81 FR 37502 - Interim Policy on Compounding Using Bulk Drug Substances Under Section 503A of the Federal Food, Drug, and Cosmetic Act; Guidance for Industry; Availability.

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Federal Register Volume 81, Issue 112 (June 10, 2016)

Page Range		37502-37504
FR Document		2016-13799

The Food and Drug Administration (FDA or Agency) is announcing the availability of a guidance for industry entitled ``Interim Policy on Compounding Using Bulk Drug Substances Under Section 503A of the Federal Food, Drug, and Cosmetic Act.'' The guidance describes FDA's interim regulatory policy regarding the use of bulk drug substances by licensed pharmacists in State-licensed pharmacies or Federal facilities and by licensed physicians to compound human drug products while FDA develops the list of bulk drug substances that can be used in compounding under section 503A of the Federal Food, Drug, and Cosmetic Act (the FD&C Act).

Federal Register, Volume 81 Issue 112 (Friday, June 10, 2016)

[Federal Register Volume 81, Number 112 (Friday, June 10, 2016)]
[Rules and Regulations]
[Pages 37502-37504]
From the Federal Register Online  [www.thefederalregister.org]
[FR Doc No: 2016-13799]


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

DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Chapter I

[Docket No. FDA-2015-D-3517]


Interim Policy on Compounding Using Bulk Drug Substances Under 
Section 503A of the Federal Food, Drug, and Cosmetic Act; Guidance for 
Industry; Availability.

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of availability.

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

SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the availability of a guidance for industry entitled ``Interim Policy 
on Compounding Using Bulk Drug Substances Under Section 503A of the 
Federal Food, Drug, and Cosmetic Act.'' The guidance describes FDA's 
interim regulatory policy regarding the use of bulk drug substances by 
licensed pharmacists in State-licensed pharmacies or Federal facilities 
and by licensed physicians to compound human drug products while FDA 
develops the list of bulk drug substances that can be used in 
compounding under section 503A of the Federal Food, Drug, and Cosmetic 
Act (the FD&C Act).

DATES: Submit electronic or written comments on Agency guidances at any 
time.

ADDRESSES: You may submit comments as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to http://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 http://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): Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Division of 
Dockets Management, 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-2015-D-3517 for ``Interim Policy on Compounding Using Bulk Drug 
Substances 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 
http://www.regulations.gov or at the Division of Dockets Management 
between 9 a.m. and 4 p.m., Monday through Friday.
     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 http://www.regulations.gov. 
Submit both copies to the Division of Dockets Management. 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

[[Page 37503]]

the information at: http://www.fda.gov/regulatoryinformation/dockets/default.htm.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to http://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 Division of Dockets Management, 5630 Fishers 
Lane, Rm. 1061, Rockville, MD 20852.
    Submit written requests for single copies of this 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 
requests. See the SUPPLEMENTARY INFORMATION section for electronic 
access to the guidance document.

FOR FURTHER INFORMATION CONTACT: Sara Rothman, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 51, Rm. 5197, Silver Spring, MD 20993-0002, 301-
796-3110.

SUPPLEMENTARY INFORMATION: 

I. Background

    FDA is announcing the availability of a guidance for industry 
entitled ``Interim Policy on Compounding Using Bulk Drug Substances 
Under Section 503A of the Federal Food, Drug, and Cosmetic Act.'' 
Section 503A of the FD&C Act (21 U.S.C. 353a) 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 505 (21 U.S.C. 355) (concerning the approval of 
drugs under new drug applications or abbreviated new drug 
applications);
     Section 502(f)(1) (21 U.S.C. 352(f)(1)) (concerning the 
labeling of drugs with adequate directions for use); and
     Section 501(a)(2)(B) (21 U.S.C. 351(a)(2)(B)) (concerning 
current good manufacturing practice requirements).
    One of the conditions that must be met for a compounded drug 
product to qualify for these exemptions is that a licensed pharmacist, 
or licensed physician, compounds the drug product using bulk drug 
substances that:
    (1) Comply with the standards of an applicable United States 
Pharmacopeia (USP) or National Formulary (NF) monograph, if a monograph 
exists, and the USP chapter on pharmacy compounding;
    (2) If such a monograph does not exist, are drug substances that 
are components of drugs approved by the Secretary; or
    (3) If such a monograph does not exist and the drug substance is 
not a component of a drug approved by the Secretary, appears on a list 
developed by the Secretary through regulations issued by the Secretary 
under subsection (c) of section 503A (503A bulks list).
    (See section 503A(b)(1)(A)(i) of the FD&C Act).
    This guidance describes the conditions under which FDA does not 
intend to take action against a licensed pharmacist or licensed 
physician for compounding a drug product from a bulk drug substance 
that is not the subject of an applicable USP or NF monograph, is not a 
component of an FDA-approved drug, or does not appear on the list of 
bulk drug substances that can be used in compounding under section 
503A(b)(1)(A)(i)(III) of the FD&C Act while FDA is developing the 503A 
bulks list.\1\ The guidance also describes FDA's process to establish 
the 503A bulks list and describes categories of substances that were 
nominated for inclusion on the 503A bulks list. The guidance includes a 
link to FDA's Web site listing bulk drug substances in each of the 
following categories:
---------------------------------------------------------------------------

    \1\ Elsewhere in this issue of the Federal Register, the Agency 
is making available a final guidance entitled ``Interim Policy on 
Compounding Using Bulk Drug Substances Under Section 503B of the 
Federal Food, Drug, and Cosmetic Act,'' which describes the 
conditions under which FDA does not intend to take action against an 
outsourcing facility for compounding a drug product from certain 
bulk drug substances while FDA develops the list of bulk drug 
substances that can be used in compounding under section 
503B(a)(2)(A)(i) of the FD&C Act.
---------------------------------------------------------------------------

    503A Category 1--Bulk Drug Substances Under Evaluation: These bulk 
drug substances may be eligible for inclusion on the 503A bulks list, 
were nominated with sufficient supporting information for FDA to 
evaluate them, and do not appear on any other list.
    503A Category 2--Bulk Drug Substances That Raise Significant Safety 
Risks: These bulk drug substances were nominated with sufficient 
supporting information to permit FDA to evaluate them and they may be 
eligible for inclusion on the 503A bulks list. However, FDA has 
identified significant safety risks relating to the use of these bulk 
substances in compounding, and therefore does not intend to adopt the 
policy described for the bulk substances in Category 1.
    503A Category 3--Bulk Drug Substances Nominated Without Adequate 
Support: These bulk drug substances may be eligible for inclusion on 
the 503A bulks list, but were nominated with insufficient supporting 
information for FDA to evaluate them. These substances can be re-
nominated with sufficient supporting information through a docket that 
FDA has established.
    In the Federal Register of October 27, 2015 (80 FR 65781), FDA 
issued a notice announcing the availability of the draft version of 
this guidance. The comment period on the draft guidance ended on 
December 28, 2015. FDA received 14 comments on the draft guidance. In 
response to received comments or on its own initiative, FDA made 
several changes to the guidance to clarify particular points. In 
addition, FDA has made the following updates to the lists on its Web 
site of bulk drug substances that were nominated for inclusion on the 
503A bulks list: \2\
---------------------------------------------------------------------------

    \2\ In the future, if FDA makes changes to the categories of 
bulk drug substances on its Web site, we intend to follow the 
procedure identified in the guidance.
---------------------------------------------------------------------------

    1. 503A Category 2: FDA has added two bulk drug substances to 
Category 2, quinacrine hydrochloride for intrauterine administration 
and germanium sesquioxide, because FDA identified significant safety 
risks relating to the use of these bulk substances in compounding.
    2. 503A Category 3: FDA removed bulk drug substances from Category 
3 that the Agency previously included on this list in error. Many of 
these substances are components of FDA-approved drugs or the subject of 
an applicable USP or NF monograph, and, therefore, can be used in 
compounding under section 503A without being placed on the 503A bulks 
list.
    3. 503A Category 4: The draft interim guidance included a fourth 
category of bulk drug substances that would have identified substances 
that FDA evaluated for inclusion on the 503A bulks list but, after 
notice-and-comment rulemaking, decided not to place on the 503A bulks 
list. In the final interim guidance, FDA removed this fourth category 
because the Agency intends to identify the bulk drug substances that 
will not be placed on the 503A bulks list in the final rule that 
establishes the 503A bulks list. Therefore, we do not believe it is 
necessary to also include them in the categories identified in this 
guidance.
    In this document, FDA is also announcing a Level 2 change to the 
final guidance, ``Pharmacy Compounding of

[[Page 37504]]

Human Drug Products Under Section 503A of the FD&C Act,'' (503A Final 
Guidance) published in 2014 (79 FR 37742) and revised in 2015 (80 FR 
65781). That guidance stated, ``Until a bulk drug substances list is 
published in the Federal Register as a final rule, human drug products 
should be compounded using only bulk drug substances that are 
components of drugs approved under section 505 of the FD&C Act, or are 
the subject of USP or NF monographs.''
    When FDA issued the interim guidance concerning compounding using 
certain bulk drug substances under section 503A (Interim 503A Bulks 
Guidance) as a draft guidance for public comment, FDA announced in the 
notice of availability that because this draft interim guidance 
proposed to change the Agency's policy relating to compounding with 
bulk drug substances while FDA develops a list of bulk drug substances 
that can be used in compounding, FDA was adding a footnote to the 503A 
final guidance referencing this draft interim guidance. FDA stated that 
once this Interim 503A Bulks Guidance is finalized, FDA would remove 
that footnote from the 503A final guidance and cross-reference the 
final Interim 503A Bulks Guidance as establishing the policy for 
compounding with bulk drug substances during the development of the 
503A bulks list.
    Therefore, concurrent with the issuance of the final Interim 503A 
Bulks Guidance, FDA is removing the sentence in the 503A final guidance 
referenced previously and is replacing it with the following statement, 
which the Agency proposed for public comment in the draft Interim 503A 
Bulks Guidance: ``FDA's interim policy concerning bulk drug substances 
that are not components of drugs approved under section 505 of the FD&C 
Act or that are not the subject of applicable USP or NF monographs can 
be found in the guidance, `Interim Policy on Compounding Using Bulk 
Drug Substances Under Section 503A of the Federal Food, Drug and 
Cosmetic Act.' '' This change is a Level 2 change under 21 CFR 10.115, 
and comments on the proposed change in policy were solicited as part of 
the notice of availability of the draft Interim 503A Bulks Guidance.

II. Electronic Access

    Persons with access to the Internet may obtain the guidance at 
either http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm or http://www.regulations.gov.

    Dated: June 7, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-13799 Filed 6-9-16; 8:45 am]
 BILLING CODE 4164-01-P

37504 Federal Register / Vol. 81, No. 112 / Friday, June 10, 2016 / Rules and Regulations

Human Drug Products Under Section Dated: June 7, 2016. is insolvent. Section 108(d)(1) through
503A of the FD&C Act,’’ (503A Final Leslie Kux, (3) provide the meaning of the terms
Guidance) published in 2014 (79 FR Associate Commissioner for Policy. ‘‘indebtedness of the taxpayer,’’ ‘‘title 11
37742) and revised in 2015 (80 FR [FR Doc. 2016–13799 Filed 6–9–16; 8:45 am] case,’’ and ‘‘insolvent,’’ for purposes of
65781). That guidance stated, ‘‘Until a BILLING CODE 4164–01–P
applying section 108, and each
bulk drug substances list is published in definition uses the term ‘‘taxpayer.’’
the Federal Register as a final rule, Section 7701(a)(14) defines ‘‘taxpayer’’
human drug products should be as any person subject to any internal
DEPARTMENT OF THE TREASURY
compounded using only bulk drug revenue tax.
substances that are components of drugs Internal Revenue Service On April 13, 2011, the Treasury
approved under section 505 of the FD&C Department and the IRS published in
Act, or are the subject of USP or NF 26 CFR Part 1 the Federal Register (76 FR 20593) a
monographs.’’ notice of proposed rulemaking (REG–
[TD 9771] 154159–09) (the proposed regulations)
When FDA issued the interim
guidance concerning compounding RIN 1545–BJ14 to provide rules under section 108(a)
using certain bulk drug substances regarding the term ‘‘taxpayer’’ for
under section 503A (Interim 503A Bulks Guidance Under Section 108(a) purposes of applying section 108 to the
Guidance) as a draft guidance for public Concerning the Exclusion of Section discharge of indebtedness income of a
comment, FDA announced in the notice 61(a)(12) Discharge of Indebtedness grantor trust or an entity that is
of availability that because this draft Income of a Grantor Trust or a disregarded as an entity separate from
interim guidance proposed to change Disregarded Entity its owner (disregarded entity). The
the Agency’s policy relating to proposed regulations provide that, for
AGENCY: Internal Revenue Service (IRS), purposes of applying section
compounding with bulk drug
Treasury. 108(a)(1)(A) and (B) to the discharge of
substances while FDA develops a list of
bulk drug substances that can be used ACTION: Final regulation. indebtedness income of a grantor trust
in compounding, FDA was adding a or a disregarded entity, the term
SUMMARY: This document contains final ‘‘taxpayer,’’ as used in section 108(a)(1)
footnote to the 503A final guidance regulations relating to the exclusion
referencing this draft interim guidance. and (d)(1) through (3), refers to the
from gross income of discharge of owner of the grantor trust or the
FDA stated that once this Interim 503A indebtedness income of a grantor trust disregarded entity. The proposed
Bulks Guidance is finalized, FDA would or an entity that is disregarded as an regulations also provide that, in the case
remove that footnote from the 503A entity separate from its owner. These of a partnership, the owner rules apply
final guidance and cross-reference the final regulations provide rules regarding at the partner level to the partners to
final Interim 503A Bulks Guidance as the term ‘‘taxpayer’’ for purposes of whom the discharge of indebtedness is
establishing the policy for compounding applying the exclusion from gross allocable. For example, if a partnership
with bulk drug substances during the income of discharge of indebtedness holds an interest in a grantor trust or a
development of the 503A bulks list. income of a grantor trust or a disregarded entity, the applicability of
Therefore, concurrent with the disregarded entity. These final section 108(a)(1)(A) and (B) to the
issuance of the final Interim 503A Bulks regulations affect grantor trusts, discharge of indebtedness income is
Guidance, FDA is removing the disregarded entities, and their owners. tested by looking to each partner to
sentence in the 503A final guidance whom the income is allocable. Lastly,
DATES: Effective Date: These regulations
referenced previously and is replacing it the proposed regulations clarify that,
are effective on June 10, 2016.
with the following statement, which the subject to the special rule for
Applicability Date: These regulations
Agency proposed for public comment in partnerships under section 108(d)(6),
apply to discharge of indebtedness
the draft Interim 503A Bulks Guidance: the insolvency exclusion is available
income occurring on or after June 10,
‘‘FDA’s interim policy concerning bulk only if the owner is insolvent and the
2016.
drug substances that are not bankruptcy exclusion is available only if
components of drugs approved under FOR FURTHER INFORMATION CONTACT:
the owner is under the bankruptcy
section 505 of the FD&C Act or that are Frank J. Fisher or Amy Chang, (202) court’s jurisdiction.
not the subject of applicable USP or NF 317–6850 (not a toll-free number). The Treasury Department and the IRS
monographs can be found in the SUPPLEMENTARY INFORMATION: received written comments responding
guidance, ‘Interim Policy on to the notice of proposed rulemaking.
Compounding Using Bulk Drug Background
The comments are available for public
Substances Under Section 503A of the These final regulations contain inspection at www.regulations.gov. No
Federal Food, Drug and Cosmetic Act.’ ’’ amendments to the Income Tax public hearing was requested or held.
This change is a Level 2 change under Regulations (26 CFR part 1) under The comments are discussed in this
21 CFR 10.115, and comments on the section 108 of the Internal Revenue preamble.
proposed change in policy were Code (Code). Section 61(a)(12) provides
solicited as part of the notice of that income from the discharge of Summary of Comments and
availability of the draft Interim 503A indebtedness is includible in gross Explanation of Revisions
Bulks Guidance. income. However, such income may be After consideration of all the
asabaliauskas on DSK3SPTVN1PROD with RULES

excludable from gross income under comments, the final regulations adopt
II. Electronic Access
section 108 in certain circumstances. the proposed regulations as modified by
Persons with access to the Internet Section 108(a)(1)(A) and (B) exclude this Treasury decision. The purpose and
may obtain the guidance at either http:// from gross income any amount that scope of the proposed regulations and
www.fda.gov/Drugs/Guidance would be includible in gross income by these final regulations are primarily
ComplianceRegulatoryInformation/ reason of the discharge of indebtedness limited to defining the term ‘‘taxpayer’’
Guidances/default.htm or http:// of the taxpayer if the discharge occurs for purposes of applying the bankruptcy
www.regulations.gov. in a title 11 case or when the taxpayer and the insolvency exclusions from

VerDate Sep<11>2014 16:32 Jun 09, 2016 Jkt 238001 PO 00000 Frm 00020 Fmt 4700 Sfmt 4700 E:\FR\FM\10JNR1.SGM 10JNR1

Document Created: 2018-02-08 07:35:35
Document Modified: 2018-02-08 07:35:35

Category		Regulatory Information
Collection		Federal Register
sudoc Class		AE 2.7: GS 4.107: AE 2.106:
Publisher		Office of the Federal Register, National Archives and Records Administration
Section		Rules and Regulations
Action		Notice of availability.
Dates		Submit electronic or written comments on Agency guidances at any time.
Contact		Sara Rothman, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 5197, Silver Spring, MD 20993-0002, 301- 796-3110.
FR Citation		81 FR 37502

81 FR 37502 - Interim Policy on Compounding Using Bulk Drug Substances Under Section 503A of the Federal Food, Drug, and Cosmetic Act; Guidance for Industry; Availability.

DEPARTMENT OF HEALTH AND HUMAN SERVICESFood and Drug Administration

Federal Register Volume 81, Issue 112 (June 10, 2016)

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration