Notice2021-21970
Hospital and Health System Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act; Revised Draft Guidance for Industry; Availability
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Published
October 7, 2021
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA) is announcing the availability of a revised draft guidance for industry entitled ``Hospital and Health System Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act'' (``revised draft guidance''). This revised draft guidance, when finalized, will describe how FDA intends to apply certain provisions of the Federal Food, Drug, and Cosmetic Act (FD&C Act) to human drug products compounded by State- licensed pharmacies that are not outsourcing facilities and distributed for use within a hospital or health system. First, it addresses the requirement that compounding be based on the receipt of a valid prescription order for an identified individual patient. Second, it addresses the provision concerning compounded drug products that are essentially copies of a commercially available drug product. This draft guidance revises the draft guidance issued in 2016 entitled, ``Hospital and Health System Compounding Under the Federal Food, Drug, and Cosmetic Act'' (``draft guidance''). FDA is revising the draft guidance to address stakeholder feedback and provide further clarification on policies regarding hospital and health system compounding. This revised draft guidance is not final nor is it in effect at this time.
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<title>Federal Register, Volume 86 Issue 192 (Thursday, October 7, 2021)</title>
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[Federal Register Volume 86, Number 192 (Thursday, October 7, 2021)]
[Notices]
[Pages 55847-55851]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2021-21970]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2016-D-0271]
Hospital and Health System Compounding Under Section 503A of the
Federal Food, Drug, and Cosmetic Act; Revised Draft Guidance for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) is announcing the
availability of a revised draft guidance for industry entitled
``Hospital and Health System Compounding Under Section 503A of the
Federal Food, Drug, and Cosmetic Act'' (``revised draft guidance'').
This revised draft guidance, when finalized, will describe how FDA
intends to apply certain provisions of the Federal Food, Drug, and
Cosmetic Act (FD&C Act) to human drug products compounded by State-
licensed pharmacies that are not outsourcing facilities and distributed
for use within a hospital or health system. First, it addresses the
requirement that compounding be based on the receipt of a valid
prescription order for an identified individual patient. Second, it
addresses the provision concerning compounded drug products that are
essentially copies of a commercially available drug product. This draft
guidance revises the draft guidance issued in 2016 entitled, ``Hospital
and Health System Compounding Under the Federal Food, Drug, and
Cosmetic Act'' (``draft guidance''). FDA is revising the draft guidance
to address stakeholder feedback and provide further clarification on
policies regarding hospital and health system compounding. This revised
draft guidance is not final nor is it in effect at this time.
DATES: Submit either electronic or written comments on the revised
draft guidance by December 6, 2021 to ensure that the Agency considers
your comment on this revised draft guidance before it begins work on
the final version of the guidance. Submit electronic or written
comments on the proposed collection of information in the revised draft
guidance by December 6, 2021.
ADDRESSES: You may submit comments on any guidance at any time as
follows:
Electronic Submissions
Submit electronic comments in the following way:
[[Page 55848]]
<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-2016-D-0271 for ``Hospital and Health System Compounding Under
Section 503A of the Federal Food, Drug, and Cosmetic Act.'' 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 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 this revised draft
guidance to the Division of Drug Information, Center for Drug
Evaluation and Research, Food and Drug Administration, 10001 New
Hampshire Ave., Hillandale Building, 4th Floor, Silver Spring, MD
20993-0002. Send one self-addressed adhesive label to assist that
office in processing your request or include a fax number to which the
revised draft guidance may be sent. See the SUPPLEMENTARY INFORMATION
section for information on electronic access to the revised draft
guidance.
FOR FURTHER INFORMATION CONTACT:
With regard to the revised draft guidance: Tracy Rupp, Center for
Drug Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, Silver Spring, MD 20993, 301-796-3100.
With regard to 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#46161407153227202006202227682e2e3568212930"><span class="__cf_email__" data-cfemail="144446554760757272547270753a7c7c673a737b62">[email protected]</span></a>.
SUPPLEMENTARY INFORMATION:
I. Background
FDA is announcing the availability of a revised draft guidance for
industry entitled ``Hospital and Health System Compounding Under
Section 503A of the Federal Food, Drug, and Cosmetic Act.'' Pharmacies
located within a hospital, or standalone pharmacies that are part of a
health system, frequently provide compounded drug products for
administration within the hospital or health system. Some of these
compounders seek to compound under section 503A of the FD&C Act (21
U.S.C. 353a) and others have registered with FDA as outsourcing
facilities and are subject to section 503B of the FD&C Act (21 U.S.C.
353b).
Section 503A of the FD&C Act describes the conditions that must be
satisfied for human drug products compounded by a licensed pharmacist
in a State-licensed pharmacy or Federal facility, or by a licensed
physician, to be exempt from the following three sections of the FD&C
Act:
<bullet> Section 501(a)(2)(B) (21 U.S.C. 351(a)(2)(B)) (concerning
current good manufacturing practice (CGMP) requirements);
<bullet> Section 502(f)(1) (21 U.S.C. 352(f)(1)) (concerning the
labeling of drugs with adequate directions for use); and
<bullet> Section 505 (21 U.S.C. 355) (concerning the approval of
drugs under new drug applications or abbreviated new drug
applications).
This revised draft guidance proposes policies for FDA's application
of certain provisions of section 503A of the FD&C Act to human drug
products compounded by State-licensed pharmacies that are not
outsourcing facilities and distributed for use within a hospital or
health system. First, the revised draft guidance addresses the
requirement that compounding be based on the receipt of a valid
prescription order for an identified individual patient. Second, it
addresses the provision concerning compounded drug products that are
essentially copies of a commercially available drug product. This
revised draft guidance does not apply to human drug products compounded
by outsourcing facilities under section 503B of the FD&C Act,
compounded drug products that are not distributed for use within a
hospital or health system, or drug products compounded for use in
animals.
In the Federal Register of April 18, 2016 (81 FR 22610), FDA
announced the availability of a draft guidance for industry entitled,
``Hospital and Health System Compounding Under the Federal Food, Drug,
and Cosmetic Act''
[[Page 55849]]
(``draft guidance''). The draft guidance proposed new policies for the
application of section 503A of the FD&C Act to drug products compounded
by licensed pharmacists or physicians in State-licensed hospital or
health system pharmacies. In particular, the draft guidance described
certain circumstances under which FDA generally would not intend to
take action if a hospital or health system pharmacy distributed
compounded drug products without first receiving a patient-specific
prescription or order.
The comment period on the initial draft guidance ended on July 18,
2016. FDA received approximately 76 comments on the draft guidance. FDA
is issuing a revised draft guidance with certain changes made in
response to received comments or on its own initiative. For example,
the prescription requirement enforcement policy described in the
revised draft guidance does not consider whether the drug products are
distributed only to healthcare facilities that are located within a 1-
mile radius of the compounding pharmacy (``1-mile radius policy'').
Instead, the Agency is proposing a two-part, risk-based compliance
policy.
In addition, the revised draft guidance proposes new policies for
hospital and health system pharmacies regarding the provision in
section 503A of the FD&C Act which states that to qualify for the
exemptions under section 503A of the FD&C Act, among other conditions,
a drug product must be compounded by a licensed pharmacist or physician
who does not compound regularly or in inordinate amounts any drug
products that are essentially copies of a commercially available drug
product.
FDA is issuing this revised draft guidance to address stakeholders'
feedback, reflect additional Agency consideration of the proposed
policies, and enable the public to further review and comment before
finalization.
This revised draft guidance is being issued consistent with FDA's
good guidance practices regulation (21 CFR 10.115). The revised draft
guidance, when finalized, will represent the current thinking of FDA on
``Hospital and Health System Compounding Under Section 503A of the
Federal Food, Drug, and Cosmetic Act.'' 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.
II. Paperwork Reduction Act of 1995
Under the Paperwork Reduction Act of 1995 (PRA) (44 U.S.C. 3501-
3521), Federal Agencies must obtain approval from the Office of
Management and Budget (OMB) for each collection of information they
conduct or sponsor. ``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 concerning each proposed
collection of information before submitting the collection to OMB for
approval. To comply with this requirement, FDA is publishing notice of
the proposed collection of information set forth in this document. We
are consolidating the information collection in the revised draft
guidance with the information collections and approvals under OMB
control number 0910-0800.
With respect to the following collection of information, FDA
invites 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.
Human Drug Compounding Under Sections 503A and 503B the Federal Food,
Drug, and Cosmetic Act
OMB Control Number 0910-0800--Revision
This notice solicits comments on certain information collections
found in the revised draft guidance entitled ``Hospital and Health
System Compounding Under Section 503A of the Federal Food, Drug, and
Cosmetic Act'' (``revised draft guidance''). This guidance, when
finalized, will support implementation of the copies provisions of the
1997 Food and Drug Administration Modernization Act (FDAMA) (Pub. L.
105-115) discussed in section 503A of the FD&C Act, which were
maintained by the 2013 Drug Quality and Security Act (DQSA) (Title I of
Pub. L. 113-54).
For efficiency of Agency operations, we are revising OMB control
number 0910-0800 to include information collections relating to the
copies policies for hospital and health system pharmacies that are not
outsourcing facilities, as proposed in the revised draft guidance
document.
As proposed in section III.B of the revised draft guidance, among
other conditions, we generally would not intend to take action against
a hospital or health system pharmacy that is not an outsourcing
facility for compounding a drug product regularly or in inordinate
amounts that is essentially a copy of a commercially available drug
product, if the compounded drug product is administered only to
patients within the hospital or health system and the pharmacy obtains
from the prescriber a statement that: (1) Specifies a change between
the compounded drug product and the commercially available drug
product; (2) indicates that the compounded drug product will be
administered only to patients for whom the change produces a
significant difference from the commercially available drug product;
and (3) describes the intended patient population for the compounded
drug product. In addition, the revised draft guidance specifies that
the statement would be maintained in the hospital or health system
pharmacy to address routine orders for patients for whom the change
produces a significant difference, and a statement would be on file for
each prescriber that covers each drug product that is compounded.
As provided in section III.B of the revised draft guidance, except
for the policy proposed above regarding the documentation of a
prescriber's determination of significant difference, we propose to
apply the policies described in the guidance, ``Compounded Drug
Products That Are Essentially Copies of a Commercially Available Drug
Product Under Section 503A of the Federal Food, Drug, and Cosmetic
Act'' (``503A copies guidance'') to drug products compounded by
hospital and health system pharmacies that are not outsourcing
facilities.
As described in section III.B.2 of the 503A copies guidance, and
proposed in the revised draft guidance to apply to hospital and health
system pharmacies, if a compounder intends to rely on a prescriber
determination of significant difference to establish that a compounded
drug is not essentially a copy of a commercially available drug
product, the compounder should ensure that the determination is
documented on the prescription. If a prescription
[[Page 55850]]
does not make clear that the prescriber made the determination required
by section 503A(b)(2) of the FD&C Act, or a compounded drug is
substituted for the commercially available drug product, the compounder
can contact the prescriber and if the prescriber confirms it, make a
notation on the prescription that the compounded drug product contains
a change that makes a significant difference for the patient. The
notations should be as specific as those described in the 503A copies
guidance, and the date of the conversation with the prescriber should
be included on the prescription.
With respect to the determination of significant difference
described above, we estimate that, annually, a total of approximately
3,075 hospital or health system pharmacies (table 1) will obtain a
prescriber determination of significant difference. This estimate
represents approximately half of the hospitals in the United States,
including those that are in health systems. Of these, we estimate that
approximately half (1,538) will have hospital or health system
pharmacies that will follow the policy in the revised draft guidance,
obtaining a statement of significant difference for the intended
patient population, and approximately half (1,537) will have hospital
or health system pharmacies that will follow the policy with respect to
prescriber determination of significant difference in the 503A copies
guidance, documenting the notation on the individual patient
prescription. This estimate assumes that most pharmacies in smaller
hospitals and health systems will follow the policy in the 503A copies
guidance because a prescriber determination of significant difference
will not be routinely needed and can be most efficiently managed on a
patient-by-patient basis. On the other hand, this estimate assumes that
most pharmacies in larger hospitals and health systems will follow the
policy in the revised draft guidance because the need for a prescriber
determination of significant difference is more routinely necessary
and, therefore, most efficiently managed with a statement of
significant difference that is maintained in the hospital or health
system pharmacy to address routine orders for patients for whom the
change produces a significant difference.
We estimate that, annually, approximately 1,538 hospital or health
system pharmacies following the policy in the revised draft guidance
will obtain approximately 30 statements of significant difference for
compounded drug products, for a total of approximately 46,140
statements (table 1, row 1). We estimate that the consultation between
the hospital or health system pharmacy and the prescriber to obtain the
statement of significant difference will require approximately 5
minutes per statement (table 1, row 1).
We estimate that, annually, approximately 1,537 hospital or health
pharmacies following the policy in the 503A copies guidance will
consult a prescriber to determine whether the prescriber has made a
determination that the compounded drug product has a change that
produces a significant difference for a patient as compared to the
comparable commercially available drug and that the compounders will
document this determination on approximately 76,850 prescription orders
for compounded drug products (table 1, row 2). We estimate that the
consultation between the compounder and the prescriber and adding a
notation to each prescription that does not already document this
determination will take approximately 3 minutes per prescription order
(table 1, row 2). The average burden per consultation and notation for
pharmacies following the significant difference policy in the 503A
copies guidance, compared to pharmacies following the significant
difference policy in the revised draft guidance, is estimated to be
less (3 minutes) because the significant difference determination
described in the 503A copies policy is specific to one patient, whereas
the statement of significant difference in the revised draft guidance
describes the intended patient population.
In addition, as described in section III.B.3 of the 503A copies
guidance, and proposed in the revised draft guidance to apply to
hospital and health system pharmacies, if the drug product was
compounded because the approved drug product was not commercially
available because it was on the FDA drug shortage list, the
prescription or a notation on the prescription should note that it was
on the drug shortage list and note the date the list was checked. We
estimate that a total of approximately 4,613 hospital or health system
pharmacies will document this information on approximately 922,600
prescription orders for compounded drug products (table 1, row 3). We
estimate that checking FDA's drug shortage list and documenting this
information will require approximately 2 minutes per prescription order
(table 1, row 3).
With respect to maintaining records of the statement of significant
difference proposed in section III.B of the revised draft guidance, we
estimate that a total of approximately 1,538 hospital or health system
pharmacies will maintain approximately 46,140 statements of significant
difference (table 2, row 1). We estimate that maintaining the records
will require approximately 2 minutes per record (table 2, row 1). With
respect to maintaining records of the significant difference
determination, as provided in section III.B.5 of the 503A copies
guidance, we estimate that a total of approximately 1,537 hospital or
health system pharmacies will maintain approximately 76,850 records
(table 2, row 2). We estimate that maintaining records will require
approximately 2 minutes per record (table 2, row 2).
Also with respect to maintenance of records, as described in
section III.B.5 of the 503A copies guidance, and proposed in the
revised draft guidance to apply to hospital and health system
pharmacies, compounders under section 503A should maintain records of
(1) the frequency in which they have compounded drug products that are
essentially copies of commercially available drug products and (2) the
number of prescriptions that they have filled for compounded drug
products that are essentially copies of commercially available drug
products. We estimate that a total of approximately 3,075 hospital or
health system pharmacies will maintain approximately 61,500 records of
prescriptions that they have filled for compounded drug products that
are essentially copies of commercially available drug products (table
2, row 3). We estimate that maintaining the records will require
approximately 2 minutes per record (table 2, row 3).
We estimate the burden of this collection of information as
follows:
[[Page 55851]]
Table 1--Estimated Annual Third-Party Disclosure Burden \1\
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Number of Total
Activity Number of disclosures annual Average burden per Total hours
respondents per respondent disclosures disclosure
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Consultation between the 1,538 30 46,140 .08 (5 minutes)........ 3,691
hospital or health system
pharmacy and the prescriber to
document the statement of
significant difference (revised
draft guidance).
Consultation between the 1,537 50 76,850 .05 (3 minutes)........ 3,843
hospital or health system
pharmacy and prescriber and the
notation on the prescription
documenting the prescriber's
determination of significant
difference (503A copies
guidance).
Hospital or health system 4,613 200 922,600 .03 (2 minutes)........ 27,678
pharmacy checking FDA's drug
shortage list and documenting
on the prescription that the
drug is in shortage (503A
copies guidance).
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Total....................... ........... .............. ........... ....................... 35,212
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
Table 2--Estimated Annual Recordkeeping Burden \1\
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Number of Total
Activity Number of records per annual Average burden per Total hours
recordkeepers recordkeeper records recordkeeping
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Records of the statement of 1,538 30 46,140 .03 (2 minutes)....... 1,384
significant difference
(revised draft guidance).
Records of documentation of 1,537 50 76,850 .03 (2 minutes)....... 2,306
significant difference (503A
copies guidance).
Records of frequency and number 3,075 20 61,500 .03 (2 minutes)....... 1,845
of prescriptions filled for
compounded drug products that
are essentially a copy (503A
copies guidance).
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Total...................... ............. .............. ........... ...................... 5,535
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\1\ There are no capital costs or operating and maintenance costs associated with this collection of
information.
IV. Electronic Access
Persons with access to the internet may obtain an electronic
version of the revised draft guidance at either <a href="https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm">https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm</a> or
<a href="https://www.regulations.gov">https://www.regulations.gov</a>.
Dated: October 4, 2021.
Lauren K. Roth,
Associate Commissioner for Policy.
[FR Doc. 2021-21970 Filed 10-6-21; 8:45 am]
BILLING CODE 4164-01-P
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