[Federal Register Volume 86, Number 192 (Thursday, October 7, 2021)]
[Notices]
[Pages 55847-55851]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[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Federal Food, Drug, and Cosmetic Act; Revised Draft Guidance for 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availability of a revised draft guidance for industry entitled 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Federal Food, Drug, and Cosmetic Act'' (``revised draft guidance''). 
This revised draft guidance, when finalized, will describe how FDA 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 This draft 
guidance revises the draft guidance issued in 2016 entitled, ``Hospital 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Cosmetic Act'' (``draft guidance''). FDA is revising the draft guidance 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draft guidance is not final nor is it in effect at this time.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draft guidance by December 6, 2021 to ensure that the Agency considers 
your comment on this revised draft guidance before it begins work on 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comments on the proposed collection of information in the revised draft 
guidance by December 6, 2021.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]]

     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to https://www.regulations.gov 
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 https://www.regulations.gov.
     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:
     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.
     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 https://www.regulations.gov or at the Dockets Management Staff between 9 a.m. 
and 4 p.m., Monday through Friday, 240-402-7500.
     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 https://www.regulations.gov. 
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: https://www.govinfo.gov/content/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to https://www.regulations.gov 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, PRAStaff@fda.hhs.gov.

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:
     Section 501(a)(2)(B) (21 U.S.C. 351(a)(2)(B)) (concerning 
current good manufacturing practice (CGMP) requirements);
     Section 502(f)(1) (21 U.S.C. 352(f)(1)) (concerning the 
labeling of drugs with adequate directions for use); and
     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
----------------------------------------------------------------------------------------------------------------
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).
                                 -------------------------------------------------------------------------------
    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\
----------------------------------------------------------------------------------------------------------------
                                                   Number of       Total
            Activity               Number of      records per      annual      Average burden per    Total hours
                                 recordkeepers   recordkeeper     records         recordkeeping
----------------------------------------------------------------------------------------------------------------
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).
                                --------------------------------------------------------------------------------
    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 https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm or 
https://www.regulations.gov.

    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


