Systemic Antibacterial and 
Antifungal Drugs:  Susceptibility 
Test Interpretive Criteria 
Labeling for NDAs and ANDAs 
Guidance for Industry 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
 
 
December 2017 
Labeling 
   
Systemic Antibacterial and 
Antifungal Drugs:  Susceptibility 
Test Interpretive Criteria 
Labeling for NDAs and ANDAs 
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 
https://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) 
 
December 2017 
Labeling 
   
TABLE OF CONTENTS 
 
I.  INTRODUCTION..................................................................................................1 
II.  BACKGROUND ....................................................................................................2 
III.  LABELING RECOMMENDATIONS.................................................................3 
A.  Information to Be Removed from Antimicrobial Drug Labeling ................................. 3 
B.  Information to Be Added to Antimicrobial Drug Labeling ........................................... 4 
C.  Information to Be Retained in Antimicrobial Drug Labeling ....................................... 4 
IV.  REPORTING LABELING CHANGES ..............................................................5 
V.  PAPERWORK REDUCTION ACT OF 1995 .....................................................5 
APPENDIX:   EXAMPLE FORMAT FOR SUSCEPTIBILITY TEST  
INTERPRETIVE CRITERIA LABELING ....................................................................6 
 
 
  Contains Nonbinding Recommendations 
Systemic Antibacterial and Antifungal Drugs:  Susceptibility Test  
Interpretive Criteria Labeling for NDAs and ANDAs 
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 staff responsible for this guidance as listed on the 
title page. 
 
 
 
I.  INTRODUCTION 
 
  This guidance provides recommendations on fulfilling the new labeling requirements for 
susceptibility test interpretive criteria for prescription systemic antibacterial and 
antifungal drugs as established by section 3044 of the 21st Century Cures Act (Cures 
Act) (Public Law 114-255).2   
 
  This guidance describes FDAs recommendations on (1) how to make these labeling 
changes for antimicrobial drugs with approved new drug applications (NDAs) or 
abbreviated new drug applications (ANDAs), (2) language to remove from the labeling of 
such drugs, and (3) labeling language to use for all antimicrobial drugs to reference the 
FDAs Susceptibility Test Interpretive Criteria web page.3   
 
  This guidance supersedes sections I, II(B), III, and IV of the guidance for industry 
Updating Labeling for Susceptibility Test Information in Systemic Antibacterial Drug 
Products and Antimicrobial Susceptibility Testing Devices.4  
                                                 
1 This guidance has been prepared by the Office of Antimicrobial Products in the Center for Drug Evaluation and 
Research at the Food and Drug Administration.  You may submit comments on this guidance at any time.  Submit 
comments to Docket No. FDA-2017-D-6821 (available at https://www.regulations.gov/docket?D=FDA-2017-D-
6821) (see the instructions for submitting comments in the docket). 
 
2 Consistent with the Cures Act, for the purposes of this guidance, all references to antimicrobial drugs refers to 
systemic antibacterial and antifungal drugs.  See section 511A(f)(4) of the Federal Food, Drug, and Cosmetic Act 
(FD&C Act).  Currently, biological products, as defined in section 351 of the Public Health Service Act, are not 
included in the definition of antimicrobial drug for purposes of section 511A of the FD&C Act.  Under section 
511A(f)(4)(B), FDA may, by regulation, add certain biological products to the definition of antimicrobial drug. 
 
3 See the FDA Susceptibility Test Interpretive Criteria (Interpretive Criteria) web page at https://www.fda.gov/STIC.  
 
4 We update guidances periodically.  To make sure you have the most recent version of a guidance, check the FDA 
Drugs guidance web page at 
https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.  
1  Contains Nonbinding Recommendations 
 
  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. 
 
 
II.  BACKGROUND 
 
  Antimicrobial susceptibility testing is used to determine if certain microorganisms 
isolated from a patient with an infection are likely to be killed or inhibited by a particular 
antimicrobial drug.  Historically, susceptibility test interpretive criteria have been 
contained in the Microbiology subsection of antimicrobial drug labeling.  There have 
been significant challenges associated with ensuring that this information is up to date in 
antimicrobial drug labeling.  
 
  Section 3044 of the Cures Act added section 511A to the Federal Food, Drug and 
Cosmetic Act (FD&C Act).  Section 511A clarifies FDAs authority to identify and 
efficiently update susceptibility test interpretive criteria for antimicrobial drugs.  This 
authority includes FDAs recognition of standards established by standards development 
organizations.  Section 511A(b) states that FDA retains full authority to accept a standard 
in whole or in part or to establish alternative susceptibility test interpretive criteria.  
Section 511A also clarifies that sponsors of antimicrobial susceptibility test devices may 
rely upon these FDA-recognized or listed susceptibility interpretive criteria to support 
premarket authorization of their devices so long as certain conditions are met.  This 
provides for a more streamlined process for incorporating up-to-date information about 
antimicrobial susceptibility into the labeling for such devices. 
 
  Section 511A(b) of the FD&C Act required FDA to establish a Susceptibility Test 
Interpretive Criteria (Interpretive Criteria) web page within one year of enactment of the 
Cures Act.  This web page contains a list of FDA-recognized susceptibility test 
interpretive criteria standards, as well as other susceptibility test interpretive criteria 
identified by FDA.  See the FDA Susceptibility Test Interpretive Criteria web page at 
https://www.fda.gov/STIC. 
 
  At least every six months, FDA will publish on the Interpretive Criteria web page a 
notice that does the following:  
 
  Recognizes new or updated susceptibility test interpretive criteria standards or parts 

of standards  
 
  Withdraws recognition of susceptibility test interpretive criteria standards or parts of 

standards  
 
2  Contains Nonbinding Recommendations 
  Makes any other necessary updates to the lists published on the Interpretive Criteria 

web page  
 
  In addition, FDA will update the Interpretive Criteria web page with susceptibility test 
interpretive criteria upon approval of an NDA for an antimicrobial drug, as appropriate.  
 
  Section 511A(d)(1) of the FD&C Act requires that, within one year of establishment of 
the Interpretive Criteria web page, all application holders of antimicrobial drugs legally 
marketed before the establishment of the Interpretive Criteria web page5 remove the 
susceptibility test interpretive criteria information, if any, and related information from 
approved labeling and replace the criteria with a reference to the Interpretive Criteria web 
page.6  
 
  Section 511A(d)(2) of the FD&C Act requires all antimicrobial drugs approved on or 
after the date of establishment of the Interpretive Criteria web page to include in labeling 
a reference to the Interpretive Criteria web page in lieu of susceptibility test interpretive 
criteria and related information.  See section III.B., Information to Be Added to 
Antimicrobial Drug Labeling.7  
 
 
III.  LABELING RECOMMENDATIONS 
 
A.  Information to Be Removed from Antimicrobial Drug Labeling 
 
  Holders of approved applications should remove the following information from the 
labeling of approved antimicrobial drugs within one year of the date of the establishment 
of the Interpretive Criteria web page, December 13, 2017:  
 
                                                 
5 The requirements under section 511A(d)(1) apply to all antimicrobial drugs approved before the establishment of 
the Interpretive Criteria web page, which includes antimicrobial drug products that are approved under both NDAs 
and ANDAs. 
 
6 Under section 502(dd) of the FD&C Act, as added by Section 3044(b)(2) of the Cures Act, an antimicrobial drug is 
misbranded if its labeling fails to conform to the labeling requirements under section 511A(d) of the FD&C Act.  
 
7 In general, FDA requires that ANDAs include information to show that the labeling proposed for the generic drug 
is the same as the labeling approved for the reference listed drug (RLD) except for changes required because of 
differences approved under a suitability petition (see section 505(j)(2)(C) of the FD&C Act and 21 CFR 314.93) or 
because the generic drug and the RLD are produced or distributed by different manufacturers (see section 
505(j)(2)(A)(v) of the FD&C Act).  FDA implementing regulations include examples of permissible labeling 
differences that may result because the generic drug and RLD are produced or distributed by different manufacturers 
(21 CFR 314.94(a)(8)(iv)).  One such permissible difference is labeling revisions made to comply with current FDA 
labeling guidelines or other guidance (21 CFR 314.94(a)(8)(iv)).   For ANDAs approved after the implementation of 
the Interpretive Criteria web page, if the ANDA holder submits proposed labeling changes to comply with the 
requirements of section 511A of the FD&C Act and the current RLD labeling does not include these labeling 
changes, FDA may consider such differences in labeling between the generic drug and RLD to be permissible 
differences in labeling under FDAs authorities. See generally, sections 505(j)(2)(A) and 505(j)(4) of the FD&C Act 
and 21 CFR 314.94. 
 
3  Contains Nonbinding Recommendations 
  Information on susceptibility test interpretive criteria and associated test methods and 

quality control standards in the Microbiology subsection of the CLINICAL 
PHARMACOLOGY section, generally under the headings Susceptibility Test 
Methods and Quality Control.  
 
  Related citations included in the REFERENCES section.  

 
  For antimicrobial drugs approved following the establishment of the Interpretive Criteria 
web page, susceptibility test interpretive criteria and related information should not be 
included in the Microbiology subsection of the CLINICAL PHARMACOLOGY section 
of labeling, except as described in Section III.B., Information to Be Added to 
Antimicrobial Drug Labeling.8  
 
B.  Information to Be Added to Antimicrobial Drug Labeling 
  
  FDA recommends that antimicrobial drugs, including those approved following the 
establishment of the Interpretive Criteria web page, contain the following statement in the 
Microbiology subsection of the CLINICAL PHARMACOLOGY section of labeling, in 
lieu of the previously listed susceptibility test interpretive criteria and related 
information: 
 
Susceptibility Testing 
 
For specific information regarding susceptibility test interpretive criteria and associated 
test methods and quality control standards recognized by FDA for this drug, please see: 
https://www.fda.gov/STIC. 
 
C.  Information to Be Retained in Antimicrobial Drug Labeling 
 
  Section 511A of the FD&C Act only applies to the information in labeling describing 
susceptibility test interpretive criteria and associated test methods and quality control 
standards with associated references for antimicrobial drugs.  All other guidance, 
regulations, and statutory requirements remain applicable.  
 
  Section 511A of the FD&C Act does not affect the antimicrobial drug labeling 
information within the Microbiology subsection of the CLINICAL PHARMACOLOGY 
section on Mechanism of Action, Resistance, Interactions With Other Antimicrobials, 
and Antimicrobial Activity, which includes the first and second lists of target bacteria, or 
other information in antimicrobial drug labeling other than the susceptibility test 
interpretive criteria, associated test methods, and quality control standards, with 
associated references.9  
 
                                                 
8 Section 511A(d) of the FD&C Act. 
 
9 For more information about labeling antimicrobial drugs, see the guidance for industry Microbiology Data for 
Systemic Antibacterial Drugs  Development, Analysis, and Presentation.  
4  Contains Nonbinding Recommendations 
 
IV.  REPORTING LABELING CHANGES 
 
  As mentioned above, all holders of approved antimicrobial drug applications under 
section 505 of the FD&C Act (i.e., both NDAs and ANDAs), as applicable, are required 
to submit updated labeling consistent with section III., Labeling Recommendations, 
within one year of the establishment of the Interpretive Criteria web page.10 
 
  As described in section 511A(d)(1)(B) of the FD&C Act, such labeling changes are 
considered to be minor changes under 21 CFR 314.70 that can be reported in the 
application holders next annual report.11 Although not required, an application holder 
can report the labeling changes in a supplement to an approved application.  
 
  FDA strongly encourages an application holder to identify in the cover letter of the 
annual report, or in the supplement containing the changes, that the enclosed submission 
fulfills the requirements of section 511A(d)(1) of the FD&C Act.12 
 
 
V.  PAPERWORK REDUCTION ACT OF 1995 
 
This guidance refers to previously approved collections of information found in FDA 
regulations.  The collections of information are subject to review by the Office of Management 
and Budget under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520).  The collections 
of information in 21 CFR 201.56(a)(2) have been approved under OMB Control No. 0910-0572; 
the collections of information in 21 CFR 314.70(b)(2)(v) and 314.81(b)(2)(i) have been approved 
under OMB Control No. 0910-0001. 
 
                                                 
10 See section 511A(d)(1) of the FD&C Act. 
 
11 Application holders for drug products approved under section 505(j) of the FD&C Act may submit labeling 
changes to comply with the requirements under section 511A(d)(1) as part of the next annual report even if such 
changes are not reflected in the last approved labeling for the respective RLD.     
 
12 If the application holder submits the labeling changes to comply with the requirements of section 511A of the 
FD&C Act as part of a labeling supplement to an already approved ANDA and the labeling changes are not reflected 
in the last approved labeling for the respective RLD, FDA may consider the labeling changes proposed by the 
ANDA holder to be permissible differences in labeling under FDAs authorities.  See generally, sections 
505(j)(2)(A) and 505(j)(4) of the FD&C Act and 21 CFR 314.94 and 21 CFR 314.127. 
5  Contains Nonbinding Recommendations 
APPENDIX:   
EXAMPLE FORMAT FOR SUSCEPTIBILITY TEST  
INTERPRETIVE CRITERIA LABELING 
 
Per changes to labeling requirements for antimicrobial drugs under section 511A of the Federal 
Food, Drug, and Cosmetic Act, the following is an example of recommended language to be 
removed in drug labeling and sample replacement text with additional FDA recommendations in 
italics. For more information concerning this section of labeling, see the guidance for industry 
Microbiology Data for Systemic Antibacterial Drugs  Development, Analysis, and 
Presentation.1   
 
12  CLINICAL PHARMACOLOGY 
 
12.4  Microbiology 
 
Mechanism of Action 
 
Resistance 
 
Interaction With Other Antimicrobials 
 
Antimicrobial Activity 
 
Susceptibility Testing 
 
Remove information on susceptibility test interpretive criteria and associated test methods 
and quality control standards found generally under the headings Susceptibility Test 
Methods and Quality Control, and add the following statement: 
 
For specific information regarding susceptibility test interpretive criteria and associated test 
methods and quality control standards recognized by FDA for this drug, please see:  
https://www.fda.gov/STIC.  
 
The following is sample text that would be removed from existing approved labeling of an 
antimicrobial drug: 
 
When available, the clinical microbiology laboratory should provide cumulative reports of in 
vitro susceptibility test results for antimicrobial drugs used in local hospitals and practice 
areas as periodic reports that describe the susceptibility profile of nosocomial and 
community-acquired pathogens.  These reports should aid in the selection of an appropriate 
antibacterial drug for treatment. 
 
 
                                                 
1 We update guidances periodically.  To make sure you have the most recent version of a guidance, check the FDA 
Drugs guidance web page at 
https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.  
6  Contains Nonbinding Recommendations 
Dilution Techniques 
Quantitative methods are used to determine antimicrobial MICs.  These MICs provide 
estimates of the susceptibility of bacteria to antimicrobial compounds.  The MICs should 
be determined using a standardized test method1,2 (broth and/or agar).  The MIC values 
should be interpreted according to criteria provided in Table [insert table number]. 
 
 
Diffusion Techniques 
Quantitative methods that require measurement of zone diameters can also provide 
reproducible estimates of the susceptibility of bacteria to antimicrobial compounds.  The 
zone size should be determined using a standardized test method.2,3  This procedure uses 
paper disks impregnated with [x] mcg [name of drug] to test the susceptibility of bacteria 
to [name of drug].  The disc diffusion breakpoints are provided in Table [insert table 
number]. 
 
Anaerobic Techniques 
For anaerobic bacteria, the susceptibility to [name of drug] can be determined by a 
standardized test method.4  The MIC values obtained should be interpreted according to 
the criteria provided in Table [insert table number]. 
 
 
Table [insert table number].  Susceptibility Test Interpretive Criteria  
for [name of drug] 
  Minimum Inhibitory    Disk Diffusion  
Concentrations  (zone diameters in 
(mcg/mL)  mm) 
Pathogen  S  I  R    S  I  R 
               
Pathogen #1  < #  # - #  >#  >#  # - #  < # 
               
Pathogen #2  < #  # - #  >#  >#  # - #  < # 
etc.  etc.    etc. 
 
A report of Susceptible (S) indicates that the antimicrobial drug is likely to inhibit growth 
of the pathogen if the antimicrobial drug reaches the concentration usually achievable at 
the site of infection.  A report of Intermediate (I) indicates that the result should be 
considered equivocal, and, if the microorganism is not fully susceptible to alternative, 
clinically feasible drugs, the test should be repeated.  This category implies possible 
clinical applicability in body sites where the drug is physiologically concentrated or in 
situations where a high dosage of the drug can be used.  This category also provides a 
buffer zone that prevents small uncontrolled technical factors from causing major 
discrepancies in interpretation.  A report of Resistant (R) indicates that the antimicrobial 
drug is not likely to inhibit growth of the pathogen if the antimicrobial drug reaches the 
concentration usually achievable at the infection site; other therapy should be selected. 
 
 
7  Contains Nonbinding Recommendations 
Quality Control 
Standardized susceptibility test procedures require the use of laboratory controls to monitor 
and ensure the accuracy and precision of supplies and reagents used in the assay, and the 
techniques of the individuals performing the test.1,2,3,4  Standard [name of drug] powder 
should provide the following range of MIC values noted in Table [insert table number].  For 
the diffusion technique using the [disk content of antimicrobial] mcg disk, the criteria in 
Table [insert table number] should be achieved. 
 
 
Table [insert table number].  Acceptable Quality Control Ranges  
for [name of drug] 
  Minimum Inhibitory  Disk Diffusion 
Concentrations  (zone diameters in 
(mcg/mL)  mm) 
     
QC strain #1  # - #  # - # 
     
QC strain #2  # - #  # - # 
 
etc.  etc.  etc. 
 
15  REFERENCES 
 
Retain and renumber any references not related to susceptibility testing. 
 
1. Clinical and Laboratory Standards Institute (CLSI).  Methods for Dilution Antimicrobial 
Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard  [Edition].  CLSI 
document M07-[Edition number].  Clinical and Laboratory Standards Institute, 950 West Valley 
Road, Suite 2500, Wayne, PA 19087, USA, [Year]. 
 
2. Clinical and Laboratory Standards Institute (CLSI).  Performance Standards for Antimicrobial 
Susceptibility Testing; [Supplement Edition].  CLSI document M100-[Supplement Edition 
number].  Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, 
Wayne, PA 19087, USA, [Year]. 
 
3. Clinical and Laboratory Standards Institute (CLSI).  Performance Standards for Antimicrobial 
Disk Diffusion Susceptibility Tests:  Approved Standard  [Edition].  CLSI document M02-
[Edition number].  Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 
2500, Wayne, PA 19087, USA, [Year]. 
 
4. Clinical and Laboratory Standards Institute (CLSI).  Methods for Antimicrobial Testing of 
Anaerobic Bacteria; [Edition].  CLSI document M11-[Edition number].  Clinical and Laboratory 
Standards Institute, 950 West Valley Road, Suite 2500, Wayne, PA 19087, USA, [Year]. 
8