Contains Nonbinding Recommendations 
 
 
Coordinated Development of 
Antimicrobial  Drugs and 
Antimicrobial  Susceptibility Test 
Devices 
 
 
 
Guidance for Industry and Food and 
Drug Administration Staff
 
 
GUIDANCE 
 
Document issued on: February 1, 2019. 
 
The draft of this document was issued on: September 21, 2016. 
 
 
For questions regarding this document that relate to CDRH, contact Ribhi Shawar at 301-796-
6698 or ribhi.shawar@fda.hhs.gov,  or the Office of In Vitro Diagnostics and Radiological  Health 
at 301-796-5450.   For questions for CDER, contact Joseph Toerner at 301-796-1400,  or 
joseph.toerner@fda.hhs.gov. 
 
   
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Devices and Radiological Health 
Center for Drug Evaluation and Research
 
  Contains Nonbinding Recommendations 
 
 
Preface 
 
Public Comment 
 
You may submit electronic comments and suggestions at any time for Agency 
consideration to https://www.regulations.gov.  Submit written comments to the Dockets 
Management Staff, Food and Drug Administration,  5630 Fishers Lane, Room 1061, (HFA-
305), Rockville,  MD 20852. Identify all comments with the docket number FDA-2016-D-
2561. Comments may not be acted upon by the Agency until the document is next revised 
or updated. 
 
Additional Copies 
 
Center for Devices and Radiological Health (CDRH) 
 
Additional  copies are available from the Internet. You may also send an e-mail request to 
CDRH-Guidance@fda.hhs.gov  to receive a copy of the guidance.  Please use the document 
number 1400061 to identify  the guidance you are requesting. 
 
Center for Drug Evaluation and Research (CDER) 
 
Center for Drug Evaluation and Research 
Division  of Drug Information 
10903 New Hampshire Ave., Bldg. 51, rm. 2201 
Silver Spring, MD 20993-0002 
Tel: 301-796-3400;  Fax: 301-847-8714;  E-mail:  druginfo@fda.hhs.gov 
https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/de
fault.htm 
 
  Contains Nonbinding Recommendations 
 
 
 
I.  Table of Contents 
I.  Introduction.................................................................................................................. 1 
II.  Background .................................................................................................................. 2 
III.  Interactions Between Antimicrobial Drug Sponsors and AST Device Manufacturers ...... 3 
IV.  Considerations for Coordinated Development of Antimicrobial Drugs and AST Devices 3 
APPENDIX 1: Pathway for the Coordinated Development of AST Devices .......................... 6 
 
  Contains Nonbinding Recommendations 
 
Coordinated Development of 
Antimicrobial  Drugs and 
Antimicrobial  Susceptibility Test 
Devices 
 
 
Guidance for Industry and Food and 
Drug Administration Staff
 
 
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 or Office responsible for this guidance as listed on the title page.  
I.  Introduction 
 
This guidance is intended to assist drug sponsors and device manufacturers who are planning  to 
develop new antimicrobial  drugs and antimicrobial  susceptibility  test (AST) devices and who seek 
to coordinate development of these products such that the AST device could be cleared either at the 
time of new drug approval or shortly thereafter.  
Specifically,  the guidance intends to accomplish the following: 
  Describe interactions between drug sponsors and device manufacturers for coordinated 
development of a new antimicrobial  drug and an AST device;  
  Explain the considerations  for submitting  separate applications  to the Center for Drug 
Evaluation  and Research (CDER) and the Center for Devices and Radiological  Health 
(CDRH) when seeking clearance of an AST device coincident with, or soon following, 
antimicrobial  drug approval; and 
  Clarify that the review of the new antimicrobial  drug product and AST device(s) will 
remain independent,  and that coordinated development  does not influence the Medical 
Device User Fee Act (MDUFA) and the Prescription Drug User Fee Act (PDUFA) 
review timelines for either product.  
 
FDA's guidance documents, including  this guidance, do not establish legally  enforceable 
responsibilities.   Instead, guidances describe the Agency's current thinking  on a topic and should 
be viewed only as recommendations,  unless specific regulatory or statutory requirements are 
cited.  The use of the word should in Agency guidances means that something is suggested or 
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recommended, but not required. 
II.  Background 
 
Antimicrobial  susceptibility  testing is an important component in supporting  the development of 
new antimicrobial  drugs and the subsequent clinical  use of these agents.  In addition  to informing 
the appropriate clinical  use of antimicrobial  drugs for individual  patients, antimicrobial 
susceptibility  testing used in epidemiological  studies can identify the emergence of drug 
resistance and monitor  overall population  changes in antimicrobial  susceptibility.   
 
This guidance applies to AST devices, including  qualitative  disc diffusion  or elution tests,1 
manual and automated systems that provide qualitative  and quantitative  susceptibility 
information,2  and other growth-based devices3 used for the testing of in vitro susceptibility  of 
bacterial pathogens to antimicrobial  drugs.  This guidance may also apply to molecular-based 
devices that infer antimicrobial  resistance through the detection of microbial  resistance markers.  
 
AST devices are subject to premarket notification  510(k) requirements.  Such devices are often 
updated to accommodate new antimicrobial  drugs or other improvements.  A new submission  is 
required for modifications  to a cleared AST device when the modifications  could significantly 
affect the safety or effectiveness of the device.4  For example, when seeking to add a new 
antimicrobial  drug to an existing  AST panel, a 510(k) submission  is generally required because 
this could significantly  affect the safety or effectiveness of the device and is a major modification 
to the intended use of the device.  Firms manufacturing a device of a type classified under 21 CFR 
866.1645 must show that the device addresses the issues of safety and effectiveness identified  in 
the Class II Special Controls Guidance Document on AST Systems,5 either by meeting the special 
controls identified  in the Class II Special Controls Guidance Document on AST Systems or by 
some other means that provides equivalent assurances of safety and effectiveness.  Although AST 
devices classified under other classification regulations  are not subject to these special controls, 
we recommend the studies and performance characteristics outlined  in the Class II Special 
Controls Guidance Document on AST Systems to support 510(k) submissions  for these devices. 
 
Historically,  the development  of antimicrobial  drugs and AST devices that test for in vitro 
antibiotic  susceptibility  of bacterial pathogens has not been optimally coordinated,  with AST 
device development sometimes occurring late in the drug development  process or after the drug 
development/approval  process is completed.  This has contributed to delays in the availability  of 
AST devices for newly approved drugs.  FDA encourages sponsors of new antimicrobial  drugs 
and AST devices to collaborate early in the drug development  process to minimize  the time 
between the new antimicrobial  drug approval and the clearance of an AST device that tests for in 
                                                             
1 21 CFR 866.1620. 
2 21 CFR 866.1640; 21 CFR 866.1645. 
3 21 CFR 866.1700. 
4 See 21 CFR 807.81(a)(3) and FDA Guidance, Deciding When to Submit a 510(k) for a Change to an Existing 
Device, available at https://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/ 
guidancedocuments/ucm514771.pdf. 
5 Available at 
https://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm3889
61.pdf. 
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vitro susceptibility  of pathogens to that drug product.  Drug sponsors may benefit from this 
collaboration  by having access to AST device technology during clinical  studies of the 
antimicrobial  drug, and AST device manufacturers may benefit by having access to clinical 
isolates obtained during the drug development process that may aid in device validation.   Patients 
and health care professionals benefit by the early availability  of AST devices to determine 
susceptibility  to approved antimicrobial  drugs.   
III.  Interactions Between Antimicrobial Drug Sponsors 
and AST Device Manufacturers  
 
FDA encourages antimicrobial  drug sponsors and AST device manufacturers to discuss 
coordinated development opportunities.   Ideally, these discussions would occur early during 
new antimicrobial  drug development to enable information  helpful to the development of AST 
devices to be generated during clinical  trials for the drug product.  This approach may be 
broadly applicable to various types of AST devices, including  AST broth dilution  panels, disc 
diffusion or elution,  or gradient diffusion  devices used with antimicrobial  test systems, and for 
new or existing molecular-based devices that can identify mutations associated with decreased 
antimicrobial  susceptibility.   The nature of these interactions can take many forms and need 
not be restricted to a single device manufacturer.  Even simple availability  of a drug to 
multiple  device manufacturers for use during AST device development may translate to 
earlier AST device development and the ultimate goal of having clinical  laboratory access to 
FDA-cleared AST devices at the time of drug approval or shortly thereafter. 
 
In the circumstance where an AST sponsor has not directly coordinated development with the 
drug manufacturer, most of the principles  described below remain applicable.  AST sponsors 
who seek to submit a 510(k) application  (e.g., for a disc AST) but have not coordinated 
development with the drug manufacturer as part of a New Drug Application  (NDA) may 
obtain feedback on device development through the Q-Submission  Program at CDRH.6  For 
disc diffusion  tests, where (or whose) performance data is available through reference to an 
NDA, such data may be sufficient to support a 510(k) submission by the AST sponsor who 
took part in those studies with the drug manufacturer.  
IV.  Considerations for Coordinated Development of 
Antimicrobial Drugs and AST Devices 
 
Because the goal of coordinated development is timely clearance of an AST device, the device 
sponsor should utilize  the Q-Submission  Program to obtain feedback from FDA throughout the 
coordinated development process, as described below. 
                                                             
6 CDRH feedback on device development can be obtained through the Q-Submission Program.  Please refer to 
FDA Guidance for Industry and Food and Drug Administration Staff, Requests for Feedback on Medical Device 
Submissions: The Pre-Submission Program and Meetings with Food and Drug Administration Staff, available at: 
https://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM311
176.pdf.   
 
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FDA recommends that the AST device manufacturer submit a coordinated development plan 
through the Q-Submission  Program7 to CDRH for review and comment prior to or no later than 
shortly after the NDA submission.   The plan should include:  (1) identification  of the antimicrobial 
drug under development;  and (2) letters of authorization  from the device manufacturer and drug 
sponsor permitting  FDA to reference information  from any relevant IND or NDA.  Please refer to 
Appendix A in this document for information  on critical points that should be considered in the 
coordinated development process.  CDRH intends to consult with the CDER review team for the 
antimicrobial  drug and provide joint feedback on the coordinated development  plan.   
 
After an initial  Q-Submission  has been submitted,  additional  Q-Submission  supplements may be 
submitted,  as appropriate, following  NDA submission and during NDA review to facilitate a 
future 510(k) submission.  In particular, FDA recommends an additional  Q-Submission  if the 
AST device under development is to be used in phase 2 and/or phase 3 drug clinical  trial(s).  
Depending on the use, an investigational  device exemption (IDE) may also be required (21 CFR 
part 812).    
 
FDA welcomes joint  meetings with the drug sponsor, the device manufacturer, and personnel 
from both CDER and CDRH at any point in the coordinated development process.  The AST 
device manufacturer or drug sponsor may request such a meeting through the CDRH Q-
Submission  Program.  If CDER participation  is requested, CDRH intends to coordinate to include 
CDER.  
 
FDA recommends submission  of a 510(k) for the AST device 4 to 6 weeks before anticipated 
drug approval.  The submission  may be based on provisional  susceptibility  test interpretive 
criteria (breakpoints) and updated as needed when final breakpoints are identified  or 
recognized by CDER.  If appropriate documentation  has been provided giving  FDA 
permission  to share information  from the NDA with the AST device sponsor, FDA can 
communicate to the AST device sponsor information  regarding breakpoint(s) and indicated 
organisms that are communicated to the drug sponsor during the NDA review process and 
prior to approval.  Alternatively,  if such agreements do not exist, the final breakpoints and 
indicated organisms would become publicly  available once the drug is approved.8  
Regardless, CDRH review of the 510(k) submission  can begin during the NDA review 
process to maximize  the likelihood  that AST device clearance can occur either coincident with 
or shortly after drug approval.   
 
If the device manufacturer does not wish to solicit early FDA feedback on their device 
performance, coordinated development may still be achieved through direct interaction 
between the device and drug manufacturers without a Q-Submission for the device, with the 
510(k) submission  occurring prior to or shortly after drug approval.  However, without prior 
FDA interaction through the Q-Submission  process, there may be a delay in availability  of the 
                                                             
7 The Q-submission program provides several mechanisms for feedback from FDA, including face-to-face 
meetings, teleconferences, or written feedback.  Additional information is provided in FDA Guidance for 
Industry and Food and Drug Administration Staff, Requests for Feedback on Medical Device Submissions: The 
Pre-Submission Program and Meetings with Food and Drug Administration Staff, available at: 
https://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM311
176.pdf. 
8 Information regarding FDA-recognized breakpoints is available at https://www.fda.gov/STIC.  
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device due to a potentially  longer review time and/or the need for additional  information  to be 
submitted.  
 
FDA intends to continue to make review decisions for the antimicrobial  drug product and the 
AST device independently.   Although  coordinated development of the antimicrobial  drug 
product with an AST device does not alter performance goals associated with review 
timelines,  or approval or clearance of either product, FDA intends to facilitate clearance of the 
AST device coincident with or shortly after drug approval, as appropriate.  
 
Appendix A below provides details regarding critical points in the coordinated development 
process. 
   
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APPENDIX A: 
 
Review process for coordinated development with a device Q-Submission (refer to 
Figure A) 
Each of the following  steps should be considered optional,  and individual  device 
manufacturers may use pieces of the process below as applicable to their specific needs.  
However, FDA emphasizes that close communication  during AST development can facilitate 
510(k) review and successful device clearance coincident  with or soon after drug approval.  
1.  During the drug development process, the device manufacturer submits an initial  Q-
Submission  to solicit  preliminary  FDA feedback regarding their plans for coordinated 
development with the drug manufacturer, including,  as appropriate, any anticipated 
need for an IDE and proposals for data collection and analysis. 
2.  The device manufacturer submits a supplement to the Q-Submission  for the device, the 
content of which should describe the anticipated 510(k) submission  and information 
based on provisional  breakpoints provided by the drug manufacturer if available.  
(Note: There is no change in data submitted for an AST device using coordinated 
development for their 510(k). The information  expected to be provided is the same as 
that described in the Class II Special Controls Guidance Document: Antimicrobial 
Susceptibility  Test (AST) Systems.9) 
3.  FDA reviews each Q-Submission  or Q-Submission  supplement and communicates 
feedback regarding a future 510(k) submission  to the sponsor.  The device 
manufacturer may then provide CDRH with any necessary additional  information  in a 
Q-Submission  supplement, or the requested information  may be included in the 510(k) 
submission  without prior FDA review. 
4.  A 510(k) can be submitted at any time during the NDA review process; however, it is 
strongly encouraged that interactions occur through the Q-Submission  process and that 
formal 510(k) submission  occur close to the anticipated time of drug approval 
(approximately  4-6 weeks prior to anticipated drug approval).  For device clearance to 
occur either coincident with or shortly after drug approval, the AST device 510(k) 
submission  should be submitted early enough to allow sufficient time for FDA to 
complete its review. 
5.  CDRH and CDER intend to communicate during the drug review process such that 
when changes to tentative breakpoint(s) for the drug under review and indicated 
organisms as determined by CDER are communicated to the drug sponsor, this 
information  can be communicated to the device manufacturer on condition  that the 
drug and device manufacturer have the necessary agreements in place to enable such 
communication.   Alternatively,  if such agreements do not exist, the final breakpoints 
and indicated organisms would become publicly  available once the drug is approved. 
6.  Once breakpoints are finalized  by CDER, if necessary, the device manufacturer should 
modify the 510(k) package with the final data analysis using the approved breakpoints.  
                                                             
9 Available at: 
https://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM311
176.pdf. 
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7.  Assuming all issues previously  communicated to the device manufacturer have been 
addressed and analysis of the data in the 510(k) confirms adequate performance, 
CDRH should be able to arrive at a regulatory decision coincident with or shortly after 
drug approval.  
8.  If there are circumstances that suggest a need for modification  of the procedures noted 
above, they should be communicated to CDRH through the Q-Submission  process. 
   
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Figure A 
Note: The figure below is an outline of the process of coordinated development  and is 
intended to show the flow of information between the AST device manufacturer, the drug 
manufacturer, and FDA.  As a representation of the overall process, it is not intended to 
convey exactly what information  is required, nor the exact timing  of the exchanges, which 
may differ based on the drug, the device, and the specifics of the relationship  between their 
respective manufacturers.  For example, it is not expected that CDRH and CDER review 
during the development stage will occur at identical times, or that a 510(k) application  will be 
received by FDA the same day as the NDA submission.   
 
 
8