Interim Policy on Compounding Using Bulk Drug Substances Under Section 503B of the Federal Food, Drug, and Cosmetic Act

Administrative guidance, not enacted legislation. This captured publisher edition preserves the listed document and attachments; later developments are not independently consolidated.

Interim Policy on Compounding
Using Bulk Drug Substances
Under Section 503B of the
Federal Food, Drug, and
Cosmetic Act
Guidance for Industry
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
January 2025
Compounding and Related Documents

Interim Policy on Compounding
Using Bulk Drug Substances
Under Section 503B of the
Federal Food, Drug, and
Cosmetic Act
Guidance for Industry
Additional copies are available from:
Office of Communications, Division of Drug Information
Center for Drug Evaluation and Research
Food and Drug Administration
10001 New Hampshire Ave., Hillandale Bldg., 4 th Floor
Silver Spring, MD 20993-0002
Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353
Email: druginfo@fda.hhs.gov
https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
January 2025
Compounding and Related Documents

Contains Nonbinding Recommendations
TABLE OF CONTENTS
I. 	INTRODUCTION AND SCOPE..................................................................................... 1
II. 	BACKGROUND ............................................................................................................... 2
A. 	Compounding From Bulk Drug Substances Under Section 503B ............................................. 2
B. 	Section 503B Bulks List ................................................................................................................. 3
1. Section 503B Bulks List History ...................................................................................................... 3
2. Nominations for the 503B Bulks List ............................................................................................... 3
3. Process for Developing the 503B Bulks List .................................................................................... 6
C. 	Categorization Under FDA’s Interim Policy ............................................................................... 8
III. 	POLICY ........................................................................................................................... 10
A. 	Compounding From Bulk Drug Substances Nominated for the 503B Bulks List ................. 11
B. 	Substances Not Nominated, Nominated Without Adequate Support, or Nominated On or
After the Publication Date of This Guidance January 7, 2025 ................................................ 12
C. 	Comments About Nominated Bulk Drug Substances ............................................................... 13

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Interim Policy on Compounding Using Bulk Drug Substances
Under Section 503B of the Federal Food, Drug, and Cosmetic Act
Guidance for Industry1
This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on
this topic. 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.
To discuss an alternative approach, contact the FDA office responsible for this guidance as listed on the
title page.
I. 	INTRODUCTION AND SCOPE
This guidance sets forth the Food and Drug Administration’s (FDA or the Agency) interim
regulatory policy concerning compounding by outsourcing facilities registered under section
503B of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 353b)2 using bulk
drug substances. Section 503B of the FD&C Act includes certain restrictions on the bulk drug
substances that outsourcing facilities can use in compounding and directs FDA to develop a list
of bulk drug substances that can be used in compounding under that section. FDA is developing
that list of bulk drug substances (the 503B bulks list), and this guidance describes FDA’s interim
regulatory policy regarding outsourcing facilities that compound human drug products using
bulk drug substances while the list is being developed.3,4
This guidance revises and replaces the guidance for industry Interim Policy on Compounding
Using Bulk Drug Substances Under Section 503B of the Federal Food, Drug, and Cosmetic Act
1 This guidance has been prepared by multiple offices in the Center for Drug Evaluation and Research at the Food
and Drug Administration.
2 Outsourcing facility refers to a facility that meets the definition of an outsourcing facility under section 503B(d)(4)
of the FD&C Act.
3 Drug products compounded for use in animals are not within the scope of this guidance.
4 FDA is developing a separate list of bulk drug substances that can be used in compounding under section 503A of
the FD&C Act (the 503A bulks list). Because section 503A contains different criteria for the 503A bulks list and
provides for a different process for its development, the 503A bulks list is discussed in a separate guidance (see the
guidance for industry Interim Policy on Compounding Using Bulk Drug Substances Under Section 503A of the
Federal Food, Drug, and Cosmetic Act (January 2025). We update guidances periodically. To make sure you have
the most recent version of a guidance, check the FDA guidance web page at https://www.fda.gov/regulatory-
information/search-fda-guidance-documents.

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issued in January 2017 (2017 503B Interim Policy Guidance).5 This revision does not change
FDA’s policy with respect to bulk drug substances that were nominated for inclusion on the
503B bulks list before the publication date of this guidance, January 7, 2025. In contrast, bulk
drug substances that are nominated on or after the date of publication of this guidance are not
within the scope of the policy described in section III.A.2 of this guidance. FDA intends to
continue to receive and evaluate new nominations of bulk drug substances for inclusion on the
503B bulks list consistent with the process and clinical need standard established in the FD&C
Act.
In general, FDA’s guidance documents do not establish legally enforceable responsibilities.
Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only
as recommendations, unless specific regulatory or statutory requirements are cited. The use of
the word should in Agency guidances means that something is suggested or recommended, but
not required.
II. 	BACKGROUND
A. 	Compounding From Bulk Drug Substances Under Section 503B
Section 503B of the FD&C Act describes the conditions that must be satisfied for human drug
products compounded by an outsourcing facility to be exempt from the following three sections
of the FD&C Act: (1) section 505 (21 U.S.C. 355) (concerning the approval of drugs under new
drug applications or abbreviated new drug applications); (2) section 502(f)(1) (21 U.S.C.
352(f)(1)) (concerning the labeling of drugs with adequate directions for use); and (3) section
582 (21 U.S.C. 360eee-1) (concerning drug supply chain security requirements).
One of the conditions that must be met for a drug product compounded by an outsourcing facility
to qualify for these exemptions is that the outsourcing facility does not compound drug products
using a bulk drug substance unless (a) it appears on a list established by the Secretary of the
Department of Health and Human Services (Secretary) identifying bulk drug substances for
which there is a clinical need, or (b) the drug compounded from such bulk drug substances
appears on the drug shortage list in effect under section 506E of the FD&C Act (21 U.S.C. 356e)
at the time of compounding, distribution, and dispensing (see section 503B(a)(2)(A) of the
FD&C Act).
A bulk drug substance is defined as meaning “the same as ‘active pharmaceutical ingredient’ as
defined in [21 CFR] 207.1.”6 Active pharmaceutical ingredient is defined 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
5 The 2017 version of the guidance revised the original guidance published in 2016, Guidance for industry, Interim
Policy on Compounding Using Bulk Drug Substances Under Section 503B of the Federal Food, Drug, and Cosmetic
Act (June 2016) (the 2016 503B Interim Policy Guidance).
6 21 CFR 207.3.

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prevention of disease, or to affect the structure or any function of the body,” but the term “does
not include intermediates used in the synthesis of the substance.”7,8
Bulk drug substances used in compounding under section 503B must also meet certain other
requirements, including: (1) if an applicable monograph exists under the United States
Pharmacopeia (USP), National Formulary (NF), or another compendium or pharmacopeia
recognized by the Secretary for purposes of this paragraph, the bulk drug substance complies
with the monograph; (2) the bulk drug substance must be manufactured by an establishment that
is registered under section 510 of the FD&C Act (21 U.S.C. 360); and (3) the bulk drug
substance must be accompanied by a valid certificate of analysis (COA).9
B. 	Section 503B Bulks List
1. 	Section 503B Bulks List History
Section 503B, added to the FD&C Act by the Drug Quality and Security Act (DQSA) in 2013,
requires that FDA create a list of bulk drug substances for which there is a clinical need by
publishing a notice in the Federal Register proposing bulk drug substances for inclusion on the
list, providing a public comment period of 60 calendar days, and then publishing a notice in the
Federal Register designating bulk drug substances for inclusion on the list.10 In the December 4,
2013, Federal Register (78 FR 72838), FDA published a notice inviting all interested persons to
nominate bulk drug substances for inclusion on a list of bulk drug substances that can be used for
compounding under section 503B of the FD&C Act.
2. 	Nominations for the 503B Bulks List
In response to the December 2013 Federal Register notice, over 2,000 substances were
nominated for the 503B bulks list. However, many of the nominations for the 503B bulks list
were not for substances used in compounding as active ingredients, or they did not include
sufficient supporting information to allow FDA to evaluate the nominated substances for
7 See section 503B(a)(2) and 21 CFR 207.3. Section 503B references the definition of bulk drug substance in
FDA’s drug establishment registration and listing regulations, which was codified at 21 CFR 207.3(a)(4) at the time
section 503B was enacted. In August 2016, FDA published a final rule, “Requirements for Foreign and Domestic
Establishment Registration and Listing for Human Drugs, Including Drugs That Are Regulated Under a Biologics
License Application and Animal Drugs” (Aug 31, 2016; 81 FR 60170), to update its registration and listing
regulations in 21 CFR part 207, which made minor changes to the definition of bulk drug substance and moved the
definition to 21 CFR 207.3. The definition is also found in 21 CFR 207.1. Under the previous definition, bulk drug
substance was defined to mean “any substance that is represented for use in a drug and that, when used in the
manufacturing, processing, or packaging of a drug, becomes an active ingredient or a finished dosage form of the
drug, but the term does not include intermediates used in the synthesis of such substances.”
8 Inactive ingredients are not subject to section 503B(a)(2) or the policies described in this guidance because they
are not included within the definition of a bulk drug substance. See 21 CFR 207.3. Pursuant to section 503B(a)(3),
inactive ingredients used in compounding must comply with the standards of an applicable United States
Pharmacopeia or National Formulary monograph, if a monograph exists.
9 See section 503B(a)(2).
10 See section 503B(a)(2)(A)(i).

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placement on the list. To improve the efficiency of the process for developing the 503B bulks
list, FDA reopened the nomination process on July 2, 2014 (79 FR 37750) and provided more
detailed information on what it needs to evaluate nominations for the list. FDA stated that bulk
drug substances that were previously nominated would not be further considered unless they
were renominated and those nominations were adequately supported. Substances that were not
adequately supported would not be evaluated by FDA to be placed on the 503B bulks list. The
notice stated that the following information about clinical need is necessary to provide adequate
support for nominations to the 503B bulks list:
• 	A statement describing the medical condition(s) that the drug product to be compounded
with the nominated bulk drug substances is intended to treat;
• 	A list of FDA-approved drug products, if any, that address the same medical condition;
• 	If there are any FDA-approved drug products that address the same medical condition, an
explanation of why a compounded drug product is necessary;
• 	If the FDA-approved drug product is not suitable for a particular patient population, an
estimate of the size of the population that would need a compounded drug product;
• 	A bibliography of safety and efficacy data for the drug product compounded using the
nominated substance, if available, including any relevant peer-reviewed medical
literature; and
• 	If there is an FDA-approved drug product that includes the bulk drug substance
nominated, an explanation of why the drug product proposed to be compounded must be
compounded from the bulk drug substance rather than with the FDA-approved drug
product.
In the Federal Register of October 27, 2015 (80 FR 65770), FDA established a docket (October
2015 docket) where new nominations for these substances can be submitted with sufficient
supporting information or where nominations for substances that were not previously nominated
can be submitted.
In response to this request for nominations, as of publication of the 2016 503B Interim Policy
Guidance, approximately 2,590 unique substances were nominated. Of those nominated
substances:
• 	Approximately 1,740 are biological products (these are individual allergenic extracts)
subject to approval in a biologics license application (BLA) under section 351 of the
Public Health Service Act (PHS Act) (42 U.S.C. 262).
These products are not eligible for the 503B bulks list because biological products subject
to approval in a BLA under section 351 of the PHS Act are not eligible for the

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exemptions in section 503B of the FD&C Act.11 No biological products subject to
approval in a BLA will be considered for the 503B bulks list.
• 	At least one12 of the nominated substances is not a bulk drug substance.
This is a finished drug product that was nominated by its brand name. Finished drug
products are not eligible for the 503B bulks list because they do not meet the definition of
a bulk drug substance in 21 CFR 207.3.
• 	At least four of the nominated substances appear on the list of drugs that have been
withdrawn or removed from the market because such drug products or components of
such drug products have been found to be unsafe or not effective (withdrawn or removed
list).
Such substances cannot be used in compounding under section 503B of the FD&C Act
and, therefore, are not eligible for inclusion on the 503B bulks list.13
• 	One of the nominated substances has no currently accepted medical use and is included
on Schedule I of the Controlled Substances Act (CSA) (21 U.S.C. 812(c)).14
The CSA does not allow possession or distribution of Schedule I substances (see 21
U.S.C. 841(a)(1) and 829), except for research purposes (21 U.S.C. 823(f)), and these
substances will not be considered for the 503B bulks list at this time. Those desiring to
do research on a Schedule I substance can apply to do so under an investigational new
drug application (IND).
• 	Of the substances that may be eligible for use in compounding under section 503B,
approximately 650 substances were nominated without sufficient supporting evidence for
FDA to evaluate them.
• 	The remaining substances that were nominated for inclusion on the 503B bulks list may
be eligible for inclusion on the list and were nominated with sufficient supporting
information for FDA to evaluate them. However, FDA has identified significant safety
risks relating to the use in compounded drug products of some of these bulk drug
substances.
11 See the guidance for industry Mixing, Diluting, or Repackaging Biological Products Outside the Scope of an
Approved Biologics License Application (January 2018) for FDA’s policies regarding State-licensed pharmacies,
Federal facilities, and outsourcing facilities that mix, dilute, or repackage biological products outside the scope of an
approved BLA.
12 The nonprescription finished drug product Maalox was nominated. Maalox is not a bulk drug substance.
13 See section 503B(a)(4) of the FD&C Act. See also 21 CFR 216.24.
14 An extract of cannabidiol and tetrahydrocannabinol derived from marijuana (marihuana) was nominated. This is a
Schedule I substance.

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FDA’s website identifies the following categories of substances nominated for the 503B bulks
list:15
503B Category 1 – Substances Nominated for the Bulks List Currently Under
Evaluation: These substances may be eligible for inclusion on the 503B bulks list, were
nominated with sufficient supporting information for FDA to evaluate them, and do not
appear on any other list.
503B Category 2 – Substances Nominated for the Bulks List That Raise Significant
Safety Risks: These substances were nominated with sufficient supporting information to
permit FDA to evaluate them, and they may be eligible for inclusion on the 503B bulks list.
However, FDA has identified significant safety risks relating to the use of these substances in
compounding pending further evaluation and, therefore, does not intend to adopt the policy
described for the substances in Category 1. If FDA adds a substance to Category 2, it will
publish a public communication (e.g., a safety alert) describing the safety risks and will post
the communication on FDA’s human drug compounding website16 advising that the
substance has been added to Category 2 and is not within the scope of the policies regarding
substances in Category 1.
503B Category 3 – Substances Nominated for the Bulks List Without Adequate
Support: These substances may be eligible for inclusion on the 503B bulks list but were
nominated with insufficient supporting information for FDA to evaluate them. These
substances can be renominated with sufficient supporting information through a docket that
FDA has established, as discussed below in section III.B.
3. 	Process for Developing the 503B Bulks List
FDA is currently evaluating the bulk drug substances nominated for the 503B bulks list with
sufficient supporting information for evaluation. FDA is considering a number of factors in
prioritizing the order in which it reviews these nominated bulk drug substances, including but not
limited to the following:
15 See Bulk Drug Substances Used in Compounding Under Section 503B of the FD&C Act, updated September 27,
2024, available at https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-
under-section-503b-fdc-act. As discussed in the July 2014 Federal Register notice requesting nominations for the
503B bulks list (79 FR 37750), nominators were to confirm that all substances nominated for the list are active
ingredients that meet the definition of a bulk drug substance. Inclusion of a substance in any of these categories
does not reflect a determination by FDA that the substance is a bulk drug substance. Whether a substance is a bulk
drug substance subject to the conditions in section 503B(a)(2) depends on whether it meets the definition of a bulk
drug substance in 21 CFR 207.3. If the substance is used in a compounded drug product as an inactive ingredient,
then it does not meet the definition of a bulk drug substance in 21 CFR 207.3, is not subject to the conditions in
section 503B(a)(2), and need not appear on the 503B bulks list to be eligible for use in compounding. Instead, when
used as an inactive ingredient, the substance is subject to the conditions in section 503B(a)(3), which applies to
ingredients other than bulk drug substances used in compounded drug products.
16 See https://www.fda.gov/drugs/guidance-compliance-regulatory-information/human-drug-compounding. FDA
also encourages compounding facilities to subscribe to FDA’s list serve to receive updates at
https://www.fda.gov/drugs/human-drug-compounding/information-outsourcing-facilities#subscribe.

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• 	Safety concerns about use of the bulk drug substance in compounding
• 	Whether the bulk drug substance was nominated by multiple parties or identified as
necessary by medical professional organizations
• 	The efficiency with which the evaluation can be completed, based on ease of acquiring
the necessary information to conduct the review, available resources, and other logistical
issues
FDA may also group some nominated drug substances to facilitate efficient review and
discussion. These include drug substances that raise similar issues (e.g., vitamins, botanicals) or
that are nominated for the treatment of the same condition (e.g., warts).
FDA intends to publish a notice in the Federal Register that describes FDA’s proposed position
on each substance FDA has evaluated, along with the rationale for that proposal, for public
comment. We note that there is no requirement in section 503B to consult the Pharmacy
Compounding Advisory Committee (PCAC) before developing a 503B bulks list, as is required
by section 503A(c)(1) for a separate list of bulk drug substances that can be used in
compounding under section 503A of the FD&C Act (503A bulks list). However, after
considering public comment on the nominated substances, FDA will determine whether PCAC
input on any of the substances would be helpful to the Agency in making its determination, and
if so, it will seek PCAC input. Once FDA makes a determination, it will publish in the Federal
Register a list identifying the bulk drug substances for which it has determined there is a clinical
need and FDA’s rationale in making that determination. FDA will also publish in the Federal
Register a list of those substances it considered but found that there is no clinical need to use in
compounding and FDA’s rationale in making this determination.
Once FDA publishes a 503B bulks list in the Federal Register that reflects its determination
regarding particular bulk drug substances, drug products compounded with substances on the
503B bulks list will be eligible for the section 503B exemptions, provided the drug products
meet the other conditions of section 503B.17 Once FDA has published in the Federal Register its
decision not to place a particular substance on the 503B bulks list, the substance is no longer
within the scope of the policy described in this guidance.
FDA intends to evaluate the substances nominated for the 503B bulks list on a rolling basis.
FDA will begin by publishing a Federal Register notice identifying a group of substances (e.g.,
10 substances) that it has considered and whether it proposes the substances for inclusion on the
503B bulks list. 	Under section 503B, an outsourcing facility may only compound using bulk
drug substances that are on FDA’s 503B bulks list or that are used to compound drug products
that appear on FDA’s drug shortage list in effect under section 506E of the FD&C Act at the
time of compounding, distribution, and dispensing. To avoid unnecessary disruption to patient
treatment while FDA considers the substances that were nominated with sufficient support to
permit FDA to evaluate them, FDA is issuing this guidance stating that at this time it does not
intend to take action against an outsourcing facility for failing to compound in accordance with
section 503B(a)(2) if certain conditions are met. Those conditions include that the nomination
17 See section 503B(a)(11) of the FD&C Act.

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for the relevant bulk drug substance appears on Category 1 on FDA’s website. As described
below, FDA does not intend to categorize bulk drug substances as described in section II.B.2 that
are nominated on or after the publication date of this guidance.
C. 	Categorization Under FDA’s Interim Policy
Section 503B of the FD&C Act directs FDA to establish a list of bulk drug substances for which
there is a clinical need.18 Stakeholders advised FDA that some of the compounded drug
products, which patients may have received before enactment of DQSA in 2013, were important
for patient care. Stakeholders further advised FDA that some of the compounded drug products
containing nominated bulk drug substances were important for “office stock” or for “office use”
by hospitals, clinics, or health care practitioners to administer to patients who present with an
immediate need for a compounded drug product.19 In 2016, FDA issued 2016 503B Interim
Policy Guidance setting forth its interim policy on compounding using bulk drug substances by
outsourcing facilities. The guidance explained that the purpose of the interim policy was to
“avoid unnecessary disruption to patient treatment while FDA considers the bulk drug substances
that were nominated . . . with sufficient support to permit FDA to evaluate them.”20 As
described in the 2016 503B Interim Policy Guidance, FDA categorized bulk drug substances that
had been nominated by a certain date and explained an interim policy under which the Agency
did not intend to take action against an outsourcing facility for compounding drug products using
those bulk drug substances if certain conditions were met. However, stakeholders advised FDA
that, less than 3 years after DQSA was enacted, certain compounded drug products containing
bulk drug substances that had not yet been nominated were important for patient care.
Accordingly, in 2017, FDA published the 2017 503B Interim Policy Guidance to provide for
ongoing categorization of bulk drug substances newly nominated to the October 2015 docket.
As discussed further below, since FDA developed the 2017 503B Interim Policy Guidance,
stakeholders have had substantial opportunity to nominate new bulk drug substances for
categorization. As reflected in the updated policy described in section III below, FDA has
determined that ongoing categorization of newly nominated substances, as described in the 2017
503B Interim Policy Guidance, no longer serves the interim policy’s stated objective of avoiding
unnecessary disruption to patient treatment and does not otherwise benefit public health.
Categorizing substances nominated on or after the publication date of this guidance would
unnecessarily expose patients to the risks associated with drug products compounded from such
bulk drug substances.
18 See section 503B(a)(2)(A)(i) of the FD&C Act.
19 In contrast to compounders operating under section 503A, outsourcing facilities can distribute compounded drug
products to health care practitioners or health care facilities without first receiving a prescription for an identified
individual patient. Compare sections 503B(d)(4)(C) and section 503A(a) of the FD&C Act; see also the guidance
for industry Prescription Requirement Under Section 503A of the Federal Food, Drug, and Cosmetic Act (December
2016).
20 2016 503B Interim Policy Guidance at 7, available at https://www.regulations.gov/document/FDA-2015-D-3539-
0014.

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Drug products compounded from bulk drug substances nominated for inclusion on the 503B
bulks list may present particular risks when FDA has not yet completed the process to conclude
whether they will be placed on the 503B bulks list. Pursuant to the clinical need standard in
section 503B(a)(2)(A) of the FD&C Act, FDA places a bulk drug substance on the 503B bulks
list if the Agency concludes that there is a clinical need for an outsourcing facility to compound a
drug product, and the drug product must be compounded using the bulk drug substance.21 Under
this standard, FDA proposes adding a bulk drug substance to the 503B bulks list only after
Agency medical and scientific experts have, among other things, evaluated the physical and
chemical characterization of the substance; any safety issues raised by the use of the substance in
compounded drug products; current and historical use of the substance in compounded drug
products; and available evidence of effectiveness or lack of effectiveness of a drug product
compounded with the substance, if any such evidence exists, and preliminarily concluded that
these factors weigh in favor of inclusion of the bulk drug substance on the list. FDA must
consider public comment regarding a proposal before making its final determination.22 Although
FDA’s evaluation of a substance for the 503B bulks list is, necessarily, far less rigorous and less
comprehensive than the Agency’s review of drugs as part of the new drug approval process, this
evaluation process for clinical need is important to help limit patient exposure to compounded
drug products, which have not been demonstrated to be safe and effective, to those situations in
which the compounded drug product is necessary for patient treatment, and serves an important
role in preserving the integrity of the drug approval process.23
In the early days of DQSA implementation, FDA recognized that patients may have a medical
need for treatment with certain drugs that they may have received prior to enactment of the
DQSA, but that were compounded from bulk drug substances that the Agency had not yet
evaluated for inclusion on the 503B bulks list. In developing the 2017 503B Interim Policy
Guidance, FDA weighed these public health interests and concluded that, at that early stage of
section 503B implementation, the potential patient benefits of such a policy outweighed the
risks. Importantly, FDA characterized the guidance as an interim policy because the Agency
intended for it to be temporary. For the reasons that follow, FDA is ending categorization of
newly nominated substances because the Agency believes such a policy no longer serves the
guidance’s stated objective of preventing unnecessary disruption to patient treatment, and
therefore, the balance of public health interests supporting the policy has changed.
In the approximately 7 years since FDA issued the 2017 503B Interim Policy Guidance,
providing for ongoing categorization of bulk drug substances newly nominated to the October
2015 docket, nominators have had substantial opportunity to nominate bulk drug substances with
sufficient supporting information for placement in Category 1. A substance that has not been
21 In addition, with respect to a bulk drug substance that is a component of an FDA-approved drug product, FDA
considers whether there is an attribute of the FDA-approved drug product that makes it medically unsuitable for the
proposed condition and the compounded drug product is intended to address that attribute, and whether the drug
product must be compounded from a bulk drug substance. See the guidance for industry Evaluation of Bulk Drug
Substances Nominated for Use in Compounding Under Section 503B of the Federal Food, Drug, and Cosmetic Act
(March 2019) (503B Evaluation Guidance) at 9.
22 Sections 503B(a)(2)(A)(i)(II) and (III) of the FD&C Act.
23 See the 503B Evaluation Guidance at 9.

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used to compound drug products during that period cannot reasonably be considered necessary to
avoid disruption to patient treatment. Nor do we expect the policy in section III.B to adversely
affect market stability because, among other reasons, FDA intends to retain the policy, described
in section III.A.2 of this guidance, for bulk drug substances already placed in existing Category
1. In addition, FDA intends to continue to receive and evaluate new nominations for inclusion
on the 503B bulks list consistent with the process and clinical need standard established in the
FD&C Act.
Accordingly, the balance of public health interests relating to categorization of newly nominated
bulk drug substances has changed. As discussed above, FDA’s process for evaluating and
proposing inclusion of bulk drug substances on the 503B bulks list ensures that FDA and the
public can carefully consider a bulk drug substance nominated for the 503B bulks list before
outsourcing facilities can use it in compounding under section 503B of the FD&C Act. During
this process, FDA may, for example, uncover safety risks or effectiveness concerns, or concerns
about the physical and chemical characterization of the substance, that could place patients at
risk. These concerns may not be apparent until FDA and other experts conduct the evaluation of
the substance under consideration for the 503B bulks list.24 FDA also believes that the public
health is best served by FDA leveraging its limited resources to develop the 503B bulks list
rather than to categorize newly nominated substances.
However, FDA does recognize that certain substances that currently appear in Category 1 may
be important for patient care and that the Agency has not yet made a final determination as to
whether these substances will appear on the 503B bulks list. Thus, at this time, FDA is retaining
the policy outlined in section III.A.2 of this guidance, which concerns substances nominated
prior to the date of publication of this guidance, until the Agency publishes a notice in the
Federal Register making a final listing determination for such substances, or unless the Agency
removes the substances from Category 1 based on, for example, information about safety risks.
III. 	POLICY
As discussed below, FDA does not intend to categorize bulk drug substances that the public
nominates for inclusion on the 503B bulks list on or after the publication date of this guidance
January 7, 2025. Although the Agency intends to continue to receive and evaluate new
nominations of bulk drug substances for possible inclusion on the 503B bulks list, FDA does not
intend to place such bulk drug substances in categories published on FDA’s website prior to
evaluating them in accordance with section 503B(a)(2). FDA is evaluating bulk drug substances
nominated for the 503B bulks list on a rolling basis.
24 Prior to placing an adequately supported substance in Category 1, it has been FDA’s practice to preliminarily
assess whether the substance appears to present significant safety risks such that it should be placed in Category 2.
However, some risks may not be apparent until FDA conducts the evaluation under the statutory clinical need
standard, considers public comment, and makes a determination as to whether the substance meets the statutory
clinical need standard for placement on the 503B bulks list.

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A. 	Compounding From Bulk Drug Substances Nominated for the 503B Bulks
List
Under section 503B(a)(2)(A) of the FD&C Act, a bulk drug substance cannot be used in
compounding unless it is used to compound a drug product that appears on FDA’s drug shortage
list at the time of compounding, distribution, and dispensing, or it appears on the 503B bulks
list.25 However, at this time, FDA does not intend to take action against an outsourcing facility
for compounding drug products using certain bulk drug substances that are not eligible for use in
compounding under section 503B, as outlined below.
1. 	Bulk drug substances used to compound drug products in shortage
At this time, FDA does not intend to take action against an outsourcing facility for compounding
a drug product using a bulk drug substance that is not on the 503B bulks list if the drug product
compounded from the bulk drug substance: (i) appeared on FDA’s drug shortage list within 60
days of distribution and dispensing and (ii) was to fill an order that the outsourcing facility
received for the drug product while it was on FDA’s drug shortage list.26
2. 	Bulk drug substances not used to compound drug products in shortage
At this time FDA does not intend to take action against an outsourcing facility for compounding
a drug product using a bulk drug substance that does not appear on the 503B bulks list, that is not
used to compound a drug product that appears on FDA’s drug shortage list at the time of
compounding, distribution, and dispensing, and that is not within the scope of the policy
described in (1)(i) and (ii) above, if all of the following circumstances are present:
a. 	The bulk drug substance appears on 503B Category 1 on FDA’s website at
https://www.fda.gov/media/94164/download. A Category 1 substance may be eligible
for inclusion on the 503B bulks list, was nominated for inclusion on the 503B bulks list
before the publication date of this guidance with adequate supporting information for
FDA to evaluate the substance, and has not been identified by FDA as a substance that
appears to present a significant safety risk in compounding before a determination as to
whether to place it on the 503B bulks list has been made.
25 See section 503B(a)(2)(A) of the FD&C Act.
26 An outsourcing facility may not be able to predict when a drug shortage will be resolved, and the facility may
have orders for a compounded drug product in-house that were in progress when the drug product was removed
from FDA’s drug shortage list (e.g., the outsourcing facility may have compounded a drug product while it was in
shortage, but the shortage ended while the outsourcing facility awaits the results of sterility testing before release).
This policy provides some regulatory flexibility where an outsourcing facility fills orders that it received while a
drug was in shortage. However, this policy does not pertain to an outsourcing facility continuing to fill orders
received after the shortage ends or if the outsourcing facility continues to fill orders more than 60 days after the drug
product was removed from FDA’s drug shortage list.

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b. 	The original manufacturer and all subsequent manufacturers of the bulk drug substance
are establishments that are registered under section 510 (including foreign establishments
that are registered under section 510(i)) of the FD&C Act;
c. 	The bulk drug substance is accompanied by a valid COA;
d. 	If the bulk drug substance is the subject of an applicable USP or NF monograph, the bulk
drug substance complies with the monograph; and
e. 	The drug product compounded using the bulk drug substance is compounded in
compliance with all other provisions of section 503B of the FD&C Act.
Original manufacturer means the entity that originally produced the bulk drug substance and not
a subsequent packer, repacker, labeler, or distributor.
A drug product compounded using a bulk drug substance is not within the scope of the policy
described in section III.A.2 unless all of the above circumstances (a)-(e) are present. For
example, drug products compounded from the following bulk drug substances are not within the
scope of this policy: (1) substances not nominated for the 503B bulks list or that were nominated
on or after the publication date of this guidance January 7, 2025; and (2) substances that are the
subject of a final determination as to whether they will be included, or not included, on the 503B
bulks list.
B. 	Substances Not Nominated, Nominated Without Adequate Support, or
Nominated On or After the Publication Date of This Guidance January 7,
2025
As stated above, one of the categories of bulk drug substances FDA has identified on its website
contains nominated substances that may be eligible for inclusion on the 503B bulks list, but that
FDA is unable to evaluate for inclusion on the list at this time because the substances were
nominated with insufficient supporting evidence for FDA to evaluate them (503B Category 3).
New nominations for these substances with sufficient supporting information or nominations for
substances that were not previously nominated can be submitted to the October 2015 docket.
After a substance is nominated to the October 2015 docket,27 FDA will determine whether the
nomination is supported with sufficient supporting information to allow FDA to evaluate it.
Previously, after FDA made that determination, the nominated substance was placed in one of
the three categories described in section II.B.2 above, and the categorization was published on
the FDA website. Section III.A.2 of this guidance sets forth a policy that addresses substances
once they have been categorized. This guidance retains the policy described in section III.A.2
with respect to substances that appear in the categories described in section II.B.2.
27 This includes new nominations of substances submitted with sufficient supporting information.

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However, with respect to substances nominated on or after the publication date of this guidance
January 7, 2025, including new nominations of substances that currently appear in Category 3,28
FDA does not intend to place such substances into the categories described in section II.B.2.
Accordingly, substances nominated on or after the publication date of this guidance are not
within the scope of the policy described in section III.A.2 of this guidance. FDA intends to
continue to evaluate such substances, provided they are nominated with sufficient supporting
information to permit an evaluation, for inclusion on the 503B bulks list pursuant to section
503B(a)(2) of the FD&C Act.29
C. 	Comments About Nominated Bulk Drug Substances
If a nominator feels that a substance that it nominated before the publication date of this
guidance does not appear on the appropriate category as described in this guidance, the
nominator can submit a comment to docket number FDA-2015-N-3469. If the nominator has
additional information on a previously nominated substance that was placed in Category 3, the
nominator can submit a new nomination for the substance that includes the additional
information. As described in section III.B of this guidance, FDA does not intend to categorize a
substance nominated on or after the publication date of this guidance January 7, 2025. However,
if the new nomination includes sufficient supporting information to permit an evaluation, FDA
intends to consider the substance for inclusion on the 503B bulks list.
A nominator may also submit a comment to the docket requesting withdrawal of any of its
nominations. If the substance that is the subject of such nomination appears in one of the
categories, and the party nominating the substance was the sole nominator, FDA will update the
categories described in this guidance to reflect the withdrawn nomination.30 FDA intends to
provide notice to the public before removing any nominated substances from Category 1 or
Category 2.
Withdrawal of a nomination upon the nominator’s request, and if applicable, a resulting update
to the categories described in this guidance, do not reflect a determination by FDA regarding the
validity of the nomination or of any reasons given by the nominator for requesting withdrawal.
In addition, FDA may continue to evaluate a substance at its discretion even if the nominator
submits a comment requesting withdrawal of the nomination.
28 This includes new nominations of substances in Category 3 that include sufficient supporting information to
permit FDA evaluation for the 503B bulks list.
29 See also the 503B Evaluation Guidance.
30 If multiple parties nominated the same substance, each party that nominated the substance must withdraw its
nomination for the nominated substance to be considered withdrawn and for the categories to be updated, if
applicable, to reflect that withdrawal.