: You may submit either electronic or written nominations and
comments at any time.
ADDRESSES: You may submit nominations and comments by any of the
following methods.
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 in the following ways:
<bullet> Mail/Hand Delivery/Courier (for 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-N-4626 for ``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.''
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.
<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
[[Page 22223]]
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
nominations and 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.
FOR FURTHER INFORMATION CONTACT: Cindy Burnsteel, Office of
Surveillance and Compliance (HFV-200), Food and Drug Administration,
7519 Standish Pl., Rockville, Rockville, MD 20855, 240-402-7011,
<a href="/cdn-cgi/l/email-protection#dbb8adb6b8b4b6abb7b2bab5b8be9bbdbfbaf5b3b3a8f5bcb4ad"><span class="__cf_email__" data-cfemail="1b786d767874766b77727a75787e5b7d7f7a35737368357c746d">[email protected]</span></a>.
SUPPLEMENTARY INFORMATION:
I. Background
Except with respect to the limited exemption provided by the
Federal Food, Drug, and Cosmetic Act (FD&C Act) described in the
following paragraph, statutory provisions applicable to manufactured
animal drugs under the FD&C Act also apply to animal drugs compounded
from bulk drug substances (also known as active pharmaceutical
ingredients (APIs)).\1\
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\1\ FDA regulations define ``bulk drug substance'' and ``active
pharmaceutical ingredient'' as ``any substance that is intended for
incorporation into a finished drug product and 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.'' The terms do
not include intermediates used in the synthesis of the substance. 21
CFR 207.1. ``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.'' 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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Sections 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
compounded animal drugs made from already FDA-approved animal or human
drugs. Such use is considered an extralabel use. The FD&C Act provides
that a compounded drug is exempt from the approval requirements in
section 512(a) of the FD&C Act and requirements for adequate directions
for use in section 502(f)(1) of the FD&C Act (21 U.S.C. 352(f)(1)) if
it meets the conditions set out in the statute and the extralabel use
regulations at 21 CFR part 530.
Elsewhere in this issue of the Federal Register, FDA is announcing
the availability of guidance for industry #256 entitled ``Compounding
Animal Drugs from Bulk Drug Substances'' (GFI #256).\2\ Animal drugs
compounded from bulk drug substances by pharmacists and veterinarians
violate the FD&C Act because they do not meet the requirements for
approval, current good manufacturing practice (CGMP) requirements, or
adequate directions for use. The guidance 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 512(a),
502(f), and 501(a)(2)(B) and (a)(5) (21 U.S.C 351(a)(2)(B) and (a)(5))
of the FD&C Act under the circumstances described in GFI #256.
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\2\ <a href="https://www.fda.gov/media/132567/download">https://www.fda.gov/media/132567/download</a>.
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II. Nominating Bulk Drug Substances
In a Federal Register notice published November 19, 2019, FDA
established a public docket (FDA-2018-N-4626) so that interested
parties could nominate bulk drug substances to a list of bulk drug
substances for compounding office stock drugs for use in nonfood-
producing animals or antidotes for food-producing animals (the List)
and comment on nominated and evaluated bulk drug substances (the 2019
request for nominations notice).
In conjunction with finalizing GFI #256, FDA is expanding
nominations to include drugs compounded for use as sedatives or
anesthetics for free-ranging wildlife species. We are also reorganizing
the List into two separate Lists:
1. The List of Bulk Drug Substances for Compounding Office Stock Drugs
for Use in Nonfood-Producing Animals \3\ and
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\3\ Available at <a href="https://www.fda.gov/animal-veterinary/animal-drug-compounding/list-bulk-drug-substances-compounding-office-stock-drugs-use-nonfood-producing-animals">https://www.fda.gov/animal-veterinary/animal-drug-compounding/list-bulk-drug-substances-compounding-office-stock-drugs-use-nonfood-producing-animals</a>.
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2. The List of Bulk Drug Substances for Compounding Drugs for Use in
Food-Producing Animals or Free-Ranging Wildlife Species \4\
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\4\ Available at <a href="https://www.fda.gov/animal-veterinary/animal-drug-compounding/list-bulk-drug-substances-compounding-drugs-use-food-producing-animals-or-free-ranging-wildlife">https://www.fda.gov/animal-veterinary/animal-drug-compounding/list-bulk-drug-substances-compounding-drugs-use-food-producing-animals-or-free-ranging-wildlife</a>.
Interested parties can nominate bulk drug substances to either
List, renominate bulk drug substances with adequate supporting
information that were previously nominated without adequate supporting
information, or comment on previously nominated bulk drug substances
that have been added to a List. This docket will remain open
indefinitely so that individuals may nominate and comment on bulk drug
substances at any time.
A. When will FDA include a bulk drug substance on either of the Lists?
FDA intends to include a bulk drug substance on either of the Lists
when:
1. There is no marketed FDA-approved, conditionally approved, or
indexed animal drug(s) that can be used as labeled to treat the
condition;
2. There is no marketed FDA-approved, conditionally approved, or
indexed animal or human drug(s) with the same active ingredient(s) that
could be used in an extralabel manner to treat the condition; and
3. FDA has not identified a significant safety concern specific to
the use of the bulk drug substance in animals.
For bulk drug substances used to compound drugs intended as office
stock for nonfood-producing animals, in addition to 1 to 3 above:
4. Urgent treatment with the compounded drug is necessary to avoid
animal suffering or death, or to protect public safety.
For bulk drug substances used to compound drugs intended for use as
antidotes in food-producing animals or for use as sedatives or
anesthetics for free-ranging wildlife species, in addition to 1 to 3
above:
5. There is sufficient scientific information for the prescribing
veterinarian to determine appropriate withdrawal, withholding, or
discard time(s) for meat, milk, eggs, or any food that might be derived
from the treated animal(s).
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B. How do I submit a nomination for one of the Lists?
You may submit nominations and comments to the docket through
<a href="https://www.regulations.gov">https://www.regulations.gov</a>. The information to support nominations can
be uploaded as attachments to your comment. The docket number is FDA-
2018-N-4626.
You may submit written submissions to the Dockets Management Staff
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061,
Rockville, MD 20852. All submissions must include the Docket No. FDA-
2018-N-4626 for ``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.''
C. What information should I submit with the nomination?
You may nominate specific bulk drug substances for inclusion on
either of the Lists. Each bulk drug substance should be submitted to
the docket as its own, separate nomination. Submissions to the docket
containing more than one bulk drug substance will not be considered an
adequate nomination and will not be reviewed. Nominated substances that
do not meet the definition of a bulk drug substance will not be
evaluated for inclusion on a List.
For FDA to evaluate a bulk drug substance for inclusion on a List,
you should submit the following information about the bulk drug
substance and the compounded animal drug in the nomination:
1. Description of the Bulk Drug Substance:
(a) Chemical name(s);
(b) common name(s);
2. Description of the Animal Drugs That Will be Compounded with the
Nominated Bulk Drug Substance:
(a) Dosage form(s) into which the bulk drug substance will be
compounded (e.g., capsule, tablet, suspension);
(b) strength(s) of the compounded drug(s); and
(c) intended route(s) of administration of the compounded drug(s)
(e.g., oral, topical, injection, etc.).
3. Information Requested for FDA to Evaluate Bulk Drug Substances
for Inclusion on a List:
(a) The species the drug to be compounded with the nominated bulk
drug substance is intended to treat;
(b) The disease or condition(s) the drug to be compounded with the
nominated bulk drug substance is intended to treat;
(c) If there is a marketed FDA-approved, conditionally approved, or
indexed animal drug(s) that addresses the same condition(s) in the same
species, an explanation of why a compounded drug is necessary (e.g.,
why FDA-approved, conditionally approved, or indexed animal drug(s) is
not suitable for a particular animal population);
(d) Confirmation that there is no marketed FDA-approved,
conditionally approved, or indexed drug(s) that could be prescribed to
treat the condition in the species that the drug compounded with the
nominated substance is intended to address;
(e) If known by the nominator, if the bulk drug substance is an
active ingredient in a marketed FDA-approved, conditionally approved,
or indexed animal or human drug(s), an explanation of why the animal
drug cannot be compounded from the marketed FDA-approved, conditionally
approved, or indexed animal or human drug(s).
(f) If known by the nominator, a description of any human user or
animal safety concerns associated with use of the nominated bulk drug
substance or finished compounded drug for the condition(s) in the
species that the compounded drug is intended to address. If there are
concerns, an explanation of why the concerns should not preclude
inclusion of that bulk drug substance on the List;
(g) For compounded drugs intended as office stock for nonfood-
producing animals, an explanation of why the animal drug to be
compounded with the nominated bulk drug substance is important to be
available to the veterinarian for urgent treatment to avoid animal
suffering or death, e.g., why 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
(h) For compounded drugs intended for use as antidotes to treat
toxicoses in food-producing animals, or as sedatives or anesthetics for
free-ranging wildlife species, relevant scientific literature or other
evidence that demonstrates that the prescribing veterinarian has a
basis for determining appropriate withdrawal, withholding, or discard
time(s) for meat, milk, eggs, or any food which might be derived from
the treated animal(s).
4. Contact information for FDA should there be followup questions
regarding the nomination.
D. What about drugs that have been nominated for one of the Lists and
are still under review?
FDA identifies those bulk drug substances that have been nominated
and under review at ``Bulk Drug Substances Currently Under Review.''
\5\ At this time, FDA generally intends to refrain from taking
enforcement action when these bulk drug substances currently under
review are used to compound a finished drug as described in the
nomination. Bulk drug substances will remain on ``Bulk Drug Substances
Currently Under Review'' only during FDA's review of their nomination.
If FDA completes its review and declines to place the bulk drug
substance on a List based on the information provided, FDA will place
the bulk drug substance on ``Bulk Drug Substances Reviewed and Not
Listed''; \6\ however, FDA will continue to accept and review any
adequate additional information submitted by any party that supports
the previously reviewed nomination. Should adequate additional
information be provided such that FDA can conduct further substantial
review, the bulk drug substance will again be placed on ``Bulk Drug
Substances Currently Under Review.''
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\5\ Available at: <a href="https://www.fda.gov/animal-veterinary/animal-drug-compounding/bulk-drug-substances-currently-under-review">https://www.fda.gov/animal-veterinary/animal-drug-compounding/bulk-drug-substances-currently-under-review</a>.
\6\ Available at <a href="https://www.fda.gov/animal-veterinary/animal-drug-compounding/bulk-drug-substances-reviewed-and-not-listed">https://www.fda.gov/animal-veterinary/animal-drug-compounding/bulk-drug-substances-reviewed-and-not-listed</a>.
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E. What happens when FDA approves or indexes a drug made with a bulk
substance as described on one of the Lists?
FDA intends to remove a bulk substance from a List if a finished
drug containing that substance in the appropriate dosage form and
strength is approved or indexed. Please see ``Bulk Drug Substances
Reviewed and Not Listed.''
F. What happens when FDA reviews a bulk drug substance and determines
that it cannot be placed on a List because of insufficient information
or because of other reasons (e.g., safety concerns)?
Please see ``Bulk Drug Substances Reviewed and Not Listed'' for
those bulk drug substances that have been reviewed by FDA but are not
on either List.
In a Federal Register notice published on May 19, 2015 (80 FR
28622), FDA invited all interested parties to nominate bulk drug
substances for inclusion on a list of bulk drug substances that could
be used by outsourcing facilities registered under the FD&C Act to
compound animal drugs under the conditions described in draft GFI #230,
``Compounding Animal Drugs from Bulk Drug Substances'' (announced in
the same issue of the
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Federal Register (80 FR 28624)) (the 2015 request for nominations
notice).
Although that draft guidance was subsequently withdrawn in November
2017, FDA received over 30 comments containing nominations for multiple
bulk drug substances in response to the 2015 request for nominations
notice. FDA's approach for determining whether to include a bulk drug
substance on the list described in the 2015 request for nominations
notice was substantially the same as the approach described above for
including a bulk drug substance on the ``List of Bulk Drug Substances
for Compounding Office Stock Drugs for Use in Nonfood-Producing
Animals'' in accordance with GFI #256. Therefore, and in keeping with
our intention as stated in the 2019 request for nomination notice, the
Agency is including certain of these nominated bulk drug substances on
this List. For other of these nominated bulk drug substances, finished
drugs containing the bulk drug substances in the appropriate dosage
form and strength have subsequently been approved; thus, these
nominated bulk drug substances will not appear on the List.
Some bulk drug substances were nominated in response to the 2015
request for nominations notice with insufficient supporting
information. FDA subsequently searched for additional supporting
information for these bulk substances, conducted further review, and
added those with sufficient supporting information to the ``List of
Bulk Drug Substances for Compounding Office Stock Drugs for Use in
Nonfood-Producing Animals.''
In addition, on its own initiative, FDA has identified certain bulk
drug substances that are used in minor species. Several have been
evaluated and are included on the ``List of Bulk Drug Substances for
Compounding Office Stock Drugs for Use in Nonfood-Producing Animals.''
Those identified bulk drug substances still under evaluation are
included on ``Bulk Drug Substances Currently Under Review.'' As FDA
continues to identify and evaluate bulk drug substances that are used
in minor species, we also encourage outside nominations.
Dated: April 11, 2022.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2022-08018 Filed 4-13-22; 8:45 am]
BILLING CODE 4164-01-P
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