1 

Welcome to Today’s FDA/CDRH

Webinar

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participants.

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Conference Number: PWXW5928257

November 16, 2017 Webinar
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Deciding When to Submit a 510(k) for a Change to an 

Existing Device 

Final Guidance for Industry and FDA Staff

and 

Deciding When to Submit a 

510(k) for a Software Change to an Existing Device 

Final Guidance for Industry and FDA Staff

Published: October 25, 2017
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Presenters

Rebecca Nipper & Linda Ricci

Office of Device Evaluation

Center for Devices and Radiological Health
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Agenda

• Background on 510(k) device modifications

• Development of FDA’s modifications guidances

• FDA guidance goals

• General guidance highlights

• Software guidance highlights

• Questions and answers
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510(k) Device Modifications Background 

• Medical device innovation cycle requires 

continual modifications

• FDA’s policy has two goals:

1. Ensure patients and providers have timely access to 

modified devices; and

2. Provide essential flexibility for industry and FDA to 

enable innovation and ensure effective public health 

oversight of modified devices 
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Regulatory Basis for FDA’s policy

• FDA’s 510(k) device modifications policy 

is based on two regulations:

– 21 CFR 807.81(a)(3)

• Regulation that describes when a new 510(k) is 

required

– 21 CFR 820

• Quality System Regulation
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When a 510(k) is Required for a Change

21 CFR 807.81(a)(3): The device is one that the person 

currently has in commercial distribution or is reintroducing 

into commercial distribution, but that is about to be 

significantly changed or modified in design, components, 

method of manufacture, or intended use. 

The following constitute significant changes or 

modifications that require a premarket notification:

(i) A change or modification in the device that could significantly 

affect the safety or effectiveness of the device, e.g., a significant 

change or modification in design, material, chemical composition, 

energy source, or manufacturing process.

(ii) A major change or modification in the intended use of the 

device. 
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Quality System Regulation

• 21 CFR 820.30(i) Design changes - Each 

manufacturer shall establish and maintain 

procedures for the identification, 

documentation, validation or where appropriate 

verification, review, and approval of design 

changes before their implementation. 

– Robust documentation is helpful to both FDA and 

manufacturers
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Stakeholder Input

• Guidance content based on stakeholder 

feedback, including comments on draft 

guidances and FDA’s 2013 Public Meeting

• Consensus around retaining the basic 

paradigm of original Deciding When to Submit: 

– No paradigm changes from original guidance

– Clarification needed in certain areas

– Rely on risk management and Quality System 

regulation (21 CFR 820) where possible
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FDA Guidance Goals

• FDA has made targeted changes to original 

Deciding When to Submit guidance from 1997:

• Clarity, including interpretation of key regulation terms such 

as “could significantly affect”

• Flowcharts – matched with text

• Key principles

• Materials changes

• Examples to illustrate use of guidances 

• Documentation recommendations and examples

• Separate software guidance based on same key 

principles

• Addition of risk assessment paradigm
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Guidance Scope

• Both guidances apply to legally marketed 

devices subject to 510(k) requirements 

– Excludes PMA devices and 510(k)-exempt devices

• General Guidance and Software:

– General guidance does not apply to software- specific changes

– General guidance does apply to non-software 

changes to software devices or devices containing 

software (e.g., labeling)

– Guiding principles are aligned between the 

guidances
Guidance Scope

• Software Guidance

– Does not apply to software for which FDA has 

stated in guidance that it does not intend to 

enforce compliance with applicable regulatory 

controls 

– Does not address:

• the software lifecycle

• what documentation should be included in a 510(k) for 

a software modification, or 

• the principles that are applicable to the validation of 

medical device software

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Evaluating Software and NonSoftware Changes

• When multiple changes affect labeling/hardware in addition 

to software, assess the changes using both guidances. 

– If use of either guidance leads to a “New 510(k)” 

conclusion, submission of a new 510(k) is likely required.

• For example:

– To add a new mode to software device (no hardware), use 

Software Mods. Only need to use General Mods for 

labeling revisions or if changes to indications for use are 

warranted (e.g., to explain new mode)

– To add a new mode to an infusion pump, use Software 

Mods for the software revisions and General Mods for the 

change to pump specifications 13
14

• Referred to as “Assumptions/Axioms” in the 

“Deciding When to Submit a 510(k) for a Change to 

an Existing Device (K97-1) published January 10, 1997

• Essential principles necessary for use of both 

guidances

• Principles should be used in conjunction with the 

more specific guidance sections 

Guiding Principles 

(Applies to both General and Software 510(k) 

Modifications Guidances) 
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Guiding Principles Cont.

• Modifications made with intent to significantly 

affect safety or effectiveness of a device

– Per 21 CFR 807.81(a)(3)(i), a change that could 

significantly affect safety or effectiveness requires a 

510(k) 

– Change that’s intended to significantly affect safety or 

effectiveness (e.g., to address adverse events) 

requires a 510(k)

– Changes not intended to significantly affect safety or 

effectiveness should still be evaluated using this 

guidance

 
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Guiding Principles Cont.

• “Could significantly affect” and the role of testing

– Risk-based assessment should be used to make initial 

determination of whether a 510(k) is necessary 

• Assessment should cover new risks and changes in known risks 

resulting from device modification

– Risk-based determinations not to submit should be 

confirmed by verification and validation (V&V)

• If V&V activities produce unexpected results, decisions not to 

submit should be reconsidered

• Unintended consequences of changes

– Manufacturers should consider whether there are 

unintended consequences or effects of device 

modifications

– Example: sterilization changes may affect device materials
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Guiding Principles Cont.

• Use of risk management

– Plays a central role in determining when a change “could 

significantly affect” safety or effectiveness

– Guidances intended to leverage manufacturers’ existing 

risk processes to determine when change requires a 

510(k) 

– Risk terminology in guidance primarily based on ISO 

14971, but an individual manufacturer’s terminology may 

differ 

– Because 21 CFR 807.81(a)(3)(i) requires 510(k) for change 

that “could significantly affect safety or effectiveness,” 

both safety and effectiveness should be considered
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Guiding Principles Cont.

• Evaluating simultaneous changes

– Changes should be assessed separately and together

• Appropriate comparative device and cumulative effect of 

changes

– To determine whether changes “could significantly affect 

safety or effectiveness,” manufacturer should compare 

modified device to unmodified device, as most recently 

cleared by FDA

– For purposes of determining whether a 510(k) is necessary, 

changes should not be compared to other predicate devices 

(this is not a substantial equivalence (SE) determination)

• Documentation requirement

– Quality system regulation requires documentation of design 

changes 
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Guiding Principles Cont.

• 510(k) submissions for modified devices

– When a 510(k) is required, 510(k) should describe all 

changes that trigger the requirement

– Changes that do not trigger the requirement should also 

be described, if they would have been described in the 

original 510(k) for that device

– Example: labeling changes should be described, even if 

they do not trigger 510(k) requirement, to ensure 

complete understanding of changes for a substantial 

equivalence (SE) comparison

• Substantial equivalence determinations

– Following this guidance does not ensure SE 

determination 
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How to Use The 510(k) Modifications 

Guidances 

• Guidances describe a logic 

scheme for determining 

when a 510(k) is required

• Include flowcharts for ease 

of use, but flowcharts are 

not intended to be used 

alone

Reminder: Flowcharts 

are provided as a 

visual aid, but do not 

capture all necessary 

considerations. Refer 

to accompanying text 

when using this 

flowchart.
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Labeling Changes

• Focuses on changes to indications for use, and changes to 

other pieces of labeling that could affect indications for use 

– Rather than refer to intended use, K97 and new guidances refer to 

changes that have major impact on intended use, including certain 

indications for use changes (new intended use would be NSE)

• Describes common indications changes that likely do/don’t 

require 510(k)s

• Describes indications changes that depend on various factors, 

and provides factors to consider

• Example: For changes in use environment, consider whether the 

device user changes, whether the environment presents different 

challenges such as a lower level of cleanliness, etc.

• For labeling changes that do not affect the indications for use, 

does a risk assessment identify any new or significantly 

modified existing risks?
22

Technology, Engineering, and 

Performance Changes

• Begins with recommendations on a few specific 

changes:

– Fundamental device changes that almost always require 

510(k)s, such as operating principle changes

– Sterility and packaging changes, which depend on 

described factors

• For all other technology changes:

– Does the change significantly affect the use of the device?

– Does risk assessment identify new or significantly 

modified existing risks?

– Is clinical data necessary? 

– Any unexpected results from V&V activities? 
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Technology, Engineering, and 

Performance Section

• Role of verification and validation (V&V) 

activities

– Concept from K97. Reconsider the significance of a 

change if:

– A change drives need for new V&V activities because 

activities used on previous versions are no longer 

applicable

– “Unexpected issues” are encountered during V&V. e.g., 

acceptance criteria cannot be met
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Materials Changes

• Focuses on risk assessment of material changes

– Does the new material have new or increased biocompatibility 

concerns compared to the unmodified material?

– If so, has manufacturer used same material previously in a similar 

device? 

• If yes, manufacturer may be able to determine the new material 

could not significantly affect safety or effectiveness

• If no, a 510(k) is likely required 

• If there are no new or increased concerns, or material 

doesn’t have direct/indirect contact, could the change affect 

device performance?

– If so, evaluate as technology change
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Technology, Engineering, Performance, 

and Materials Changes for In Vitro 

Diagnostics (IVD) 

• Modifications to IVDs other than labeling are handled in an 

IVD-specific section

• Analysis is similar to that found in non-IVD Technology and 

Materials sections, but is tailored to use language relevant to 

IVDs in explaining how decisions should be made for IVDs

– Focuses on risk-based assessment and changes that can affect IVD 

performance

• Guiding Principles, Labeling, and Risk Assessment sections also 

apply to IVDs
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Considerations for Risk-Based 

Assessments of Modified Devices

• Provides general recommendations on how to use riskbased assessment to evaluate device modifications

– Thought process to consider changes not directly addressed by 

the guidance

– Based on principles of ISO 14971 and benefit-risk principles

• Risk likelihood or probability (could the change affect?) 

– If it’s determined that the likelihood of a risk occurring due to 

a change is negligible, that change probably could not 

significantly affect safety or effectiveness

• Risk severity (could the change significantly affect?)

– New risks, changes in risk acceptability or risk score, and 

duration of risk should be considered to determine if risk is 

significant 
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Considerations for Risk-Based 

Assessments of Modified Devices Cont.

• Effectiveness concerns should also be considered

– 21 CFR 807.81(a)(3)(i) requires 510(k) for change that 

“could significantly affect safety or effectiveness” 

– Therefore, manufacturers should consider the possible 

effects modifications may have on device effectiveness

• What’s the likelihood or probability that a change will affect 

device effectiveness? 

• If the change could affect effectiveness, could that affect be 

significant? 

– Consider the criticality of the device feature 

(labeling/design aspect/material/etc.) being modified

• If a feature is critical to the effective operation of the device, 

changing it is more likely to be significant
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Appendix A: Examples

• Appendix A includes hypothetical examples 

intended to illustrate process of determining 

whether a 510(k) is required

• Each example includes an explanation of why it 

would/wouldn’t require a 510(k)

• Important to note: examples can’t account for 

every possible detail and are not intended to be 

definitive
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Appendix A: Examples
30

Appendix B: Documentation

• Most 510(k) devices must comply with quality system 

regulation, which requires documentation of design 

changes prior to implementation

• Documentation is particularly important when 

manufacturers determine a 510(k) is not required

• Appendix B recommends basic elements of good 

documentation that every manufacturer should use

– Also provides examples of documentation that can be adapted 

to the complexity of a given change (manufacturers can use 

these or adapt these as needed)
Software Modifications

• Same General Principles as with the General 

Guidance

• Software-specific policy

– 4 Questions

– Additional considerations

• Software-specific examples in appendix of 

Software Modifications Guidance only

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Decision Making Process
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Question #1

• To answer yes:

– No other changes to the software or architecture are included

– The change does not have impact on the device

• e.g. Adding encryption where it was not used before may have impact 

on software or device

• If the answer to this question is yes, document the 

change and the rationale as discussed previously.

• If the answer is no, continue to Question 2

Is the change made solely to strengthen cybersecurity 

and does not have any other impact on the software or 

device?
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Question #2

• To answer yes:

– Specification is for most recently cleared device 

– The change does not have an overall impact on the device 

that could significantly affect safety, effectiveness or intended 

use

• If the answer to this question is yes, document the 

change and the rationale as discussed previously.

• If answer is no, continue to Question 3

Is the change made solely to return the system into 

specification of the most recently cleared device? 
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Question #3

• Two-part question assessing the impact of changes 

to risk

3a: Does the change introduce a new risk or modify an existing 

risk that could result in significant harm and that is not 

effectively mitigated in the most recently cleared device?

• Criteria for assessing:

– The change creates a new or modifies a hazard, hazardous situation, or 

cause in the risk management file

– The level of harm associated with the new or modified hazard, hazardous 

situation, or cause is considered serious or more severe

– The hazard, hazardous situation, or cause is not already effectively 

mitigated in the most recently cleared device

• If the all criteria are met, a new 510(k) is likely required.

• If answer is no, continue to Question 3a
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Question #3

3b: Does the change create or necessitate a new risk control 

measure or a modification of an existing risk control measure 

for a hazardous situation that could result in significant harm?

– Changes to or additions of risk control measures may be necessary due to 

new, modified, or previously unknown hazardous situations or causes 

thereof. 

– If the changes to risk controls are necessary to prevent significant harm, 

submission of a new 510(k) is likely required. 

– Submission is likely not required when implementing redundant risk control 

measures or enhancing existing risk control measures if the risk control 

measures in the most recently cleared device effectively mitigated the 

hazardous situation.

• If the answer to this question is no, continue to Question 4.
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Question # 4

• Addition or change to clinical functionality or 

performance specifications

• Change is directly associated with intended use

– If the intended use is changed, change is outside scope of this 

guidance. 

• If the answer to this question is yes, a new 510k is likely 

required.

• If answer is no, continue to Additional Factors

Could the change significantly affect clinical functionality 

or performance specifications that are directly 

associated with the intended use of the device?
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Evaluate additional software factors that 

may affect the decision to file

• “Infrastructure” modifications made to the software 

support system. 

• “Architecture” modifications to the overall structure of 

the software.

• “Core algorithm” modifications made to an algorithm 

that directly drive the device’s intended use. 
39

Additional Factors Cont.

• “Clarification of Requirements – No change to 

Functionality” are changes made to clarify software 

requirements after a product has received premarket 

clearance. 

• “Cosmetic Changes – No change to Functionality” are 

changes made to the appearance of the device that do 

not impact the clinical use of the device. 
40

Additional Factors Cont.

• “Reengineering or refactoring” SW maintenance 

techniques. 

Reengineering - the examination and alteration of SW to 

reconstitute it in a new form, and includes the 

subsequent implementation of the new form.

Refactoring - is a disciplined technique for restructuring 

a SW program’s internal structure without changing its 

clinical performance specification, to improve a program 

structure and its maintainability. 
Software Example

# Question Yes/No Rationale

3a Does the change introduce a new risk 

or modify an existing risk that could 

result in significant harm and that is not 

effectively mitigated in the most 

recently cleared device?

Yes The hazardous situation most commonly associated with quantitative 

diagnostic parameters is the risk of incorrect or confusing information to 

the physician leading to a misdiagnosis, which could result in significant 

harm. While the causes of incorrect information for SEF and PP would be 

included in the original risk files, aEEG introduces a new cause related to 

an error in the aEEG calculation. Submission of a new 510(k) is required 

because the new cause is not effectively mitigated in the most recently 

cleared device and the hazardous situation, as discussed above, could 

result in significant harm.

41

Adding a new diagnostic parameter

Description: An electroencephalogram (EEG) diagnostic monitor was cleared with 

spectral edge frequency (SEF) and peak power (PP) as quantitative parameters. The 

device’s intended use is to monitor brain electrical activity through electrodes placed on 

the surface of the head. A software modification is made to add Amplitude Integrated 

EEG (aEEG) as an additional quantitative parameter that was not included in the original 

premarket notification.

Outcome: Submit the change in a new 510(k).
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Questions ?

Questions about the 510(k) device modifications guidances? 

510(k) Staff: 301-796-5640 

510K_Program@fda.hhs.gov

General questions about this webinar?

Contact Division of Industry and Consumer Education: 

DICE@fda.hhs.gov

Slide presentation, transcript and webinar recording will be 

available at:

http://www.fda.gov/training/cdrhlearn

Under Heading: How to Study and Market Your Device; Sub- heading: Premarket Notification (510k)