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) 
Office of Compliance/OUDLC 
 
 
January 2017 
Compounding and Related Documents 
Revision 1 
  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., 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 503B ............................................. 2 
B.  Section 503B Bulks List ................................................................................................................. 3 
III.  POLICY ............................................................................................................................. 7 
A.  Compounding from Bulk Drug Substances Under Section 503B .............................................. 7 
B.  Substances Not Nominated or Nominated Without Adequate Support ................................... 8 
C.  Comments about Nominated Bulk Drug Substances .................................................................. 9 
APPENDIX: SUMMARY OF POLICY ................................................................................... 10  Contains Nonbinding Recommendations 
 
Interim Policy on Compounding Using Bulk Drug Substances Under 
Section 503B of the Federal Food, Drug, and Cosmetic Act 
1
Guidance for Industry  
 
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 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 or Act) 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 FDAs interim 
regulatory policy regarding outsourcing facilities that compound human drug products using 
bulk drug substances while the list is being developed.3,4 
 
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 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 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. 
4 FDA is also developing a separate list of bulk drug substances that can be used in compounding under section 
503A of the FD&C Act.  Because section 503A contains different criteria for that list and provides for a different 
process for its development, the section 503A bulks list is covered under a separate guidance (see guidance for 
industry, Interim Policy on Compounding Using Bulk Drug Substances Under Section 503A of the Federal Food, 
Drug, and Cosmetic Act). 
  1     Contains Nonbinding Recommendations 
 
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: 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 582 (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 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 at the time of compounding, distribution, and dispensing.  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 21CFR 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 
503B(a)(2) and 21 CFR 207.3).5,6   
 
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; and (3) the bulk drug substance must be 
accompanied by a valid certificate of analysis (COA).  Section 503B(a)(2) of the FD&C Act.   
                                                 
5 Section 503B references the definition of bulk drug substance in FDAs drug establishment registration and listing 
regulations, which was codified at 21 CFR 207.3(a)(4) at the time section 503B 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.  The 
definition is also found in 207.1.  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 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.   
  2     Contains Nonbinding Recommendations 
 
 
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 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.  See section 503B(a)(2)(A)(i) 
of the FD&C Act.  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 information to allow FDA to evaluate the nominated substances for placement on the 
list. To improve the efficiency of the process for developing the 503B bulks list, FDA reopened 
the nomination process in July 2014 (79 FR 37747), 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 re-nominated 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 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 bulk rather than with the FDA-approved drug product. 
 
  3     Contains Nonbinding Recommendations 
 
In response to this request for nominations, approximately 2,590 unique substances were 
nominated.  Of the nominated substances: 
 
  Approximately 1,740 are biological products (all but one of these7 are individual 
allergenic extracts) subject to approval in a biologics license application (BLA) under 
section 351 of the Public Health Service (PHS) Act.  
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 exemptions in 
section 503B.8  No biological products subject to approval in a BLA will be considered for 
the 503B bulks list. 
  At least one9 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 one of the nominated substances is a radiopharmaceutical.10   
Compounding of radiopharmaceutical products will be addressed in a separate guidance 
document.11   
  At least five 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.12 
  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)).13   
                                                 
7 The product is sodium hexachloroplatinate (IV) hexahydrate.  
 
8 See the 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. 
 
9 The over-the-counter finished drug product Maalox was nominated.  Maalox is not a bulk drug substance. 
 
10 The substance is sodium iodide I-131. 
 
11 FDA has published a draft guidance, Compounding and Repackaging of Radiopharmaceuticals by Outsourcing 
Facilities, for public comment.  That draft guidance proposes the Agencys policy regarding the use of bulk drug 
substances to compound radiopharmaceuticals under section 503B of the FD&C Act.  Once that guidance is final, 
FDA intends to update this guidance to reflect the policies set forth therein. 
12 See section 503B(a)(4) of the FD&C Act.  See also 21 CFR 216.24.  The five substances are: chloroform reagent, 
cobalt chloride hexahydrate, cobalt gluconate, methapyrilene fumarate, and phenacetin. 
  4     Contains Nonbinding Recommendations 
 
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 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).   
  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. 
 
FDAs website identifies the following categories of substances nominated for the 503B bulk 
drug substances list:14   
 
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 
                                                                                                                                                             
13 An extract of cannabidiol (CBD) and tetrahydrocannabinol (THC) derived from marijuana (marihuana) was 
nominated.  Marijuana (marihuana) is a Schedule I substance. 
 
14 http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/PharmacyCompounding/UCM467374.pdf.  
As discussed in the July 2014 Federal Register notice requesting nominations for the 503B bulks list ((79 FR 
37747), 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 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 drugs 
  5     Contains Nonbinding Recommendations 
 
the communication on FDAs human drug compounding website15 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. 
 
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 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 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:   
 
  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 or 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 its proposed position on 
each substance it 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 the 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 FDAs 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 
FDAs rationale in making this determination.  
 
                                                 
15  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.  
  6     Contains Nonbinding Recommendations 
 
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 503B exemptions, provided the drug products are 
compounded in compliance with the other conditions of section 503B.16 Once FDA has 
published in the Federal Register its decision not to place a particular substance on the 503B 
bulks list, the policy described in section III of this guidance no longer applies.    
 
FDA intends to evaluate the substances nominated for the 503B 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 list.   
Under section 503B, an outsourcing facility may only compound using bulk drug substances that 
are on FDAs 503B bulks list or that are used to compound drugs that appear on the 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 for the relevant bulk drug 
substance was submitted with adequate information for FDA to evaluate the substance and that 
FDA has not identified significant safety risks about its use in compounding prior to publication 
of the Federal Register notice identifying those substances FDA has determined will or will not 
be placed on the 503B bulks list.   
 
III.  POLICY17  
 
A.  Compounding from Bulk Drug Substances Under Section 503B 
 
Under section 503B of the FD&C Act, a bulk drug substance cannot be used in compounding 
unless it is used to compound a drug that appears on the FDA drug shortage list at the time of 
compounding, distribution, and dispensing, or it appears on the 503B bulks list.   
 
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 compounded 
from the bulk drug substance: (i) appeared on FDAs 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 while it was on FDAs drug shortage list.18     
                                                 
16 See section 503B(a)(11) of the FD&C Act. 
 
17 See Appendix A for a summary of FDAs interim policy. 
 
18 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 in-house that were in progress when the drug was removed from FDAs drug 
shortage list (e.g., the outsourcing facility may have compounded a drug 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 apply if an outsourcing facility continues to fill orders received after the shortage 
 
  7     Contains Nonbinding Recommendations 
 
 
In addition, at this time FDA does not intend to take action against an outsourcing facility for 
compounding a drug using a bulk drug substance that does not appear on the 503B bulks list and 
that is not used to compound a drug that appears on the FDA drug shortage list at the time of 
compounding, distribution, and dispensing, provided that the following conditions are met:  
 
1.  The bulk drug substance appears on 503B Category 1 on FDAs website at 
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Pharmac
yCompounding/UCM467374.pdf.  A Category 1 substance may be eligible for inclusion on 
the 503B bulks list, was nominated for inclusion on the 503B bulks list with adequate 
supporting information for FDA to evaluate it, 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.   
 
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; 
 
4.  If the bulk drug substance is the subject of an applicable USP or NF monograph, the bulk 
drug substance complies with the monograph; and 
 
5.  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.  
 
This policy does not apply to an outsourcing facility that compounds a drug using a bulk drug 
substance that does not meet each of the above conditions and where the bulk drug substance 
was not used to compound a drug that appears on the FDA drug shortage list at the time of 
compounding, distribution, and dispensing, or that appeared on the FDA drug shortage list within 
60 days of distribution and dispensing. 
 
B.  Substances Not Nominated or Nominated Without Adequate Support 
 
As stated above, FDA is providing a list on its website of substances nominated for the 503B 
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 (503B Category 3).  In the Federal Register of 
October 27, 2015, FDA established a docket (October docket) where these substances can be re-
                                                                                                                                                             
ends, or if the outsourcing facility continues to fill orders more than 60 days after the drug was removed from FDAs 
drug shortage list.   
  8     Contains Nonbinding Recommendations 
 
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,19 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 
 
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-3469.  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.20  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 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.   
 
   
                                                 
19 This includes re-nominations of substances with sufficient supporting information.  
 
20 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. 
  9     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 is in 503B Category 1 on FDAs  The bulk drug substance is not on the 503B bulks list.  
website at  However, pending a determination about whether to put the bulk 
http://www.fda.gov/downloads/Drugs/GuidanceComplianceReg drug substance on the 503B bulks list, FDA does not intend to 
ulatoryInformation/PharmacyCompounding/UCM467374.pdf.   take action against an outsourcing facility for compounding a 
  drug product from a bulk drug substance that does not meet the 
Such substances may be eligible for inclusion on the  conditions of section 503B(a)(2) provided that the bulk drug 
503B bulks list, were nominated with adequate  substance is  manufactured by an establishment registered with 
supporting information for FDA to evaluate them, and  FDA under section 510 of the FD&C Act, is accompanied by a 
have not been identified by FDA as presenting significant  valid COA, complies with an applicable USP monograph, if one 
safety risks.   exists, and provided that the drug compounded from the bulk 
drug substance is compounded in compliance with the other 
conditions of section 503B.   
The bulk drug substance appears on the withdrawn or  The bulk drug substance cannot be used in compounding under 
removed list.   section 503B of the FD&C Act. 
The bulk drug substance is in 503B Category 2 on FDAs   The bulk drug substance is not on the 503B bulks list, and 
website at  cannot be used for compounding consistent with section 
http://www.fda.gov/downloads/Drugs/GuidanceComplianceReg 503B(a)(2) unless it is  used to compound a drug that appears on 
ulatoryInformation/PharmacyCompounding/UCM467374.pdf.  FDAs drug shortage list.   
The substance has been identified by FDA as presenting  
a significant safety risk in compounding pending further 
evaluation. 
The bulk drug substance is a biological product subject to  The bulk drug substance is not eligible for the 503B bulks list.  
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.21 
The bulk drug substance is a radiopharmaceutical  Compounding radiopharmaceuticals will be addressed in a 
product.  separate guidance document. 
The bulk drug substance is in 503B Category 3 on FDAs  The bulk drug substance is not on the 503B bulks list, and 
website at  cannot be used for compounding consistent with section 
http://www.fda.gov/downloads/Drugs/GuidanceComplianceReg 503B(a)(2) unless the bulk drug substance is used to compound 
ulatoryInformation/PharmacyCompounding/UCM467374.pdf.   a drug that appears on FDAs drug shortage list.  See section 
The substance may be eligible for inclusion on the 503B  III.B of this guidance for information about supplementing 
bulks list but was nominated with insufficient supporting  inadequately supported nominations. 
information for FDA to evaluate it. 
 
                                                 
21 See FDAs revised draft guidance, Mixing, Diluting, and Repackaging Biological Products Subject to Approval in 
a Biologics License Application. 
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