Immediately-in-effect guidance: Antimicrobial Susceptibility Test System Devices - Updating 

Breakpoints in Device Labeling

December 5, 2023

Moderator: CDR Kim Piermatteo

CDR Kim Piermatteo: Hello everyone and welcome to today's CDRH webinar. Thanks for joining us. This 

is Commander Kim Piermatteo of the United States Public Health Service and I serve as the Education 

Program Administrator in the Division of Industry and Consumer Education in CDRH's Office of 

Communication and Education. I'll be the moderator for today's webinar. 

Today, we will discuss the immediately-in-effect guidance titled "Antimicrobial Susceptibility Test 

System Devices - Updating Breakpoints and Device Labeling," which was issued on September 29, 2023, 

and answer your questions about the guidance. This guidance is intended to provide industry and FDA 

staff with information regarding updating susceptibility test interpretive criteria, or STIC, which is 

synonymous with the term breakpoints, as well as provide information regarding associated 

performance data and device labeling for antimicrobial susceptibility test, or AST, system devices in 

response to breakpoint changes posted on the FDA-Recognized Antimicrobial Susceptibility Test 

Interpretive Criteria website. 

Before we begin, I'd like to provide a few reminders for the webinar. First, please make sure you've 

joined us through the Zoom app and not through a web browser to avoid technical issues. Second, the 

intended audience for this webinar is industry. Trade press reporters are encouraged to consult with the 

CDRH Trade Press Team at CDRHTradePress@fda.hhs.gov. And members of national media may consult 

with FDA's Office of Media Affairs at FDAOMA@fda.hhs.gov. And lastly, we look forward to interacting 

with you during the live question and answer segment of today's webinar. If you have a question, please 

wait and raise your hand at the end of today's presentation to get into the queue. 

I now have the pleasure of introducing our presenters for today's webinar, Dr. Ribhi Shawar, Assistant 

Director of the Division of Microbiology Devices in the Office of Health Technology Number 7, or OHT7, 

for in vitro diagnostics, within the Office of Product Evaluation and Quality, or OPEQ, in CDRH. Joining 

Ribhi is Dr. Sarah Alsamarai, Medical Officer in the Division of Microbiology Devices in OHT7 in OPEQ as 

well, and Dr. Natasha Griffin, Team Lead in the Division of Microbiology Devices in OHT7 in OPEQ as 

well. 

We'll begin with a presentation from our presenters and then field your questions about our topic. 

Thank you all again for joining us. I'll now turn it over to Sarah to start today's presentation. 

Sarah Alsamarai: Thank you very much. I will now start the in-depth discussion of the immediately-ineffect guidance. 

Our learning objectives from this webinar are to discuss the clinical significance of using updated 

breakpoints with AST system devices, to describe the background and scope of the guidance, and to 

describe the approaches outlined in the guidance for updating breakpoints in AST system devices.

 

I will first talk about the clinical significance of breakpoints. 
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First, we'll define an AST system device, which is an in vitro diagnostic device in which results are used to 

determine the susceptibility or resistance of a specific organism to a given antimicrobial agent, to inform 

therapeutic decisions, and importantly, to identify epidemiologic trends of antimicrobial-resistant 

organisms. And this is used to detect things like emerging resistance.

How are breakpoints established, and how are they used clinically? Well, breakpoints are wellestablished qualitative interpretations of quantitative results. They're determined based on 

microbiological, pharmacological, and clinical evidence to correlate interpretive categories with clinical 

outcomes. Importantly, breakpoints may be revised over time due to changing epidemiology and 

emerging resistance. 

This slide explains the interpretive categories of breakpoints. So, the first is susceptible, meaning that 

there is a high likelihood of therapeutic success. Intermediate means that there is uncertain probability 

of therapeutic effect. And in the case of resistance, this means there's a high likelihood of therapeutic 

failure. 

I will now share a clinical example demonstrating the use of breakpoints to inform clinical decision 

making. We see, in this example, we are looking at the organism enterobacterales and the antimicrobial 

ciprofloxacin. We can see that the breakpoints for this organism and antimicrobial combination have 

been revised. When we look at the graphical representation of this below, we see that at an MIC equal 

to one, under the old breakpoint interpretive criteria, this interpretive category would be susceptible, 

meaning that there would be a high likelihood of therapeutic success if this organism were treated with 

this antimicrobial agent. This would signal to clinicians that this antimicrobial could be effectively used. 

However, when we look at the line below, using the new breakpoint, we see that with the most updated 

breakpoint, at an MIC of one, the interpretive category is actually resistant, meaning that there is a high 

likelihood of therapeutic failure. In this case, we see the importance of having updated breakpoints in 

order to guide clinicians to choose the most appropriate antibiotic to treat the infection. Using 

antibiotics that are ineffective against organisms can lead to progression of disease and undertreating of 

infection. 

Now I will turn to Ribhi Shawar for the next part of this presentation. 

Ribhi Shawar: Thank you, Sarah, for this highlight of the clinical relevance and importance of 

breakpoints for interpretation of results from AST devices. 

Good afternoon, everyone. In the next few slides I'll provide some pertinent background and elaborate 

on the scope and applicability as they relate to this guidance.

But first, some background. As many on this call may be familiar, there are several guidance documents, 

initiatives, and other developments related to antimicrobial and antifungal drugs from CDER, the Center 

for Drug Evaluation and Research, and to AST devices from CDRH, the Center for Devices and 

Radiological Health. Without going too deep into history, in 2009, there was a need to revise guidance 

documents, including the joint CDER/CDRH guidance, as a result of multiple interactions and citizens' 

petition regarding appropriate breakpoints to use. 
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This guidance described a mechanism for updating breakpoints in AST system devices but did not 

provide specifics on processes. With the issuance of the immediate-in-effect AST guidance we are 

discussing today, that original 2009 was withdrawn. Now I want to take the opportunity to highlight 

some resources and initiatives that FDA had made throughout the years to facilitate and streamline 

development of AST devices and applicability of up-to-date breakpoints.

One such important development occurred as a result of the 21st Century Cures Act, signed into law on 

December 13, 2016. As a result, in 2017, a website was established by FDA referred to as a STIC, this is 

short for Susceptibility Test Interpretive Criteria, which provides in a single place a list of all FDArecognized or established breakpoints for such drug organism or organism group combinations. This is 

pertinent to the discussions we are having at this webinar today since FDA-recognized breakpoints on 

the STIC website should be used when developing or updating AST devices. The slide contains a 

hyperlink to this website if you wish to go to it. 

A couple of other initiatives are worth mentioning, as they are extremely valuable. One is the CDC and 

FDA Antimicrobial Resistance Isolate Bank, known as the AR Bank, or referred to as the AR Bank. The AR 

Bank was an FDA initiative established over eight years ago as an interagency agreement between FDA 

and CDC. I want to thank and acknowledge the hard work by our CDC colleagues for maintaining and 

continuing to support this effort. This has been a tremendously valuable source and resource of wellcharacterized isolates that can be used in developing or updating AST devices, as well as in clinical and 

public health laboratories. The isolates are provided free of charge and this slide contains a hyperlink to 

this website. Please visit it. 

And the final point on this slide is the Coordinated Development Guidance, which was issued in 2019. 

This is, again, a combined CDER/CDRH guidance, offers steps that drug and device manufacturers can 

take to facilitate availability of AST devices for use in clinical lab in a timely manner after new drug 

approval. 

Now let's turn our attention to the subject matter for updating breakpoints in AST devices. Since 2019, 

FDA has established a mechanism whereby an AST device manufacturer can include, along with their 

regulatory submission for clearance, a breakpoint change protocol, abbreviated here as BCP. But this 

does not flow from the tongue very well, at least not for me, so, I might just keep saying breakpoint 

change protocol. At any rate, this, in essence, is an SOP, standard operating procedure, which describes 

steps an AST device manufacturer will take to update the breakpoint information in labeling, or package 

insert, if certain conditions apply without the need to submit a regulatory application to FDA. 

To date, FDA has reviewed and cleared over 60 AST device applications with such breakpoint change 

protocol and this facilitates availability of devices with updated information. However, up until recently, 

such breakpoint change protocols were only applicable to devices and drug-organism combinations for 

that specific drug-organism combination used on that device.

With the issuance of the immediate-in-effect guidance, AST device label can be updated using a 

predetermined change control plan, or PCCP, or a previously cleared, between brackets, breakpoint 

change protocol. Most importantly, this will be applicable to what we call legacy devices, which Dr. 

Griffin will describe in a few minutes in more details. Next, I will briefly go over the scope of this 

guidance. 
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As you know, there are multiple types of qualitative and quantitative manual or automated AST devices. 

The scope of this guidance is limited to those devices classified under the Code of Federal Regulations, 

or CFR, which appear on this slide, along with the product codes. Modifications to these devices, the 

device package inserts specifically, can be made if the conditions stated in a breakpoint change protocol 

or a PCCP reviewed and cleared by FDA are applicable. 

Now I'm going to turn the floor over to Natasha to guide us through specifics outlined in this guidance 

and how this will all work. Natasha? 

Natasha Hardesty: Thanks, Ribhi. 

I will now provide details of the specific policies outlined in the guidance. 

The immediately-in-effect guidance describes the use of a predetermined change control plan, or PCCP, 

to update breakpoints in AST system devices in the event of a future FDA-recognized breakpoint change.

A PCCP is documentation provided in a premarket submission that proactively prespecifies and seeks 

premarket authorization for future changes as outlined in the PCCP. Please note that as it relates to AST 

devices, this documentation was referred to as a breakpoint change protocol prior to issuance of this 

guidance. As such, the specifications previously described in breakpoint change protocols are generally 

the same as those described in PCCPs. 

The IIE guidance describes how to establish a PCCP, what content should be included in a PCCP, and how 

to utilize a PCCP in the event of a future FDA-recognized breakpoint change. I'll describe each in the 

upcoming slides. 

As I mentioned, prior to issuance of the guidance, breakpoint change protocols were received and 

reviewed for AST devices. The breakpoint change protocols are now being received and reviewed as 

PCCPs. As such, the purpose, content, and subsequent action remain the same in that PCCPs can be 

provided for review and clearance with an AST device so that in the event of an FDA-recognized 

breakpoint change, the PCCP can be followed, and if certain criteria are met, the label can be updated 

and sent to the AST device's inbox without a new 510(k) submission. 

The IIE guidance describes how to establish a PCCP to proactively seek clearance of updated breakpoints 

and labeling without a new 510(k). FDA is recommending that all AST device manufacturers include a 

PCCP in future submissions to ensure timely breakpoint updates in the event of a future FDA-recognized 

breakpoint change. In general, the PCCP should contain procedures that help ensure that the breakpoint 

update does not significantly change the performance of the previously cleared device. 

In general, a PCCP will describe modifications determined to be appropriate for inclusion in the PCCP, as 

well as the protocol in place to adopt the modification. The guidance states that the PCCP should 

describe the applicability of the PCCP to AST system devices with the same technological characteristics. 

This is to allow use of a single PCCP across multiple AST devices, as I will describe later. 

In addition, the PCCP should state that the breakpoints to be updated are those that are recognized on 

the FDA STIC web page. Importantly, the updated breakpoints should fall within the reporting range of 

the previously cleared device. 
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In addition, the PCCP should include procedures that will be performed to re-evaluate the clinical data 

provided in the most recent 510(k) clearance to support the updated breakpoints. This includes 

determining whether the re-evaluated data demonstrates acceptable performance, as well as includes a 

sufficient number of resistant isolates. Finally, the PCCP should describe how the AST device label will be 

updated, including sending the updated labeling to the AST device's inbox, which will be described next.

 

In the event of an FDA-recognized breakpoint change, an AST device that was cleared with a PCCP can 

utilize the PCCP to adopt the breakpoint update in accordance with the PCCP. Notably, there may be 

some scenarios in which the AST device label cannot be updated per the PCCP. In those cases, we 

recommend that manufacturers refer to the FDA guidance, "Deciding When to Submit a 510(k) for a 

Change to an Existing Device." 

When updating the AST device label, it's important to note that the breakpoint update must be 

documented per the manufacturer's quality system. In addition, the updated labeling should be emailed 

to the AST devices inbox, ASTdevices@fda.hhs.gov. 

To describe how to update breakpoints in AST devices with a PCCP, we've illustrated three different 

scenarios. In the first scenario, the PCCP is used with the AST device it was cleared with. In this example, 

an AST device for testing ciprofloxacin is cleared with a PCCP. At some point after clearance, CDER 

recognized updated breakpoints for ciprofloxacin. At that time, the manufacturer uses the PCCP, and 

updates the ciprofloxacin device label, and sends it to the AST devices inbox. 

The guidance also describes how a PCCP, or breakpoint change protocol, that was cleared for an AST 

device can be used for a legacy device, which is a device that was cleared without a PCCP, or breakpoint 

change protocol. For the PCCP or breakpoint change protocol to be applicable, when compared to the 

AST device cleared with the PCCP or breakpoint change protocol, the legacy device should have been 

cleared under the same classification regulation and product code, have the same intended use, and 

have the same technological characteristics. 

As previously described, the breakpoint update should be implemented in accordance to the cleared 

PCCP or breakpoint change protocol. This is because updates that are outside of the scope of the PCCP 

generally require submission of a 510(k) prior to updating the labeling. In addition, the breakpoint 

update must be documented per the manufacturer's quality system, as well as internally documented. 

This documentation should include a reference to the 510(k) submission of the AST device that had the 

cleared breakpoint change protocol or PCCP that was used. In addition, it should have a summary 

indicating that the breakpoint change protocol or PCCP that was used was appropriately followed and a 

final determination that the update falls within the enforcement policy, which is outlined in the 

guidance. The updated label, as well as the referenced 510(k) submission number, should be emailed to 

the AST devices inbox. 

The second scenario describes use of a previously cleared PCCP or breakpoint change protocol with a 

legacy AST device. In this illustration, an AST device for testing piperacillin-tazobactam, or pip-tazo, is 

cleared. Later, an AST device for testing ciprofloxacin is cleared with a breakpoint change protocol or 

PCCP. At some point in the future, CDER recognizes updated breakpoints for pip-tazo. At that time, the 

manufacturer uses the breakpoint change protocol or PCCP that was cleared for ciprofloxacin to update 

the pip-tazo device label. The updated pip-tazo device label, as well as a reference to the ciprofloxacin 

510(k) submission, are sent to the AST devices inbox. 
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The guidance also describes how to incorporate by reference a cleared breakpoint change protocol or 

PCCP in a future 510(k) submission. Similar to the legacy devices, new AST devices that incorporate 

cleared breakpoint change protocols or PCCPs by reference in a new 510(k) submission should have the 

same intended use and technological characteristics as the AST device that was cleared with the 

breakpoint change protocol or PCCP. As previously described, the breakpoint update should be 

implemented according to the cleared PCCP or breakpoint change protocol, be documented per the 

manufacturer's quality system, and the updated labels should be sent to the AST devices inbox. 

The third and final scenario describes updating breakpoints with a breakpoint change protocol or PCCP 

that was incorporated by reference in a new AST device clearance. In this illustration, an AST device for 

testing ciprofloxacin is cleared with a breakpoint change protocol or PCCP. In the future, an AST device 

for testing sulbactam-durlobactam is cleared, along with a reference to the breakpoint change protocol 

or PCCP that was cleared with ciprofloxacin. At some point in the future, CDER recognizes updated 

breakpoints for sulbactam-durlobactam. At that time, the manufacturer uses the breakpoint change 

protocol or PCCP that was referenced in the sulbactam-durlobactam clearance, and updates the

sulbactam-durlobactam device label, and sends it to the AST devices inbox. 

In summary, we want to reiterate that the use of AST devices with updated breakpoints is essential to 

provide accurate results for patient care and to monitor the emergence of antimicrobial resistance. 

Breakpoint change protocols have been successfully used to update breakpoints in AST devices. Going 

forward, we anticipate that PCCPs will continue to be successful in ensuring timely updates to 

breakpoints. 

The immediately-in-effect guidance provides least burdensome recommendations for manufacturers to 

update breakpoints in AST devices, including legacy AST devices. As such, manufacturers that have a 

cleared breakpoint change protocol can immediately begin using it to update breakpoints of legacy AST 

devices. 

Further, AST device manufacturers without a clear breakpoint change protocol should submit a 510(k) 

for an AST device and include a PCCP for review. After clearance, the PCCP can be used to update 

breakpoints for legacy AST devices, as described in the guidance. 

Here are the resources that were mentioned earlier in the presentation, along with the full URL that you 

can access after the presentation. 

Although this immediately-in-effect guidance was implemented without prior public comment, 

comments may be submitted to the docket number FDA-2023-D-4045. FDA will consider all comments 

received and revise the guidance as appropriate. 

Thank you for your time and attention. We look forward to answering your questions. I'll now turn it 

back over to Kim. 

CDR Kim Piermatteo: Thank you Natasha. And thank you to Sarah and Ribhi for your presentation as 

well. We will now transition to our interactive question and answer segment. 
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Before we begin, I'd like to go over how we will manage this segment and give you a few reminders. 

First, to ask a question, please select the Raise Hand icon, which should appear on the bottom of your 

Zoom screen. I'll announce your name and give you permission to talk. When prompted, please select 

the blue button to unmute your line and then ask your question. When asking your question, please 

remember to limit yourself to asking one question only and try to keep it as short as possible. And we 

appreciate that you may have a very specific question involving your device or scenario; however, we 

might not be able to answer such specific questions. Therefore, we'll try to frame a broader response 

based on what's described in this guidance. After you ask your question, please lower your hand. And if 

you have another question, please raise your hand again to get back into the queue and I'll call on you as 

time permits. 

While we await your questions, I would like to ask our presenters a few questions we've received 

regarding the immediately-in-effect guidance. So, Ribhi, I'd like to ask you this question. Why are disk 

devices outside of the scope of the guidance? 

Ribhi Shawar: Alright, thank you, Kim. Yeah, I'd be happy to take that. The answer to this one is, we 

expect that question to have come, really, from several. For the majority of AST disk devices, as many of 

the people in attendance here will know, the clearance relies on leveraging information used to 

establish disk-to-MIC correlates as part of the antimicrobial drug review and approval. And so, we are 

actively working on an approach to allow a breakpoint change protocol, or revisions, or PCCP of some 

sort, to disk package inserts in order to allow for that updated information to get in the hands of users. 

In the meantime, if you have any specific questions, please submit them to ASTdevices@fda.hhs.gov

inbox. 

CDR Kim Piermatteo: Thanks, Ribhi. Now I'd like to ask Natasha a question. Natasha, the question is, if a 

manufacturer has a previously cleared breakpoint change protocol, do they need to submit a PCCP? 

Natasha Griffin: Thanks. Thanks, Kim. No. A manufacturer with a previously cleared breakpoint change 

protocol does not need to submit a PCCP. As the least burdensome approach, the guidance allows 

manufacturers to use previously cleared breakpoint change protocols in lieu of submitting a PCCP. As 

noted in the guidance, previously cleared protocols can be applied to legacy devices and can also be 

incorporated by reference in future AST device premarket submissions. 

CDR Kim Piermatteo: Great. Thanks, Natasha. And for this last question, Sarah, I'll be directing that to 

you. Sarah, the question is, how can end users and manufacturers easily identify FDA-recognized 

breakpoint updates? 

Sarah Alsamarai: Thank you, Kim. So, for current up-to-date breakpoint information, you can go to the 

FDA STIC website, and this is also noted on the Resources slide of our PowerPoint. And note that when 

applicable, the FDA STIC website may refer to CLSI documents for current breakpoints. We also do 

recommend that manufacturers sign up to receive the FDA-recognized antimicrobial STIC breakpoints 

email notifications, available on the STIC website, to make sure that they receive notifications on future 

updates. 

CDR Kim Piermatteo: Great. Thanks again, Sarah. Thanks for your response. We'll now take our first live 

question, which is coming from Briget. Briget, I have unmuted your line. Please unmute yourself and ask 

your question. 
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Briget, are you able to unmute yourself? 

Alright, Briget if you are double muted, please check that and I will try to circle back to you in a few.

Our next, what I'd like to do is I'd like to circle back to Natasha and ask you a question we've received 

previously as well. And that question is, if a company did not have any previously cleared PCCP or BPC

protocol, what should they do?

Natasha Griffin: Thanks, Kim. We are strongly encouraging manufacturers without a previously cleared 

PCCP or breakpoint change protocol to submit a 510(k) submission for their AST system device with a 

PCCP. As a reminder, before PCCP can be applied to legacy devices, it will need to first be reviewed and 

cleared by FDA. 

CDR Kim Piermatteo: Thanks, Natasha. Alright, I'm going to call on Lacey. Lacey, I have unmuted your 

line. Please unmute yourself and ask your question. 

Lacey Harbour: Hi, everyone. Can you hear me just fine?

CDR Kim Piermatteo: Yes, we can. 

Lacey Harbour: Thank you. I'm actually curious on how you see the breakpoint change device and the 

PCCP, whatever you want to call it, would be overlapping with the letter to file process. You stated that 

you need to follow your internal quality management system. But I was wondering if you guys could go 

in a little bit more detail on what you see that process looking like and if it would be different from the 

BCPs versus the PCCPs. 

CDR Kim Piermatteo: Thank you, Lacey. I'm going to turn it over to Ribhi to provide you a response. 

Ribhi Shawar: Yeah. Thank you, Lacey, for this question. Clearly, any device manufacturer knows about 

the quality system that they need to follow. In essence, the breakpoint change protocol or PCCP are 

documents that a sponsor establishes for certain steps and processes that they want to follow within 

their own systems when certain conditions apply. So, in essence, this is still following up on their overall 

quality system regulation, irrespective of how they, as a manufacturer, intend to provide those 

documentations within their own system. So, this way, this is not a different approach or a, it in fact, is a 

least burdensome approach, such as no need for duplication of any type of effort. I hope I addressed 

that. But if not, then if we have time, we can maybe circle back with further information. 

CDR Kim Piermatteo: Thanks, Ribhi. Lacey, did you have any follow-up questions? 

Lacey Harbour: I don't. I think that that answers it. So you're not saying that if you had a letter to file 

method, that if you were following, if you did an analysis that proved that you were still within the PCCP, 

and you knew you had to update the labeling, you were going through that process, you had the 

procedures in place and the SOPs in place, that you don't need to then turn around to your letter to file 

procedure. You can just update your, am I understanding that you're saying, if someone were to update 

their letter to file procedures and reference that if there is a PCCP that's been established, that you 
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follow that? Or is that what you're saying, or something to that effect? I'm just trying to make sure that 

it's 100% understood. 

Ribhi Shawar: Yeah. I'll try and clarify it further. But if not, please feel free to send us an email to the 

AST devices inbox and we can address it that way. But in general, as Natasha explained, there's the 

processes that need to be followed, meaning that a PCCP or breakpoint change protocol would have 

been reviewed by FDA, would have been concurred with, before any manufacturer on their own decided 

to do those kind of things. FDA needs to know and be informed about how these processes are working 

and that they concur with the SOP, if you will, of how things are to be applied. But again, please feel free 

to send us an email to the inbox if there are still questions. 

Lacey Harbour: Thank you. Yeah, I'm partially asking because, as you are likely aware, software as a 

medical device has the new PCCP application guidance documents. And so, you as you have already 

established this process, just trying to understand how to use it for devices that are not just the ASTs. 

So, thank you so much. I think that made quite a bit, that added clarity. Thank you. 

Ribhi Shawar: Thank you. 

CDR Kim Piermatteo: Thanks Lacey for your question and thanks Ribhi for your response. Next, I am 

going to circle back to Sarah for a question we previously received. Sarah, the question is, can a 

manufacturer send in a 510(k) with only a PCCP? Or does the PCCP have to accompany a request for a 

device clearance?

Sarah Alsamarai: Thanks, Kim. So, no. As described in the guidance, a PCCP must accompany a 

premarket submission with a device. 

CDR Kim Piermatteo: Great. Thanks for clarifying, Sarah. Next, I'd like to call on Sharon. Sharon, I have 

unmuted your line. Please unmute yourself and ask your question.

Sharon Cullen: Hi, this is Sharon. So first of all, thanks for the tremendous progress in establishing a 

process for legacy devices. So, I wanted to acknowledge that. Then I wanted to follow up with a question 

of, there are limited situations where we could use these PCCPs. Specifically, currently, if we test 

additional isolates or have to do additional testing, then it doesn't qualify for the PCCP. My question is, 

do you have plans to pursue further expansion of when we can apply the PCCP? And if so, what would 

that look like? 

CDR Kim Piermatteo: Thank you Sharon for your question. Would anyone on the team like to provide a 

response? It does, Sharon, that does sound a little bit outside the scope of our webinar for today. I don't 

know, Ribhi or Natasha, if you wanted to expand on that or have-- I guess, Sharon, we would suggest 

you could email the AST email box if you wanted some specific information, or the docket that we had 

mentioned earlier. 

Sharon Cullen: OK. STMA can probably then respond through the docket with a couple of questions. 

That would be a good approach.

CDR Kim Piermatteo: Great. Thanks, Sharon. Alright, our next question is coming from a number. That 

number is 10021728. I've unmuted your line. Please unmute yourself and ask your question.
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Nathan Hardesty: Hi, yes. We have a quick question regarding indications for use and things that change 

within breakpoints. If we had a previously cleared organism group, and now the FDA changes the 

breakpoints, and only a specific organism is now recognized, does that mean that that is still covered 

under a PCCP or BCP? Or would we have to submit specifically to the new indication for use for that 

antimicrobial?

CDR Kim Piermatteo: Hi. Thanks for your question. If you could just provide your name real quick and...

Nathan Hardesty: Yes.

CDR Kim Piermatteo: Oh, go ahead. 

Nathan Hardesty: Yeah, sorry. This is Nathan Hardesty. 

CDR Kim Piermatteo: Great. Thank you, Nathan. I think we're going to turn it over to Ribhi. Did you want 

to provide a first response? Or if anyone else on the team has anything they want to add, please chime 

in.

Ribhi Shawar: Yes, I can give it a try. Thank you, Nathan. Appreciate the question. Changes to intended 

use, like the addition of an organism, taking out of an organism, is still outside of what exactly the intent 

of this, but could be a result of it, meaning that, as a result of applying something that your SOP stated, 

there will be changes to it. But again, I think the specifics and nuances for each device are really going to 

be very hard to cover in a webinar like this. Again, encourage you to either submit to the docket or 

submit to the AST devices, which I know you have done. But I'm going to also ask, maybe Natasha, if you 

have any additional thoughts on this, because we discussed those kind of things before. 

Natasha Griffin: Nothing more than what Ribhi's already mentioned. So, I'll guess I'll reiterate. In the 

event that FDA removes breakpoints for a particular organism group, there is an expectation that from 

the manufacturer side that the intended use for that drug would be updated to reflect FDA's current 

thinking or decision for that antimicrobial. Again, it's outside the scope of the PCCP, but that is 

something that should be handled by manufacturers. 

CDR Kim Piermatteo: Thanks, Natasha. And thanks, Ribhi. Nathan, I think we want to reiterate that we 

would like you to submit your comment via email, not through the docket. So, this would be something 

that you could submit to the AST devices email.

Nathan Hardesty: OK, thank you very much.

Ribhi Shawar: Kim, one other point, sorry this is Ribhi. 

CDR Kim Piermatteo: Sure.

Ribhi Shawar: Since this is being recorded, perhaps, also, Pre-Submission depends, again, on the details 

and the intensity of it. A Pre-Submission might actually be a good one for those types of things because 

the details will be provided in that Pre-Submission rather than, a simple email might not contain all the 

information that is needed. So just a suggestion here also. 
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Nathan Hardesty: OK, sounds great. Thank you.

CDR Kim Piermatteo: Great. Thanks, Ribhi, for that clarification. Alright, I would like to come to Natasha 

again. Natasha, I'm going to ask you a question we've previously received. And that question is, does the 

PCCP have to include a listing of legacy devices to which the PCCP may apply? 

Natasha Griffin: So, the short answer is no. A PCCP should not include a listing of legacy devices to 

which it may apply. As noted in the guidance, the PCCP should be generally written for an AST system 

device and not for a specific drug tested with that system. When updating breakpoints for legacy 

devices, manufacturers should reference the 510(k) submission number of the cleared PCCP when 

sending the updated label to the AST devices inbox. In addition, the PCCPs can be incorporated by 

reference in future AST device submissions. 

CDR Kim Piermatteo: Thanks, Natasha. Alright Ribhi, I'm going to come back to you with a question that 

we have previously received. And that question is, what should happen if all breakpoints for a drug are 

completely removed from FDA STIC, or STIC?

Ribhi Shawar: Alright thank you, Kim, for the question. Again, those are really good questions, whoever 

submitted them. So, in general, marketing of an AST device to test for a drug organism combination for 

which there is no FDA breakpoints would not be in the interest of public health, because usually, this 

occurs when there is insufficient data to support testing or interpreting that particular combination.

As such, breakpoint information for this drug-organism combination should not be appearing in that 

label, it should be removed from the labeling. In general, device manufacturers are the ones responsible 

for ensuring, are responsible for ensuring the continued use of the device in a safe and effective 

manner, which, of course, includes labeling with up-to-date breakpoints and the removal of 

unrecognized breakpoints is appropriate. Again, this may be a detailed question and answer, but 

hopefully, that is clear. Since this is a submitted question, I think that that's all I can say at this point, 

unless Sarah or Natasha want to add anything. 

CDR Kim Piermatteo: OK. Thanks, Ribhi. Hearing none from Sarah and Natasha, we're going to head and 

move on to another question that I'd like to direct towards Sarah. And Sarah, that question is, what type 

of submission can a PCCP be submitted with?

Sarah Alsamarai: So, a PCCP can be submitted with any premarket submission for an AST device, 

regardless of the purpose. And also note that acceptance of a PCCP in a premarket submission will be 

determined during the review.

CDR Kim Piermatteo: Thanks, Sarah. Alright at this time, I don't see any more raised hands. So, I'd like to 

make a call out, if you have a question that you would like to ask our presenters today on our topic, 

please click on that button in Zoom to raise your hand and we can call on you and you can ask our 

presenters your question. 

While we wait for that, Natasha, I'm going to come back to you with another question we've received. 

And that question is, what is the difference between a breakpoint change protocol and a predetermined 

change control plan?
12

 

Natasha Griffin: So, documents submitted prior to issuance of the IIE guidance are referred to as 

breakpoint change protocols, while documents submitted after issuance are referred to as PCCPs. As 

noted in the presentation, the content, scope, and purpose remain the same between both documents. 

And please note that the format of the PCCP remains at the discretion of the manufacturer. 

CDR Kim Piermatteo: Thanks, Natasha. Alright, I'm going to make one more call out. Does anyone on 

the call today have any questions that they would like to ask today? 

If so, I need you to raise your hand in Zoom. 

Alright, seeing none, then, we will go ahead and move to close our webinar. That will wrap up our 

question and answer segment today. Thank you to all of you for your questions and participation. And 

I'd now like to turn it back over to Ribhi to provide his final thoughts. Ribhi? 

Ribhi Shawar: Thank you, Kim. Yes, happy to. So, thank you for attending this webinar. And we hope 

that the information we shared and the answers to your questions were helpful. As noted in the 

information we shared, the use of breakpoint change protocols was introduced by FDA several years ago 

and has shown success. 

Many sponsors have taken advantage of the breakpoint change protocol and instituted changes to AST 

device labels upon FDA-recognized revisions to the breakpoints, such as on the STIC website, thus 

assuring safe and effective use of these devices. As explained, this new guidance formalizes the use of 

breakpoint change protocols, now referred to as predetermined change control plans, or PCCPs, to 

further facilitate the process of breakpoint updates in AST device labeling, while broadening the 

applicability of clear breakpoint change protocols or PCCPs to legacy AST devices, as Natasha had 

mentioned.

 

We strongly encourage manufacturers to take advantage of this least burdensome approach to update 

their labeling to ensure continued appropriate, safe, and effective use of AST devices. Thank you and

have a great rest of your day. 

CDR Kim Piermatteo: Thanks, Ribhi, for those final thoughts. For your information, printable slides of 

today's presentation are currently available on CDRH Learn at the link provided on this slide, under the 

section titled In Vitro Diagnostics. A recording of today's webinar and a transcript will be posted to CDRH 

Learn under the same section and subsection in the next few weeks. And a screenshot of where you can 

find these webinar materials has been provided on this slide as well. 

Again, if you have additional questions about this guidance, please submit them to 

ASTdevices@fda.hhs.gov. And if you have additional questions about today's webinar, feel free to reach 

out to us in DICE at DICE@fda.hhs.gov. 

And lastly, we hope you're able to join us for a future CDRH webinar. You can find a listing of all of our 

upcoming webinars via the link provided on the bottom of the slide at www.fda.gov/CDRHWebinar. 
13

This concludes today's webinar. And thank you all again for joining us. Have a great day. 

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