Interim Policy on Compounding 
Using Bulk Drug Substances 
Under Section 503A 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) 
Office of Compliance/OUDLC 
 
 
January 2017 
Compounding and Related Documents 
Revision 1 
 
 
     
Interim Policy on Compounding 
Using Bulk Drug Substances 
Under Section 503A 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., 4th Floor  
Silver Spring, MD 20993-0002  
Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353 
Email: druginfo@fda.hhs.gov  
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
Office of Compliance/OUDLC 
 
January 2017 
Compounding and Related Documents 
Revision 1  Contains Nonbinding Recommendations 
 
 
TABLE OF CONTENTS 
 
 
I.  INTRODUCTION AND SCOPE .................................................................................... 1 
II.  BACKGROUND ............................................................................................................... 2 
A.  Compounding From Bulk Drug Substances Under Section 503A of the Act ........................... 2 
B.  Efforts to Develop the List of Bulk Drug Substances under Section 503A ............................... 4 
III.  POLICY ............................................................................................................................. 9 
A.  Compounding from Bulk Drug Substances under Section 503A .............................................. 9 
B.  Substances Not Nominated or Nominated Without Adequate Support ................................. 10 
C.  Comments about Nominated Bulk Drug Substances ................................................................ 10 
APPENDIX:  SUMMARY OF POLICY .................................................................................. 12  Contains Nonbinding Recommendations 
 
1
Guidance for Industry  
 
Interim Policy on Compounding Using Bulk Drug Substances Under 
Section 503A of the Federal Food, Drug, and Cosmetic Act 
 
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 Administrations (FDA or Agency) interim 
regulatory policy concerning compounding using bulk drug substances under section 503A of the 
Federal Food, Drug, and Cosmetic Act (FD&C Act or Act).  Section 503A of the FD&C Act 
includes certain restrictions on the bulk drug substances that can be used 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 this list of bulk drug substances (the 503A bulks list), and this 
guidance describes FDAs interim regulatory policy for licensed pharmacists in State-licensed 
pharmacies and Federal facilities and for licensed physicians that compound human drug 
products using bulk drug substances while the list is being developed.2,3  
 
In general, FDAs guidance documents do not establish legally enforceable responsibilities.  
Instead, guidances describe the Agencys 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.  
 
                                                 
1 This guidance has been prepared by multiple offices in the Center for Drug Evaluation and Research (CDER), in 
consultation with the Office of Regulatory Affairs at the Food and Drug Administration. 
2 This guidance does not apply to drugs compounded from bulk drug substances for use in animals.  For proposed 
policies pertaining to compounding drug products from bulk drug substances for use in animals, see FDAs draft 
guidance, Compounding Animal Drugs from Bulk Drug Substances. 
All FDA guidances are available on the FDA guidance web page.  FDA updates guidances regularly.  To 
make sure you have the most recent version of a guidance, always consult the guidance web page at 
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm. 
3 FDA is developing a separate list of bulk drug substances that can be used in compounding under section 503B of 
the FD&C Act.  Because section 503B contains different criteria for that list and provides for a different process for 
its development, the section 503B bulks list is covered under a separate guidance (see guidance for industry, Interim 
Policy on Compounding Using Bulk Drug Substances Under Section 503B of the Federal Food, Drug, and Cosmetic 
Act). 
  1     Contains Nonbinding Recommendations 
 
II.  BACKGROUND 
 
A.  Compounding From Bulk Drug Substances Under Section 503A of the Act 
 
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 505 (concerning the approval of drugs under new drug applications or abbreviated new 
drug applications); section 502(f)(1) (concerning the labeling of drugs with adequate directions 
for use); and section 501(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.4  
 
A bulk drug substance is defined as meaning the same as active pharmaceutical ingredient as 
defined in 21 CFR 207.1(b).  See 21 CFR 207.3.  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 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 (see section 
503A(b)(1)(A) and 21 CFR 207.3).5,6  FDA has interpreted an applicable USP or NF 
                                                 
4 See Section 503A(b)(1)(A)(i) of the FD&C Act. 
 
5 Section 503A references the definition of bulk drug substances in FDAs drug establishment registration and 
listing regulations, which was codified at 21 CFR 207.3(a)(4) when section 503A was enacted.  On August 31, 2016, 
FDA published a final rule in the Federal Register to update its registration and listing regulations in Part 207, which 
made minor changes to the definition of bulk drug substance and moved the definition to 21 CFR 207.3  See 81 FR 
169 (August 31, 2016).  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. 
 
6 Inactive ingredients are not subject to section 503A(b)(1)(A)(i) 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 
503A(b)(1)(B), inactive ingredients used in compounding must comply with the standards of an applicable United 
States Pharmacopeia or National Formulary monograph, if a monograph exists, and the USP chapter on pharmacy 
compounding.   
 
  2     Contains Nonbinding Recommendations 
 
monograph to mean an official USP or NF drug substance monograph. Accordingly, FDA 
does not consider USP monographs for dietary supplements to be applicable USP or NF 
monographs within the meaning of section 503A(b)(1)(A)(i)(I).     
 
Under section 503A(c)(1), before developing this list through regulation, FDA must convene and 
consult an advisory committee on compounding unless FDA determines that the issuance of such 
regulation before consultation with the advisory committee is necessary to protect the public 
health.  FDA must also consult with USP when promulgating the regulations.7  The criteria for 
determining which bulk drug substances should appear on the section 503A bulks list shall 
include historical use, reports in peer reviewed medical literature, or other criteria the Secretary 
may identify.8   
 
Bulk drug substances used in compounding under section 503A must also meet certain other 
requirements, including: (1) the bulk drug substance must be manufactured by an establishment 
registered under section 510 of the FD&C Act and (2) the bulk drug substance must be 
accompanied by a valid certificate of analysis (COA).9 
   
In July 2014, FDA issued a guidance, Pharmacy Compounding of Human Drug Products Under 
Section 503A of the Federal Food, Drug, and Cosmetic Act, that states: 
 
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.10 
 
FDA has received comments that this policy could be causing unnecessary and inappropriate 
disruptions in patient care because there are patients receiving drugs compounded with bulk drug 
substances that are not components of FDA-approved drugs, or the subject of an applicable USP 
or NF monograph, but that may ultimately be included on the 503A bulks list, and those patients 
care should not be disrupted while the list is under development.  After considering this issue, 
FDA has decided to use this guidance to describe its interim policy concerning compounding 
with bulk drug substances while the 503A bulks list is being developed.  FDA has revised the 
July 2014 guidance to state: 
 
FDAs 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 
                                                                                                                                                             
 
7 See section 503A(c)(2) of the FD&C Act. 
8 See section 503A(c)(2) of the FD&C Act. 
9 See section 503A(b)(1)(A) of the FD&C Act. 
10 See page 5 of the guidance, Pharmacy Compounding of Human Drug Products Under Section 503A of the 
Federal Food, Drug, and Cosmetic Act. 
  3     Contains Nonbinding Recommendations 
 
Compounding Using Bulk Drug Substances Under Section 503A of the Federal Food, 
Drug and Cosmetic Act.  
 
FDA seeks to avoid unnecessary disruption to patient treatment while the Agency considers the 
bulk drug substances that were nominated with sufficient support to permit FDA to evaluate 
them and promulgates the regulations required under section 503A.  Therefore, as described 
further below, FDA is issuing this interim guidance stating that it does not intend to take 
regulatory action for compounding drug products under section 503A using a bulk drug 
substance  when an applicable USP or NF monograph for the substance does not exist and the 
substance is not a component of an FDA-approved product if, among other conditions, FDA has 
determined that the nomination for the bulk drug substance included adequate information for 
FDA to evaluate the substance and at this time, the substance does not appear to present 
significant safety risks.    
 
B.  Efforts to Develop the List of Bulk Drug Substances under Section 503A 
  
1.  Section 503A Bulks List  Early History  
 
Section 503A was enacted in 1997 as part of the Food and Drug Administration Modernization 
Act.  In the Federal Register of April 7, 1998 (63 FR 17011), FDA invited all interested persons 
to nominate bulk drug substances for inclusion on the list of bulk drug substances that can be 
used in compounding under section 503A and received nominations for 41 different drug 
substances.  In November 1998, FDA published a guidance for industry, Enforcement Policy 
During Implementation of Section 503A of the Federal Food, Drug, and Cosmetic Act. In this 
guidance, FDA announced that it would not normally take regulatory action relating to a drug 
product that had been compounded with a bulk drug substance that had been nominated for 
inclusion on the bulk drug substances list on or before November 21, 1999, while the substance 
was being evaluated, as long as the compounding complied with the other effective 
requirements in section 503A and did not appear to present a significant safety risk.11 
 
In January 1999, after evaluating the nominated drug substances and consulting with the 
Pharmacy Compounding Advisory Committee (PCAC) as required by section 503A, FDA 
published a proposed rule listing 20 drug substances on the section 503A bulks list (64 FR 996, 
January 7, 1999).  The preamble to the proposed rule indicated that 10 of the 41 nominated 
substances were the subject of a USP or NF monograph, or components of FDA approved drugs 
and did not need to be considered for inclusion on the list.12  The proposed rule also described 
10 nominated substances that were still under consideration for the bulk drug substances list and 
stated that one of the substances was withdrawn by its nominator at the first meeting of the 
PCAC.  The PCAC reconvened in May 1999 to discuss bulk drug substances included in the 
proposed rule, in addition to other bulk drug substances (64 FR 19791; April 22, 1999).  
                                                 
11 The 1998 guidance was withdrawn in the Federal Register notice announcing the availability of the draft guidance 
Pharmacy Compounding of Human Drug Products Under Section 503A of the Federal Food, Drug, and Cosmetic 
Act. See 78 FR 72901 (Dec. 4, 2013). The final guidance was published in July 2014.   
12 See 64 FR 996, at 997 (January 7, 1999). 
  4     Contains Nonbinding Recommendations 
 
However, after a 2002 U.S. Supreme Court decision holding that certain provisions of section 
503A were unconstitutional,13 FDA suspended its efforts to develop the bulk drugs list under 
section 503A.  
 
Because of the amount of time that had passed between the publication of the proposed rule and 
the enactment of the 2013 Drug Quality and Security Act, which removed the provisions of the 
FD&C Act that the U.S. Supreme Court held to be unconstitutional in 2002, FDA felt it was 
necessary to begin again to develop the section 503A bulk drug substance list. In the December 
4, 2013, Federal Register (78 FR 72841), FDA published a notice withdrawing the 1999 
proposed rule and 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 503A of the 
FD&C Act. 
 
2.  Current Nominations for the 503A Bulks List  
 
In response to the December 2013, Federal Register notice, over 2,000 substances were 
nominated for the 503A bulks list.  However, many of the substances nominated for the 503A list 
were for substances that can be compounded without being on the list because they are the 
subject of an applicable USP or NF monograph or are a component of an FDA-approved drug.  
In addition, many of the nominations were not for substances used in compounding as active 
ingredients, or did not include sufficient information for FDA to evaluate the nominated 
substances for inclusion on the list. To improve the efficiency of the process for developing the 
503A bulks list, FDA reopened the nomination process in July 2014 (79 FR 37742) and provided 
more detailed information on what it needs to evaluate nominations for the 503A bulks list.  
FDA stated that bulk drug substances that were previously nominated would not be considered 
further unless they were re-nominated with adequate support to permit a meaningful evaluation.  
Substances that were already eligible for use in compounding or that were not adequately 
supported would not be evaluated for placement on the 503A bulks list.  
 
In response to this request for nominations, approximately 740 unique substances were 
nominated.  Of the nominated substances: 
 
  Approximately 315 substances are already eligible for use in compounding under section 
503A.   
 
These are the subject of an applicable USP or NF monograph or components of an FDA-
approved drug product, which can be used in compounding pursuant to sections 
503A(b)(1)(A)(i)(I) and (II) and, therefore, can be compounded without being included on 
the 503A bulks list.  To determine if a bulk drug substance is the subject of an applicable 
USP or NF monograph, see the USP-NF available at www.USPNF.com.  To determine if a 
bulk drug substance is a component of an FDA approved drug, see the FDAs Orange Book: 
                                                 
13 For additional legal history of section 503A, see the guidance Pharmacy Compounding of Human Drug Products 
Under Section 503A of the Federal Food, Drug, and Cosmetic Act.    
  5     Contains Nonbinding Recommendations 
 
Approved Drug Products with Therapeutic Equivalence Evaluations, available at 
http://www.accessdata.fda.gov/scripts/cder/ob/default.cfm. 
 
  At least one14 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 503A bulks list because they do not meet the definition of a 
bulk drug substance in 21 CFR 207.3.   
 
  At least one of the substances is considered a biological product subject to approval in a 
biologics license application (BLA) under section 351 of the Public Health Service (PHS) 
Act when used for the indication proposed in the nomination.   
 
This substance is not eligible for the 503A bulks list because biological products subject to 
approval in a BLA under section 351 of the PHS Act are not eligible for the exemptions in 
section 503A of the FD&C Act.15  No biological products subject to approval in a BLA will 
be considered for the 503A bulks list. 
 
  At least four of the nominated substances appear on the list published by FDA of 
substances 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).16   
 
Such substances cannot be used in compounding under section 503A of the FD&C Act and, 
therefore, are not eligible for inclusion on the 503A bulks list.   
 
  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)).17   
 
The CSA does not allow possession or distribution of Schedule I substances (21 USC  
841(a)(1) and 829), except for research purposes (21 U.S.C.  823(f)),  and these substances 
will not be considered for the 503A bulk drug substances 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). 
   
                                                 
14 The over-the-counter finished drug product Maalox was nominated.  Maalox is not a bulk drug substance. 
15 The nominated substance is sodium hexachloroplatinate (IV) hexahydrate.  See the revised draft guidance, 
Mixing, Diluting, or Repackaging Biological Products Outside the Scope of an Approved Biologics License 
Application for FDAs proposed policies regarding State-licensed pharmacies, Federal facilities, and outsourcing 
facilities that mix, dilute, or repackage biological products outside the scope of an approved BLA. 
16 See Section 503A(b)(1)(C) of the FD&C Act.  See also 21 CFR 216.24.  The four substances are: chloroform 
reagent, cobalt chloride hexahydrate, cobalt gluconate, and phenacetin. 
17 An extract of cannabidiol (CBD) and tetrahydrocannabinol (THC) derived from marijuana (marihuana) was 
nominated.  Marijuana (marihuana) is a Schedule I substance. 
  6     Contains Nonbinding Recommendations 
 
  Of the substances that are not components of an approved drug or the subject of an 
applicable USP or NF monograph and that are not biological products subject to licensure 
in a BLA or included on Schedule I of the CSA, and do not appear on the withdrawn or 
removed list, approximately 350 substances were nominated without sufficient 
supporting evidence for FDA to evaluate them. 
 
  The remaining substances may be eligible for inclusion on the 503A list and were 
nominated with sufficient supporting information for FDA to evaluate them.  However, 
FDA has identified significant safety risks relating to the use of some of these bulk drug 
substances in compounded drug products.   
 
FDAs website identifies the following categories of substances nominated for the 503A bulks 
list:18   
 
503A Category 1  Substances Nominated for the Bulks List Currently Under 
Evaluation:  These 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  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 503A 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 FDAs human drug compounding website,19 advising that the 
substance has been added to Category 2 and is no longer eligible for the policies that apply to 
substances in Category 1. 
 
503A Category 3  Substances Nominated for the Bulks List Without Adequate 
Support:  These substances may be eligible for inclusion on the 503A bulks list, but were 
                                                 
18 http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/UCM467373.pdf. 
As discussed in the July 2014 Federal Register notice requesting nominations for the 503A bulks list (79 FR 37742), 
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 503A(b)(1)(A) 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 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 503A(b)(1)(A), and need not 
appear on the 503A 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 503A(b)(1)(B), which applies to ingredients other than bulk drug 
substances used in compounded drugs.     
 
19 http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/default.htm.  FDA also 
encourages compounding facilities to subscribe to FDAs list serve to receive updates at: 
http://service.govdelivery.com/service/subscribe.html?code=USFDA_429.  
  7     Contains Nonbinding Recommendations 
 
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, as discussed below in section III.B. 
   
3.  Process for Developing the 503A List 
 
FDA is currently evaluating the substances that were nominated for the 503A bulks list with 
sufficient information to permit evaluation.  FDA is considering a number of factors in 
prioritizing the order in which it reviews the nominated bulk drug substances, including but not 
limited to the following:   
 
  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 drugs that raise similar issues (e.g., vitamins or botanicals) or have 
been nominated for the treatment of the same condition (e.g., warts).   
 
In conducting its evaluations, FDA reviews the information provided in support of the 
nomination and other available information to assess each bulk drug substance according to the 
following four criteria discussed at the PCAC meeting on February 23, 2015: 
     
  The physical and chemical characterization of the substance   
  Any safety issues raised by the use of the substance in compounded drug products  
  Historical use of the substance in compounded drug products, including information 
about the medical condition(s) the substance has been used to treat and any references in 
peer-reviewed medical literature  
  The available evidence of effectiveness or lack of effectiveness of a drug product 
compounded with the substance, if any such evidence exists   
 
In evaluating candidates for the 503A bulks list under these criteria, FDA is using a balancing 
test.  No single one of these criteria is dispositive; rather, FDA is considering each criterion in 
the context of the others and balancing them, on a substance-by-substance basis, to evaluate 
whether a particular substance is appropriate for inclusion on the list.  
 
Once the evaluation of a substance is complete, FDA will present the results of its review to the 
PCAC to obtain its advice on whether to include the substance on the list.20   
                                                 
20 See Section 503A(c)(1) of the FD&C Act. 
  8     Contains Nonbinding Recommendations 
 
 
Section 503A requires that FDA create the 503A bulks list by regulation in consultation with the 
USP.  To this end, FDA has been periodically meeting with USP and discussing the list.  FDA 
will publish a notice of proposed rulemaking (NPRM) that identifies substances FDA proposes 
for placement on the 503A bulks list and the substances FDA has evaluated but is not proposing 
to include on the 503A bulks list.  After publication of the NPRM, the public will have an 
opportunity to comment on the proposed rule.  After considering the comments submitted to the 
docket, FDA will publish a final rule that establishes the 503A bulks list and identifies the 
substances that were considered and will not be placed on the list.  FDA does not intend to 
evaluate all of the sufficiently supported nominations before publishing the first NPRM.  Instead, 
after FDA has made a decision on whether to propose a group of substances (e.g., 10 substances) 
it intends to publish an NPRM with respect to that group of substances and continue to prepare 
the list on a rolling basis.   
 
A final rule will list the substances that FDA has determined can be used in compounding under 
section 503A and those substances that have been evaluated and not placed on the 503A bulks 
list, if any.   
 
After a final rule is published, drug products compounded using the substances on the 503A 
bulks list will be eligible for the section 503A exemptions provided the drug product is 
compounded in compliance with the other conditions of section 503A.  Those substances that 
have been evaluated and not placed on the 503A bulks list will not qualify for the policies 
described for the substances in Category 1. 
 
III.  POLICY21  
 
A.  Compounding from Bulk Drug Substances under Section 503A 
 
Under section 503A of the FD&C Act, a bulk drug substance that is not the subject of an 
applicable USP or NF monograph or is not a component of an FDA-approved drug cannot be 
used in compounding unless it appears on a list promulgated as a regulation pursuant to section 
503A(b)(1)(A)(i)(III) of the FD&C Act.  This list will be codified at 21 CFR part 216 subpart E.  
 
However, until a substance has been evaluated and is identified in a final rule as being included 
or not included on the 503A bulks list, FDA does not intend to take action against a State-
licensed pharmacy, Federal facility, or licensed physician compounding a drug product using a 
bulk drug substance that is not a component of an FDA-approved drug product and that is not the 
subject of an applicable USP or NF monograph, provided that the following conditions are met: 
 
1.  The bulk drug substance appears in 503A Category 1 on FDAs website at 
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Pharmac
yCompounding/UCM467373.pdf.  A Category 1 substance may be eligible for inclusion on 
the 503A bulks list, was nominated with sufficient supporting information for FDA to 
                                                 
21 See the Appendix for a chart summarizing FDAs interim policy. 
  9     Contains Nonbinding Recommendations 
 
evaluate it and has not been identified by FDA as a substance that presents a significant 
safety risk in compounding prior to the publication of a final rule.   
  
2.  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);  
 
3.  The bulk drug substance is accompanied by a valid COA; and  
 
4.  The drug product compounded using the bulk drug substance is compounded in compliance 
with all other conditions of section 503A 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.  
 
This policy does not apply to a licensed pharmacist in a State-licensed pharmacy or Federal 
facility, or a licensed physician, that compounds a drug using a bulk drug substance that does not 
meet each of the above conditions, and the bulk drug substance is not the subject of an applicable 
USP or NF monograph or a component of an FDA-approved drug.  
 
B.  Substances Not Nominated or Nominated Without Adequate Support 
 
As stated above, one of the categories of bulk drug substances FDA has identified on its website 
is substances nominated for the 503A bulks list that may be eligible for inclusion on the 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 (503A Category 3).  
In the Federal Register of October 27, 2015, FDA established a docket (October docket) where 
these substances can be re-nominated with sufficient supporting information or where 
nominations for substances that were not previously nominated can be submitted.   
 
After a substance is nominated to the October docket,22 FDA will determine whether the 
nomination is supported with sufficient information to allow FDA to evaluate it.  After FDA 
makes that determination, the nominated substance will be placed in one of the three categories 
described in section II.B.2 above, and the categorization will be published on the FDA website. 
Once the category of a substance is published, FDA intends to apply the policy described in 
Section III.A of this guidance to that substance.  FDA generally expects to categorize bulk drug 
substances nominated to the October docket and to publish updated categories on its website on 
the first business day of each month.  Please note that until substances nominated for the October 
docket have been categorized, the policy does not apply to those substances.  
 
C.  Comments about Nominated Bulk Drug Substances 
 
                                                 
22 This includes re-nominations of substances with sufficient supporting information.  
 
  1 0    Contains Nonbinding Recommendations 
 
If you feel that a substance that you nominated does not appear on the appropriate list or 
category as described in this guidance you can submit your comment to docket number FDA-
2015-N-3534.  If you have new information on a previously nominated substance that was 
placed in Category 3, the substance can be re-nominated with the additional information. 
 
A nominator may also submit a comment to the docket requesting withdrawal of any of its 
nominations.  If the party nominating the substance was the sole nominator, FDA will update the 
categories described in this guidance to reflect the withdrawn nomination.23  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 nominators request and the resulting updates 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.   
 
   
                                                 
23 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 to reflect 
that withdrawal. 
  1 1    Contains Nonbinding Recommendations 
 
 APPENDIX: SUMMARY OF POLICY 
 
 
The following table summarizes the interim policy for bulk drug substances set forth in this 
guidance: 
 
Category  FDA Policy 
The bulk drug substance appears in 503A Category  FDA does not intend to take action for compounding a drug 
1 on FDAs website at  product from a bulk drug substance in Category 1 that does 
http://www.fda.gov/downloads/Drugs/GuidanceComplia not meet the conditions of section 503A(b)(1)(A)(i), provided 
nceRegulatoryInformation/PharmacyCompounding/UC that the bulk drug substance was  manufactured by an 
M467373.pdf.    establishment registered with FDA under section 510 of the 
  FD&C Act and is accompanied by a valid COA from the 
Such substances may be eligible for inclusion on  entity that originally produced the bulk drug substance  and 
the 503A bulks list, were nominated with sufficient  provided that the drug compounded from the bulk drug 
supporting information for FDA to evaluate them,  substance is compounded in compliance with the other 
and do not appear to present a significant safety  conditions of section 503A.  
risk. 
The bulk drug substance is a component of an  The bulk drug substance can be used in compounding under 
FDA-approved drug and/or the subject of an  section 503A of the FD&C Act, provided it complies with the 
applicable USP or NF monograph.  standards of the monograph (if one exists)  and is 
compounded in compliance with the other conditions of 
section 503A.   
The bulk drug substance appears on the withdrawn  The bulk drug substance cannot be used in compounding 
or removed list.  under section 503A of the FD&C Act.  A drug compounded 
using the bulk drug substance is subject to regulatory action. 
The bulk drug substance appears in 503A Category  The bulk drug substance cannot be used in compounding 
2 on FDAs website at  under section 503A of the FD&C Act unless and until FDA 
http://www.fda.gov/downloads/Drugs/GuidanceComplia publishes a final rule authorizing its use under section 503A.   
nceRegulatoryInformation/PharmacyCompounding/UC
M467373.pdf. The substance has been identified by 
FDA as presenting a significant safety risk pending 
further evaluation.  
The bulk drug substance is a biological product  The bulk drug substance is not eligible for the 503A bulks list.  
subject to approval in a BLA.  FDA has issued a separate draft guidance document 
describing the Agencys proposed policies concerning mixing, 
diluting, and repackaging biological products subject to 
approval in a BLA.24 
The bulk drug substance appears in 503A Category  The bulk drug substance cannot be used in compounding 
3 on FDAs website at  under section 503A of the FD&C Act.  See section III.B of 
http://www.fda.gov/downloads/Drugs/GuidanceComplia this guidance for information about re-nominating substances 
nceRegulatoryInformation/PharmacyCompounding/UC that were previously nominated with insufficient supporting 
M467373.pdf. The substance may be eligible for  information. 
inclusion on the 503A bulks list, but was 
nominated with insufficient supporting information 
for FDA to evaluate it. 
 
 
                                                 
24 See FDAs revised draft guidance, Mixing, Diluting, and Repackaging Biological Products Subject to Approval in 
a Biologics License Application. 
  1 2