Contains Nonbinding Recommendations 
 
Antimicrobial Susceptibility Test 
(AST) System Devices  Updating 
Breakpoints in Device Labeling 
______________________________________________________________________________ 
Guidance for Industry and 
Food and Drug Administration Staff 
 
 
Document issued on September 29, 2023 
 
 
This document supersedes Updating Labeling for Susceptibility Test 
Information in Systemic Antibacterial Drug Products and Antimicrobial 
Susceptibility Testing Devices (June 2009). 
 
 
For questions about this document, contact the Division of Microbiology Devices at 
ASTdevices@fda.hhs.gov.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Devices and Radiological Health 
 
  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-
1740. Identify all comments with the docket number FDA-2023-D-4045. Comments may not be 
acted upon by the Agency until the document is next revised or updated. 
 
Additional Copies 
 
Additional copies are available from the Internet. You may also send an email request to CDRH-
Guidance@fda.hhs.gov to receive a copy of the guidance. Please include the document number 
GUI00007019 and complete title of the guidance in the request. 
 
 
 
 
  Contains Nonbinding Recommendations 
 
Table of Contents
 
 
I.  Introduction ............................................................................................................................. 1 
 
II.  Background ............................................................................................................................. 2 
III.  Scope ....................................................................................................................................... 4 
IV.  Updating Breakpoints in AST System Device Labeling ........................................................ 5 
  Establishing and Utilizing a PCCP for Breakpoint Updates in a 510(k) Submission for 
an AST System Device ............................................................................................................... 5 
(1)  Establishing a PCCP ..................................................................................................... 6 
(2)  Utilizing a PCCP .......................................................................................................... 6 
(3)  Content of a PCCP ........................................................................................................ 7 
  Applying a PCCP or Breakpoint Change Protocol for Breakpoint Updates to a Cleared 
AST System Device (Legacy AST System Devices) ................................................................. 8 
  Incorporating By Reference an Authorized PCCP or Breakpoint Change Protocol in a 
New 510(k) Submission for an AST System Device.................................................................. 9 
 
 
 
 
  Contains Nonbinding Recommendations 
 
Antimicrobial Susceptibility Test 
(AST) System Devices  Updating 
Breakpoints in Device Labeling 
______________________________________________________________________________ 
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 provide industry and FDA staff with information regarding updating 
susceptibility test interpretive criteria (STIC)/breakpoints1 and associated performance data in 
device labeling for antimicrobial susceptibility test (AST) system devices in response to 
breakpoint changes posted on the FDA-Recognized Antimicrobial Susceptibility Test 
Interpretive Criteria website (STIC Website).2 This guidance is expected to facilitate the timely 
adoption of updated breakpoints in AST system devices, which helps to ensure device safety and 
effectiveness.   
 
This guidance supersedes Sections II.A and V of the FDA guidance Updating Labeling for 
Susceptibility Test Information in Systemic Antibacterial Drug Products and Antimicrobial 
Susceptibility Testing Devices issued in June 2009 (June 2009 guidance).3 As described in 
the June 2009 guidance, updating the STIC will significantly affect the safety and effectiveness 
of the AST system device and, therefore, ordinarily would require submission of a premarket 
 
1 Susceptibility test interpretive criteria (STIC) is considered synonymous with breakpoints, and these terms are 
used interchangeably throughout this guidance. 
2 Available at https://www.fda.gov/drugs/development-resources/fda-recognized-antimicrobial-susceptibility-test-
interpretive-criteria 
3 The STIC Website was established on December 13, 2017, and the guidance entitled Systemic Antibacterial and 
Antifungal Drugs: Susceptibility Test Interpretive Criteria Labeling for NDAs and ANDAs (December 2017) 
(available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/systemic-antibacterial-
and-antifungal-drugs-susceptibility-test-interpretive-criteria-labeling-ndas) superseded Sections I, II.B, III, and IV of 
the June 2009 guidance. With the issuance of this final guidance, the June 2009 guidance is superseded in its entirety 
and has been withdrawn.  
1  Contains Nonbinding Recommendations 
 
notification (510(k)) prior to updating device labeling.4 In the June 2009 guidance, FDA 
described an enforcement policy where FDA would generally not object to device sponsors 
updating STIC in their AST system device labeling without a new 510(k) where the updated 
STIC did not affect acceptable device performance, as described in the Antimicrobial 
Susceptibility Test (AST) Systems - Class II Special Controls Guidance,5 and the only change 
to the AST system device labeling was updating STIC. While FDA interpreted this policy to also 
include breakpoint change protocols, as discussed further below, the June 2009 guidance did not 
describe the procedures for updating AST system device labeling when using a breakpoint 
change protocol. This guidance describes approaches for AST system device sponsors to update 
their STIC in device labeling via predetermined change control plans (PCCPs), and also 
describes an enforcement policy regarding applying such updates to AST system devices that 
were cleared without breakpoint change protocols.  
 
This guidance is being implemented without prior public comment because FDA has determined 
that prior public participation for this guidance is not feasible or appropriate (see section 
701(h)(1)(C)(i) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) and 21 CFR 
10.115(g)(2)). FDA has determined that this guidance document presents a less burdensome 
policy that is consistent with public health and the urgent public health need for sponsors to 
update breakpoints for legacy AST system devices. This guidance document is being 
implemented immediately, but it remains subject to comment in accordance with the Agencys 
good guidance practices. 
 
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 
AST system devices are intended to determine the in vitro susceptibility of bacterial or fungal 
pathogens to different antimicrobial agents. Accurate results are essential for guiding the 
treatment of infections by clinicians and for monitoring the spread of antimicrobial resistant 
microorganisms.  
 
Generally, healthcare professionals rely on AST system devices to help choose an appropriate 
treatment as STIC are the criteria used to interpret AST results. Accumulating clinical and 
scientific information regarding the use of specific antimicrobials against specific bacteria or 
fungi may lead to the need to change breakpoint recommendations over time. Changes may 
occur in response to new information regarding successful treatment of infections, the emergence 
of new resistance mechanisms, or other factors. Historically, there have been delays in updates of 
AST system device labelingfollowing the recommendations of standards development 
 
4 21 CFR 807.81(a)(3). 
5 Available at https://www.fda.gov/medical-devices/guidance-documents-medical-devices-and-radiation-emitting-
products/antimicrobial-susceptibility-test-ast-systems-class-ii-special-controls-guidance-industry-and-fda 
2  Contains Nonbinding Recommendations 
 
organizations that breakpoints be changeduntil after the relevant antimicrobial drug labeling 
was revised to include the updated breakpoint. 
 
Antimicrobial resistance (AMR) is a major public health threat to the U.S. According to the 
Centers for Disease Control and Prevention (CDC), as of 2019, more than 2.8 million 
antimicrobial-resistant infections occur each year in the U.S., and more than 35,000 people die as 
a result.6 The Federal Task Force for Combating Antibiotic-Resistant Bacteria was established to 
help address the public health threat of AMR.7 Notably, the Coronavirus Disease 2019 (COVID-
19) pandemic had a harmful impact on efforts to combat AMR, resulting in both more resistant 
infections and more antibiotic use.8 People of color, pregnant women, older adults, and people 
with weakened immune systems or certain medical conditions, such as diabetes, are at higher 
risk.9 Critical to addressing the urgent public health threat of AMR is its detection. AST system 
devices with current breakpoints are necessary to detect drug-resistant infections and guide 
clinicians to the selection of an efficacious antimicrobial. Ensuring current breakpoints in AST 
system devices supports the National Strategy for Combating Antibiotic-Resistant Bacteria.  
 
As part of this effort, section 3044 of the 21st Century Cures Act (Cures Act), signed into law on 
December 13, 2016, added section 511A (21 U.S.C. 360a-2), Susceptibility Test Interpretive 
Criteria for Microorganisms, to the FD&C Act. Section 511A(c) authorizes FDA to recognize, 
in whole or in part, a consensus standard that provides antimicrobial STIC or establish 
alternative STIC, and section 511A(b) requires FDA to establish and maintain a dedicated 
website that contains a list of any appropriate new or updated STIC and standards. Section 
511A(e) also clarifies that sponsors of AST system devices may rely on these FDA-recognized 
or listed STIC to support premarket authorization of their devices, so long as certain conditions 
are met. This provides for a more streamlined process for incorporating updated antimicrobial 
susceptibility information into device labeling. In accordance with section 511A(b) of the FD&C 
Act, FDA established the STIC Website, which serves as the dedicated repository of FDA-
recognized STIC. Antimicrobial drug labeling no longer includes breakpoint information, but 
instead refers to the STIC Website for breakpoint information.  
 
Generally, updating the STIC could significantly affect the safety and effectiveness of the AST 
system device and, therefore, ordinarily would require submission of a 510(k) prior to updating 
device labeling.10 FDA has reviewed and cleared many 510(k) submissions for new AST system 
devices with breakpoint change protocols that allow for changes to breakpoints without a new 
510(k) since the establishment of the STIC Website in 2017, as described further below. This has 
allowed for timely updates to breakpoints in those AST system devices. However, many AST 
system devices were reviewed and cleared by FDA that did not include a breakpoint change 
protocol (referred to in this guidance as legacy AST system devices). 
 
6 See CDCs website on COVID-19 & Antimicrobial Resistance, available at 
https://www.cdc.gov/drugresistance/covid19.html 
7 See the Office of the Assistant Secretary for Planning and Evaluations National Action Plan for Combating 
Antibiotic-Resistant Bacteria, 2020-2025, available at https://aspe.hhs.gov/reports/national-action-plan-combating-
antibiotic-resistant-bacteria-2020-2025 
8 See CDCs website on COVID-19 & Antimicrobial Resistance. 
9 See CDCs website on CDCs Priority to Address Health Equity Issues Across Antibiotic-Resistant Threats, 
available at https://www.cdc.gov/drugresistance/solutions-initiative/stories/ar-health-equity.html 
10 21 CFR 807.81(a)(3). 
3  Contains Nonbinding Recommendations 
 
 
Additionally, section 3308 of the Food and Drug Omnibus Reform Act of 2022, Title III of 
Division FF of the Consolidated Appropriations Act, 2023, Pub. L. No. 117-328 (FDORA), 
enacted on December 29, 2022, added section 515C Predetermined Change Control Plans for 
Devices to the FD&C Act. Section 515C provides FDA with express authority to approve or 
clear PCCPs for devices requiring premarket approval or premarket notification. For example, 
section 515C provides that supplemental applications (section 515C(a)) and new premarket 
notifications (section 515C(b)) are not required for a change to a device that would otherwise 
require a premarket approval supplement or new premarket notification if the change is 
consistent with a PCCP approved or cleared by FDA. Section 515C also provides that FDA may 
require that a PCCP include labeling for safe and effective use of a device as such device 
changes pursuant to such plan, notification requirements if the device does not function as 
intended pursuant to such plan, and performance requirements for changes made under the 
plan.11 For purposes of this guidance, consistent with FDORA and section 515C of the FD&C 
Act, all breakpoint change protocols submitted and cleared in future 510(k) submissions 
following the publication date of this guidance will be referred to as PCCPs, and breakpoint 
change protocols cleared prior to the publication date of this guidance will be referred to as 
breakpoint change protocols. In this guidance, we provide recommendations on the marketing 
submission content for PCCPs for new AST system devices, describe an enforcement policy for 
legacy AST system devices, and clarify the process for incorporating by reference a cleared 
PCCP or breakpoint change protocol into a new 510(k) submission for an AST system device.  
 
III.  Scope 
The scope of this guidance is limited to devices classified under 21 CFR 866.1640, 21 CFR 
866.1645, or 21 CFR 866.1650 with the product codes listed below in Table 1 and does not 
include antimicrobial susceptibility test discs classified under 21 CFR 866.1620.12 The scope of 
this guidance is also limited to recommendations and marketing submission content expectations 
for PCCPs that include planned modifications to update AST system device labeling to include 
the updated breakpoints. This guidance does not describe recommendations for other planned 
modifications to AST system devices, including other planned modifications to update AST 
system device labeling unrelated to updating breakpoints. It is possible that other modifications 
could significantly affect the safety or effectiveness of the device and may require a new 
510(k).13 FDA recommends consulting the relevant device regulations, including 21 CFR 
807.81(a)(3), and the FDA guidance Deciding When to Submit a 510(k) for a Change to an 
Existing Device.14 
 
Table 1 
 
11 Sections 515C(a)(3) and (b)(3) of the FD&C Act. 
12 As described in Section IV.B below, the scope of the enforcement policy described in this guidance is limited to 
legacy AST system devices with product codes listed in Table 1 that have the same intended use and the same 
technological characteristics, classification regulation, and product code as the AST system device manufactured by 
the same sponsor for which a PCCP or breakpoint change protocol has been cleared by FDA. 
13 21 CFR 807.81(a)(3). 
14 Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/deciding-when-submit-
510k-change-existing-device 
4  Contains Nonbinding Recommendations 
 
 
Regulation Number15  Product Code  Device Type  
Instrument For Auto Reader & Interpretation Of 
21 CFR 866.1640  LRG 
Overnight Suscept. Systems 
Manual Antimicrobial Susceptibility Test 
21 CFR 866.1640  JWY 
Systems 
21 CFR 866.1640  LTT  Panels, Test, Susceptibility, Antimicrobial 
21 CFR 866.1640  JTT  Susceptibility Test Powders, Antimicrobial 
21 CFR 866.1640  LTW  Susceptibility Test Cards, Antimicrobial 
21 CFR 866.1640  NGZ  Susceptibility Test Plate, Antifungal 
System, Test, Automated, Antimicrobial 
21 CFR 866.1645  LON 
Susceptibility, Short Incubation 
21 CFR 866.1650  PRH  Positive Blood Culture Identification And Ast Kit 
 
FDA encourages manufacturers to contact the Division of Microbiology Devices, Office of 
Health Technology 7, Office of Product Evaluation and Quality, Center for Devices and 
Radiological Health (DMD/OHT7/OPEQ/CDRH) with additional questions not addressed in this 
guidance, including questions regarding whether this guidance is applicable for a specific device. 
Sponsors may also request feedback through the pre-submission process. In particular, if you are 
interested in proposing a PCCP in your marketing submission, we encourage you to submit a 
Pre-Submission to engage in further discussion with CDRH. Please refer to the guidance entitled 
Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission 
Program.16 
 
IV.  Updating Breakpoints in AST System Device Labeling 
   Establishing and Utilizing a PCCP for Breakpoint 
Updates in a 510(k) Submission for an AST System Device  
Generally, updating the STIC of an AST system device could significantly affect the safety and 
effectiveness of the device, and therefore, such modifications, if not included in a PCCP or 
breakpoint change protocol, would likely require submission of a 510(k) prior to updating device 
labeling.17 In this guidance, FDA describes an approach that would often be least burdensome 
 
15 Some of these devices are also subject to special controls. FDA recommends that you look at the classification 
regulation for information on applicable special controls. 
16 Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/requests-feedback-and-
meetings-medical-device-submissions-q-submission-program 
17 21 CFR 807.81(a)(3). 
5  Contains Nonbinding Recommendations 
 
for manufacturers to incorporate updated breakpoints in AST system device labeling in a timely 
manner by using a PCCP.  
 
(1)  Establishing a PCCP 
By proposing a PCCP in a 510(k) submission, AST system device manufacturers can proactively 
prespecify and seek clearance for breakpoint updates to their device labeling without submitting 
another 510(k) that would otherwise be required for such a change. FDA recommends that all 
AST system device 510(k) submissions that do not already have an applicable PCCP include a 
proposed PCCP in any future 510(k) submission to facilitate the adoption of breakpoint updates 
in AST system device labeling. 
 
Generally, premarket authorization for an AST system device with a PCCP must be established 
through the 510(k) pathway, as a PCCP must be reviewed and cleared as part of a 510(k) for the 
device prior to a sponsor incorporating STIC updates in AST system device labeling under that 
PCCP.18 For 510(k) submissions, in making a determination of substantial equivalence where the 
predicate device was cleared with a PCCP, the subject device must be compared to the version of 
the predicate device cleared prior to changes made under the PCCP.19  
 
The recommended elements for a PCCP to help ensure the AST system devices have the same 
intended use and technological characteristics are outlined below. The PCCP should contain 
procedures to help ensure that updates to the breakpoints consistent with those recognized on the 
STIC Website do not significantly change the performance of the updated AST system device 
such that the performance of the updated device is maintained when compared to the same most 
recently cleared AST system device. 
 
(2)  Utilizing a PCCP 
Once a PCCP has been reviewed and cleared in a 510(k) for an AST system device, the PCCP is 
considered part of the 510(k) clearance. In general, a PCCP should be evaluated within the 
existing risk management framework of the device and implemented in accordance with the 
manufacturers quality system. If the STIC update is consistent with the cleared PCCP, i.e., the 
STIC update is specified and implemented in accordance with the cleared PCCP, then the 
sponsor can update the STIC in the labeling of their AST system device without a new 510(k) 
submission to FDA. The manufacturer must document the change in accordance with the 
manufacturers quality system.20 If the STIC update is not consistent with the cleared PCCP  
including if the STIC update is not included in the cleared PCCP or if the STIC update is 
included in the cleared PCCP but is not implemented in accordance with the cleared PCCP  the 
sponsor should then proceed to evaluate the modification in accordance with applicable FDA 
authorities and the FDA guidance Deciding When to Submit a 510(k) for a Change to an 
Existing Device,21 and proceed accordingly. If, after review of applicable FDA authorities, a 
 
18 See section 515C(b) of the FD&C Act. 
19 See section 515C(c) of the FD&C Act. 
20 See 21 CFR Part 820. 
21 Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/deciding-when-submit-
510k-change-existing-device 
6  Contains Nonbinding Recommendations 
 
new 510(k) is required, then the sponsor must submit a 510(k) before the modified device is 
marketed.22 
 
Deviations from a cleared PCCP for breakpoint updates could significantly affect the safety or 
effectiveness of the device. For example, when updating breakpoints in a manner that is a 
deviation from the PCCP, the devices clinical functionality or performance specifications could 
be compromised. Deviations from the PCCP include instances where the PCCP is not followed 
or cannot be followed. Accordingly, breakpoint updates for an AST system device that are not 
specified in, or implemented in accordance with, the cleared PCCP generally require submission 
of a 510(k) prior to updating the AST system device labeling (see Section IV.B of this guidance 
for discussion on when FDA does not intend to object to certain breakpoint updates applied to 
cleared AST device systems).23 In such a circumstance, the modified AST system device would 
generally be adulterated and misbranded under sections 501(f)(1) and 502(o) of the FD&C Act, 
respectively. 
 
As mentioned, in accordance with section 515C of the FD&C Act, when using a cleared PCCP, 
sponsors may implement breakpoint update changes in AST system device labeling without 
submission of a new 510(k). Updated labeling should be sent to the electronic inbox FDA has 
designated for receipt, ASTDevices@fda.hhs.gov. FDA believes that this approach will facilitate 
timely updates to breakpoints in AST system device labeling.   
 
(3)  Content of a PCCP 
The PCCP should describe: (1) how updated breakpoints will be evaluated by the sponsor; and 
(2) the procedures the sponsor will use to demonstrate that the use of updated breakpoints, when 
applied to existing data that support, or have supported, clearance of the device, (a) demonstrates 
device performance that is maintained when compared to the most recently cleared device, and 
(b) supports that application of updated breakpoints do not reveal new risks or significantly 
modify existing risks such that prior submission of a 510(k) would otherwise be required.24  
 
If an AST system device manufacturer is interested in establishing a PCCP for breakpoint 
updates in a 510(k) submission, FDA recommends that their proposed PCCP include the 
following:   
 
1.  A Description of Modifications that includes:  
a.  A description of the general applicability of the PCCP to AST system devices 
with the same technological characteristics; and 
b.  The updated breakpoint(s) being adopted, which should be identical to the 
relevant breakpoint(s) recognized by FDA on the STIC Website and fall 
within the drug concentration range reviewed and cleared by FDA. 
2.  A Modification Protocol that includes: 
a.  The specific procedures that will be followed to reevaluate previously 
collected clinical data submitted to and reviewed by FDA in the most recently 
 
22 21 CFR 807.81(a)(3). 
23 21 CFR 807.81(a)(3). 
24 21 CFR 807.81(a)(3). 
7  Contains Nonbinding Recommendations 
 
cleared 510(k) submission for the AST system device demonstrating that 
device performance with the updated breakpoint(s) for the drug/organism 
combination is unchanged or continues to meet prespecified performance 
criteria for category agreement (CA), essential agreement (EA), and error 
rates, as applicable; 
b.  A sufficient number of resistant isolates, based on the microbiology activity 
spectrum and minimum inhibitory concentration (MIC) distribution data, if 
applicable, for the drug/organism combination since the most recently cleared 
510(k) submission for that AST system device in which the drug/organism 
combination was evaluated, as determined by the updated breakpoint(s);  
c.  The planned updates to device labeling as a result of breakpoint updates on 
the STIC Website; and 
d.  The planned updates to device labeling to incorporate the new breakpoint 
information and update the devices performance characteristics or 
limitations, as determined by the sponsors evaluation. 
 
  Applying a PCCP or Breakpoint Change Protocol for 
Breakpoint Updates to a Cleared AST System Device (Legacy 
AST System Devices)  
FDA intends to help facilitate sponsor updates to their AST system device labeling based on 
FDA-recognized breakpoint updates for their cleared AST system devices where a PCCP or 
breakpoint change protocol was not previously submitted as part of a 510(k) submission for that 
device. As previously stated, generally, updating the STIC of an AST system device could 
significantly affect the safety and effectiveness of the device, and therefore, such modifications, 
if not included in a PCCP or breakpoint change protocol, would likely require submission of a 
510(k) prior to updating device labeling.25 For additional information on device modifications 
that may require a new 510(k), please see FDAs guidance Deciding When to Submit a 510(k) 
for a Change to an Existing Device.26 
 
At this time, FDA does not intend to object if a sponsor chooses to utilize a PCCP or breakpoint 
change protocol that has been cleared as part of a sponsors separate 510(k) to implement 
breakpoint updates for the sponsors legacy AST system device that is under the same 
classification regulation and product code and has the same intended use and the same 
technological characteristics (e.g., same instrument(s) or device design) as the device for which 
the protocol was cleared by FDA without submitting a 510(k) prior to making STIC labeling 
updates. 
 
Use of a cleared PCCP or breakpoint change protocol for updating breakpoints in another AST 
system device may facilitate timely and efficient updates to these devices, while helping to 
ensure device safety and effectiveness. In addition, the cleared PCCP or breakpoint change 
protocol includes procedures to help ensure that updates to the breakpoints consistent with those 
 
25 21 CFR 807.81(a)(3). 
26 Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/deciding-when-submit-
510k-change-existing-device 
8  Contains Nonbinding Recommendations 
 
recognized on the STIC Website do not significantly change the performance of the newly 
updated (legacy) AST system device such that performance of the updated device is maintained 
when compared to the same most recently cleared AST system device. In the circumstances 
described above, even though AST system devices may have different indications for use based 
on the drug/organism combinations for which they are intended to be used, these devices have 
the same technological characteristics, fall within the same classification regulation and product 
code, and have the same intended uses. In these situations, the procedures for implementing 
breakpoint updates are the same. As such, the risk of raising new issues of safety and 
effectiveness is mitigated when: (1) a sponsor utilizes a cleared PCCP or breakpoint change 
protocol from the sponsors separate 510(k) for an AST system device; (2) that cleared PCCP or 
breakpoint change protocol is applied to the sponsors legacy AST system device; and (3) both 
AST system devices are under the same classification regulation and product code, and have the 
same intended use and the same technological characteristics. 
 
When a sponsor utilizes a PCCP or breakpoint change protocol that has been cleared as part of 
that sponsors separate 510(k) for an AST system device in the circumstances described above, 
that same sponsor should utilize and reference that protocol to test and evaluate whether FDA-
recognized breakpoint updates specified on the STIC Website affect device performance for their 
legacy AST system device. When the breakpoint updates fall within the prespecified 
performance criteria in the cleared PCCP or breakpoint change protocol, at this time, FDA 
generally does not intend to object to distribution and use of the AST system device with the 
updated STIC labeling without submission of a new 510(k), consistent with the policy described 
in this guidance.   
 
As previously described, deviations from the cleared PCCP or breakpoint change protocol could 
significantly affect the safety or effectiveness of the device. Accordingly, this enforcement 
policy does not apply to other labeling updates to an AST system device that are not specified in, 
or implemented in accordance with, a cleared PCCP or breakpoint change protocol as described 
above.  
 
The manufacturer must document the change and use of the cleared PCCP or breakpoint change 
protocol in accordance with the manufacturers quality system.27 The internal documentation 
supporting the breakpoint updates should include the 510(k) submission number that contained 
the referenced cleared PCCP or breakpoint change protocol that was followed, a summary of the 
evaluation in which it was determined that the protocol was appropriately followed, and the 
determination that this falls within the enforcement policy outlined in this guidance. The sponsor 
should reference use of the cleared PCCP or breakpoint change protocol, including the 510(k) 
submission number in which that protocol was reviewed and cleared by FDA, when submitting 
the updated labeling to FDA via the designated electronic inbox, ASTDevices@fda.hhs.gov.  
 
  Incorporating By Reference an Authorized PCCP or 
Breakpoint Change Protocol in a New 510(k) Submission for 
an AST System Device   
 
27 See 21 CFR Part 820. 
9  Contains Nonbinding Recommendations 
 
For sponsors who are submitting a new 510(k) and want to rely on a cleared PCCP or breakpoint 
change protocol that the sponsor previously submitted in a 510(k) submission, the sponsor 
should incorporate by reference the cleared PCCP or breakpoint change protocol into the new 
510(k) submission for their AST system device as described above in Section IV.A. In addition, 
the sponsor of such a protocol should include in their 510(k) submission a reference to the prior 
submission (i.e., 510(k) submission number). 
 
FDA believes that this approach would often be least burdensome for device sponsors to provide 
timely breakpoint updates for their AST system devices to keep appropriate pace with the STIC 
Website, which may help ensure device safety and effectiveness to support patient care and 
public health.  
10