Contains Nonbinding Recommendations 
 
Deciding When to Submit a 510(k) for 
a Change to an Existing Device 
 
Guidance for Industry and  
Food and Drug Administration Staff  
 
Document issued on October 25, 2017.  
 
The draft of this document was issued on August 8, 2016. 
 
 This document supersedes Deciding When to Submit a 510(k) for a Change to 
an Existing Device, dated January 10, 1997. 
    
 
For questions about this document regarding CDRH-regulated devices, contact the 510(k) Staff at 
301-796-5640. 
 
For questions about this document regarding CBER-regulated devices, contact the Office of 
Communication, Outreach, and Development (OCOD) at 1-800-835-4709 or 240-402-8010.  
   
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Devices and Radiological Health 
Center for Biologics Evaluation and Research 
 
   
  1  Contains Nonbinding Recommendations 
 
Preface 
 
Public Comment 
 
You may submit electronic comments and suggestions at any time for Agency consideration to 
http://www.regulations.gov . Submit written comments to the Division of Dockets Management, 
Food and Drug Administration, 5630 Fishers Lane, Room 1061, (HFA-305), Rockville, MD 
20852. Identify all comments with the docket number FDA-2011-D-0453. Comments may not be 
acted upon by the Agency until the document is next revised or updated. 
 
Additional Copies 
 
CDRH 
Additional copies are available from the Internet. You may also send an e-mail request to 
CDRH-Guidance@fda.hhs.gov to receive a copy of the guidance. Please use the document 
number 1500054 to identify the guidance you are requesting. 
 
CBER 
Additional copies are available from the Center for Biologics Evaluation and Research (CBER) 
by written request, Office of Communication, Outreach, and Development (OCOD), 10903 New 
Hampshire Ave., WO71, Room 3128, Silver Spring, MD 20903, or by calling 1-800-835-4709 or 
240-402-8010, by email, ocod@fda.hhs.gov, or from the Internet at  
http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformatio
n/Guidances/default.htm.  
 
  2  Contains Nonbinding Recommendations 
 
Table of Contents
 
 
I.  Introduction  4 
II.  Background  5 
III. Scope  6 
IV. Guiding Principles  8 
V.  How to Use This Guidance  11 
A.  Labeling Changes  14 
B.  Technology, Engineering, and Performance Changes  23 
C.  Materials Changes  32 
D.  Technology, Engineering, Performance, and Materials Changes for In Vitro Diagnostic 
Devices  37 
E.  Considerations for Risk-Based Assessments of Modified Devices  41 
Appendix A: Examples  44 
Appendix B: Documentation  62 
Appendix C: Significant Terminology  73 
 
Figure 1 - Main Flowchart  12 
Figure 2 - Flowchart A: Labeling Changes  16 
Figure 3 - Flowchart B: Technology, Engineering, and Performance Changes  24 
Figure 4 - Flowchart C: Materials Changes  33 
Figure 5 - Flowchart D: Technology, Engineering, Performance, and Materials Changes for In 
Vitro Diagnostic Devices  37 
 
   
  3  Contains Nonbinding Recommendations 
 
 
Deciding When to Submit a 510(k) for 
a Change to an Existing Device 
 
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 
Almost from the enactment of the Medical Device Amendments to the Federal Food, Drug, and 
Cosmetic Act (the FD&C Act) in 1976, the Food and Drug Administration (FDA or the Agency) 
has attempted to define with greater clarity when a change in a medical device would trigger the 
requirement that a manufacturer submit a new premarket notification (510(k)) to the Agency.   
This document supersedes FDAs guidance Deciding When to Submit a 510(k) for a Change to 
an Existing Device (K97-1), issued on January 10, 1997. This guidance is not intended to 
implement significant policy changes to FDAs current thinking on when submission of a new 
510(k) is required. Rather, the intent of this guidance is to enhance the predictability, 
consistency, and transparency of the when to submit decision-making process by providing a 
least burdensome approach, and describing in greater detail the regulatory framework, policies, 
and practices underlying such a decision.  
 
For the current edition of the FDA-recognized standards referenced in this document, see the 
FDA Recognized Consensus Standards Database at 
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm. 
 
FDAs guidance documents, including this guidance, 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 guidance means that something is suggested or 
recommended, but not required. 
  4  Contains Nonbinding Recommendations 
 
II.  Background 
The regulatory criteria in 21 CFR 807.81(a)(3) state that a premarket notification must be 
submitted when: 
 
(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. 
 
FDA issued the original guidance Deciding When to Submit a 510(k) for a Change to an Existing 
Device (K97-1) on January 10, 1997 to provide guidance on this regulatory language. As stated 
in that guidance, the key issue in the interpretation of 21 CFR 807.81(a)(3) is that the phrase 
could significantly affect the safety or effectiveness of the device and the use of the adjectives 
"major" and "significant" sometimes lead FDA and device manufacturers to different 
interpretations. The original guidance provided the Agencys interpretation of these terms, with 
principles and points for manufacturers to consider in analyzing how changes in devices may 
affect safety or effectiveness and determining whether a new 510(k) must be submitted for a 
particular type of change. The current guidance preserves the basic format and content of the 
original, with updates to add clarity. The added clarity is intended to increase consistent 
interpretations of the guidance by FDA staff and manufacturers and provide a more transparent 
framework for determining when submission of a new 510(k) is required.  
 
The 510(k) Process and the Quality System Regulation 
 
Any guidance on 510(k)s for changes to a legally marketed device should consider the role the 
Quality System (QS) regulation, 21 CFR Part 820, plays in changes to devices. For some types 
of changes to a device, the Agency believes that submission of a new 510(k) is not required and 
that reliance on existing QS requirements is the least burdensome approach to reasonably assure 
the safety and effectiveness of the changed device.  
 
Regardless of whether a change requires premarket review, the QS regulation requires 
manufacturers of finished medical devices to review and approve changes to device design and 
production (21 CFR 820.30 and 820.70) and document changes and approvals in the device 
master record (21 CFR 820.181). Any process whose results cannot be fully verified by 
subsequent inspection and testing must be validated (21 CFR 820.75), and changes to the process 
require review, evaluation, and revalidation of the process where appropriate (21 CFR 
820.75(c)).  
 
The net effect of the QS regulation is to require that, when manufacturers of a finished medical 
device make a change in the design of a device, there is a process in place to demonstrate that the 
  5  Contains Nonbinding Recommendations 
 
manufactured device meets the change in design specifications (or the original specifications, if 
no change was intended). They must keep records, and these records must be made available to 
an FDA investigator upon request (see Section 704(e) of the FD&C Act). For many changes to a 
device, submission of a new 510(k) may not be required. In these cases, including for many 
design changes, compliance with the QS regulation can reasonably assure the safety and 
effectiveness of the changed device.  
 
Least Burdensome Principles 
 
The least burdensome provision concerning 510(k)s states that FDA shall only request 
information that is necessary... and shall consider the least burdensome means of 
demonstrating substantial equivalence... (see section 513(i)(1)(D)(i) of the FD&C Act). While 
not changing the standard for substantial equivalence, this provision states that FDA shall only 
request the minimum required information necessary to support a determination of substantial 
equivalence (see sections 513(i)(1)(D)(ii)-(iii) of the FD&C Act). The recommendations 
discussed in this guidance for evaluating when a change in a medical device would trigger the 
requirement that a manufacturer submit a new 510(k) to the Agency are consistent with least 
burdensome principles, and applies them in discussing the considerations that may affect the 
decision-making about when to submit a new 510(k) for a device change or modification.  
III.  Scope 
This guidance will aid manufacturers of medical devices subject to premarket notification 
requirements who intend to modify a 510(k)-cleared device (or group of devices) or other device 
subject to 510(k) requirements, such as a preamendments device or a device that was granted 
marketing authorization via the De Novo classification process1 under section 513(f)(2) of the 
FD&C Act (also referred to together as existing devices), during the process of deciding 
whether the change exceeds the regulatory threshold of 21 CFR 807.81(a)(3) for submission and 
clearance of a new 510(k). Note that any person required to register under 21 CFR 807.20 who 
plans to introduce a device into commercial distribution for the first time must, per 21 CFR 
807.81(a)(2), submit a 510(k) if that device is not exempt from premarket notification 
requirements. Also note that devices with changes requiring submission of a new 510(k) may not 
be legally commercially distributed before FDA clears the changed device (21 CFR 807.100(a) 
and sections 513(f)(1) and 513(i) of the FD&C Act). This guidance is not intended to address 
changes to devices that are 510(k)-exempt or that require premarket approval (PMA). Also, the 
scope of key terminology used in this guidance, particularly intended use and indications for use, 
is limited to medical devices and not other FDA-regulated products. 
 
This document incorporates concepts and recommendations from existing FDA guidance and 
policy, such as Submission and Review of Sterility Information in Premarket Notification 
(510(k)) Submissions for Devices Labeled as Sterile 
(http://www.fda.gov/downloads/MedicalDevices/.../ucm109897.pdf), and device-specific final 
guidance documents that identify and characterize specific scenarios regarding when submission 
of new 510(k)s are required or not required based on changes to an existing device. In some 
                                                 
1 This guidance applies to devices granted marketing authorization via the De Novo 
classification process that are not exempt from premarket notification requirements. 
  6  Contains Nonbinding Recommendations 
 
cases, FDAs thinking has derived from its experience in situations involving only a few 
manufacturers of a limited number of devices. In such instances, we have attempted to generalize 
the concepts to apply to a broader range of devices. However, special cases exist where FDA has 
established definitive final guidance for changes to specific devices, e.g., FDAs guidance on 
daily wear contact lenses, Premarket Notification (510(k)) Guidance Document for Daily Wear 
Contact Lenses 
(http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm0
80928.htm). This guidance is not intended to supersede such final device-specific guidance but 
may cover areas not addressed in such device-specific guidance.  
 
Recalls: This guidance is also intended to apply to situations when a legally marketed existing 
device is the subject of a recall, correction, or removal, and a change in the device or its labeling 
is necessary. For more information on recommended procedures in a recall situation, please see 
Blue Book Memorandum K95-1, 510(k) Requirements During Firm-Initiated Recalls 
(https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm
080297.htm). As stated in that guidance, if a correction alters a device rather than simply 
restoring it to its original specifications, submission of a new 510(k) may be required. FDA may 
use this guidance in determining whether submission of a new 510(k) is warranted in cases 
where the correction does alter the device. 
 
Private Label Distributors and Repackagers: Private label distributors and repackagers are 
exempt from submitting a 510(k) if they satisfy the requirements of 21 CFR 807.85(b).  
 
Software Changes: This guidance does not address software changes or modifications.  Please 
refer to FDAs guidance Deciding When to Submit a 510(k) for a Software Change to an Existing 
Device 
(https://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocu
ments/UCM514737.pdf) for recommendations regarding software changes.  
This guidance does apply to non-software changes to devices containing software and non-
software changes to software that is a medical device on its own. For example, labeling changes 
to software are covered by Section A of this guidance, and non-software technology changes and 
materials changes to existing devices that contain software are covered by Sections B through D 
of this guidance.  
 
When there are multiple changes that affect labeling or hardware in addition to software, the 
manufacturer should assess the changes using both the general and software-specific 
modifications guidances. If use of either guidance leads to a New 510(k) conclusion, 
submission of a new 510(k) is likely required.  
 
Combination Products: This guidance does not specifically address combination products, such 
as drug/device or biologic/device combinations; however, the general principles and concepts 
described herein may be helpful to manufacturers in determining whether submission of a 510(k) 
is required for changes to device constituent parts of combination products.  
 
Remanufactured or Reprocessed Single Use Devices: This guidance is not intended to address 
whether submission of 510(k)s are required from remanufacturers of existing devices who do not 
hold the 510(k) for the device, such as reprocessors of single-use devices. This guidance does 
apply to reprocessors and remanufacturers who hold their own 510(k) and are addressing 
  7  Contains Nonbinding Recommendations 
 
changes or modifications. Remanufacturer is defined at 21 CFR 820.3(w) as any person who 
processes, conditions, renovates, repackages, restores, or does any other act to a finished device 
that significantly changes the finished devices performance or safety specifications, or intended 
use.  
IV.  Guiding Principles 
In using this guidance for deciding whether to submit a new 510(k) for a change to an existing 
device, a number of guiding principles should be followed. Some derive from existing FDA 
510(k) policy and are widely known, and others are necessary for using the logic scheme 
contained in this guidance. Thus, anyone using this guidance should bear in mind the following 
Guiding Principles: 
 
1.  Changes made with intent to significantly affect safety or effectiveness of a device  
If a manufacturer modifies their device with the intent to significantly affect the safety or 
effectiveness of the device (for example, to significantly improve clinical outcomes, to 
mitigate a known risk, in response to adverse events, etc.), submission of a new 510(k) is 
likely required. A change intended to significantly affect the safety or effectiveness of the 
device is considered to be a change that could significantly affect the safety or 
effectiveness of the device and thus requires submission of a new 510(k) regardless of 
the considerations outlined below.  Changes that are not intended to significantly affect 
the safety or effectiveness of a device, however, should still be evaluated to determine 
whether the change could significantly affect device safety or effectiveness. 
 
If a manufacturer modifies their device to address a violation or recall, they should refer 
to FDA guidances Blue Book Memorandum K95-1, 510(k) Requirements During Firm-
Initiated Recalls 
(http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocument
s/ucm080297.htm) and Distinguishing Medical Device Recalls from Medical Device 
Enhancements (http://www.fda.gov/ucm/groups/fdagov-public/@fdagov-meddev-
gen/documents/document/ucm418469.pdf). 
 
2.  Initial risk-based assessment  To determine whether a change or modification could 
significantly affect the safety or effectiveness of a device, the manufacturer should first 
conduct a risk-based assessment, using the guidance below, of whether the change could 
significantly affect the devices safety or effectiveness, either positively or negatively. 
This risk-based assessment should identify and analyze all new risks and changes in 
existing risks resulting from the device change, and lead to an initial decision whether or 
not submission of a new 510(k) is required.  
 
For the purposes of this guidance, we have chosen the term risk-based assessment to 
describe the analysis that should be completed to assist in the determination of whether or 
not a change could significantly affect safety or effectiveness of the device. Although 
common risk analysis methods define risk in terms of device harms and their effects on 
safety, it is important to note that whether submission of a new 510(k) is required 
depends on whether the change could significantly affect the safety or effectiveness of the 
device. Therefore, manufacturers should also consider the possible effects a device 
  8  Contains Nonbinding Recommendations 
 
change may have on device effectiveness. As such, we have chosen to use the distinct 
terminology of risk-based assessment. 
 
3.  Unintended consequences of changes  After a manufacturer considers whether the 
change was made with the intent to significantly affect safety or effectiveness, the 
manufacturer should also consider whether the change could have unintended 
consequences. In order to fully assess device changes, manufacturers should consider the 
effects of the planned device changes and whether these changes create any intended 
and/or unintended consequences.  For example, changes in sterilization may 
unintentionally affect device materials, or changes to materials may unintentionally affect 
the performance of the device. Any unintended consequences such as these should be 
evaluated according to the relevant flowcharts (and their companion text) to determine 
whether submission of a new 510(k) is required. For instance, a change in sterilization 
that may unintentionally affect device performance should be reviewed as a sterilization 
change under B3 and as a performance specification change under B5.   
 
4.  Use of risk management  A risk-based assessment as referred to throughout this 
document is based on the combination of multiple risk concepts that are important for 
managing the risks of medical devices. Hazards and hazardous situations, risk estimation, 
risk acceptability, risk control, risk/benefit analysis and overall risk evaluation are all 
concepts that can be applied during the design and development of a medical device. The 
concept of risk, as defined in ISO 14971: Medical devices  Application of risk 
management to medical devices, is the combination of the probability of occurrence of 
harm and the severity of that harm. Although the risk terminology used in this document 
is primarily derived from ISO 14971, we recognize that an individual manufacturers 
terminology may differ. Because 21 CFR 807.81(a)(3)(i) requires submission of a new 
510(k) when a change could significantly affect safety or effectiveness, both safety and 
effectiveness should be considered in evaluating a devices risk profile and performing a 
risk-based assessment, as explained in Section E. 
This guidance states throughout that submission of a new 510(k) is likely required when a 
risk-based assessment of the changed device identifies any new risks or significantly 
modified existing risks. For the purposes of this guidance, a new risk is a new hazard or 
hazardous situation that did not exist for the original device (see discussion of appropriate 
comparative device below) and the pre-mitigation risk level associated with the new risk 
is not considered to be acceptable. For the purposes of this guidance, a device change 
could be considered to significantly modify an existing risk if it changes the risk score, 
risk acceptability category, or duration of risk. See Section E for further explanation.  
 
5.  The role of testing (i.e., verification and validation activities) in evaluating whether a 
change could significantly affect safety and effectiveness - If the initial decision 
following the risk-based assessment is that submission of a new 510(k) is not required, 
this decision should be confirmed by successful, routine verification and validation 
activities. If routine verification and validation activities produce any unexpected results, 
any prior decision that submission of a new 510(k) is not required should be 
reconsidered, as discussed in B5.4 for non-IVD devices and D4 for IVD devices. 
Routine activities in this context refer to the original design verification and validation 
activities that were done to assess the original device design. Because 21 CFR 
  9  Contains Nonbinding Recommendations 
 
807.81(a)(3) requires submission of a new 510(k) for a change that could significantly 
affect safety or effectiveness, if the result of a risk-based assessment is that a change 
could significantly affect safety or effectiveness, submission of a new 510(k) is required  
even if routine verification and validation activities are conducted successfully without 
any unexpected results. Note that verification and validation requirements apply for all 
devices subject to 21 CFR 820.30, and must be conducted regardless of whether 
submission of a new 510(k) is required.  
 
6.  Evaluating simultaneous changes to determine whether submission of a new 510(k) 
is required  Because many simultaneous changes may be considered at once, each 
change should be assessed separately, as well as in aggregate.  
 
7.  Appropriate comparative device and cumulative effect of changes  In using this 
guidance to help determine whether a particular change requires submission of a new 
510(k), manufacturers should conduct a risk-based assessment that compares the changed 
device to their device as previously found to be substantially equivalent in their most 
recently cleared 510(k), to their preamendments device (if the device was in commercial 
distribution before May 28, 1976 and there have not been changes to it subsequently 
cleared in a 510(k)), or to their device that was granted marketing authorization via the 
De Novo classification process (if there have not been changes to it subsequently cleared 
in a 510(k)). The appropriate comparative device is referred to as the original device 
throughout this guidance document.  Of note, this comparison is different from a 
substantial equivalence comparison between the modified device and a legally marketed 
predicate device. Manufacturers may make a number of changes without having to 
submit a new 510(k), but each time they make a change, the modified device should be 
compared to the original device (i.e., the device described in their most recently cleared 
510(k) for the device, their legally marketed preamendments device, or their device that 
was granted marketing authorization via the De Novo classification process). When the 
cumulative effect of individual changes triggers the regulatory threshold for submission, 
the manufacturer should submit a new 510(k). When it does not, the manufacturer must 
document the change(s) (see 21 CFR Part 820.30).  
 
8.  Documentation requirement  Whenever manufacturers change their device, they must 
take certain actions to comply with the QS regulation, 21 CFR Part 820, unless the device 
in question is exempt by regulation from the QS regulation. The QS regulation requires, 
among other things, that device changes be documented. The scope and type of 
documentation may vary, but the process of documenting the decisions described in this 
guidance should be established as part of the manufacturers own quality system.   See 
Appendix B for further explanation and recommendations on documentation. 
 
9.  510(k) submissions for modified devices  When a new 510(k) is submitted for a device 
with multiple changes, that 510(k) should describe all changes that trigger the 
requirement for submission of a new 510(k). To help ensure that FDA has a complete 
understanding of the device under review, that 510(k) should also describe other changes 
since the most recently cleared 510(k) (i.e., those that did not require submission of a new 
510(k)) that would have been documented as part of the first 510(k) for that device. For 
instance, 510(k)s typically include a listing of device warnings in the labeling, so if a 
warning in the devices labeling had been changed, that change should be described in 
  10  Contains Nonbinding Recommendations 
 
the new 510(k), even if that change did not itself trigger the requirement for submission 
of a new 510(k).  However, a 510(k) would not typically identify or describe individual 
components of a circuit board, such as resistors, and therefore FDA would not expect 
changes to the resistors to be listed in the new 510(k) for a modified device because the 
first 510(k) would not have included information about the resistors.   
If a manufacturer makes multiple changes to a device, but only one change triggers the 
requirement for submission of a new 510(k), the changes that do not require submission 
of a new 510(k) may be immediately implemented, so long as those changes can be 
implemented independently of changes that do require submission of a new 510(k). Any 
immediately implemented change should still be documented in accordance with 
applicable QS regulations and the manufacturers documentation procedures. Those 
changes should, however, also be described in the new 510(k) for the change that does 
require submission.  
 
10. Substantial equivalence determinations  Manufacturers should understand that, even 
though they may follow this guidance and submit a new 510(k), a substantially equivalent 
determination is not assured. See FDAs guidance The 510(k) Program: Evaluating 
Substantial Equivalence in Premarket Notifications (510(k)) 
(https://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidanced
ocuments/ucm284443.pdf) for more information on the decision-making process FDA 
uses to determine substantial equivalence. 
V.  How to Use This Guidance 
This guidance uses flowcharts and text to guide manufacturers through the logic scheme we 
recommend to arrive at a decision on whether to submit a new 510(k) for a change to an existing 
device. A single logic scheme containing all the necessary steps would be large and cumbersome 
and could be quite daunting. Rather, for ease of use, the single scheme has been broken down 
into smaller sections that include: 
 
  The main types of changes that might be made to a device (this section, Main Flowchart) 
  Labeling changes (Section A, Flowchart A) 
  Technology, engineering, and performance changes (Section B, Flowchart B) 
  Materials changes (Section C, Flowchart C) 
  Technology, engineering, performance, and materials changes for in vitro diagnostic 
devices (IVDs) (Section D, Flowchart D) 
  Considerations for risk-based assessments of modified devices (Section E) 
 
The main flowchart is provided in Figure 1 below and guides the manufacturer to the appropriate 
specific section(s) and flowchart(s) to assess their specific change(s). 
When using the flowcharts, the reader should interpret new 510(k) as submission of a new 
510(k) is likely required and documentation as submission of a new 510(k) is likely not 
required, document your analysis and file it for future reference. Please refer to Appendix C: 
Significant Terminology for the meaning of terms used in the guidance, including in the 
flowcharts.  
 
  11  Contains Nonbinding Recommendations 
 
Note that the first question is whether the change is being made with the intent to significantly 
improve the safety or effectiveness of the device, for example, to significantly improve clinical 
outcomes, to mitigate a known risk, in response to adverse events, etc. (Figure 1  Main Flowchart).   
If so, the change likely could significantly affect safety or effectiveness and submission of a new 
510(k) is likely required. If not, you should continue to follow the logic scheme shown in Figure 1, 
below.  
 
Change made with intent to 
Reminder: Flowcharts are 
significantly improve the 
Yes New 510(k) provided as a visual aid, but 
safety or effectiveness of the 
do not capture all necessary 
device
considerations. Refer to 
accompanying text when 
using this flowchart. 
No
Labeling change? Yes Go to Chart A
No
Technology, engineering,  Go to Chart B,
Yes
or performance change? or Chart D if IVD
No
Go to Chart C, 
Materials change? Yes
or Chart D if IVD
Refer to Section E as 
No
directed by the text for 
additional 
recommendations on 
use of risk assessment.
Documentation
 
Figure 1 - Main Flowchart 
 
  12  Contains Nonbinding Recommendations 
 
Note that sections B and C are only applicable to non-IVDs, and section D is only applicable to 
IVDs. All other sections apply to both IVDs and non-IVDs.  
 
Each of the questions listed on the detailed flowcharts are identified by the flowchart letter (A 
through D) and a sequential number. Those questions on the main spine of the flowcharts relate 
to major questions to be answered. Subsidiary questions are identified by the flowchart letter, the 
question number, a decimal point, and another sequential number (e.g., B4.1 is a decision point 
containing a follow-up question that builds off a determination made in decision point B4).  
 
Manufacturers should use the flowcharts in concert with the Guiding Principles above, the 
recommendations in the sections below, and the examples provided in Appendix A. 
Manufacturers should follow all the applicable flowcharts and use their companion text to 
answer the questions posed for each individual type of change (e.g., performance change, 
material change) until a decision is made either to submit a new 510(k), or to document the basis 
for concluding that submission of a new 510(k) is not required. As mentioned above, when 
making the decision on whether to submit a new 510(k) for changes, the manufacturer's basis for 
comparison of any changed device should be the original device. Manufacturers are required to 
submit a new 510(k) when a change (or changes) exceeds the 21 CFR 807.81(a)(3) threshold, 
could significantly affect the safety or effectiveness of the device, or constitutes a major 
change or modification in the intended use of the device. This significant effect could be 
positive or negative. One must keep in mind that what may on the surface appear to be one 
discrete change to a device may involve multiple changes of various types. 
 
Although this guidance does not specifically discuss manufacturing changes, a 
manufacturer should consider the impact of all manufacturing changes on device labeling, 
technology/engineering/performance, and/or materials. If the manufacturing change affects 
any of these three areas, manufacturers should evaluate the impact of the resulting labeling, 
technology/engineering/performance, or material change using the appropriate flowcharts and 
companion text. Specifically, consideration should be given to those devices for which 
manufacturing information was submitted in the most recently cleared 510(k) in order to assist in 
the characterization of the device and technology, such as bioresorbables, polymers, and 
biological fixation type devices. When manufacturing changes do not impact device labeling, 
technology/engineering/performance, and/or materials, there is no need to use the  flow charts 
and their companion text to document the decision not to submit a new 510(k). 
 
In cases with multiple changes, manufacturers should use all applicable flowcharts and 
companion text, including the Guiding Principles in Section IV of this guidance. Consider 
the following examples: 
 
Example 1: Multiple changes caused by a manufacturing process change 
 
A manufacturer decides to change the manufacturing process for a patient-contacting part 
from a machining process to a stamping process. The use of the stamping process 
requires a change in the grade of stainless steel and also results in a change of the 
dimensional tolerances. To evaluate the impact of this change, the manufacturer should 
use both Sections B (Technology, Engineering, and Performance) and C (Materials). 
 
  13  Contains Nonbinding Recommendations 
 
Example 2: Multiple changes related to a change in shelf-life 
 
A manufacturer changes one or more materials in a device to improve the shelf-life of the 
product. The material change also affects some of the performance characteristics, 
resulting in the need to update the labeling. To evaluate the impact of the change, the 
manufacturer should use Sections A (Labeling), B (Technology, Engineering, and 
Performance) and C (Materials) or D (Technology, Engineering, Performance, and 
Materials Changes for IVD Devices). 
 
Changes not addressed in Sections A through D should be evaluated with a risk-based 
assessment using the recommendations provided in Section E.  In instances where the 
specific flowcharts do not address a given change, Section E provides recommendations for how 
manufacturers should utilize risk management principles to evaluate their own specific changes 
and modifications.   Because 21 CFR 807.81(a)(3)(i) requires submission of a new 510(k) when 
a change could significantly affect safety or effectiveness, both safety and effectiveness should 
be considered in evaluating a devices risk profile, as explained in the Guiding Principles and 
Section E. For those circumstances where the proposed change is not addressed in this guidance 
or in a device-specific guidance document, manufacturers are encouraged to contact CDRH staff 
 
or CBER staff. 
A.  Labeling Changes 
As noted above, the guidance focuses on the following types of changes: labeling changes, 
technology, engineering, or performance changes, and materials changes. This guidance 
identifies several types of labeling changes or modifications to an existing device, including 
certain changes to the indications for use, that can have a major impact on intended use and thus 
require submission of a new 510(k) under 21 CFR 807.81(a)(3).2  All labeling changes should be 
evaluated using a separate logic scheme that concentrates on changes in indications for use and 
applies a risk-based assessment framework for determining whether submission of a new 510(k) 
is required. Focusing on indications for use and using a risk-based assessment for labeling 
changes will also help identify those changes that are more frequently recommended for 
documentation only.  
 
Flowchart A describes the logic scheme to be used when determining when submission of a new 
510(k) is required for a labeling change. Changes in device labeling often pose the most difficult 
questions to be addressed by device manufacturers when deciding whether submission of a new 
510(k) is required. Frequently, an apparently subtle change in a devices labeling can have a 
significant impact on the safe and effective use of the device.  
 
Confusion often results when discussing the distinction between indications for use and the 
intended use of the device. For purposes of substantial equivalence, and for the purposes of 
this guidance, the term intended use means the general purpose of the device or its function, and 
encompasses the indications for use.3 The indications for use generally describe the disease or 
                                                 
2 Labeling changes are not the only type of changes that could result in a major change in intended use. See 21 CFR 
801.4.  
3 When submitting a 510(k) premarket notification to FDA for review, an applicant must submit, among other 
things, information concerning a devices intended use(s), as described in the proposed labeling (21 CFR 807.92(a)). 
 
  14  Contains Nonbinding Recommendations 
 
condition the device will diagnose, treat, prevent, cure or mitigate, including a description of the 
patient population for which the device is intended.4 The indications include all the labeled 
patient uses of the device. As it relates to medical devices, the indications for use statement is a 
factor in determining a devices intended use; however, a change in indications for use that 
requires the submission of a new 510(k) does not necessarily mean that the device has a new 
intended use (such that the device would not be substantially equivalent under section 513(i) of 
the FD&C Act).5  
 
                                                                                                                                                             
FDA looks to this aspect of the submission to make a substantial equivalence determination under section 513(i) of 
the Federal Food, Drug, and Cosmetic Act (FD&C Act), which requires FDA to evaluate whether, based on the 
proposed labeling, the device and a predicate device have the same intended use. If a particular labeling change 
results in an intended use of the device that is not the same as the intended use of the original device, the device 
would not be substantially equivalent. See also FDAs guidance The 510(k) Program: Evaluating Substantial 
Equivalence in Premarket Notifications (510(k)) 
(https://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm284443.pdf)  
Although, in evaluating substantial equivalence in reviewing a 510(k), FDA must determine the intended use of a 
device based on the proposed labeling, see 21 USC 513(i)(1)(E), FDA may consider other evidence of intended use 
in determining whether there has been a major change or modification in the intended use of the device under 21 
CFR 807.81(a)(3). 
4 See FDAs guidance The 510(k) Program: Evaluating Substantial Equivalence in Premarket Notifications (510(k)) 
(https://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm284443.pdf) 
5 Ibid. 
  15  Contains Nonbinding Recommendations 
 
Reminder: Flowcharts are  From Main Chart Refer to Section E as 
provided as a visual aid, but  directed by the text for 
do not capture all necessary  additional 
considerations. Refer to  recommendations on use 
accompanying text when  of risk assessment.
using this flowchart. A1 A1.1
Is it a change in the  Is it a change from a device 
Yes
indications for use  labeled for single use only to a 
statement? device labeled as reusable?
No
No
A2
Does the change add or 
delete a contraindication?
Yes
A1.2
Yes Is it a change from Rx to over 
No Yes the counter OTC use?
A3 
Is it a change in the  New 510(k)
warnings or precautions?
No No
A4
Yes
Could it affect the directions  Yes
for use?
A1.3
Is it a change to the device 
No Documentation Yes
name or to solely improve 
readability or clarity?
No
No
A1.4
Does the change 
A1.5
describe a new disease, 
New 510(k) (If only adding a  Does a risk-based assessment  
condition, or pt pop that the 
contraindication, submit  Yes identify any new risks or  No
device is intended  in 
CBE 510(k)) significantly modified existing 
diagnosing, treating, 
risks
preventing, curing or 
mitigating?
Yes
 
Figure 2 - Flowchart A: Labeling Changes 
 
  16  Contains Nonbinding Recommendations 
 
A1.   Is it a change in the indications for use statement? Changes in the indications for use 
statement raise more Agency concern than any other aspect of labeling. In fact, most  
labeling changes that affect the substance, meaning, or scope of the indications for use 
could significantly affect safety or effectiveness and will require submission of a new 
510(k). Changes that clarify the indications without affecting the substance or meaning of 
the indications usually do not require submission of a new 510(k). In addition, some 
changes in the indications for use that limit use within the currently cleared indication 
may occur without submission of a new 510(k). For example, if a device was cleared for 
use with three specific indications and the firm decides to market the device for only two 
of those indications, this change would not likely require submission of a new 510(k).  
 
If the labeling change is to the indications for use statement, proceed to A.1.1.  
Otherwise, proceed to A.2. 
 
It should be noted the decision points in A1.1-A1.5 may apply not only to changes to the 
indications for use statement of the labeling, but also to changes to other sections of the labeling, 
such as the directions for use of the device. You should review these decision points when 
directed by the text of this guidance and Flowchart A: Labeling Changes. 
 
A1.1  Is it a change from a device labeled for single use only to a device labeled as 
reusable? 
 
FDA has found that the performance and risks associated with a reusable device can be 
significantly different from the performance and risks associated with that same device 
when it is labeled for single use only. Therefore, changing a device labeled for single use 
only to a device that is labeled as reusable typically could significantly affect the safety 
or effectiveness and would likely require submission of a new 510(k). Changing a device 
labeled for reuse to single use only, however, would likely not require submission of a 
new 510(k) because a single use is a limitation of the previously cleared indications for 
multiple uses, and the risks of single use were inherently considered within the risks of 
multiple uses.  
 
If it is not this type of labeling change, proceed to A.1.2. 
  
A.1.2  Is it a change from prescription (Rx) to over the counter (OTC) use? 
 
FDA has found that the directions for use necessary for health care professionals to use a 
device safely and effectively can be significantly different from the directions for use 
necessary for lay users to use that same device safely and effectively. Therefore, 
changing a device labeled for prescription use only to a device that is labeled for OTC 
use typically could significantly affect the safety or effectiveness and would likely 
require submission of a new 510(k).  Changing a device labeled for OTC use to 
prescription use, however, would likely not require submission of a new 510(k) because 
it is unlikely that the associated labeling changes could significantly affect the safety or 
effectiveness of the device.  
 
If it is not this type of labeling change, proceed to A.1.3.  
 
  17  Contains Nonbinding Recommendations 
 
A.1.3.  Is it a change to the device name or a change solely to improve readability or 
clarity? 
 
Changes to the device name or description that are consistent with the cleared indications 
for use typically do not significantly affect the safety or effectiveness and would likely 
not require  submission of a new 510(k). Changes that are solely to improve readability or 
clarity that are consistent with the cleared indications for use typically do not 
significantly affect the safety or effectiveness and likely would not require submission of 
a new 510(k).  
 
If it is not this type of labeling change, proceed to A.1.4. 
 
A.1.4  Does the change describe a new disease, condition, or patient population that the 
device is intended for use in diagnosing, treating, preventing, curing or mitigating? 
 
Differences in indications for use should be analyzed to explain how they are or are not 
critical to the intended therapeutic, diagnostic, prosthetic, or surgical use of the device, 
and how the differences do or do not affect the safety and effectiveness of the device.  
Specific changes that could significantly affect the safety and effectiveness include 
describing a new disease, condition, or patient population that the device is intended for 
use in diagnosing, treating, preventing, curing or mitigating (or an anatomical site from 
which a new disease, condition, or population may be inferred).  The criticality of these 
types of changes and their direct effect on safety and effectiveness means that a change to 
add a new disease, condition, or patient population likely requires submission of a new 
510(k).    
 
As introduced prior to Section A.1.1., not all changes that describe a new disease, 
condition, or patient population that the device will diagnose, treat, prevent, cure or 
mitigate are necessarily made in the indications for use section of the labeling. These 
types of changes could also result from a change to other sections of the labeling, such as 
the directions for use of the device. For example, a devices directions for use may be 
revised from providing that the device is to be used when symptoms occur (i.e., use in the 
treatment of a disease or condition) to providing that the device is to be used once per 
day, even in the absence of symptoms (i.e., use in the prevention of a disease or 
condition). In this example, the patient population has changed from patients who have 
been previously diagnosed with a disease or condition to asymptomatic or healthy 
individuals. Because this change describes a new patient population, submission of a new 
510(k) is likely required. 
 
To evaluate whether a change in patient population is a new and distinguishable patient 
population, manufacturers should compare the demographics, diagnosis, prognosis, 
comorbidity, and potential for complications of the patient population described in the 
previously cleared 510(k) to those of the modified patient population. If the change 
describes a patient population with similar demographics, diagnosis, prognosis, 
comorbidity and potential for complications, then submission of a new 510(k) is likely 
not required. However, if any of these factors differ between patient populations, 
submission of a new 510(k) would likely be required.  
 
  18  Contains Nonbinding Recommendations 
 
One method for determining whether changes to the demographics, diagnosis, prognosis, 
comorbidity, and potential for complications of the previously cleared patient populations  
result in a new and distinguishable patient population is to assess if the changes could 
significantly affect a devices risk profile through a risk-based assessment as described in 
A.1.5 and Section E. For example, if the most recently cleared patient population 
included only individuals with Stage IV carcinoma, and the modified patient population 
added individuals with Stage III carcinoma, a risk-based assessment considering the 
factors outlined in section A.1.5 could help determine whether there are any new risks or 
significantly modified existing risks that would require submission of a new 510(k).  
 
If it is not this type of labeling change, you should proceed to A.1.5. 
 
A.1.5. Does a risk-based assessment of the changed device identify any new risks or 
significantly modified existing risks?  
 
For changes that are not addressed by the previous questions in this section, thus 
necessitating the use of a risk-based assessment as described in Section E, the factors 
discussed below should be considered as part of such an assessment for a labeling 
change.  
 
As discussed in Question 1 of the Main Flowchart, if a change is intended to significantly 
affect safety or effectiveness, particularly those meant to significantly improve clinical 
outcomes, to mitigate a known risk, or in response to adverse events, that change likely 
requires submission of a new 510(k); this includes changes to the indications for use. For 
labeling changes that are not intended to significantly affect safety or effectiveness, 
manufacturers should consult Flowchart A and Section E and consider whether the 
change creates new risks or significantly modifies existing risks.  
 
Changes to the labeling can affect a devices risk profile by affecting how, when, where, 
or by whom the device is used. As part of the risk-based assessment of a labeling change, 
manufacturers should consider whether the change could introduce human factors or 
usability issues that could significantly affect users understanding of the labeling and use 
of the device. Changes that significantly affect a devices risk profile likely require 
submission of a new 510(k).  
 
As further described in Section E, the risk-based assessment should include an analysis of 
both safety and effectiveness. A risk-based assessment will help manufacturers determine 
whether changes such as the following could significantly affect safety or effectiveness 
and would require submission of a new 510(k).   
 
Changes to the type of joint, organ, bone, vasculature, or tissue applied to or 
interacted with, regardless of the section of labeling in which this information is 
contained: Although some changes to the type of joint, organ, bone, vasculature, or 
tissue applied to or interacted with would involve a new disease, condition, or patient 
population, and thus lead to a decision to submit a new 510(k) under A.1.4, a risk-based 
assessment would be appropriate for other changes in this category. How a change to the 
type of joint, organ, bone, vasculature, or tissue applied to or interacted with affects a 
devices risk profile depends on the specific change. For example, a change from use of a 
  19  Contains Nonbinding Recommendations 
 
bone fixation system  plates, screws, and wires  in an extremity to use in the skull is 
likely to significantly affect the devices risk profile and require submission of a new 
510(k). Alternatively, a bone fixation system used on one type of long bone changed to 
use on a different type of long bone may not significantly affect the devices risk profile 
and is less likely to require submission of a new 510(k).    
 
Changes in user or use environment: How a change of this type affects a devices risk 
profile depends on the differences in use environment and environmental specifications. 
For example, a change from use in a surgical suite to use in a hospital recovery room, 
both of which will have professional healthcare supervision, may not significantly affect 
the devices risk profile. Similarly, changes between users with similar training on a 
specific device, such as changes between a general physician and a specialist using basic 
medical equipment may not significantly affect a devices risk profile. However, changes 
from professional use to home use6 or hospital use to ambulatory transport are more 
likely to affect the devices risk profile and require submission of a new 510(k) because 
the different environments have different levels of professional healthcare supervision 
and offer different environmental challenges, such as presence of other electronic devices 
that can cause electromagnetic interference, different levels of cleanliness, or shocks and 
vibrations associated with patient travel or ambulatory use. Similarly, changes from 
professional use to home use, hospital use to ambulatory transport, or between any other 
healthcare providers with different levels of training on specific devices are more likely 
to affect the devices risk profile and require submission of a new 510(k) because the 
different level of training could significantly affect the safe and effective use of the 
device.  
 
Changes in frequency or duration of use: Changes in the frequency or duration of use 
of a device include changes indicating that a device can or should be used more or less 
often, changes indicating that a device can perform a task or treat a condition in or for a 
different duration of time, or changes between periodic and continuous monitoring. 
Manufacturers should evaluate the effect such changes could have on the performance of 
a device, and whether such changes significantly affect the devices risk profile. 
 
Changes concerning the compatibility or interoperability of a device with other 
devices, components, or accessories: Two examples of such changes would include 1) 
changes indicating an IVD reagent for use with a new system, and 2) changes that 
describe how to use an infusion pump with inputs from other devices not described in the 
previously cleared 510(k), such as a pulse oximeter or blood pressure monitor.  
  
To evaluate whether these changes significantly affect the devices risk profile, 
manufacturers should carefully consider the following factors: 
 
                                                 
6 A home use medical device is a medical device intended for users in any environment outside of a professional 
healthcare facility. This includes devices intended for use in both professional healthcare facilities and homes. See 
FDAs Home Use Devices website for more information: 
http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/HomeHealthandConsumer/HomeUseDevices/d
efault.htm.  
  20  Contains Nonbinding Recommendations 
 
  Differences between the other devices, components, or accessories referred to in 
the previously cleared indications and the ones referred to in the modified 
indications. Manufacturers should be able to clearly identify and analyze the risks 
associated with such differences, including whether the change may affect 
biocompatibility, performance, connectivity, etc. If the change is to indicate 
compatibility with a type of device, component, or accessory that was not 
indicated as compatible previously, that change will likely require submission of a 
new 510(k).  
  The criticality of the other device, component, or accessory; the more critical the 
other device, component, or accessory is to overall system function, the more 
likely a labeling change regarding compatibility or interoperability could 
significantly affect safety or effectiveness.  
  The labeling of the other device, component, or accessory. If the change is to 
indicate compatibility or interoperability with another device that is labeled for 
use with the subject device or device type, it is less likely that the change 
introduces a compatibility or interoperability issue that could significantly affect 
safety or effectiveness.  
 
IVD manufacturers should see also FDAs guidance Replacement Reagent and 
Instrument Family Policy 
(http://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidanced
ocuments/ucm071465.pdf).  
 
Changes from a general use to a more specific use: These types of changes include 
those changes made to identify a specific use when the cleared device has a general 
indication for use. These changes are among the most difficult to assess. FDAs 
Guidance for Industry: General/Specific Intended Use 
(https://www.fda.gov/RegulatoryInformation/Guidances/ucm073944.htm) provides 
information on when a specific indication for use is reasonably included within a general 
indication for use for purposes of determining substantial equivalence, i.e., whether a 
510(k) can be cleared or whether, instead, a PMA or De Novo request is required. The 
factors discussed therein  particularly those discussing the risk and public health impact 
of an indications for use change  may be helpful to consider in deciding whether to 
submit a new 510(k) for a change to an existing device, but that guidance should not be 
used in and of itself to justify that submission of a new 510(k) is not required. The 
General/Specific guidance is not intended to provide guidance on when submission of a 
new 510(k) is required for changes to an existing device.  
 
If a risk-based assessment indicates that the change leads to a significant change in the 
devices risk profile, submission of a new 510(k) is likely required.  
 
A2.   Does the change add or delete a contraindication? Changes in the labeled 
contraindications for device use generally could significantly affect safety or 
effectiveness of a device and should typically be reviewed by the Agency; however, FDA 
recognizes that, in general, the addition of a contraindication based on new information is 
important to public health. Thus, FDA does not intend to object if manufacturers add new 
contraindications to their labeling and notify existing users of their device as 
expeditiously as possible whenever a pressing public health need arises. In this situation, 
  21  Contains Nonbinding Recommendations 
 
the new labeling should be submitted to FDA as part of a new 510(k) that is prominently 
labeled change being effected (CBE, in Figure 2- Flowchart A). Manufacturers should 
ensure they are thoroughly familiar with the definition of a contraindication in such 
situations.  
 
   Deletion or modification of a contraindication also usually requires submission of a new 
510(k) prior to effecting the change, because this type of labeling change typically 
changes the indications for use in a way that could significantly affect safety or 
effectiveness. Deletions of contraindications would expand the indications for use. For 
example, if a physical restraint was contraindicated for use with individuals weighing less 
than 100 pounds because of established life-threatening and other serious adverse events, 
and the manufacturer subsequently wishes to remove this contraindication, submission of 
a new 510(k) is likely required. 
 
  Similar to changes in indications for use, minor changes that clarify or reword a 
contraindication without changing the meaning of the contraindications would not 
typically require submission of a new 510(k).  
 
If the change adds or deletes a contraindication, submission of a new 510(k) is likely 
required. Otherwise, proceed to A3. 
 
A3.  Is it a change in warnings or precautions? In order to facilitate a continuous upgrading 
in device labeling, manufacturers should monitor device usage and promptly revise the 
warnings and precautions section(s) based on user experience. Events that precipitate 
changes of this type may be those reported under the medical device reporting regulation 
(MDR), 21 CFR Part 803. Submission of new 510(k)s for such labeling changes are 
generally not required. However, to determine whether the change in warnings or 
precautions requires submission of a new 510(k), manufacturers should proceed to A.1.1 
and follow Flowchart A through A.1.5.  If it is not a change in warnings or precautions, 
manufacturers should proceed to A4. 
 
A4.  Could the change affect the directions for use of the device? Device labeling may be 
changed for a multitude of reasons. Many labeling changes result from attempts to clarify 
labeling. Manufacturers should consider whether the change is intended to or could affect 
how the device is used in practice.  
 
Manufacturers should evaluate labeling changes to determine whether the change affects 
the directions for use of the device, including IVD labeling required under 21 CFR 
809.10. If the change affects the directions for use, the change should subsequently be 
analyzed under A.1.1 through A.1.5. If the change could not affect the directions for use 
of the device, submission of a new 510(k) is likely not required based on the labeling 
change. 
 
Examples of changes that affect the directions for use of the device, and that should be 
analyzed under A1.1 through A1.5 include: 
 
  22  Contains Nonbinding Recommendations 
 
  Adding additional or new instructions on how to interpret diagnostic data from a 
diagnostic device. 
  Adding a new procedural technique not described in the original labeling. 
  Use of a product for a duration/frequency that is different than what is described 
in the labeling of the cleared device. 
  Changing from labeling a device as non-sterile to labeling it as sterile or vice 
versa. 
  Adding instructions for device use in a new patient population not described in 
the original indications for use. 
  Adding instructions for device use in a different type of joint, organ, bone, 
vasculature, or  tissue. 
 
FDA believes that, if manufacturers follow this approach to changes in device labeling, only 
necessary new 510(k)s (those changes that could significantly impact safety and effectiveness) 
will be submitted, while the submission of unnecessary new 510(k)s (those that could not 
significantly affect safety and effectiveness) will be minimized. At the same time, manufacturers 
should be able to retain the flexibility to improve their labeling to assure safe and effective use of 
their devices. 
B.  Technology, Engineering, and Performance Changes 
These types of changes encompass a broad span of design activities, from minor engineering 
changes in a circuit board layout to a change from electromechanical to microprocessor control 
of device function. Flowchart B illustrates the decision-making logic scheme for such 
technology, engineering, and performance changes to a device. These changes should be 
evaluated using this scheme, and then the changes should be verified and/or validated according 
to the QS requirements (21 CFR 820.30(i)). If the results of the verification and/or validation 
raise any unexpected issues, the decision of whether submission of a new 510(k) is required 
should be re-evaluated per B5.4. 
  23  Contains Nonbinding Recommendations 
 
B1
From Main Chart Yes Go to Chart D
Is the device an IVD?
No
B2
Is it a control 
mechanism, operating  Yes New 510(k)
principle, or energy 
type change? Yes
No
B3.1
B3.2
B3 Is it a change to a Cat. B 
Could the change 
Is it a change in  or novel method, does 
Yes No significantly affect  Yes
sterilization, cleaning,  it lower the SAL, or is it 
performance/
or disinfection? a change to how the 
biocompatibility?
device is provided?
No
B4.1
No
Is the same 
B4 method or 
Is there a change in  protocol, 
Yes No
packaging or expiration  described in 
dating? previous 510(k), 
used to support 
change?
No
Yes Documentation
B5
Is it any other change in design  B5.1
(e.g., dimensions, performance  Does the change 
specifications, wireless  Yes significantly  Yes
communications, components or  affect the use of 
accessories, patient/user  the device?
interface)?
Reminder: Flowcharts are  No
provided as a visual aid, but do 
not capture all necessary  B5.2
considerations. Refer to  Does a risk assessment 
accompanying text when using  No identify any new or  Yes
this flowchart.  significantly modified 
risks?
No
Documentation
B5.3
Is clinical data  Yes
necessary?
Refer to Section E as 
directed by the text for 
additional  No
recommendations on use 
of risk assessment.
B5.4
Any unexpected 
No Yes
issues  from V&V 
activities?
 
Figure 3 - Flowchart B: Technology, Engineering, and Performance Changes 
 
  24  Contains Nonbinding Recommendations 
 
 
B1.   Is the device an in vitro diagnostic device? If the device is an IVD, refer to the later 
section of this guidance which is specific to technology, engineering, and performance 
changes in IVDs (Section D  Technology, Engineering, Performance, and Materials 
Changes for In Vitro Diagnostic Devices). 
 
B2.  Is it a control mechanism, operating principle, or energy type change?  
 
Control mechanism changes: A control mechanism, for the purpose of this guidance, is 
the manner by which the actions of a device are directed. Almost all changes in the 
control mechanism for a device could significantly affect safety and effectiveness. 
Therefore, such changes will usually require submission of a new 510(k). This is also true 
for changes in operating principle as well as for changes in energy type (discussed 
below). Changes of these types tend to be more revolutionary than evolutionary.  
 
One example of a control mechanism change would be a change from analog to digital 
control of a medical device. While the change to digital control can markedly improve 
device performance specifications and effectiveness, the integration of a digital control 
into a previously all-analog system is complex and usually undertaken only as part of a 
major redesign of a product. Thus, it would be rare that submission of a new 510(k) 
would not be required. Most often, such changes in control mechanism represent the 
introduction of a new product line. Another example of a change that would likely 
require submission of a new 510(k) is the change from pneumatic to electronic control of 
a respiratory care device. 
 
  Operating principle changes: Similar to a control mechanism change, a change in 
operating principle would also usually require  submission of a new 510(k). An example 
of a new operating principle for a device would be changing the image reconstruction 
algorithm used in a computed tomography x-ray system from simple back projection to a 
new, more radiation-efficient method. In this case, testing both at the bench and in the 
clinic would be necessary to support a finding of substantial equivalence for the new 
device. Another example would be a change in a water droplet dispersal method used by 
a respiratory gas humidifier from piezoelectric material to a wick and fan method. The 
two mechanisms use the same design principle, but apply it in different ways. The 
differences between the two could significantly affect safety and effectiveness.   
 
Such changes may also be accompanied by significant labeling changes and, sometimes, 
by a need for operator retraining to ensure continued safe and effective operation.  
 
Energy type changes: Submission of a new 510(k) will usually be required for energy 
type changes. These changes include both energy output and input changes. A change 
from emitting microwave energy to radiofrequency (RF) energy would be an example of 
an energy output change; this type of change would likely be part of a significant 
redesign. An example of an energy type input change is a change from AC to battery 
power; this type of change is usually part of a redesign to provide a portable device that 
can be used under different environmental conditions than the original device. Such a 
change would normally be accompanied by significant labeling changes, including a new 
or expanded indication for use. Note that this type of change does not include a change in 
  25  Contains Nonbinding Recommendations 
 
voltage, such as from 3V to 9V operation or a change between different types of 
batteries, such as from NiCad to lead acid storage batteries. Such changes should be 
considered changes in performance specifications or device design, as discussed at 
decision point B5.  
 
B3.  Is it a change in sterilization, cleaning, or disinfection? Changes in sterilization, 
cleaning, or disinfection should be carefully assessed. If there is a change of this type, 
proceed to B3.1. 
 
B3.1  Is it a change to an established category B or novel sterilization method, does 
the change lower the sterility assurance level, or is it a change to how the device is 
provided? Changes from established category A sterilization methods to established 
category B or novel sterilization methods generally require submission of a new 
510(k). Changes from one established category A method to another established 
category A method, or from an established category B or novel method to an 
established category A method, should be evaluated under B3.2. See FDAs guidance 
Submission and Review of Sterility Information in Premarket Notification (510(k)) 
Submissions for Devices Labeled as Sterile 
(https://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidanced
ocuments/ucm109897.pdf) for a discussion of sterilization methods and their 
categorization (e.g., established A, established B, or novel). 
 
If the sterility assurance level (SAL) is lowered, manufacturers should consider whether 
device safety or effectiveness may be compromised by the new level. In general, 
reductions in SAL require submission of a new 510(k) unless the SAL remains better 
than 10-6. Note that changes to cleaning and disinfection processes for reprocessed 
devices can also affect the bioburden levels on a device, which may invalidate subsequent 
processing steps such as sterilization; manufacturers should carefully consider whether 
these changes could significantly affect the safety or effectiveness of the device. It is 
likely that changes to reprocessing procedures for devices listed in Appendix E of FDAs 
guidance Reprocessing Medical Devices in Health Care Settings: Validation Methods 
and Labeling 
(https://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidanced
ocuments/ucm253010.pdf), could significantly affect safety or effectiveness. FDA has 
identified the devices there as a subset of medical devices that pose a greater likelihood 
of microbial transmission and represent a high risk of infection (subclinical or clinical) if 
they are not adequately reprocessed. 
 
Some changes to how a device is provided to the user or patient could also significantly 
affect safety or effectiveness. For the purposes of this question, how the device is 
provided refers to whether the device is provided sterile or non-sterile, and to whether 
the device is provided for (1) single-patient, single-use, (2) single-patient, multi-use, or 
(3) multi-patient, multi-use. If a device is changed from (1) to (2), (1) to (3), or (2) to (3), 
i.e., provided for more patients and/or more uses, submission of a new 510(k) is likely 
required. However, the reverse would not be true; it would be unlikely that a change from 
(3) to (2), (3) to (1), or (2) to (1) could significantly affect safety or effectiveness and 
therefore would not likely require submission of a new 510(k). In addition, if a device 
that was originally provided sterile is modified to be provided non-sterile  either to be 
  26  Contains Nonbinding Recommendations 
 
sterilized by the user or to be used without sterilization  submission of a new 510(k) is 
likely required. Submission of a new 510(k) is also likely required if a device originally 
provided non-sterile is modified to be provided sterile.  
   
If the answer to this question is yes, submission of a new 510(k) is likely required. If the 
answer is no, proceed to B3.2. 
 
B3.2  Could the change significantly affect the performance or biocompatibility of the 
device? Changes in the method of sterilization, cleaning, or disinfection have the 
potential to change material or performance characteristics of a device. This is 
particularly true of the properties of polymeric materials or surface coatings, resorbable 
materials, or animal-derived materials. When manufacturers make changes in 
sterilization, cleaning, or disinfection methods, they should consider whether the 
properties or specifications of the device could be significantly affected.  
 
To determine whether the cleaning, disinfection, and/or sterilization change could 
significantly affect device performance, the manufacturer should consider known 
information on the sterilization, cleaning or disinfection method, its parameters, and the 
material being sterilized, cleaned, or disinfected, and determine if there are any new or 
significantly modified existing risks associated with using the proposed method and its 
parameters with the devices materials of construction. If there are new or significantly 
modified existing risks (see Section E), this likely indicates that the change could 
significantly affect the devices safety or effectiveness. Note also that if verification 
and/or validation of the new methods show any unexpected results, manufacturers should 
re-evaluate whether submission of a new 510(k) is required (see B5.4). 
 
Cleaning, disinfection, and/or sterilization changes may also affect the biocompatibility 
of a device. For instance, changes to an ethylene oxide sterilization process may leave 
increased ethylene oxide residuals on the device surface, or changes to a cleaning process 
may incorporate chemicals that are inappropriate for use with a patient-contacting device. 
Manufacturers should consider whether sterilization, cleaning, or disinfection changes 
could significantly affect the biocompatibility of their device. If a manufacturer 
determines their cleaning, disinfection, or sterilization change could significantly affect 
the performance or biocompatibility of the device, submission of a new 510(k) is likely 
required. Otherwise, it is unlikely submission of a new 510(k) is required as a result of 
this type of change.  
 
B4.  Is there a change in packaging or expiration dating? If yes, proceed to B4.1. 
 
B4.1  Is the same method or protocol, as described in a previously cleared 510(k), used to 
support the change? Generally, changes in device packaging or changes in the 
expiration date for use of a device do not require submission of a new 510(k). FDA relies 
on the QS regulation (21 CFR Part 820) to reasonably assure the safety and effectiveness 
of devices with these types of changes. This is true whether or not the manufacturer 
applies an expiration date because of package integrity considerations, e.g., sterility, or 
because of a finite shelf-life of the device. However, where methods or protocols that are 
not described in a previously cleared 510(k) are used to support new package integrity or 
shelf-life claims, submission of a new 510(k) is likely required. FDA recognizes that 
  27  Contains Nonbinding Recommendations 
 
methods or protocols may be updated to reflect newly recognized versions of consensus 
standards. Submission of a new 510(k) is likely not required in such circumstances.  
 
B5.  Is it any other change in design (e.g., dimensions, performance specifications, 
wireless communication, components or accessories, or the patient/user interface)? 
These types of design or engineering changes encompass everything from the routine 
specification changes necessary to maintain or improve device performance as a result of 
feedback from users, field or plant personnel, etc., up to and including significant product 
redesign. The bullets below highlight some, but not all, of these changes, and provide 
points to consider for each type of change. 
 
  Dimension changes: In determining whether submission of a new 510(k) is required 
for these types of changes, per B5.1-B5.4, the manufacturer should consider not only 
the magnitude of the dimension or dimensional specification change, but the 
criticality of the modified dimension. The more critical the dimensions being 
modified are to the safe and effective operation of the device, the more likely it is that 
the change could significantly affect safety or effectiveness. For instance, a 1 mm 
change to the diameter of a working channel of an endoscope is more likely to 
significantly affect safety or effectiveness than a 1 mm change to the length of an 
endoscope.  
 
If a modified dimension is within a range of dimensions previously cleared for the 
original device, submission of a new 510(k) would not typically be required. For 
instance, if the original device was cleared with two models that were 2 and 4 mm in 
diameter, and the modified device of the same length has a diameter of 3 mm, 
submission of a new 510(k) is likely not required for this change. 
 
  Device performance changes: This category covers a broad range of changes. As 
discussed in the Main Flowchart, Question 1, changes that are intended to 
significantly affect device safety or effectiveness likely require submission of a new 
510(k). Changes that are not intended to affect device safety or effectiveness should 
be considered per B5.1-B5.4.  
 
  Wireless communication changes: Changes to device communication between 
device components or between the modified device and other products, particularly 
from wired to wireless, may change a devices risk profile by introducing or 
modifying risks regarding data transmission or cybersecurity.7 Changes to employ 
wireless communication in devices where it was previously not used are likely to 
significantly affect safety or effectiveness and likely require submission of a new 
510(k). This is particularly true when wireless communication is used to control 
device operations. When evaluating other changes, including a change to a different 
wireless communication protocol, the factors in B5.1-B5.4 should be taken into 
account in determining whether submission of a new 510(k) is required. 
 
                                                 
7 See FDAs webpage on cybersecurity in medical devices, 
http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/ConnectedHealth/ucm373213.htm.  
  28  Contains Nonbinding Recommendations 
 
  Components or accessories: Changes to components or accessories could, in some 
cases, significantly affect the safety or effectiveness of the device as a whole. In B5.1, 
manufacturers should consider whether changes to the device or any of its 
components or accessories affect the use of other components or accessories, or if 
changes to a component or accessory could lead a device to be used in a new way. In 
B5.2, manufacturers should consider whether changes to the device or any of its 
components or accessories could disrupt compatibility between the device and its 
components or its accessories, and whether these changes could lead to a significant 
change in the devices risk profile.  
 
  Changes in the human factors of the patient or user interface: A device user 
interface includes all points of interaction between the product and the user, including 
elements such as displays, controls, and packaging. User interface changes refer to 
changes in the way in which a patient or user interacts with a device, including, for 
example, the way in which the device presents alarms to the user, the layout of the 
control panel, the mode of presentation of information to the user or patient, and the 
way in which the device physically interacts with the user and/or patient (e.g., the 
way in which a CPAP mask attaches to a patients face, or the way a surgical 
instrument is designed to fit in a surgeons hand). Note that this type of change 
includes changes that modify a user workflow (tasks performed by a user in order to 
complete their work). Manufacturers should consider the risk impact of changes in 
user workflow; for example, providing new information to the user or modifying the 
manner in which information is presented may impact user comprehension. In 
addition, changing the layout of device controls may impact device use differently in 
different use scenarios. For more information on applying human factors in medical 
devices, see FDAs guidance Applying Human Factors and Usability Engineering to 
Optimize Medical Device Design 
https://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidan
cedocuments/UCM259760.pdf .  
  
Changes intended only to increase user or patient comfort when interacting with the 
device may be particularly difficult to evaluate. Changes to increase user or patient 
comfort will typically not require submission of a new 510(k), but some changes 
made for the comfort of the user or patient could also change the way the device 
functions or performs and therefore could significantly affect safety or effectiveness. 
For example, if a surgical handpiece is redesigned to move a motor closer to the 
surgeons hand or the surgical site, any heating of the motor will be more likely to 
affect the surgeon or patient and could result in burns. Manufacturers should evaluate 
changes to a user interface and whether they significantly affect safety or 
effectiveness in answering B5.1-B5.4.  
 
Changes in design should be considered, along with the above bulleted points, in 
answering B5.1-B5.4. 
 
B5.1  Does the change significantly affect the use of the device? As with a labeling change, 
if a design change significantly affects how a device may be used,  submission of a new 
510(k) is likely required. In the risk-based assessment, manufacturers should consider 
whether the design change increases the likelihood that the device will be used by a 
  29  Contains Nonbinding Recommendations 
 
broader or different group of users who have less training regarding safe and effective use 
of the device (e.g., lay users instead of clinicians, or general practitioners instead of 
surgeons) and whether that design change affects the risk profile of the device. If the 
change significantly affects the risk profile (see Section E), submission of a new 510(k) is 
likely required.  
 
  Manufacturers should also consider whether the design change increases the likelihood 
that the device will be used in a new environment, and whether the new environment 
affects the risk profile of the device. If the change facilitates use in a completely different 
environment (e.g., from hospital to home use, or from hospital to ambulance transport), 
this typically will introduce new or significantly modified existing risks and will likely 
require submission of a new 510(k). If the change facilitates use only in similar 
environments, the risk profile of a device may also be changed, but this is less likely to 
require submission of a new 510(k). In deciding whether a design change that allows use 
of the device in a new environment could significantly affect the safety or effectiveness 
of the device, manufacturers should consider differences in environmental specifications 
such as: 
 
  temperatures and humidity that might affect device operation; 
  noises that might drown out the sound of auditory alarms;  
  exposure to water, soils, or light that might affect device operation;  
  presence of other devices or equipment that may cause electromagnetic 
interference; and 
  possible use in magnetic resonance imaging (MRI). 
If the design change introduces new or significantly modified existing risks, submission 
of a new 510(k) is likely required. 
 
If the design change significantly affects use of the device, submission of a new 510(k) is 
likely required. If it does not, proceed to B5.2. 
 
B5.2  Does a  risk-based assessment of the changed device identify any new risks or 
significantly modified existing risks? As discussed in the Guiding Principles and 
Section E, the manufacturer should conduct a  risk-based assessment for any modified 
device. New risks, changes to the acceptability of previously identified risks, or changes 
to device features that may be critical to the devices safe or effective operation will 
likely require submission of new 510(k)s.  
 
Manufacturers should carefully consider whether changing one aspect or feature of a 
devices design might affect a seemingly unrelated aspect or feature. For instance, a 
dimensional or component change may affect the ability to reprocess a device or the 
ability to regulate the temperature of an electronic device. Manufacturers should evaluate 
these impacts of the change as part of their  risk-based assessment.  
 
If a risk-based assessment does not identify any new risks or significantly modified 
existing risks per Section E, proceed to B5.3. 
 
  30  Contains Nonbinding Recommendations 
 
B5.3  Are clinical data necessary to evaluate safety or effectiveness for purposes of design 
validation? Whenever a manufacturer recognizes that clinical data are needed because 
bench testing or simulations are not sufficient to assess the impact of the change on safety 
or effectiveness to validate the design change, submission of a new 510(k) is likely 
required. For the purposes of this question, clinical data does not include data used for 
purposes other than design validation, such as user or patient preference testing.  
 
If clinical data are unnecessary to evaluate safety and effectiveness for purposes of design 
validation, proceed to B5.4. 
 
B5.4  Do design verification and/or validation activities produce any unexpected issues of 
safety or effectiveness? All changes to device design should undergo some level of 
design verification and/or validation or evaluation to ensure that the device continues to 
perform as intended. See 21 CFR 820.30. As discussed in the Guiding Principles, 
manufacturers should make an initial risk-based assessment of whether a change requires 
submission of a new 510(k). If the manufacturer determines after an initial assessment 
that submission of a new 510(k) is not required, the manufacturer should conduct routine 
verification and validation activities to ensure that no new issues of safety or 
effectiveness are raised. If successful application of routine verification and validation 
activities confirms the initial assessment, manufacturers should proceed with the design 
change and document their assessment.  
 
Occasionally, routine verification and validation activities may either produce unexpected 
results or otherwise prove to be inadequate to verify and/or validate the modified design. 
In such instances, the manufacturer likely is required to submit a new 510(k).  
 
If a manufacturer encounters unexpected results performing routine verification and 
validation activities  for example, the device does not perform as expected, pre-specified 
acceptance criteria are not met, or testing demonstrates unexpected safety or effectiveness 
issues  the manufacturer should analyze the results carefully. The initial  risk-based 
assessment should be re-evaluated, and if changes to that assessment are necessary, the 
manufacturer should re-evaluate whether the device change could significantly affect 
safety or effectiveness. If different verification and/or validation test methods or 
acceptance criteria are necessary to produce the expected results, it is likely that the 
change could significantly affect safety or effectiveness and thus submission of a new 
510(k) is likely required.  
 
If the manufacturer determines prior to conducting verification and validation activities 
that routine verification and validation activities are insufficient and the design change 
necessitates a different verification and/or validation scheme or new acceptance criteria, 
submission of a new 510(k) is likely required. This does not mean that manufacturers 
should not update test methods and acceptance criteria for verification and validation 
activities in accordance with advances in science or relevant voluntary consensus 
standards, but if the design change drives the need for a new testing scheme or 
acceptance criteria (as opposed to advances in science or standards), it is likely that the 
design change could significantly affect safety or effectiveness. Note that performing a 
subset of the original suite of tests is not considered a new test scheme.  
 
  31  Contains Nonbinding Recommendations 
 
If the initial assessment determines submission of a new 510(k) is not required, and 
verification and validation activities are substantially unchanged (i.e., use the same test 
methods and same acceptance criteria) and successful, as outlined in the examples below, 
then proceed to Section C. 
 
For example, in order to better accommodate connection of a urinary drainage (Foley) 
catheter to a collection apparatus, the manufacturer increases the length of the catheter by 
several millimeters. The new length is outside of previously cleared lengths for this 
device, however, the length change is not far outside cleared lengths. Based on its risk-
based assessment, the manufacturer does not expect the length change will create any 
new risks or significantly modify existing risks. The manufacturer therefore determines 
that the length change could not significantly affect the devices safety or effectiveness, 
and does not require submission of a new 510(k). The manufacturer subsequently 
conducts design control activities, and verifies that the catheter functions safely and 
effectively, as predicted, with no unexpected results. The manufacturer documents these 
efforts and proceeds to production.  
 
In another example, a manufacturer of monitoring devices wants to use a more sensitive 
comparator circuit, and makes other design changes to accommodate the more sensitive 
component. The design change is similarly evaluated in an initial risk-based assessment 
based on models, calculations, etc., and a decision is made that the change could not 
significantly affect the devices safety or effectiveness, and therefore the changes do not 
require submission of a new 510(k). However, as part of routine verification and 
validation activities, tests with a simulator produce unexpected results, and additional 
work is necessary to understand how and why this outcome occurred. The manufacturer 
should carefully assess these results and whether new issues of safety or effectiveness 
have been uncovered.  
C.  Materials Changes 
Firms making changes to the materials from which their device is manufactured should also 
consider the other types of changes discussed above and their impact on the decision regarding 
submission of a new 510(k). For example, a material change, as discussed below, might also lead 
to a change in the labeling of the device (e.g., the removal of a contraindication or the addition of 
a new warning), or a change in specifications (e.g., a reduction in the strength of the device). 
These collateral changes should be considered in addition to the logic scheme described in this 
section.  
  32  Contains Nonbinding Recommendations 
 
C1
From Main Chart Is the device an  Yes Go to Chart D
IVD?
No
C3 C2
Will the changed  Change in material type,  
material directly or  Yes formulation, chemical  No Documentation
indirectly contact body  composition,  or the 
tissues or fluids? materials processing?
Yes
No
No
C5
C4
Could the 
Does a risk assessment 
No change affect 
identify any new or increased 
performance 
biocompatibility concerns?
specifications?
Yes
Go to B5
Yes
New 510(k)
Reminder: Flowcharts are 
provided as a visual aid, but do 
not capture all necessary 
considerations. Refer to 
C4.1
accompanying text when using 
Has the manufacturer used the same 
No this flowchart. 
material in a similar legally marketed 
device (including formulation, 
processing, type and duration of 
contact, etc.)?
Refer to Section E as 
directed by the text for 
Yes additional 
recommendations on use 
of risk assessment.
 
Figure 4 - Flowchart C: Materials Changes 
 
 
  33  Contains Nonbinding Recommendations 
 
C1.   Is the device an in vitro diagnostic device? If the device is an IVD, refer to the later 
section of this guidance which is specific to materials changes in IVDs (Section D  
Technology, Engineering, Performance, and Materials Changes for In Vitro Diagnostic 
Devices). 
 
C2.  Is this a change in material type, material formulation, chemical composition, or the 
materials processing? If there is any change in material type, formulation, or chemical 
composition, the answer to this question should be yes. Additionally, if there is any 
change in supplier or manufacturer material processing or finishing steps, the answer 
should also be yes. The biocompatibility and physical properties of a finished device 
depend not only on the materials, but also on the processing of the materials, 
manufacturing methods (including the sterilization process), and the manufacturing 
residuals that may be present on the finished device. Changes of this type should be 
further evaluated for their potential impact on safety and effectiveness. The subsequent 
questions, such as C4 and C4.1, address whether the change is significant using the 
process of risk assessment.  
 
Many material changes result from material supplier changes, including changes made by 
a material supplier, or changes from one supplier to another. When these types of changes 
occur, the manufacturer should utilize their quality system process to analyze the material 
and determine the extent of the change made, as this analysis might impact answers to 
subsequent questions, even when these changes result in materials that remain within the 
original material specifications.  
 
If there is a change in material type, material formulation, chemical composition, or the 
materials processing as described above, proceed to C3. Otherwise it is unlikely 
submission of a new 510(k) is required as a result of a materials change. 
 
C3.  Will the changed material directly or indirectly contact body tissues or fluids? Both 
direct and indirect patient and user contact should be considered in answering this 
question. Direct contact is when a material comes into physical contact with a patient or 
user while the material is still in or on the patient or user. A material with indirect contact 
is a material through which a fluid or gas passes, prior to the fluid or gas coming into 
physical contact with body tissue (i.e., the device or device component itself does not 
physically contact body tissue).8 For example, materials in a catheter hub (the part of the 
catheter which is external to the patient) can contact the patient indirectly if fluids or 
drugs are infused through the hub and directly into the patient.  
 
While most implant materials contact patients, there are some exceptions. For example, 
the internal contents of spinal cord stimulators are not patient-contacting; they are 
hermetically sealed so that there is no material transfer, fluid transfer, or leeching out of 
any material internal to the device.  
 
                                                 
8 See FDAs guidance Use of International Standard ISO-10993, Biological evaluation of medical devices - Part 
1: Evaluation and testing within a risk management process 
(https://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm348890.pdf)
. 
  34  Contains Nonbinding Recommendations 
 
If the changed material directly or indirectly contacts body tissues or fluids, proceed to 
C4. If the changed material does not contact body tissues or fluids, proceed to C5. 
 
C4.  Does a risk assessment identify any new or increased biocompatibility concerns? 
Manufacturers should conduct a biocompatibility risk assessment, which may include an 
assessment of the devices toxicological and physical properties, of any changed 
materials that may contact the patient or user to determine if there are any new or 
increased biocompatibility concerns. An example of a new concern would be a material 
change that requires a new type of biocompatibility test, such as an implantation test, that 
was not required for the original device. An example of an increased concern would be 
where a new chemical component added to a material requires a genotoxicity analysis of 
that component (because, for instance, the particular component is noted in the literature 
as potentially genotoxic), but the original device already required a genotoxicity analysis. 
See FDAs guidance Use of International Standard ISO-10993, Biological evaluation of 
medical devices - Part 1: Evaluation and testing within a risk management process 
(https://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidanced
ocuments/ucm348890.pdf) for detailed information regarding recommendations on how 
to conduct a biocompatibility risk assessment, including a specific chemical assessment.  
 
The answer to C4 may be no if a knowledgeable individual reviews the differences in 
chemical composition or physical properties and determines that the change is minor 
enough that there is no new concern about biocompatibility.  
 
A supporting toxicological assessment can be based on an analysis of the chemical 
formulations or the results of chemical characterization tests if the detailed formulation is 
not available (i.e., when the material is provided by a supplier and the formulation is 
proprietary). If, however, this analysis identifies new chemical entities or other properties 
that are either novel or have the potential to generate adverse biocompatibility responses, 
such as genotoxicity, submission of a new 510(k) may be required.  
 
If a risk assessment identifies any new or increased biocompatibility risks, consider the 
questions in C4.1. If no new or increased biocompatibility risks are identified, proceed to 
C5. 
 
C4.1  Has the manufacturer used the same material in a similar legally marketed device?9 
Manufacturers who have identified possible biocompatibility concerns in their risk 
assessment (C4) should consider whether they have used the same material, in its final, 
finished state, in another one of its own legally marketed devices that has been cleared or 
approved by the FDA. If the manufacturer has used the same material in a similar device 
                                                 
9 The term similar legally marketed device is not intended to refer to a predicate device as in the context of a 
substantial equivalence determination. The device is more akin to a reference device, as described in FDAs 
guidance The 510(k) Program: Evaluating Substantial Equivalence in Premarket Notifications [510(k)] 
(https://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocuments/UCM284443.pd
f.) For additional context, see Section III of FDAs guidance Use of International Standard ISO-10993, Biological 
evaluation of medical devices - Part 1: Evaluation and testing within a risk management 
process(https://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm34
8890.pdf). 
  35  Contains Nonbinding Recommendations 
 
that has been cleared or approved by the FDA (this would typically involve a 
biocompatibility evaluation), and there is no postmarket evidence of biocompatibility 
issues with the device, that may provide evidence that the material will be biocompatible 
in its new application in the changed device as well and the manufacturer can answer yes 
to this question.  
 
It is important to note that in order to answer yes to this question, the material in question 
should have the same formulation or chemical composition and be subjected to the same 
processing, including sterilization (i.e., the comparison should be between materials as 
they are applied in the final finished device, not between raw materials). Note that the 
size and geometry of the changed device or component could affect the material 
properties (e.g.,  affect the curing of the polymer, or result in more material in the new 
device or component).  Any change in chemical composition, manufacturing process, 
physical configuration (e.g., size, geometry, surface properties) or intended use of the 
device should be evaluated with respect to possible changes in biocompatibility and the 
need for additional biocompatibility assessment. 
 
The previously cleared or approved device should have the same or a more risky type of 
contact and the same or a longer duration of contact. For example, if a manufacturer 
intends to use a new material in a limited exposure application (<24 hours), and the 
manufacturer has used that same material in a cleared or approved device for prolonged 
exposure (24 hours to 30 days), then it is unlikely that submission of a new 510(k) will be 
required for this change. If the modified device is intended to have a riskier category of 
contact (e.g., mucosal membrane contact is riskier than contact with intact skin, and 
blood contact is riskier than tissue/bone contact) or a longer duration of contact, then the 
manufacturer should answer no to this question. Contact may be either direct or indirect. 
 
Manufacturers should not compare their changed material to materials in other 
manufacturers legally marketed devices, unless the exact formulation and processing of 
the device, which may affect the safety and effectiveness of the final finished product, 
can be verified. 
 
If the manufacturer has used the same material in a similar legally marketed device, 
proceed to C5 to determine if the material change could affect device performance. If the 
manufacturer has not used the same material in a similar legally marketed device, 
submission of a new 510(k) is likely required.  
 
C5.  Could the change affect the devices performance specifications? Manufacturers 
should consider whether the material change could affect the performance of the device 
by affecting its mechanical properties, such as strength, hardness, etc. Manufacturers 
should also consider whether the new material could be affected by any labeled cleaning, 
disinfection, and/or sterilization process of the device. If the answer to this question is 
yes, manufacturers should proceed to B5 above and consider whether the change could 
significantly affect the safety or effectiveness of the device. If the change could not affect 
the devices performance specifications, it is unlikely the change could significantly 
affect safety or effectiveness, and the manufacturer should document the change. 
  36  Contains Nonbinding Recommendations 
 
D.  Technology, Engineering, Performance, and Materials 
Changes for In Vitro Diagnostic Devices 
Changes in technology, engineering, performance, or materials of an IVD can include changes 
made to reagents or changes to a test method or protocol, among other things. 
For IVDs, performance generally refers to the analytical and clinical specifications established as 
part of the most recent 510(k) clearance. Analytical performance refers to the documented ability 
of an IVD test or test system to measure or detect a target analyte or substance that the IVD is 
represented or purported to identify or measure.Clinical performance refers to the documented 
ability of an IVD to identify, measure, monitor, or predict the presence or absence of, or the 
future development of, a clinical condition or predisposition, for which the device is intended. 
 
Firms making technology, engineering, performance, or materials changes to their IVD should 
also consider the other types of changes discussed above in Section A, Labeling Changes, and 
their impact on the decision regarding submission of a new 510(k). For example, a material 
change, as discussed below, might also be considered a design change and/or might engender a 
change in the labeling of a device (e.g., the removal of a contraindication, addition of a new 
warning, or a change in the measuring range). These collateral changes should be considered also 
when applying the logic scheme described in this section. 
 
D1
From main 
Does the change alter the operating  Yes
flowchart
principle of the IVD?
No
Reminder: Flowcharts are 
provided as a visual aid,  D2
but do not capture all  Is the change identified in a 
necessary considerations.  device-specific final guidance or  Yes
Refer to accompanying text  classification 
when using this flowchart.  regulation?
YNeos New 510(k)
D3
Refer to Section E as directed 
Does a risk-based assessment of the 
by the text for additional 
changed device identify any new risks or  Yes
recommendations on 
significantly modified existing 
use of risk assessment.
risks?
No
D4
Do design verification and 
Documentation No validation activities produce any  Yes
unexpected issues of safety or 
effectiveness?
 
Figure 5 - Flowchart D: Technology, Engineering, Performance, and Materials Changes for In Vitro 
Diagnostic Devices 
  37  Contains Nonbinding Recommendations 
 
 
D1.  Does the change alter the operating principle of the IVD?  
 
In most cases, a technology, engineering, performance, or material change that alters the 
operating principle of an IVD could significantly affect safety and effectiveness, in which 
case submission of a new 510(k) is required. Submission of a new 510(k) is not 
necessarily required for all changes in technology, engineering, performance, or materials 
for IVDs that alter the operating principle of an IVD. However, when such changes 
introduce novel technology that could have an impact on the ability of the device to 
extract, isolate, or detect the analyte(s) and could therefore affect the value assigned to 
the specimen, or could produce deviations in device performance that would result in 
modified reporting of performance in labeling, submission of a new 510(k) is likely 
required. 
 
Examples of changes in technology, engineering, performance, or materials that likely 
alter the operating principle of the IVD and for which a new 510(k) is likely required 
include:  
  changes from radioimmunoassays (RIA) to non-RIAs;  
  changes in the antibody;  
  changes in detection reagents;  
  changes in critical reaction components; and 
  changes in conjugates.  
 
Examples of changes in technology, engineering, performance, or materials that might 
alter the operating principle of the IVD include:  
 
  changes from liquid to solid reagent;  
  changes in calibration materials and quality control materials;  
  changes in substrates;  
  changes in specimen type; 
  changes in specimen processing; and 
  changes in incubation times and temperatures.  
 
Examples of changes in technology, engineering, performance, or materials of an IVD 
which do not ordinarily affect the operating principle of the IVD include:  
 
  changes to external packaging;  
  changes to use a new lot or batch for the same antibody or enzyme;  
  changes to a new vendor for the same reagent; and  
  changes in concentrations of packaged reagents provided the same diluted 
concentration was used in the assay. 
 
If such a change to an IVD does not alter the operating principle of the IVD, proceed to 
D2. 
  
D2.  Is the change identified in a device-specific final guidance or classification 
regulation?  
  38  Contains Nonbinding Recommendations 
 
 
  In the case of some IVDs, FDA has published device-specific final guidance documents, 
which provides resources to manufacturers on specific issues related to those devices. A 
searchable listing of these device-specific guidances can be found on FDAs website at 
https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocumen
ts/ucm070274.htm. When a device-specific final guidance identifies a change or 
modification that FDA has determined could significantly affect safety or effectiveness, 
submission of a new 510(k) is generally required. Additionally, in the case of some IVDs, 
FDA has established specific requirements (e.g., special controls) that are identified in 
the classification regulation. If a classification regulation identifies a change that could 
significantly affect safety or effectiveness, submission of a new 510(k) is required. Where 
a change is not identified in a device-specific final guidance or classification regulation, 
proceed to D3.  
 
D3.  Does a  risk-based assessment of the changed device identify any new risks or 
significantly modified existing risks?  
   
  As discussed in the Guiding Principles and Section E, the manufacturer of an IVD should 
conduct a  risk-based assessment for any modified device. Changes in the technology, 
engineering, design, or material used in an IVD can affect the performance, including the 
analytical or clinical performance, of the device.  Further, certain changes in an IVD 
could also present new or significantly modified existing risks that could affect the 
overall risk profile of the IVD, apart from the performance (e.g., transmission of 
pathogenic diseases, biocompatibility or sterility issues).   
 
  For IVDs, a manufacturers  risk-based assessment identifies new risks or significantly 
modified existing risks when the  risk-based assessment (1) indicates that the 
performance of the modified test could significantly change from the previously cleared 
performance claims or (2) identifies new risks or significantly modified existing risks, 
apart from performance. If a change could affect the analytical performance of a device, 
particular attention should be paid to the effect on device performance around the clinical 
decision point(s) (i.e., cut-offs, cut-points). When new risks or significantly modified 
existing risks have been identified, in general, the change to the IVD could significantly 
affect safety or effectiveness of the device and submission of a new 510(k) is likely 
required. This includes a change that is clinically significant in terms of clinical decision 
making. 
 
  Changes to components or accessories could, in some cases, significantly affect the safety 
or effectiveness of an IVD as a whole. Manufacturers should consider in their initial risk-
based assessment whether changes to the IVD or any of its components or accessories 
affect the use of other components or accessories, or if changes to a component or 
accessory could lead an IVD to be used in a new way. Manufacturers should also 
consider whether changes to the IVD or any of its components or accessories could 
disrupt compatibility between the device, its components, and/or its accessories, or 
whether these changes could significantly affect performance or the devices risk profile. 
 
  Changes in the human factors of a patient or user interface could, in some cases, 
significantly affect the safety or effectiveness of an IVD as a whole. Manufacturers 
  39  Contains Nonbinding Recommendations 
 
should evaluate in their initial  risk-based assessment whether a change in the human 
factors of a patient or user interface could significantly change the performance of the 
IVD or presents new risks or significantly modified existing risks. A device user interface 
includes all points of interaction between the product and the user, including elements 
such as displays, controls, and packaging. User interface changes refer to changes in the 
way in which a patient or user interacts with a device, including, for example, the way in 
which the device presents alarms to the user, the layout of the control panel, the mode of 
presentation of information to the user or patient, and the way in which the device 
physically interacts with the user and/or patient. Note that these changes include those 
that modify a user workflow (tasks performed by a user in order to complete their 
workflow). Manufacturers should consider the risk impact of changes in user workflow, 
such as providing new information to the user or modifying the manner in which 
information is presented, which may impact comprehension, or changing the layout of 
device controls, which may impact device use differently in different use scenarios. For 
more information on applying human factors in medical devices, see FDAs guidance, 
Applying Human Factors and Usability Engineering to Optimize Medical Device Design 
https://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidanced
ocuments/UCM259760.pdf.    
  
  Changes intended only to increase user or patient comfort when interacting with the 
device may be particularly difficult to evaluate. These changes will typically not present 
new risks or modified existing risks, but some changes made for the comfort of the user 
or patient could significantly affect safety or effectiveness. Manufacturers should 
evaluate the potential of changes to a user interface as to whether they could significantly 
affect safety or effectiveness. 
 
  If a risk-based assessment indicates that that the performance of the modified IVD could 
not significantly change from the previously cleared performance claims, or that the 
modified IVD does not present new or significantly modified existing risks apart from 
performance, proceed to D4. 
 
D4.  Do design verification and/or validation activities produce any unexpected issues of 
safety or effectiveness?  
 
As discussed above in the Guiding Principles, manufacturers should conduct an initial  
risk-based assessment of whether a change requires submission of a new 510(k); if the 
initial decision following the  risk-based assessment is that submission of a new 510(k) is 
not required, the manufacturer should conduct design verification and/or validation 
activities to confirm the decision.  
 
Verification and validation activities should reevaluate the performance claims or 
performance specifications that were part of the original 510(k) clearance, as appropriate 
based on the manufacturers routine quality processes.  Submission of a new 510(k) is 
likely not required where: 
 
1)  standard methods and performance criteria that have been established for 
evaluation of the specific device, as appropriate (e.g., (a) protocols and criteria 
used to support the original 510(k) or (b) a protocol established in the original 
  40  Contains Nonbinding Recommendations 
 
510(k) that described how anticipated changes would be evaluated), are used to 
verify and validate the modification;  
2)  the results of verification and validation indicate that the performance is within 
the criteria;  
3)  the performance of the modified IVD has not significantly changed from the 
previously cleared performance claims; and  
4)  verification and validation do not reveal new risks or significantly modified 
existing risks apart from performance.  
If all of these criteria are met, then the change is unlikely to significantly affect safety or 
effectiveness and manufacturers should proceed with the change making sure to 
document their assessment of whether submission of a new 510(k) is required.   
 
If any of these criteria are not met, for instance, if verification or validation test methods 
or acceptance criteria other than those identified in item 1 immediately above are 
necessary to evaluate the change, it is likely that the change could significantly affect 
safety or effectiveness and that submission of a new 510(k) is required.  
 
If the results of routine verification and validation produce any unexpected issues or 
otherwise prove inadequate to verify and/or validate the changefor example, pre-
specified criteria are not met, the device fails to perform as expected, or testing 
demonstrates unexpected safety or effectiveness issuesit is likely that the change could 
significantly affect the IVDs safety and effectiveness, and submission of a new 510(k) is 
likely required.  
E.  Considerations for Risk-Based Assessments of Modified 
Devices 
As discussed throughout this document, a device modification that leads to a significant change 
in the devices risk profile likely requires submission of a new 510(k). This section provides 
guidance on the principal factors to consider in conducting a  risk-based assessment to determine 
whether a device change leads to a significant change in the devices risk profile. Manufacturers 
should use the risk-based assessment considerations discussed below in conjunction with the 
logic schemes and decision-making flowcharts outlined above. 
 
Although FDA recommends that manufacturers use an accepted method of risk assessment, such 
as ISO 14971, an FDA-recognized standard that provides a framework for systematically 
managing risks of medical devices throughout the total product life cycle, this guidance uses 
terminology distinct from ISO 14971.  
 
In general, the assessment of risk in deciding whether to submit a new 510(k) should identify all 
possible risks associated with the changed or modified device, and then focus on risks whose 
existence and characteristics are supported by objective scientific evidence. It is not necessary to 
focus on hypothetical risks that are not supported by scientific evidence or those that are 
determined to be negligible due to both the low probability of occurrence and low severity of 
harm. The manufacturer should then explore the severity and probability of occurrence of the 
harm to determine whether the device change could significantly affect safety or effectiveness 
and require submission of a new 510(k). 
  41  Contains Nonbinding Recommendations 
 
 
Relationship between hazards and harm 
 
Risk assessment involves describing the relationships between a hazard (a potential source of 
harm) and the ultimate consequences in terms of physical injury or damage. For some devices, 
non-physical injury, such as psychological harm, should also be considered. As part of their risk 
assessment, manufacturers should analyze possible sequences of events, hazardous situations, 
and associated possible harm. This may include:  
 
  initiating hazards, failure modes, or circumstances;  
  the sequences of events that could lead to a hazardous situation occurring;  
  the likelihood of such situations arising;  
  the likelihood that the hazardous situations lead to harm; and 
  the nature of the harm that could result. 
 
The extent of risks and harms associated with a device change may be assessed by taking into 
account the following factors, individually and in aggregate: 
 
1.  Likelihood or probability of occurrence of harm 
 
Various approaches may be employed to estimate probabilities of hazardous situations in 
assessing risk, including, but not limited to:  
 
  use of relevant historical and real-world data; 
  prediction of probabilities of risk using analytical or simulation techniques; 
  reliability estimates; 
  production data; or 
  use of expert judgment. 
 
The use of multiple approaches may be considered as this might serve to increase confidence in 
the results. Where uncertainty exists around these estimates, it may be useful to consider a 
qualitative approach to risk probability analysis. See, for instance, Section D.3 Risk Estimation 
of ISO 14971:2007 (second edition). 
 
If its determined that the likelihood of a harm occurring due to a device change is negligible, 
then that change is unlikely to require submission of a new 510(k). If it cannot be determined 
that a harms likelihood is negligible, or the probability cannot be determined at all, then the 
below factors should also be considered.  
  
2.  Severity of harm 
 
Manufacturers should consider the following points in analyzing the severity of a potential harm 
(refer to ISO 14971:2007 (second edition), Annex D, Sections D.3.3 and D.4 on severity and risk 
acceptability): 
 
  New risks  If a device change creates a new risk  i.e., a new hazard or hazardous 
situation  that did not exist for the original device and the new risk cannot be determined 
  42  Contains Nonbinding Recommendations 
 
to be negligible, it is likely that the change could significantly affect the devices safety 
or effectiveness, and submission of a new 510(k) is likely required. An exception is a 
device change where the pre-mitigation risk level (the risk level before any risk 
mitigations or controls are accounted for or product specifications are set) associated with 
the new risk is considered to be acceptable.  
  Changes in risk acceptability  If a device change positively or negatively changes the 
pre-defined acceptability level (e.g., tolerable, acceptable, insignificant) of an individual 
risk based on the risk-based assessment, either before or after risk mitigation or control, it 
is likely that the change could significantly affect the devices safety or effectiveness, and 
submission of a new 510(k) is likely required.  
  Changes in risk score  In cases where there is no risk acceptability change for an 
affected risk, a major change to the severity score may still suggest potential significant 
impact to safety, depending on how the manufacturer determines their risk scores and 
defines risk acceptability. These types of changes will be very dependent on how a 
manufacturer conducts risk management and defines risk scores and risk acceptability.  
  Duration  Some device features expose patients and/or users to temporary, minor harm; 
some can cause repeated but reversible harm; others can cause permanent, debilitating 
injury. Duration  that is, how long the adverse consequence lasts  should be considered 
along with the other factors described in this section.  
 
Note that if a device change results in risk that could significantly affect the safety or 
effectiveness of a device, submission of a new 510(k) must be submitted, even if the risk can be 
mitigated.  
 
3.  Device effectiveness 
 
Although ISO 14971 defines risk in terms of device harms and their effects on safety, it is 
important to note that whether submission of a new 510(k) is required depends on whether the 
change could significantly affect the safety or effectiveness of the device. Therefore, 
manufacturers should also consider the possible effects a device change may have on device 
effectiveness. As with safety risks, the manufacturer should consider the probability and severity 
(i.e., magnitude) of impacts to device effectiveness.  
 
In considering a device changes effects on device effectiveness, manufacturers should 
understand the criticality of the device feature being modified to the safe and effective use of the 
device. Certain features are more critical than others. For instance, the outer case of a ventilator, 
although important to the overall design of the device and providing for connection of various 
parts, is not as critical to the safe and effective use of the ventilator as the pump that circulates air 
to the patient. Note that labeling changes, which affect user actions, can be critical as well. 
 
   
  43  Contains Nonbinding Recommendations 
 
Appendix A: Examples 
 
The following are hypothetical examples of device changes with explanations as to why they 
likely would or would not require submission of a new 510(k). These examples are intended to 
be illustrative of the thought process for different types of changes. Note that these generalized 
examples do not necessarily account for every possible detail, risk, or consideration a 
manufacturer should evaluate, and should not be taken to mean that the changes described 
definitely do or do not require submission of a new 510(k). Real-world device modification 
decisions will depend on the particular details of the change and the specific device in question.  
 
Labeling change examples 
 
1.  Change: The original indications for use for a radio frequency (RF) device is to treat mild-
moderate wrinkles on the peri-orbital area. The indications for use are modified to also 
indicate the device for treatment of severe wrinkles on the decollatage.  
Relevant questions:  
A1- Is it a change in the indications for use statement?  Yes.  The indications for use are 
being expanded from treatment of mild-moderate wrinkles on the peri-orbital area of the face 
to treatment of the peri-orbital area and severe wrinkles on the decollatage. Proceed to A1.1 -
A1.5. 
A1.4  Does the change describe a new disease, condition, or patient population that the 
device is intended for use in diagnosing, treating, preventing, curing or mitigating? No. The 
manufacturer determined that the conditions and patient populations that the device is 
intended for use in treating are the same. 
A1.5  Does a risk-based assessment of the changed device identify any new risks or 
significantly modified existing risks? Yes. A risk-based assessment identifies that while there 
are no new or increased safety risks associated with the use of the device on the decollatage, 
the new indication for use is associated with a risk of significantly reduced effectiveness on 
the decollatage due to the differences in skin types and the severity of the wrinkles, which 
could significantly affect safety and effectiveness.  
Decision: New 510(k). 
Note that if this type of change in labeling was also associated with a design change of higher 
RF output in order to address the risk of significant change in effectiveness, then the analysis 
under Section B would also apply.  
 
2.  Change: The manufacturer of an IVD updates their labeling by changing the device from 
prescription use only to over-the-counter use. 
Relevant questions: 
A1 Is it a change in the indications for use statement? Yes. The revised labeling is a change 
in the indications for use statementof the device. Proceed to A1.1 -A1.5. 
A1.2  Is it a change from prescription to over the counter (OTC) use?  Yes. The revised 
labeling expands the scope of intended users of the device to lay users, which could 
significantly affect the safety or effectiveness of the device. 
Decision: New 510(k). 
 
  44  Contains Nonbinding Recommendations 
 
3.  Change: The manufacturer of a device adds a precaution stating that the device must be 
properly sterilized prior to use for patient safety. The modified labeling does not modify the 
previously validated cleaning, disinfection, or sterilization instructions. 
Relevant questions:  
A1 Is it a change in the indications for use statement? No. This is not a change in the 
indications for use statement of the device.  
A3  Is it a change in warnings or precautions? Yes. Proceed to A1.1-A1.5. 
A1.5  Does a risk-based assessment of the changed device identify any new risks or 
significantly modified existing risks? No. The added precaution simply emphasizes proper 
sterilization and does not affect the devices risk profile. 
Decision: Documentation. 
 
4.   
a.  Change: The manufacturer of an IVD removes a limitation contained in  
their labeling that informs users that heterophilic human anti-mouse antibodies (HAMA) 
cause interference in their assay, which can lead to false results that could harm the end-user. 
The manufacturer removes this limitation without making any changes to the assay itself.  
Relevant questions: 
A1- Is it a change in the indications for use statement?  No.  This is not a change in the 
indications for use statement of the device.  
A3 Is it a change in warnings or precautions? Yes. This change removed the statement 
from the limitation section of the labeling that HAMA may cross-react with the assay. 
Proceed to A1.1-A1.5. 
A1.5  Does a risk-based assessment of the changed device identify any new risks or 
significantly modified existing risks? Yes. Removing an identified interference from the 
labeling could lead to falsely elevated or falsely low analyte concentration, depending on the 
site of the interference in the immunoassay reaction. The removal of the limitation may result 
in the user failing to be alerted to a known risk and may impact performance by changing the 
ability to accurately measure the analyte concentration.  
Decision: New 510(k).  
 
b.  Change: The manufacturer of an IVD updates their labeling by adding a new limitation after 
identifying a newly approved drug as a potential interferent. 
Relevant questions: 
Main flowchart, question 1  Change made with intent to significantly improve the safety or 
effectiveness of the device? No. The manufacturer is only aware that the newly approved 
drug may cause interference with their assay and has not received any reports of adverse 
events. The labeling change is made to add the new limitation.  
A1- Is it a change in the indications for use statement?  No.  This is not a change in the 
indications for use statement of the device.  
A3 Is it a change in warnings or precautions? Yes. The change adds a new limitation to the 
IVD labeling and the manufacturer has monitored device usage and updated the labeling 
accordingly. Proceed to A1.1-A1.5. 
A1.5  Does a risk-based assessment of the changed device identify any new risks or 
significantly modified existing risks? No. The labeling change does not significantly affect 
the devices risk profile because no new risks or significantly modified existing risks are 
identified in the risk-based assessment.  
Decision: Documentation. 
  45  Contains Nonbinding Recommendations 
 
 
5.  Change: The warning information in the labeling for an IVD is modified to account for 
recently revised hazardous material guidelines. 
Relevant questions: 
A1- Is it a change in the indications for usestatement ?  No.  This not a change in the 
indications for use statement of the device.  
A3  Is it a change in warnings or precautions? Yes. A change is made to a warning about 
hazardous materials. Proceed to A1.1-A1.5. 
A1.5  Does a risk-based assessment of the changed device identify any new risks or 
significantly modified existing risks? No. So long as the same risks are communicated to the 
device user, this change would not significantly affect the devices risk profile. 
Decision: Documentation. 
 
6.  Change: The manufacturer adds a foreign language translation of the directions for use to a 
devices labeling. The translation does not change the meaning of the instructions. 
Relevant questions:  
A1- Is it a change in the indications for usestatement ?  No.  This is not a change in the 
indications for use statement of the device.  
A4  Could the change affect the directions for use of the device? Yes. Proceed to A1.1-
A1.5. 
A1.5  Does a risk-based assessment of the changed device identify any new risks or 
significantly modified existing risks? No. As long as the translation does not change the 
meaning of the instructions, this change would not affect the devices risk profile. 
Decision: Documentation. 
 
7.  Change: The directions for use of a catheter guidewire are modified to provide instructions 
on how to access different types of vasculature that were not previously addressed in the 
labeling.  
Relevant questions:  
A1- Is it a change in the indications for usestatement ?  No.  This is not a change in the 
indications for use statement of the device.  
A4  Could the change affect the directions for use of the device? Yes. Proceed to A1.1 -
A1.5. 
A1.4 -- Does the change describe a new disease, condition, or patient population that the 
device is intended for use in diagnosing, treating, preventing, curing or mitigating? No. The 
guidewire is intended for  use in the treatment of similar patient populations with the same 
diseases, even if the access points differ.  
A1.5  Does a risk-based assessment of the changed device identify any new risks or 
significantly modified existing risks? Yes. The revised instructions suggest that the device 
can be used in new vasculature, which would be considered an expansion of the devices 
indications for use. A risk-based assessment identifies that the new vasculature is more 
tortuous and significantly increases the risk of several device failure modes, which could 
significantly affect safety and effectiveness.  
Decision: New 510(k).  
 
  46  Contains Nonbinding Recommendations 
 
8.   
a.  Change: The original directions for use for a surgical laser intended to treat stones in the 
urinary tract only included instructions on lithotripsy modes. The instructions are modified 
to provide instructions on ablating soft tissue.  
Relevant questions:  
A1- Is it a change in the indications for use statement?  No.  This is not a change in the 
indications for use statement of the device.  
A4  Could the change affect the directions for use of the device? Yes. Proceed to A1.1 -
A1.5. 
A1.4  Does the change describe a new disease, condition, or patient population that the 
device is intended for use in diagnosing, treating, preventing, curing or mitigating? Yes. 
The revised instructions would result in the device being intended for use for ablation of 
soft tissue, which is a new disease or condition that the device is intended for use in 
treating, preventing, curing or mitigating, as compared to the treatment of stones in the 
urinary tract.  
Decision: New 510(k). 
 
b.  Change: The original directions for use for a surgical laser intended to treat stones in the 
urinary tract only included instructions on lithotripsy modes. The instructions are modified 
to provide additional instructions on the existing settings for lithotripsy on the cleared 
device, and does not modify instructions regarding compatible procedures or instruments.  
Relevant questions:  
A1- Is it a change in the indications for usestatement ?  No.  This is not a change in the 
indications for use statement of the device.  
A4  Could  the change affect directions for use of the device? Yes. Proceed to A1.1 -
A1.5. 
A1.4  Does the change describe a new disease, condition, or patient population that the 
device is intended for use in diagnosing, treating, preventing, curing or mitigating? No. 
The condition that the device is intended to treat remains the same.   
A1.5  Does a  risk-based assessment of the changed device identify any new risks or 
significantly modified existing risks? No. The manufacturers risk-based assessment 
concludes that the clarification of already existing settings does not introduce any new 
device risks, and the risk acceptability for the previously existing risks is not changed. 
Decision: Documentation. 
 
9.  Change: A manufacturer changes the design of an IVD for diagnosing herpes simplex 1 and 
2 to a less strict performance specification that decreases both the sensitivity and specificity 
of the device to increase production. The manufacturer updates the performance 
specifications found in the labeling of the device.  
Relevant questions:  
A1- Is it a change in the indications for usestatement ?  No.  This is not a change in the 
indications for use statement of the device.  
A4  Could the change affect the directions for use of the device? Yes. The change could 
affect the directions for use by adding new instructions on how to interpret diagnostic data 
from  the device. Proceed to A1.1 -A1.5. 
A1.5- Does a risk-based assessment of the changed device identify any new risks or 
significantly modified existing risks? Yes. The changes to the device result in significantly 
increased existing risks. This is due to a mathematically expected increase in false positive 
  47  Contains Nonbinding Recommendations 
 
results, which would, in turn, be expected to lead to an increase in harms such as mental 
anguish, delayed diagnosis for the true cause of any symptoms, and unnecessary treatment 
(e.g., pregnant women and newborns receiving unnecessary antiviral drugs or an unnecessary 
caesarean delivery of the fetus). Further, this would also significantly increase risks due to a 
mathematically expected increase in false negative results, which would, in turn, be expected 
to lead to an increase in harms such as delayed diagnosis that would in turn delay treatment 
of the underlying condition and could lead to unintended spread of the disease (e.g., through 
sexual partners, neonatal transmission during vaginal delivery, and transplanted organs).  
 
Using only Flowchart A and the corresponding text, the decision based solely on the labeling 
change alone would be New 510(k). However, this type of change in labeling is in 
response to a design change. Accordingly, analyses under both Section A and Section D 
apply and the manufacturer is directed to D1. 
D1  Does the change alter the operating principle of the IVD? No. The change in design is 
not one that alters the operating principle of the IVD. 
D3  Does a  risk-based assessment of the changed device identify any new risks or 
significantly modified existing risks? Yes. The manufacturers risk-based assessment 
indicates that a change in the design of the IVD could significantly change the performance 
of the modified device compared to the previously cleared performance claims. 
Decision: New 510(k). 
 
10.  Change:  The manufacturer of an IVD indicated for use with patients who have   
symptoms and signs of a specified set of closely related diseases updates their labeling to 
indicate use for patients with signs and symptoms of another closely related disease not 
within the specified set cleared in its most recent 510(k). 
Relevant questions: 
A1- Is it a change in the indications for usestatement ?  Yes.  The labeling change is a 
change in the  indications for use statement of the device. Proceed to A1.1 -A1.5. 
A1.4  Does the change describe or suggest a new disease, condition, or patient population 
that the device will diagnose, treat, prevent, or mitigate?  Yes.  The labeling change 
describes a  new disease that the device is intended for use in diagnosing that was not 
previously described by the original device.  
Decision: New 510(k). 
 
11. Change: The manufacturer changes the material of the immediate container for an IVD  
reagent such that the shelf-life of the reagent is extended 3 months.  As a result of the change 
in materials to the immediate container for the IVD, the labeling is updated to reflect the 
extended shelf-life. 
Relevant questions: 
A1- Is it a change in the indications for usestatement ?  No.  This is not a change in the 
indications for use statement of the device.  
A3  Is it a change in warnings or precautions? No.  There is no precaution or warning 
pertaining to the shelf-life of the IVD. 
A4  Could the change affect the directions for use? Yes.  The labeling change to update the 
shelf-life could affect the instructions and directions for using the device. Proceed to A1.1 -
A1.5. 
A1.5. Does a  risk-based assessment of the changed device identify any new risks or 
significantly modified existing risks? No. A risk-based assessment was performed, from 
  48  Contains Nonbinding Recommendations 
 
which it was determined that the labeling change does not significantly affect the devices 
risk profile because no new risks or significantly modified existing risks are identified.   
 
Using only Flowchart A and the corresponding text, the decision based solely on the labeling 
change alone would be documentation. However, this type of change in labeling is in 
response to a change in material of the immediate container of the IVD reagent. Accordingly, 
analyses under both Section A and Section D apply and the manufacturer is directed to D1. 
D1  Does the change alter the operating principle of the IVD? No. The change in design is 
not one that alters the operating principle of the IVD. 
D3  Does a risk-based assessment of the changed device identify any new risks or 
significantly modified existing risks?  No.  The manufacturers risk-based assessment  
indicates that the change to the immediate container of the IVD reagent could not 
significantly change performance of the IVD from the previously cleared performance claims 
(for instance, the IVD performance could not be affected by an increase in exposure of the 
reagent to light) and that the modified IVD presents no new or significantly modified existing 
risks.      
D4  Do design verification and/or validation activities produce any unexpected issues of 
safety or effectiveness?  No.  Standard methods and performance criteria that have been 
established for evaluation of the device are used to verify and validate the modification and 
results of the verification and validation do not produce any unexpected issues of safety and 
effectiveness.  In assessing the impact of the modified IVD immediate reagent container on 
the reagent shelf-life, the manufacturer uses the same protocols and criteria described in the 
original 510(k). 
Decision: Documentation. 
   
Design change examples 
 
12. Change: A device is modified to use an internal battery instead of an external AC power 
source. 
Relevant questions:  
B2  Is it a control mechanism, operating principle, or energy type change? Yes. This is an 
energy type change, which typically requires submission of a new 510(k) due to the 
likelihood of such a change to significantly affect safety or effectiveness. 
Decision: New 510(k). 
 
13. Change: The manufacturer changes the packaging for their device, which is provided sterile, 
from one variant of polyethylene to another due to a material supplier change. An analysis 
shows the new polyethylene has no impurities that could affect the devices biocompatibility. 
The manufacturer will use the same package integrity test protocol as the one described in its 
previously cleared 510(k) to support the change. 
Relevant questions:  
B4  Is there a change in packaging or expiration dating? Yes.  
B4.1  Is the same method or protocol, as described in a previously cleared 510(k) used to 
support the change? Yes.  
Decision: Documentation. 
 
  49  Contains Nonbinding Recommendations 
 
14.  
a.  Change: A biliary stent manufacturer adds a new larger stent diameter to a family of 
biliary stents, 2 mm outside of the range of the manufacturers previously cleared stents. 
The stent lengths are unchanged. 
Relevant questions:  
B5  Is it any other change in design (e.g., dimensions, performance specifications, 
wireless communication, components or accessories, or the patient/user interface)? Yes.  
B5.1  Does the change significantly affect the use of the device? The answer to this 
question depends on the original diameter of the stent and the extent of change in the 
diameter.  
B5.2  Does a risk-based assessment of the changed device identify any new risks or 
significantly modified existing risks? Yes. The diameter of a biliary stent is critical to the 
devices safety and effectiveness. A risk-based assessment identifies that the changes to 
the device result in significantly increased existing risks, such as rupture of the duct and 
difficulty reaching the deployment area. Therefore, the greater stent diameter significantly 
affects existing device-related safety risks.  
Decision: New 510(k). 
 
b.  Change: A biliary stent manufacturer adds a new stent diameter to a family of stents, 
within the range of the diameters of the manufacturers previously cleared stents. The 
stent lengths are unchanged. The previously cleared 510(k) for the stents objectively 
demonstrated that the smallest and largest stent diameters (the minimum and maximum 
ends of the diameter size range) were the worst-case scenarios in terms of the safety and 
effectiveness risks. 
Relevant questions: 
B5  Is it any other change in design (e.g., dimensions, performance specifications, 
wireless communication, components or accessories, or the patient/user interface)? Yes.  
B5.1  Does the change significantly affect the use of the device? No. Because the new 
diameter is within the range of the previously cleared stents, the manufacturer determines 
that the change does not significantly affect the use of the device.  
B5.2  Does a risk-based assessment of the changed device identify any new risks or 
significantly modified existing risks? No. Since the new stent diameter is within the range 
of the manufacturers previously cleared stents of the same lengths, and the previously 
cleared 510(k) objectively demonstrated that the smallest and largest diameter sizes 
represented worst-case scenarios in terms of the safety and effectiveness risks for this stent 
length, the new diameter would not significantly affect the risk profile of the device. 
B5.3  Are clinical data necessary to evaluate safety or effectiveness for purposes of 
design validation? No. The manufacturer determines clinical data are not necessary for 
their specific change. They make the initial decision at this point to document the change 
to file. 
B5.4  Do design verification and/or validation activities produce any unexpected issues 
of safety or effectiveness? No. In this example, routine verification and validation 
activities are conducted successfully.  
Decision: Documentation.  
 
c.  Change: A biliary stent manufacturer adds a family of stents made of a different material 
to their existing line of stents, within the range of the length and diameter combinations of 
the manufacturers previously cleared stents.  Through the use of Flowchart C and its 
  50  Contains Nonbinding Recommendations 
 
companion text, the manufacturer determined that there are no biocompatibility concerns 
that would require submission of a new 510(k), but the performance of the stents could be 
affected.  
Relevant questions: 
B5  Is it any other change in design (e.g., dimensions, performance specifications, 
wireless communication, components or accessories, or the patient/user interface)? Yes.  
B5.1  Does the change significantly affect the use of the device? No. Because the new 
stent is within the size range of the previously cleared stents and is deployed using the 
same method, the manufacturer determines that the change does not significantly affect 
the use of the device.  
B5.2  Does a risk-based assessment of the changed device identify any new risks or 
significantly modified existing risks? Yes. Certain performance characteristics of a biliary 
stent are critical to the devices safety and effectiveness. A risk-based assessment 
identifies that the changes to the device material have resulted in significantly increased 
existing risks, such as stent migration or stent fracture. Therefore, the new stent material 
could significantly affect safety and effectiveness.  
Decision: New 510(k). 
 
15. Change: In order to better accommodate connection of a urinary drainage (Foley) catheter to 
a collection apparatus, the length of the catheter is increased by several millimeters. The new 
length is outside of previously cleared lengths for this device. 
Relevant questions:  
B5  Is it any other change in design (e.g., dimensions, performance specifications, wireless 
communication, components or accessories, or the patient/user interface)? Yes.  
B5.1  Does the change significantly affect the use of the device? No. The devices increased 
length would not suggest use of the device for purposes, locations, or populations other than 
those for which it was cleared, so the manufacturer determines that the change does not 
significantly affect the use of the device.  
B5.2  Does a risk-based assessment of the changed device identify any new risks or 
significantly modified existing risks? Extreme length changes may affect the risk profile of a 
urinary drainage catheter (e.g., for biocompatibility), but in general, length changes for this 
device are unlikely to create new risks or significantly affect existing risks by affecting the 
acceptability of those risks. Device specifics will be important in this example, however, in 
this example the change does not significantly affect the devices risk profile.  
B5.3  Are clinical data necessary to evaluate safety or effectiveness for purposes of design 
validation? No. The manufacturer determines clinical data are not necessary for their specific 
change. They make the initial decision at this point to document the change to file. 
B5.4  Do design verification and/or validation activities produce any unexpected issues of 
safety or effectiveness? No. In this example, routine verification and validation activities are 
conducted successfully.  
Decision: Documentation 
 
16.  
a.  Change: The manufacturer of a urinary drainage (Foley) catheter reduces the diameter of 
the catheter to supplement a family of catheters. The new diameter is within the range of 
previously cleared diameters for this device, and the previously cleared 510(k) objectively 
demonstrated the smallest and largest diameters to be worst-case scenarios in terms of the 
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safety and effectiveness risks. The new diameter is within the range of sizes used for 
smaller adult patients for increased comfort. 
Relevant questions:  
B5  Is it any other change in design (e.g., dimensions, performance specifications, 
wireless communication, components or accessories, or the patient/user interface)? Yes.  
B5.1  Does the change significantly affect the use of the device? No. This new catheter 
size would be expected to be used in the same patient population as the previously cleared 
devices.  
B5.2  Does a risk-based assessment of the changed device identify any new risks or 
significantly modified existing risks? No. Since the modified device is within the currently 
cleared range of dimensions and the smallest and largest previously cleared sizes were 
demonstrated to be worst-case scenarios in terms of the safety and effectiveness risks, this 
change would not significantly affect the risk profile of the device.  
B5.3  Are clinical data necessary to evaluate safety or effectiveness for purposes of 
design validation? No. The manufacturer determines clinical data are not necessary for 
their specific change. They make the initial decision at this point to document the change 
to file. 
B5.4  Do design verification and/or validation activities produce any unexpected issues 
of safety or effectiveness? No. In this example, routine verification and validation 
activities are conducted successfully.  
Decision: Documentation. 
 
b.  Change: The manufacturer of a urinary drainage (Foley) catheter reduces the diameter of 
the catheter. The new diameter is outside of the range of previously cleared diameters for 
this device. The new diameter is also smaller than what is typically used or has been 
shown to be functionally appropriate for adult patients, and is of a size that is typically 
used and shown to be functional for pediatric patients. The device is not cleared for 
pediatric use.  
Relevant questions:  
B5  Is it any other change in design (e.g., dimensions, performance specifications, 
wireless communication, components or accessories, or the patient/user interface)? Yes.  
B5.1  Does the change significantly affect the use of the device? Yes. Even if the 
indications for use and labeling are not changed, this new diameter significantly affects 
the use of the device by rendering the device non-functional in an adult and changing it 
from adult use to pediatric use. This could significantly affect the safety and effectiveness 
of the device.  
Decision: New 510(k).  
 
17. Change: The manufacturer of a biliary stent increases the thickness of the nitinol wire in the 
stent from that used in the previously cleared device to reduce potential for stent fractures. 
Relevant questions:  
B5  Is it any other change in design (e.g., dimensions, performance specifications, wireless 
communication, components or accessories, or the patient/user interface)? Yes.  
B5.1  Does the change significantly affect the use of the device? No. The thickness of the 
nitinol wire of the device would not significantly affect its use.  
B5.2  Does a risk-based assessment of the changed device identify any new risks or 
significantly modified existing risks? Yes. The thickness of the wire is critical to the 
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performance of the stent, so an increase could significantly affect the risk profile and the 
safety or effectiveness of the device.  
Decision: New 510(k). 
 
18. Change: The manufacturer adds a foot switch to control an endoscopic electrosurgical unit. 
The previously cleared device did not have a foot switch.  
Relevant questions:  
B5  Is it any other change in design (e.g., dimensions, performance specifications, wireless 
communication, components or accessories, or the patient/user interface)? Yes. This is a 
change to the devices user interface.  
B5.1  Does the change significantly affect the use of the device? No. The addition of a foot 
switch would not significantly affect the use of the device.  
B5.2  Does a risk-based assessment of the changed device identify any new risks or 
significantly modified existing risks? Yes. The risk analysis identified human factors and 
compatibility risks for the footswitch that did not exist for the previously cleared device. At 
least some of these risks were associated with the potential for unintentional activation of 
energy, which could result in a serious harm. 
Decision: New 510(k).  
 
19. Change: The grip portion of a diagnostic ultrasound transducer is redesigned to improve user 
comfort.  
Relevant questions:  
B5  Is it any other change in design (e.g., dimensions, performance specifications, wireless 
communication, components or accessories, or the patient/user interface)? Yes. This is a 
change to the devices user interface.  
B5.1  Does the change significantly affect the use of the device? No. In this example, the 
redesign of the grip would not significantly affect the use of the device.  
B5.2  Does a risk-based assessment of the changed device identify any new risks or 
significantly modified existing risks? No.  While the change to the transducer grip of the 
device could affect certain risks, such as the user potentially mishandling the device, the 
severity of these risks for this device is low.   
B5.3  Are clinical data necessary to evaluate safety or effectiveness for purposes of design 
validation? No. The manufacturer determines clinical data are not necessary for their specific 
change. They make the initial decision at this point to document the change to file. 
B5.4  Do design verification and/or validation activities produce any unexpected issues of 
safety or effectiveness? No. In this example, routine verification and validation activities are 
conducted successfully.  
Decision: Documentation 
   
20. Change: A particular device heats fluid in order to achieve its intended effect. The most 
recently cleared device had a low-power heater and the maximum fluid temperature was low 
enough that the severity of the worst-case thermal injury was low to moderate. In the risk 
analysis for the design of the most recently cleared device, the risk score/rating for thermal 
injury was therefore in a range identified in the risk management document as tolerable but 
undesirable, before risk control measures were added. After receiving input from customers 
that the fluid heating process was too slow, the device was changed to use a higher-powered 
heater, which increased the maximum possible fluid temperature. 
Relevant questions:  
  53  Contains Nonbinding Recommendations 
 
B5  Is it any other change in design (e.g., dimensions, performance specifications, wireless 
communication, components or accessories, or the patient/user interface)? Yes.  
B5.1  Does the change significantly affect the use of the device? No. This change would not 
significantly affect the use of the device.  
B5.2  Does a  risk-based assessment of the changed device identify any new risks or 
significantly modified existing risks? Yes. When the manufacturer performed a risk analysis 
on the new design, the severity of potential thermal injury increased and the risk of thermal 
injury became unacceptable, before application of additional risk control measures. This 
risk analysis showed that the design change had a potentially significant impact on safety by 
changing the pre-mitigation acceptability of the risk. Therefore, submission of a new 510(k) 
is likely required. This same conclusion holds whether or not the manufacturer needed to add 
new risk control measures to bring the final risk into the acceptable range. 
Decision: New 510(k). 
 
21. Change: A portable medical device receives its power through a removable, rechargeable 
battery. The device manufacturer provides a battery charging station for the battery. The 
proposed change is to the design of the battery charging station. There is no change in the 
battery itself, only the means by which it is charged. The device is not life-sustaining or life-
supporting.   
Relevant questions:  
B5  Is it any other change in design (e.g., dimensions, performance specifications, wireless 
communication, components or accessories, or the patient/user interface)? Yes.  
B5.1  Does the change significantly affect the use of the device? No. This change would not 
significantly affect the use of the device.  
B5.2  Does a risk-based assessment of the changed device identify any new risks or 
significantly modified existing risks? No. Because the device can operate without the battery 
charging station, the battery itself is easily replaced, and the device is not life-sustaining or 
life-supporting, the severities of risks surrounding the battery charging station are low. 
Unless any new risks are associated with the change or the likelihood of risks associated with 
the battery charging station are significantly increased, this change would not significantly 
affect the devices risk profile.  
B5.3  Are clinical data necessary to evaluate safety or effectiveness for purposes of design 
validation? No. The manufacturer determines clinical data are not necessary for their specific 
change. They make the initial decision at this point to document the change to file. 
B5.4  Do design verification and/or validation activities produce any unexpected issues of 
safety or effectiveness? No. In this example, routine verification and validation activities are 
conducted successfully.  
Decision: Documentation. 
 
22. Change: A manufacturer changes the surface of a titanium dental implant from an untreated 
surface to one that is acid-etched. The surface is in direct contact with the patients bone. The 
manufacturer has not previously used the acid-etching process, and a cleaning process is 
necessary to remove acid from the device surface. 
Relevant questions:  
B5  Is it any other change in design (e.g., dimensions, performance specifications, wireless 
communication, components or accessories, or the patient/user interface)? Yes. This is a 
design change because the implants surface properties are changed. 
  54  Contains Nonbinding Recommendations 
 
B5.1  Does the change significantly affect the use of the device? No. This change would not 
significantly affect the use of the device.  
B5.2  Does a risk-based assessment of the changed device identify any new risks or 
significantly modified existing risks? Yes. Surface changes can significantly affect the safety 
and effectiveness of an implant by, for example, significantly modifying the likelihood of 
implant instability. This can be considered a safety risk, and since the interaction between the 
implant and the in vivo environment is critical to the stability of the implant and therefore its 
effectiveness, this could also be considered a significant impact on the devices effectiveness.  
Decision: New 510(k). 
Note: This change could also be evaluated as a materials change. See Example 26. 
 
Materials change examples 
 
23.  
a.  Change: The manufacturer of a catheter changes the material of its catheter from polymer 
A to polymer B. The manufacturer has not previously used polymer B in any of its 
devices, but knows of another catheter on the market from a different manufacturer with 
the same cleared indications for use that uses polymer B. 
Relevant questions:  
C2  Is this a change in material type, material formulation, chemical composition, or the 
materials processing? Yes. 
C3  Will the changed material directly or indirectly contact body tissues or fluids? Yes. 
C4  Does a risk assessment identify any new or increased biocompatibility risks? Yes. 
Polymer B has a different chemical formulation than polymer A. The risk assessment 
identifies that the new formulation presents a new biocompatibility risk.  
C4.1  Has the manufacturer used the same material in a similar legally marketed device? 
No, the manufacturer has not used the same material before. Even though there is another 
catheter from a different manufacturer on the market made of polymer B, the other device 
may have a different formulation or different manufacturing or finishing processes that 
could affect the biocompatibility or performance.  
Decision: New 510(k). 
 
b.  Change: The manufacturer of a catheter changes the material of its catheter from polymer 
A to polymer B. The manufacturer has used the same polymer B, with the same 
formulation and processing, in another cleared model of catheter with the same type and 
duration of contact and the same performance specifications. 
Relevant questions:  
C2  Is this a change in material type, material formulation, chemical composition, or the 
materials processing? Yes. 
C3  Will the changed material directly or indirectly contact body tissues or fluids? Yes.  
C4  Does a risk assessment identify any new or increased biocompatibility risks? Yes. 
Polymer B has a different chemical formulation than polymer A. The risk assessment 
identifies that the new formulation presents a new biocompatibility risk.  
C4.1  Has the manufacturer used the same material in a similar legally marketed device? 
Yes. The manufacturer has used the same polymer B, with the same formulation and 
processing, in another model of catheter with the same type and duration of contact. This 
addresses the possible biocompatibility concerns identified in the risk assessment covered 
in C4.  
  55  Contains Nonbinding Recommendations 
 
C5  Could the change affect the devices performance specifications? No. The 
manufacturer has used the same polymer B in another model of catheter with the same 
performance specifications. 
Decision: Documentation. 
 
c.  Change: A manufacturer changes the material of its catheter, intended for prolonged 
blood contact, from polymer A to polymer B. The manufacturer has used the same 
polymer B in another cleared device; however, this other device was indicated for a use 
with limited duration and skin contact only.  
Relevant questions:  
C2  Is this a change in material type, material formulation, chemical composition, or the 
materials processing? Yes. 
C3  Will the changed material directly or indirectly contact body tissues or fluids? Yes.  
C4  Does a risk assessment identify any new or increased biocompatibility risks? Yes. 
Polymer B has a different chemical formulation than polymer A. The risk assessment 
identifies that the new formulation presents a new biocompatibility risk.  
C4.1  Has the manufacturer used the same material in a similar legally marketed device? 
No. The manufacturer has used the same polymer B, with the same formulation and 
processing, in another device, however, the other device was subject to a less risky type 
and duration of contact. The modified device will be subjected to additional 
biocompatibility risks compared to the other polymer B device, and therefore the use of 
polymer B in the other device does not address the biocompatibility concerns identified in 
the risk assessment covered in C4.  
Decision: New 510(k). 
 
d.  Change: A manufacturer changes the material of a device intended for limited skin 
contact from polymer A to polymer B. The manufacturer has used the same polymer B in 
another cleared device that was intended for prolonged blood contact and had the same 
performance specifications.  
Relevant questions:  
C2  Is this a change in material type, material formulation, chemical composition, or the 
materials processing? Yes. 
C3  Will the changed material directly or indirectly contact body tissues or fluids? Yes.  
C4  Does a risk assessment identify any new or increased biocompatibility risks? Yes. 
Polymer B has a different chemical formulation than polymer A. The risk assessment 
identifies that the new formulation presents a new biocompatibility risk.  
C4.1  Has the manufacturer used the same material in a similar legally marketed device? 
Yes. The manufacturer has used the same polymer B, with the same formulation and 
processing, in another cleared device with a riskier type and duration of contact, and the 
size and geometry of the new device would not affect curing of the polymer or result in 
more material in the new device. The riskier use of the material in the other cleared device 
shows that the polymer B can be expected to be biocompatible in its new application.  
C5  Could the change affect the devices performance specifications? No. The 
manufacturer used the same polymer B in another model of catheter with the same 
performance specifications. 
Decision: Documentation. 
 
  56  Contains Nonbinding Recommendations 
 
24. Change: A manufacturer changes the material of a catheter from material A to material B, 
which is used in another of the manufacturers cleared catheters. Material A is molded, and 
material B, used in the other catheter, is extruded.  
Relevant questions:  
C2  Is this a change in material type, material formulation, chemical composition, or the 
materials processing? Yes. 
C3  Will the changed material directly or indirectly contact body tissues or fluids? Yes.  
C4  Does a risk assessment identify any new or increased biocompatibility risks? Yes. The 
new material B has a different chemical formulation than the original material A. The risk 
assessment identifies that the new formulation presents a new biocompatibility risk.  
C4.1  Has the manufacturer used the same material in a similar legally marketed device? 
No. The manufacturer has used the same material in another cleared catheter, but the 
processing of the material is different, which may affect biocompatibility. The use of 
material B in the other catheter does not address the biocompatibility concerns identified in 
the risk assessment covered in C4.  
Decision: New 510(k). 
 
25.  
a.  Change: A manufacturer decides to change the material of a catheter from material A to 
material B. Material B is used in another of the manufacturers own cleared catheters with 
similar type and duration of patient contact. Material A is sterilized by gamma irradiation, 
and material B is sterilized by ethylene oxide.  
Relevant questions:  
C2  Is this a change in material type, material formulation, chemical composition, or the 
materials processing? Yes. 
C3  Will the changed material directly or indirectly contact body tissues or fluids? Yes.  
C4  Does a risk assessment identify any new or increased biocompatibility risks? Yes. 
Material B has a different chemical formulation than material A. The risk assessment 
identifies that the new formulation presents a new biocompatibility risk.  
C4.1  Has the manufacturer used the same material in a similar legally marketed device? 
No. The manufacturer has used material B in another cleared catheter, but the processing 
of the material is different, which may affect biocompatibility. The use of material B in 
the other catheter does not address the biocompatibility concerns identified in the risk 
assessment covered in C4. 
Decision: New 510(k). 
 
b.  Change: A manufacturer decides to change the material of a catheter from material A to 
material B. Material B is used in another of the manufacturers own cleared catheters, 
which has the same type and duration of patient contact, as well as the same performance 
specifications. Both materials A and B are molded and are sterilized by ethylene oxide.  
Relevant questions:  
C2  Is this a change in material type, material formulation, chemical composition, or the 
materials processing? Yes. 
C3  Will the changed material directly or indirectly contact body tissues or fluids? Yes.  
C4  Does a risk assessment identify any new or increased biocompatibility risks? Yes. 
Material B has a different chemical formulation than material A.  The risk assessment 
identifies that the new formulation presents a new biocompatibility risk.  
  57  Contains Nonbinding Recommendations 
 
C4.1  Has the manufacturer used the same material in a similar legally marketed device? 
Yes. The manufacturer has used material B in another cleared catheter, and the processing 
is the same. In addition, the size and geometry of the new device would not affect curing 
of the polymer or result in more material in the new device, and there are no differences in 
how material B is joined to other components of the catheter (e.g., type of adhesive, or 
conditions of heat welding) that could result in different interactive chemistries. 
C5  Could the change affect the devices performance specifications? No. The 
manufacturer has used the same material B in another model of catheter with the same 
performance specifications, which is processed in the same manner. 
Decision: Documentation. 
 
c.  Change: A manufacturer decides to change the material of a catheter from material A to 
material B. Material B is used in another of the manufacturers own cleared catheters, 
which has the same type and duration of patient contact, but different performance 
specifications. Both materials A and B are molded and are sterilized by ethylene oxide.  
Relevant questions:  
C2  Is this a change in material type, material formulation, chemical composition, or the 
materials processing? Yes. 
C3  Will the changed material directly or indirectly contact body tissues or fluids? Yes.  
C4  Does a risk assessment identify any new or increased biocompatibility risks? Yes. 
Material B has a different chemical formulation. The risk assessment identifies that the 
new formulation presents a new biocompatibility risk.  
C4.1  Has the manufacturer used the same material in a similar legally marketed device? 
Yes. The manufacturer has used material B in another cleared catheter, and the processing 
is the same. In addition, the size and geometry of the new device would not affect curing 
of the polymer or result in more material in the new device, and there are no differences in 
how material B is joined to other components of the catheter (e.g., type of adhesive, or 
conditions of heat welding) that could result in different interactive chemistries. 
C5  Could the change affect the devices performance specifications? Yes. The 
manufacturer used the same material B in another model of catheter; however, the 
performance specifications were different. The new material could potentially affect the 
devices performance, so the manufacturer is directed to B5. 
B5  Is it any other change in design (e.g., dimensions, performance specifications, 
wireless communication, components or accessories, or the patient/user interface)? Yes.  
B5.1  Does the change significantly affect the use of the device? No. The new material 
does not significantly affect the use of this device.  
B5.2  Does a risk assessment of the changed device identify any new risks or 
significantly modified existing risks?  
If the new material has significantly different physical properties than the material in the 
previously cleared device, the risk profile of the device could be significantly affected in 
terms of risk score, risk acceptability, etc., and submission of a new 510(k) may be 
required. However, for the purposes of this example, the new material is not expected to 
have significantly different physical properties, so a 510(k) would not be required. 
B5.3  Are clinical data necessary to evaluate safety or effectiveness for purposes of 
design validation? No. The manufacturer determines clinical data are not necessary for 
their specific change. They make the initial decision at this point to document the change 
to file. 
  58  Contains Nonbinding Recommendations 
 
B5.4  Do design verification and/or validation activities produce any unexpected issues 
of safety or effectiveness? No. In this example, routine verification and validation 
activities are conducted successfully.  
Decision: Documentation. 
 
26. Change: The manufacturer of a dental implant changes the surface of a titanium dental 
implant from an untreated surface to one that is acid-etched. The surface is in direct contact 
with the patients bone. The manufacturer has not previously used the acid-etching process, 
and a cleaning process is necessary to remove acid from the device surface. 
Relevant questions:  
C2  Is this a change in material type, material formulation, chemical composition, or the 
materials processing? Yes. The material processing of the device has been changed. 
C3  Will the changed material directly or indirectly contact body tissues or fluids? Yes.  
C4  Does a risk assessment identify any new or increased biocompatibility risks? Yes. The 
risk analysis identified that the residue from the acid-etching process is a new chemical on 
the device and introduces a new biocompatibility risk, which may affect the biocompatibility 
of the device.  
C4.1  Has the manufacturer used the same material in a similar legally marketed device? 
No. The manufacturer has not previously used the acid-etching process. 
Decision: New 510(k). 
Note: This change could also be evaluated as a design change. See Example 22. 
 
27. Change: The manufacturer of an implantable device applies a temporary tape to the device 
for identification of manufacturing steps. The tape has been demonstrated in peer-reviewed 
literature to not leave adhesive on the surface of the device. 
Relevant questions:  
C2  Is this a change in material type, material formulation, chemical composition, or the 
materials processing? Yes. The material processing of the device has been changed. 
C3  Will the changed material directly or indirectly contact body tissues or fluids? Yes.  
C4  Does a risk assessment identify any new or increased biocompatibility risks? No. A risk 
assessment was performed and identified that the tape has been previously demonstrated to 
not leave adhesive on the surface of the device. 
C5  Could the change affect the devices performance specifications? No. The tape is 
temporary for manufacturing purposes, and is removed before clinical use of the device. 
Since the tape has been demonstrated to not leave adhesive on the surface of the device, it 
would not be expected to affect the devices performance.  
Decision: Documentation. 
 
IVD technology, engineering, performance, and materials change examples 
 
28. Change: The manufacturer of a molecular assay received clearance for a quantitative real-
time PCR assay that included extraction kit reagents. The kit is therefore labeled for use with 
a set of extraction reagents. The manufacturer makes changes to the column substrate for the 
extraction method.  
Relevant questions: 
D1 Does the change alter the operating principle of the IVD? No. The change in column 
substrate would not alter the operating principle. 
  59  Contains Nonbinding Recommendations 
 
D3  Does a  risk-based assessment of the changed device identify any new risks or 
significantly modified existing risks? Yes. The manufacturers  risk-based assessment 
indicates that changing the column substrate could significantly change the analytical and 
clinical performance of the modified test compared to the previously cleared version of this 
device indicating new or significantly modified existing risks. 
Decision: New 510(k).  
 
29. Change: The manufacturer of a bilirubin test system makes a change to the reagent, 
modifying from a liquid form to a lyophilized form of the reagent. The formulation and 
concentration of the reagent remain unchanged.  
Relevant questions: 
D1  Does the change alter the operating principle of the IVD? No. This change in reagent 
would not alter the operating principle. 
D3  Does a  risk-based assessment of the changed device identify any new risks or 
significantly modified existing risks? No. The manufacturers  risk-based assessment 
indicates that the performance of the modified IVD could not significantly change from the 
previously cleared performance claims and that the modified IVD presents no new or 
significantly modified existing risks, since the change in reagent state does not change the 
concentration or formulation of the reagent.  
D4  Do design verification and/or validation activities produce any unexpected issues of 
safety or effectiveness? No. Standard methods and performance criteria that have been 
established for evaluation of the device are used to verify and validate the modification and 
results of the verification and validation do not indicate new issues of safety or effectiveness. 
In assessing the impact of the new reagent formulation, the manufacturer uses the same 
protocols and criteria described in the original 510(k). 
Decision: Documentation.  
 
30. Change: The manufacturer makes a change in the traceability of an IVD calibrator of a test 
system. 
Relevant questions: 
D1- Does the change alter the operating principle of the IVD? No. A change in the 
traceability of an IVD calibrator would not alter the operating principle of the test system. 
D3  Does a  risk-based assessment of the changed device identify any new risks or 
significantly modified existing risks? Yes. The manufacturers  risk-based assessment 
indicates that a change in the traceable reference standard for the assay calibrators could 
significantly change the clinical performance of the modified IVD test system from the 
previously cleared performance claims indicating new or significantly modified existing 
risks. 
Decision: New 510(k).  
 
31. Change: A manufacturer makes a change in the buffer solution of an IVD as a result of a 
change in vendor. The replacement buffer solution is equivalent to the previous buffer 
solution. 
Relevant questions: 
D1  Does the change alter the operating principle of the IVD? No. The change in buffer 
solution would not alter the operating principle of the IVD. 
D3  Does a  risk-based assessment of the changed device identify any new risks or 
significantly existing modified risks? No. The manufacturers  risk-based assessment 
  60  Contains Nonbinding Recommendations 
 
indicates that the new buffer solution is equivalent to the previous buffer solution and 
indicates that the performance of the modified IVD could not significantly change from the 
previously cleared performance claims of the modified IVD and that the modified IVD does 
not present new or significantly modified existing risks. 
D4  Do design verification and/or validation activities produce any unexpected issues of 
safety or effectiveness? No. Standard methods and performance criteria that have been 
established for evaluation of the device are used to verify and validate the change and results 
of the verification and validation studies do not indicate new issues of safety or effectiveness. 
Decision: Documentation.  
 
32. Change: An IVD manufacturer makes a material change to their reagent and the 
manufacturers  risk-based assessment indicates that the change in material could result in 
significantly changing the analytical performance from the previously cleared performance 
claims due to a potential change in the cut-off. 
Relevant Questions: 
D1  Does the change alter the operating principle of the IVD? No. The change in material is 
not one that alters the operating principle of the IVD. 
D3  Does a  risk-based assessment of the changed device identify any new risks or 
significantly modified existing risks? Yes. The manufacturers  risk-based assessment 
indicates that a change in the material of the reagent would result in a change in analytical 
cut-off that could significantly change the performance of the modified test compared to the 
previously cleared performance claims. In particular, this change in cut-off would be a 
change that is clinically significant in terms of clinical decision making since patients with 
samples around the cut-off could now receive a different diagnosis and treatment. 
Decision: New 510(k). 
 
 
 
        
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Appendix B: Documentation 
 
Whenever a manufacturer changes its device, it must take certain actions to comply with the QS 
regulation, 21 CFR Part 820, unless a regulatory exemption exists. The QS regulation requires 
that design changes and production and process changes be documented prior to implementation. 
21 CFR 820.30(i) and 820.70(b). If a manufacturer determines that the device change(s) does not 
require submission of a new 510(k), it should document the decision-making process and the 
basis for that conclusion. The documentation should be prepared in a way that an FDA 
investigator or other third party can understand what the change is and the rationale underlying 
the manufacturers conclusion that submission of a new 510(k) is not required.  
 
The QS regulation also requires that manufacturers establish and maintain procedures to control 
all documents that are required by the QS regulation. 21 CFR 820.40. Manufacturers may 
specify the type and level of documentation needed to evaluate changes that may or may not 
require submission of a new 510(k), as well as the methods of review and approval of such 
decisions. Manufacturers may also develop standard operating procedures (SOPs) and other 
documents that allow for different levels of documentation, depending on the nature of the 
change that must be evaluated.    
 
FDA notes that only highlighting the flowcharts in this guidance document, or simply answering 
yes or no to each question without further details or justification, is not sufficient 
documentation. The manufacturer should provide an appropriately robust justification of a 
decision that submission of a new 510(k) is not required.  
 
Documentation should include the following: 
 
  Product name 
  Date of change assessment 
  Description of the device 
  Description of the change(s)  
  Reason why the change(s) is being made 
  Applicable regulatory history, including the 510(k) number of the most recently cleared 
version of the device 
  Comparison of the modified device to the most recently cleared version of the device 
(consider including a table) 
  Applicable elements of this guidance, including the applicable questions from the body of 
the document 
  Analysis and assessment of the elements on this list and a conclusion of whether 
submission of a new 510(k) is required 
  Reference to related documents, particularly those that support the decision whether or 
not submission of a new 510(k) is required (e.g., risk analysis) 
  Signature(s) 
 
It may be helpful to document the assessment of each change in a way that corresponds to the 
decision-making framework discussed in this guidance document. If a manufacturer decides to 
do so, the documentation should list each relevant question, the answer to each of those 
  62  Contains Nonbinding Recommendations 
 
questions, and the information and analysis that support the answer. The justification may be in 
the form of a detailed response, a relevant attachment, or other robust method that provides the 
rationale. Risk analyses will be particularly helpful in supporting the manufacturers assessment. 
As a reminder, when making the decision on whether to submit a new 510(k), the manufacturer's 
basis for comparison of any changed device should be the original device, i.e., the device 
described in their most recently cleared 510(k) for the device, their legally marketed 
preamendments device, or their device that was granted marketing authorization via the De Novo 
classification process.  
 
Changes to a medical device or its processes vary in complexity. Some types of changes are 
straightforward and will generally result in a decision that submission of a new 510(k) is not 
required. To that end, a manufacturer may establish a documentation process that accommodates 
different levels of documentation depending on the complexity of the change. Simple changes 
would have simple documentation and may not necessarily go through each question in detail; 
more complex changes should have more detailed documentation. Examples of types of changes 
that can typically be documented with simple documentation include: 
 
  Change of company labels to update to new company name, e.g., following acquisitions 
or address changes 
  Labeling layout changes where content is not changed, for instance, due to a corporate 
rebranding initiative 
  Addition of a unique device identifier (UDI) to labeling  
  Raw material supplier changes that only modify the reference number or brand name of 
raw materials and do not change the raw material itself 
 
It is important that the manufacturer include, as part of the documentation process, a means to re-
evaluate the change should initial assumptions subsequently not be met. In those situations, an 
update to the existing assessment, or a new assessment, should be documented. 
 
The examples below are provided to illustrate one possible approach to documentation; other 
approaches may also be appropriate. Manufacturers are encouraged to use an approach that 
works for their specific purposes, taking into account the considerations discussed above. The 
first example below is a simple change that does not necessitate detailed analysis. The second 
example is a more complex change for which additional analysis and reference to supporting 
documentation are warranted. Note that these are generalized examples to demonstrate 
documentation principles and do not necessarily account for every possible detail, risk, or 
consideration.  
   
  63  Contains Nonbinding Recommendations 
 
Regulatory Change Assessment 
(Example 1) 
 
Product Name: Device ABC 
 
Date of Assessment: 10/25/16 
 
Device Description: ABC is intended to treat headaches. Device consists of plates and screws. 
See design specifications at Document 15-XXXX. 
 
Description of Change(s): ABC was recently acquired from Corporation X. Labeling will be 
updated to be consistent with our standard labeling. Specifically, the company logo, name, 
contact information, and labeling layout will be updated. 
 
Reason for Change(s): To make ABCs labeling consistent with our standard labeling. 
 
Applicable Regulatory History (including 510(k) #s and comparison of modified device to 
most recently cleared version):  
Device originally cleared in K10xxxx, cleared with updated plates in K12xxxx, cleared with 
updated screws in K14xxxx. Only changes between K14xxxx version and modified device are 
company logo, name, contact information, and labeling layout. 
 
Completed Checklist Attached: 
Yes     
No (include rationale if selected) 
The changes proposed are to the labeling, but do not change the content of the labeling 
aside from company name and contact information, which does not change the 
indications for use statement, is not a change to the contraindications or warnings, and 
could not affect the directions for use. Therefore the labeling change could not 
significantly affect safety or effectiveness. FDAs Deciding When to Submit a 510(k) for 
a Change to an Existing Device guidance states at A4 that Many labeling changes result 
from attempts to clarify labeling. Manufacturers should consider whether the change is 
intended to or could affect how the device is used in practice. Because this change does 
not change the indications for usestatement , is not a change to the contraindications or 
warnings, and could not affect how the device is used, submission of a new 510(k) is not 
required.  
 
Recommended Regulatory Action:  
Submit 510(k)    
Letter to file 
 
Supporting Documents: 
  Design Specifications: 15-XXXX 
  Risk-Based Assessment: N/A 
 
Signatures: xxxx   
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Regulatory Change Assessment 
(Example 2) 
 
Product Name: Cardiopulmonary Bypass (CPB) Cannula  
 
Date of Assessment: 1/17/20 
 
Device Description: Cardiopulmonary Bypass Cannula is intended to cannulate the vessels, 
perfuse the coronary arteries, and interconnect the catheters and cannulas with an oxygenator. 
The current design uses a 304 stainless steel guidewire with a coating composed of material X; 
the tips of the guidewire are partially uncoated. See design specifications at Document 18-
XXXX. 
 
Description of Change(s): The change is to remove the coating from the guidewire. Previously, 
the tips were uncoated, but now the entire guidewire will be uncoated. This change applies to 
models 1 and 2. These models were originally cleared in K10xxxx. The uncoated guidewire will 
continue to be made of 304 stainless steel. The replacement and current guidewires are identical 
in design, performance, and materials, with the exception of the coating.  
 
The current guidewire was chosen originally because it was from our current guidewire supplier 
(which supplies guidewires for other cannulas we manufacture), met the dimensional 
specifications, and was cost-effective. The coating on the original cannula was not a specific 
design feature that was required for the design, although it may contribute to longevity of the 
guidewire and enhances lubricity.  
 
The proposed change will remove the coating, which will expose the stainless steel along the 
entire length of the guidewire. This change does not introduce any new blood-contacting 
materials as the current guidewire tip is uncoated, and was tested for biocompatibility in the most 
recently cleared 510(k). We previously marketed a cannula with an uncoated 304 stainless steel 
guidewire, cleared in K08xxxx (see DHF XXXX). 
 
Removing the coating from the guidewire will also result in a small change to the diameter of the 
guidewire due to the lack of the coating. 
 
We have confirmed that the Type 304 material used for the uncoated guidewire is from the same 
supplier as we have used previously (see Communication 11/7/19-XXXX from supplier), and 
there have been no issues with rusting (which could introduce embolic particles during device 
use). In addition, we have confirmed that there are no manufacturing residuals on the surface of 
the Type 304 stainless steel guidewire that would be available to the patient now that the 
guidewire is no longer coated (see Memo 19-XXXX). 
 
Reason for Change(s): The coated guidewire has been discontinued by the supplier. 
 
Applicable Regulatory History (including 510(k) #s and comparison of modified device to 
most recently cleared version):  
CPB Cannula was originally cleared in K10xxxx. The labeling layout was changed in 2012 (see 
Regulatory Change Assessment 12-XXXX). The differences between the K10xxxx version and 
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the modified device therefore include an updated labeling layout and the removal of the 
guidewire coating. 
 
Completed Checklist Attached: 
Yes     
No (include rationale if selected) 
 
Recommended Regulatory Action:  
Submit 510(k)    
Letter to file 
 
Supporting Documents: 
  Design Specifications: 18-XXXX 
  Risk-Based Assessment: 20-XXXX 
  Verification and Validation Summary: 20-YYYY 
 
Signatures: xxxx 
 
   
  66  Contains Nonbinding Recommendations 
 
Main Flowchart Questions 
Change made with intent to significantly improve the safety or effectiveness of the device? 
Yes 
No The change was made because the supplier discontinued the coating.  
 
Labeling change? 
Yes 
No   Labeling changes section N/A  
 
Technology, engineering, or performance change? 
Yes Coating will be removed which will change the design of the device and slightly decrease 
the diameter of the guidewire. This change will be evaluated to determine if this could 
affect the performance of the device.  
No  
 
Materials change? 
Yes Removing the coating material from the device. This change will be evaluated to 
determine if processing could affect the biocompatibility of the device. 
No  
 
   
  67  Contains Nonbinding Recommendations 
 
Labeling Questions  
 
A1  Is it a change in the indications for use statement? 
Yes Go to A1.1 
No   Go to A2 
 
A1.1 -- Is it a change from a device labeled for single use only to a device labeled as reusable? 
Yes Submit 510(k) 
No   Go to A1.2 
 
A1.2 -- Is it a change from prescription (Rx) to over the counter (OTC) use? 
Yes Submit 510(k) 
No   Go to A1.3 
 
A1.3 -- Is it a change to the device name or a change solely to improve readability or clarity? 
Yes Document to file 
No   Go to A1.4 
 
A1.4 -- Does the change describe a new disease, condition, or patient population that the device 
is intended for use in diagnosing, treating, preventing, curing or mitigating? 
Yes Submit 510(k) 
No   Go to A1.5 
 
A1.5  Does a risk-based assessment of the changed device identify any new risks or significantly 
modified existing risks? 
Yes Submit 510(k) 
No   Document to file 
 
A2  Does the change add or delete a contraindication? 
Yes Submit 510(k) (If adding a contraindication, submit CBE 510(k)) 
No   Go to A3 
 
A3  Is it a change in warnings or precautions? 
Yes Go to A1.1 
No   Go to A4 
 
A4  Could the change affect the directions for use of the device? 
Yes Go to A1.1 
No   Document to file 
 
 
 
 
  68  Contains Nonbinding Recommendations 
 
Technology, Engineering, and Performance Changes 
 
B1  Is the device an in vitro diagnostic device? 
Yes Go to D1 (Technology, Engineering, Performance and Materials Changes for IVDs) 
No   Go to B2 
 
B2  Is it a control mechanism, operating principle, or energy type change? 
Yes Submit 510(k) 
No   Go to B3 
 
B3  Is it a change in sterilization, cleaning, or disinfection? 
Yes Go to B3.1 
No   Go to B4 
 
B3.1  Is it a change to an established category B or novel sterilization method, does the 
change lower the sterility assurance level, or is it a change to how the device is provided? 
Yes Submit 510(k) 
No   Go to B3.2 
 
B3.2  Could the change significantly affect the performance or biocompatibility of the device? 
Yes Submit 510(k) 
No   Document to file 
 
B4  Is there a change in packaging or expiration dating? 
Yes Go to B4.1 
No   Go to B5 
 
B4.1  Is the same method or protocol, as described in a previously cleared 510(k), used to 
support the change? 
Yes Document to file 
No   Submit 510(k) 
 
B5  Is it any other change in design (e.g., dimensions, performance specifications, wireless 
communication, components or accessories, or the patient/user interface)? 
Yes Go to B5.1 
There are two changes, one to the coating of the guidewire, one to the dimensions of the 
guidewire. Each will be considered below. 
 
No   Document to file 
 
B5.1  Does the change significantly affect the use of the device? 
Yes Submit 510(k) 
No   Go to B5.2 
  The lack of the coating and the small dimensional change are not expected to affect the 
use of the device.  
 
  69  Contains Nonbinding Recommendations 
 
B5.2  Does a risk-based assessment of the changed device identify any new risks or significantly 
modified existing risks? 
Yes Submit 510(k) 
No   Go to B5.3 
  See full risk-based assessment in Document 20-XXXX.  
  Dimensional change: it is unlikely that the small reduction in guidewire diameter could 
affect safety or effectiveness. Decreasing the diameter of the guidewire would not be 
expected to hinder the interaction between the guidewire, introducer, and cannula, and it 
would not be expected to reduce the strength of the guidewire, as the coating did not 
improve the strength of the wire and the wire itself remains unchanged. 
   
  Removal of the coating: it is unlikely, but possible, that the removal of the coating could 
impact the way the guidewire interacts with the introducer and cannula. We have 
previously obtained clearance for cannulas with uncoated stainless steel guidewires, 
however, which did not have markedly different performance (see DHF XXXX). This 
suggests that the significance of this change is low.  
 
  We have determined there are no new or significantly modified risks due to this change.  
 
B5.3  Are clinical data necessary to evaluate safety or effectiveness for purposes of design 
validation? 
Yes Submit 510(k) 
No   Go to B5.4 
 
B5.4  Do design verification and/or validation activities produce any unexpected issues of 
safety or effectiveness? 
Yes Submit 510(k) 
No   Document to file 
  See verification and validation testing report in Document 20-YYYY, conducted after the  
risk-based assessment. Functional testing evaluated the interaction between the 
guidewire, introducer, and cannula to verify that the uncoated guidewire did not affect 
device performance. There were no unexpected issues of safety or effectiveness.  
 
 
   
  70  Contains Nonbinding Recommendations 
 
Materials Changes  
 
C1  Is the device an in vitro diagnostic product (IVD)? 
Yes Go to D1 (Technology, Engineering, Performance and Materials Changes for IVDs) 
No   Go to C2 
 
C2  Is this a change in material type, material formulation, chemical composition, or the 
materials processing? 
Yes Go to C3 
The coating material X will be removed.  
 
No   Document to file 
 
C3  Will the changed material directly or indirectly contact body tissues or fluids? 
Yes Go to C4 
No   Go to C5 
 
C4  Does a risk assessment identify any new or increased biocompatibility concerns? 
Yes Go to C4.1  
No   Go to C5 
  The tips of the current guidewire are uncoated, so there is no new material here to create 
new biocompatibility concerns. The removal of the coating material is not expected to 
have a biocompatibility impact as the processing is unlikely to leave residuals that were 
previously masked by the coating. In addition, we have previously marketed cleared 
cannulas with uncoated stainless steel guidewires, which passed biocompatibility testing 
(see DHF XXXX). The source of the stainless steel used to manufacture these guidewires 
has not changed, and we have had no issues with rusting components, so embolic risk is 
not a concern. 
 
C4.1  Has the manufacturer used the same material in a similar legally marketed device? 
Yes Go to C5 
No   Submit 510(k) 
 
C5  Could the change affect the devices performance specifications? 
Yes Go to B5 
  See design change analysis above. 
 
No   Document to file 
 
   
  71  Contains Nonbinding Recommendations 
 
Technology, Engineering, Performance, and Materials Changes for In Vitro Diagnostic 
Devices 
 
D1  Does the change alter the operating principle of the IVD? 
Yes Submit 510(k) 
No   Go to D2 
 
D2  Is the change identified in a device-specific final guidance or classification regulation? 
Yes Submit 510(k)  
No   Go to D3 
 
D3  Does a  risk-based assessment of the changed device identify any new risks or significantly 
modified existing risks? 
Yes Submit 510(k) 
No   Go to D4 
 
D4  Do design verification and/or validation activities produce any unexpected issues of safety 
or effectiveness? 
Yes Submit 510(k)  
No   Document to file 
 
 
  72  Contains Nonbinding Recommendations 
 
Appendix C: Significant Terminology 
 
The following significant terminology is provided to clarify the meaning of medical device terms 
as used in this guidance document. Wherever possible, existing definitions or descriptors from 
the FD&C Act, medical device regulations, or FDA guidance documents have been used. In 
some cases, where regulatory definitions or descriptors are unavailable, we have relied on 
dictionary definitions of terms. 
 
510(k) Holder: The person who possesses the 510(k) clearance for a device. 
 
Contraindications: See precautions, warnings and contraindications below. 
 
Control Mechanism: The manner by which the actions of a device are directed. An example of a 
change in control mechanism would be the replacement of an electromechanical control with a 
microprocessor control.  
 
Dimensional Specifications: The physical size and shape of the device. Such specifications may 
include the length, width, thickness, or diameter of a device, as well as the location of a part or 
component of the device. 
 
Directions for Use: The directions or instructions under which the user can use the device safely 
and for the purposes for which it is intended.  Directions for use requirements applicable to 
prescription and over-the-counter devices appear throughout 21 CFR Part 801, and 21 CFR 
809.10 for IVD devices.  
 
Documentation: For the purpose of this guidance, documentation means recording the rationale 
behind the manufacturers decision whether to submit a new 510(k) for changes in a device. 
Consideration of each decision point should be recorded, as well as the final conclusions 
reached. If testing or other engineering analysis is part of the process, the results of this activity 
should be recorded or referenced. A copy of this documentation should be maintained for future 
reference. 
 
Energy Type, Character, or Source: The type of power input to or output from the device. 
Examples of a change in energy type or character would be a change from AC to battery power 
(input) or a change from ionizing radiation to ultrasound to measure a property of the body 
(output). 
 
Environmental Specifications: The (range of) acceptable levels of environmental parameters or 
operating conditions under which the device will perform safely and effectively. Examples of 
changes in environmental specifications are expanding the acceptable temperature range in 
which the device will operate properly or hardening the device to significantly higher levels of 
electromagnetic interference. 
 
Human Factors of Patient/User Interface: The human factors of the patient or user interface refer 
to the way in which the device and the patient or user interact. This includes the way in which 
the device presents alarms to the user, the layout of the control panel, the mode of presentation of 
information to the user or patient, and the way in which the device physically interacts with the 
  73  Contains Nonbinding Recommendations 
 
user and/or patient (e.g., the way in which a CPAP mask attaches to a patients face, or the way a 
surgical instrument is designed to fit in a surgeons hand). 
 
Expiration Date: The date beyond which the product may cease to perform safely or effectively 
and beyond which the manufacturer states the product should not be used. 
 
Harm: Physical injury or damage to the health of people.10 
 
Hazard: Potential source of harm.  
 
Intended Use: For purposes of substantial equivalence, the term intended use means the 
general purpose of the device or its function, and encompasses the indications for use.11  
 
Indications for Use: The term indications for use, as defined in 21 CFR 814.20(b)(3)(i), describes 
the disease or condition the device will diagnose, treat, prevent, cure or mitigate, including a 
description of the patient population for which the device is intended.12 
 
In Vitro Diagnostic Device: Those reagents, instruments, and systems intended for use in the 
diagnosis of disease or other conditions, including a determination of the state of health, in order 
to cure, mitigate, treat, or prevent disease or its sequelae. Such products are intended for use in 
the collection, preparation, and examination of specimens taken from the human body.13 
 
Label: The term label means a display of written, printed, or graphic matter upon the 
immediate container of any article.14 
 
Labeling: The term labeling means all labels and other written, printed, or graphic matter (1) 
upon any article or its containers or wrappers, or (2) accompanying such article.15 This can 
include, among other things, any user or maintenance manuals and, in some instances, 
promotional literature.  
 
Manufacturer: For the purposes of this document, the term manufacturer includes any 510(k) 
holder, even if that person does not actually fabricate the existing device. The term also includes 
a person who manufactures a preamendments device of a type subject to premarket notification 
(510(k)), and a person who manufactures a device that was granted marketing authorization via 
the De Novo classification process.  
 
                                                 
10 Definition based on ISO 14971. 
11 See FDAs guidance The 510(k) Program: Evaluating Substantial Equivalence in Premarket Notifications 
(510(k)) 
https://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocuments/UCM284443.pdf  
See also 21 CFR 801.4.  
12 See FDAs guidance The 510(k) Program: Evaluating Substantial Equivalence in Premarket Notifications 
(510(k))  
https://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocuments/UCM284443.pdf  
13 21 CFR 809.3(a). 
14 Section 201(k) of the FD&C Act. 
15 Section 201(m) of the FD&C Act. 
  74  Contains Nonbinding Recommendations 
 
Material Formulation: The base formulation of a polymer, alloy, etc., plus any additives, colors, 
etc., used to establish a property or the stability of the material. This does not include processing 
aids, mold release agents, residual contaminants, or other manufacturing aids that are not 
intended to be a part of the material, but that could be present as impurities on the final device. 
An example of a change in material formulation would be a change from a series 300 stainless 
steel to a series 400 stainless steel. Another example of a change in material formulation would 
be the addition or subtraction of a chemical or compound to or from a polymer. 
 
Material Supplier: The firm supplying the raw material to a finished device manufacturer. 
 
Material Type: The generic name of the material from which the device is manufactured. An 
example of a material type change would be the change from natural latex rubber to synthetic 
rubber. 
 
Method of Sterilization: The physical or chemical mechanism used to achieve sterility or to 
achieve a specific sterility assurance level (SAL). 
 
Operating Principle: The mode of operation or mechanism of action through which a device 
fulfills (or achieves) its intended use. An example of a change in operating principle would be 
using a new algorithm to compress images in a picture archiving and communications system. 
For an IVD, an example would be a change from immunofluorescence to ELISA. 
 
Packaging: Any wrapping, containers, etc., used to protect, to preserve the sterility of, or to 
group medical devices. 
 
Performance Specifications: The performance characteristics of a device as listed in device 
labeling or in finished product release specifications. Some examples of performance 
specifications are measurement accuracy, output accuracy, energy output level, and stability 
criteria. 
 
Preamendments Device: A device commercially distributed in the United States prior to May 28, 
1976 that has not been significantly changed or modified since then, and for which premarket 
approval has not been required under section 515(b) of the FD&C Act. 
 
Precautions, Warnings, and Contraindications: 
 
  Precautions describe any special care to be exercised by a practitioner or patient for the 
safe and effective use of a device. This definition also includes limitations stated for 
IVDs. 
  Warnings describe serious adverse reactions and potential safety hazards that can occur in 
the proper use or misuse of a device, along with consequent limitations in use and 
mitigating steps to take if they occur. 
 
  75  Contains Nonbinding Recommendations 
 
  Contraindications describe situations in which the device should not be used because the 
risk of use clearly outweighs any reasonably foreseeable benefits.16 
 
Reprocessing: Validated processes used to render a medical device, which has been previously 
used or contaminated, fit for a subsequent single use. These processes are designed to remove 
soil and contaminants by cleaning and to inactivate microorganisms by disinfection or 
sterilization.17 
 
Reusable Medical Device: A device intended for repeated use either on the same or different 
patients, with appropriate cleaning and other reprocessing between uses. 
 
Reuse: Use of a device more than once on a single patient or on more than one patient. Actions 
necessary for reuse of a device may include instructions for assembly/disassembly, on-site 
sterilization or disinfection, etc. This definition does not include the refurbishing or repair of a 
device for redistribution or resale. 
 
Risk: The combination of the probability of occurrence of harm and the severity of that harm. 
For the purposes of this guidance, may relate to either safety or effectiveness (e.g., risk of 
decreasing device effectiveness).  
 
Shelf-life: The term or period during which a device remains suitable for its intended use. This 
period ends at the devices expiration date. 
 
Single-use Device (SUD): A device that is intended for one use or on a single patient during a 
single procedure. 
 
Software: The set of electronic instructions used to control the actions or output of a medical 
device, to provide input to or output from a medical device, or to provide the actions of a medical 
device. This definition includes software that is embedded within or permanently a component of 
a medical device, software that is an accessory to another medical device, or software that is 
intended to be used for one or more medical purposes that performs these purposes without being 
part of a hardware medical device. 
 
Sterility Assurance Level (SAL): The probability of a single viable microorganism occurring on 
an item after sterilization. 
 
Sterilization: A validated process used to render product free from viable microorganisms.  
NOTE: In a sterilization process, the nature of microbial inactivation is described as exponential 
and, thus, the survival of a microorganism on an individual item can be expressed in terms of 
                                                 
16 ODE Bluebook Memorandum G91-1, Device Labeling Guidance 
(https://www.fda.gov/RegulatoryInformation/Guidances/ucm081368.htm). 
17 See FDAs guidance Reprocessing Medical Devices in Health Care Settings: Validation Methods and Labeling 
(https://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm253010.pdf)
. 
  76  Contains Nonbinding Recommendations 
 
probability. While this probability can be reduced to a very low number, it can never be reduced 
to zero.18 
 
User Interface: A device user interface includes all points of interaction between the product and 
the user, including elements such as displays, controls, packaging, product labels, and directions 
for use.  
 
Warnings: See precautions, warnings, and contraindications above. 
 
 
                                                 
18 See FDAs guidance Reprocessing Medical Devices in Health Care Settings: Validation Methods and Labeling 
(https://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm253010.pdf)
. 
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