Contains Nonbinding Recommendations 
The Special 510(k) Program 
______________________________________________________________________________
Guidance for Industry and 
Food and Drug Administration Staff 
Document issued on September 13, 2019. 
The draft of this document was issued on September 28, 2018. 
This document supersedes the Special 510(k) content in The New 510(k) 
Paradigm - Alternate Approaches to Demonstrating Substantial Equivalence 
in Premarket Notifications, issued on March 20, 1998. 
For questions about this document regarding CDRH-regulated devices, contact ORP: Office of 
Regulatory Programs/ DRP1: Division of Submission Support/ Premarket Notification and 
Classification Team at 510K_Program@fda.hhs.gov or 301-796-5640. For questions regarding 
this document regarding CBER-regulated devices, contact the Office of Communication, 
Outreach and Development (OCOD) in CBER at 1-800-835-4709 or 240-402-8010 or by email 
at ocod@fda.hhs.gov. 
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 
https://www.regulations.gov. Submit written comments to the Dockets Management Staff, Food 
and Drug Administration, 5630 Fishers Lane, Room 1061, (HFA-305), Rockville, MD 20852. 
Identify all comments with the docket number FDA-2018-D-3304. 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 include the document 
number 18008 and complete title of the guidance in the request. 
CBER 
Additional copies are available from the Center for Biologics Evaluation and Research (CBER), 
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 https://www.fda.gov/vaccines-blood-
biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances. 
2 Contains Nonbinding Recommendations 
Table of Contents
 
I.  Introduction ............................................................................................................................. 4 
II.  Background .............................................................................................................................. 5 
III.  Special 510(k) Program ........................................................................................................... 6 
A.  Is it a change to the manufacturers own device? ............................................................. 10 
B.  Are performance data needed to evaluate the change? ..................................................... 10 
C.  Is there a well-established method to evaluate the change? ............................................. 11 
D.  Can the data be reviewed in a summary or risk analysis format? ..................................... 12 
E.  Additional considerations ................................................................................................. 13 
Appendix A.  Recommended content of a Special 510(k) ......................................................... 15 
Appendix B.  Examples of changes ........................................................................................... 18 
Appendix C.  Examples of the summary of design control activities ....................................... 30 
3 Contains Nonbinding Recommendations 
The Special 510(k) Program 
______________________________________________________________________________ 
Guidance for Industry and 
Food and Drug Administration Staff 
This guidance represents the current thinking of the Food and Drug Administration (FDA or 
Agency) on this topic.  It does not establish any rights for any person and is not binding on 
FDA or the public.  You can use an alternative approach if it satisfies the requirements of the 
applicable statutes and regulations.  To discuss an alternative approach, contact the FDA staff 
or Office responsible for this guidance as listed on the title page. 
I.  Introduction 
This guidance provides the Food and Drug Administrations (FDA) current thinking on 
premarket notifications (510(k)s) appropriate for review as a Special 510(k). The intent of this 
guidance is to describe an optional pathway for certain well-defined device modifications where 
a manufacturer modifies its own legally marketed device, and design control procedures produce 
reliable results that can form, in addition to other 510(k) content requirements, the basis for 
substantial equivalence (SE). This guidance clarifies the types of technological changes 
appropriate for review as Special 510(k)s. Specifically, within the scope of appropriate changes, 
we are including certain design and labeling changes, including changes to the indications for 
use, by focusing on whether the method(s) to evaluate the change(s) are well-established, and 
whether the results can be sufficiently reviewed in a summary or risk analysis format. 
The Special 510(k) Program is consistent with FDAs statutory mission to protect and promote 
human health and FDAs commitment to helping patients gain timely access to new medical 
devices that are high quality, safe and effective by using efficient review practices consistent 
with least burdensome principles.1 This guidance, provides consistency, clarity, and transparency 
to industry to describe when a Special 510(k) is appropriate. This guidance supersedes the 
Special 510(k) policy in the The New 510(k) Paradigm: Alternate Approaches to Demonstrating 
Substantial Equivalence in Premarket Notifications. 
For the current edition of the FDA-recognized standard(s) referenced in this document, see 
the FDA Recognized Consensus Standards Database Web site at 
https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm. For more 
information regarding use of consensus standards in regulatory submissions, please refer to FDA 
guidance titled Appropriate Use of Voluntary Consensus Standards in Premarket Submissions 
                                                
1 Section 1003 of the Federal Food, Drug, and Cosmetic Act (FD&C Act). 
4 Contains Nonbinding Recommendations 
for Medical Devices2 and Standards Development and the Use of Standards in Regulatory 
Submission Reviewed in CBER.3
FDA's 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. 
II.  Background 
FDA established the Special 510(k) Program in 1998 and described the program and policy in 
the guidance document The New 510(k) Paradigm: Alternate Approaches to Demonstrating 
Substantial Equivalence in Premarket Notifications (New 510(k) Paradigm Guidance).4 The 
program was intended to create an efficient review process for certain changes subject to 510(k) 
submission requirements. 
Design controls were added to the Quality System (QS) Regulation and have been in effect since 
June 1, 1997 (21 CFR 820.30, 61 FR 52602). The Special 510(k) Program leverages design 
controls requirements to support SE determinations through the reliance on risk analysis and 
verification and validation for existing devices. Special 510(k)s allow FDA and industry to rely 
on previous Agency review of detailed information, where appropriate, without altering any 
statutory or regulatory requirements related to the premarket notification process under sections 
510 and 513 of the FD&C Act, and 21 CFR 807 Subpart E. The Special 510(k) Program 
provides a least burdensome approach to the review of certain changes to a manufacturers own 
legally marketed predicate device (existing device) because a Special 510(k) provides an 
efficient pathway for manufacturers to provide the minimum required information necessary to 
establish SE for a modified device. Because of this efficiency, FDA stated in the New 510(k) 
Paradigm Guidance that we intend to process Special 510(k)s within 30 days of receipt by the 
Document Control Center, rather than the 90 days for 510(k)s required by section 510(n)(1) of 
the FD&C Act. 
The Special 510(k) Program was previously limited to review of changes that did not affect the 
devices intended use nor alter the devices fundamental scientific technology. Under this 
approach, Special 510(k)s that included modifications to the indications for use or any labeling 
change that affected the devices intended use and/or modifications that had the potential to alter 
the fundamental scientific technology of the device compared to the manufacturers own legally 
marketed predicate device5 were routinely converted to Traditional 510(k)s. FDA now no longer 
                                                
2 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/appropriate-use-voluntary-consensus-
standards-premarket-submissions-medical-devices. 
3 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/standards-development-and-use-
standards-regulatory-submissions-reviewed-center-biologics-evaluation. 
4 The New 510(k) Paradigm Guidance was superseded by this guidance and The Abbreviated 510(k) Program. 
5 A legally marketed predicate device is a device that was legally marketed prior to May 28, 1976 (i.e., 
preamendments), reclassified from class III to class II or class I, found substantially equivalent through a 510(k), or 
granted marketing authorization through the De Novo classification process. 
5 Contains Nonbinding Recommendations 
intends to focus on changes that affect indications for use or alter fundamental scientific 
technology in determining whether the 510(k) is appropriate as a Special 510(k). Instead, FDAs 
approach focuses on whether the method(s) to evaluate the change(s) are well-established, and 
whether the results can be sufficiently reviewed in a summary or risk analysis format. A Special 
510(k) would generally not be appropriate for devices that manufacture a biological product at 
the point of care, because there would likely be no well-established method to evaluate such 
changes and/or the performance data would not be reviewable in a summary or risk-analysis 
format.  
Through the finalization of this guidance, we are updating the Special 510(k) Program to clarify 
existing policy and the types of changes appropriate for the program to improve the efficiency of 
510(k) review. Under this approach, certain changes to the indications for use may be made. 
FDA has also clarified the types of changes to technological characteristics that are appropriate 
for review as a Special 510(k). For more information about how FDA evaluates whether changes 
to the indications for use fall within the same intended use and how differences in technology 
affect FDAs SE determination process, see the FDA guidance document The 510(k) Program: 
Evaluating Substantial Equivalence in Premarket Notifications [510(k)].6 Special 510(k)s remain 
subject to the content and format requirements for 510(k) submissions, 510(k) summary or 
510(k) statement, and class III certifications (21 CFR 807.87, 807.90, 807.92, 807.93, and 
807.94, respectively). 
III.  Special 510(k) Program 
The Special 510(k) Program is intended to facilitate the submission, review, and clearance of a 
change to a manufacturers own legally marketed predicate device (existing device) that is 
already authorized for commercial distribution through 510(k) clearance, preamendments status, 
reclassification, or through a granted De Novo classification request under section 513(f)(2) of 
the FD&C Act. 
For certain device changes, FDA believes that design control procedures can produce reliable 
results that can form the basis for a SE determination without compromising the statutory and 
regulatory criteria for SE. Under design controls, manufacturers are required to conduct 
verification and validation (21 CFR 820.30(f) and (g)). Verification and validation include 
procedures to ensure that design outputs meet design inputs, and that devices conform to defined 
user needs and intended uses. The QS Regulation, 21 CFR Part 820, has records establishment 
and maintenance requirements that apply to design changes subject to design controls (21 CFR 
820.30 and 820.180). These records must be made available to an FDA investigator upon request 
under section 704(e) of the FD&C Act. 
When a manufacturer considers submitting a Special 510(k), FDA recommends that 
manufacturers consider all relevant guidance documents, special controls, or recognized 
voluntary consensus standards that apply to the device type or to a scientific topic area (e.g., 
biocompatibility or electromagnetic compatibility). For example, if a manufacturer is modifying 
                                                
6 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/510k-program-evaluating-substantial-
equivalence-premarket-notifications-510k. 
6 Contains Nonbinding Recommendations 
a powered lower extremity exoskeleton device, then the manufacturers design inputs should 
address the special controls that FDA has established for that device type under 21 CFR 
890.3480. If a manufacturer modifies an in vitro diagnostic (IVD), the manufacturers design 
inputs should include any relevant clinical and laboratory standards recognized by FDA. This 
guidance is not intended to supersede device-specific policies regarding the submission of 
complete test reports or Special 510(k) considerations that are identified in some guidance 
documents. For example, as discussed in the FDA guidance Reprocessing Medical Devices in 
Health Care Settings: Validation Methods and Labeling (referred to as Reprocessing Guidance),7
510(k) submissions for certain reusable devices are required to include validation data pursuant 
to section 510(q) of the FD&C Act. These devices are identified in FDAs Federal Register 
notice published in 82 FR 268078 and Appendix E of the Reprocessing Guidance. FDA does not 
consider such 510(k) submissions to be appropriate for review under the Special 510(k) Program 
because these validation data reports cannot be provided in a summary or risk analysis format. 
Subject to FDAs acceptance review in accordance with the guidance Refuse to Accept Policy 
for 510(k)s,9 FDA generally reviews Special 510(k) submissions within 30 days of receipt. If a 
manufacturer submits a Special 510(k) that FDA does not believe is appropriate for review under 
the Special 510(k) Program, FDA intends to convert the submission to a Traditional 510(k) and 
notify the submitter. 
When FDA converts a Special 510(k) to a Traditional 510(k), management concurrence occurs 
prior to the conversion. During FDAs notification of 510(k) conversion, FDA intends to provide 
an explanation of the reason(s) for conversion using the Special 510(k) factors discussed below. 
The 510(k)-conversion process can result in delayed review because complete test reports are not 
reviewed in a Special 510(k), but are typically requested in a Traditional 510(k). This difference 
in content between Special and Traditional 510(k)s often results in FDA refusing to accept the 
510(k) after conversion to a Traditional 510(k). Therefore, FDA recommends that both FDA and 
manufacturers consider the below factors to determine whether review as a Special 510(k) is 
appropriate. If the 510(k) submission was accepted for a substantive review and later converted 
to a Traditional 510(k), the review clock continues into FDAs 90-day statutory deadline under 
section 510(n)(1) of the FD&C Act and remains subject to MDUFA performance goals for 
510(k) submissions. 
In accordance with 21 CFR 807.81(a)(3), and as explained in FDAs guidance Deciding When to 
Submit a 510(k) for a Change to an Existing Device10 (510(k) Modifications Guidance), not all 
changes require a new 510(k) and manufacturers should use a risk-based assessment approach, as 
appropriate, to guide their analysis of whether a new 510(k) is likely required. If a manufacturer 
determines that a new 510(k) is likely required, then the flowchart provided in Figure 1 and the 
companion text guide FDA staff and manufacturers through the decision-making process to 
determine whether a particular submission is appropriate for review as a Special 510(k). 
                                                
7 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/reprocessing-medical-devices-health-
care-settings-validation-methods-and-labeling. 
8 June 9, 2017. 
9 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/refuse-accept-policy-510ks. 
10 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/deciding-when-submit-510k-change-
existing-device. 
7 Contains Nonbinding Recommendations 
Subject to the framework identified in sections III.A-E of this guidance, a design or labeling 
change to an existing device (including certain changes to the indications for use) may be 
appropriate for a Special 510(k) when: 
  The proposed change is submitted by the manufacturer legally authorized to market the 
existing device; 
  Performance data are unnecessary, or if performance data are necessary, well-established 
methods are available to evaluate the change; and 
  All performance data necessary to support SE can be reviewed in a summary or risk 
analysis format. 
These considerations and associated decision making are summarized in Figure 1. Examples of 
changes that are and are not appropriate for review under the Special 510(k) Program are 
included in Appendix B. 
Although most Class I devices are not subject to the design control requirements of the QS 
Regulation, manufacturers of Class I (reserved) devices11 may voluntarily elect to comply with 
the design controls regulation and submit Special 510(k)s. 
                                                
11 See section 510(l) of the FD&C Act. 
8 Contains Nonbinding Recommendations 
Figure 1. Special 510(k) flowchart. 
9 Contains Nonbinding Recommendations 
A.  Is it a change to the manufacturers own device? 
To be within the scope of the Special 510(k) Program, the 510(k) should be for a change to the 
submitters own legally marketed predicate device. This is because the Special 510(k) Program 
relies on the Agencys previous review of detailed information and a manufacturer who modifies 
its own legally marketed device is able to conduct the risk analysis and the necessary verification 
and validation activities to demonstrate that the design outputs of the modified device meet the 
design input requirements in a Special 510(k) submission. FDA intends to convert Special 
510(k)s to Traditional 510(k)s when the submitter is not the manufacturer legally authorized to 
market the predicate device. In cases where the referenced 510(k) was submitted under a 
different name than the submitter, FDA recommends that the submitter include a statement 
affirming that they are the manufacturer legally authorized to market the predicate device. 
B.  Are performance data needed to evaluate the change? 
Manufacturers should use their design control procedures and consider the information necessary 
to support SE to determine whether performance data are needed to evaluate the change. As part 
of design controls, manufacturers must establish and maintain procedures for the validation, or 
where appropriate, verification, of design changes before their implementation (21 CFR 
820.30(i)). Verification and validation testing, however, may not be necessary to support SE. For 
example, FDA may receive a 510(k) from a manufacturer requesting clearance to label their 
device as Magnetic Resonance (MR) Unsafe after previously labeling their device as Safety in 
MR Imaging Not Evaluated. As discussed in the FDA guidance document Establishing Safety 
and Compatibility of Passive Implants in the Magnetic Resonance (MR) Environment,12 MR 
Unsafe labeling is based on a scientific rationale and does not involve any performance data. In 
other cases, verification and validation testing may be necessary to support changes in 
indications for use and design. For example, identification of a new environment of use in the 
indications for use or labeling without changes to the intended users or user interface may result 
in the need for additional verification and validation testing to support continued electromagnetic 
compatibility (EMC) and other performance characteristics. 
In cases where manufacturers determine under their design control procedures that no additional 
verification or validation testing is necessary to evaluate a change that otherwise requires 
submission and clearance of a 510(k), manufacturers may submit these changes as a Special 
510(k) with a clear rationale supporting their conclusion that no performance data are necessary. 
When FDA does not agree with the manufacturers assessment about whether performance data 
will be necessary to support a SE determination, FDA intends to continue its review with the 
additional Special 510(k) factors discussed in sections III.C-E before considering whether the 
510(k) submission should be converted to a Traditional 510(k). 
                                                
12 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/establishing-safety-and-
compatibility-passive-implants-magnetic-resonance-mr-environment. 
10 Contains Nonbinding Recommendations 
C.  Is there a wellestablished method to evaluate the change?
FDA believes that in order to qualify for the Special 510(k) Program, well-established methods 
should be available to evaluate the change under design controls. The Special 510(k) Program 
should not include the submission and review of complete test reports, but summary information 
generated from well-established methods. Well-established methods are those that have been 
established for evaluation of the device, device type, or scientific topic area, and are validated 
according to scientific principles. Minor deviations to a well-established method may be 
acceptable within the context of a Special 510(k), but significant deviations to the protocol or 
acceptance criteria of a well-established method can result in the 510(k) being no longer 
appropriate for review as a Special 510(k). If manufacturers are uncertain whether protocol or 
acceptance criteria deviations from an otherwise well-established method are significant, they 
can use the Pre-Submission process to obtain feedback per the FDA guidance Requests for 
Feedback and Meetings for Medical Device Submissions: The Q-Submission Program.13
FDA believes that well-established methods may include: 
  The submitters methods, protocols, and acceptance criteria used to support the 
previously cleared 510(k) that can be applied to the subject 510(k); 
  Methods found in an FDA-recognized voluntary consensus standard14 or FDA guidance 
document; 
  Qualified medical device development tools (MDDTs); or 
  Widely available and accepted methods published in the public domain, scientific 
literature, or found acceptable by FDA through the submitters own 510(k)-clearance, a 
granted De Novo classification request, or premarket application (PMA) approval. 
FDA recommends that manufacturers describe why the methods applied to evaluate the impact 
of the changes included in a Special 510(k) are well-established. This description can include a 
discussion that the methods and acceptance criteria were the same as the predicate device and are 
relevant to the change under review. When standards undergo revision, the FDA-recognized 
version(s) as identified in our online database15 are considered to include well-established 
methods. Such methods should rely on established acceptance criteria, or a comparison of 
performance to the predicate device and/or reference device16 under the same testing 
methodology. For example, Traditional 510(k)s often identify the verification and validation 
approaches that are used for software such that many subsequent software changes may occur 
under a Special 510(k). To remain appropriate for review as a Special 510(k), all test methods 
used to support the 510(k) should be well-established. 
                                                
13 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/requests-feedback-and-meetings-
medical-device-submissions-q-submission-program. 
14 For the purposes of this guidance, FDA-recognized voluntary consensus standards include those that FDA has 
recognized or decided to recognize. For more information, see Appropriate Use of Voluntary Consensus Standards 
in Premarket Submissions for Medical Devices, available at https://www.fda.gov/regulatory-information/search-
fda-guidance-documents/appropriate-use-voluntary-consensus-standards-premarket-submissions-medical-devices. 
15 https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm. 
16 Consistent with The 510(k) Program: Evaluating Substantial Equivalence in Premarket Notifications [510(k)] 
(https://www.fda.gov/regulatory-information/search-fda-guidance-documents/510k-program-evaluating-substantial-
equivalence-premarket-notifications-510k), reference devices are other legally marketed devices that may be used to 
support scientific methodology or standard reference values for Decisions 5a and 5b of the 510(k) decision-making 
flowchart after a manufacturer successfully navigates through Decision Point 4 using a single predicate device. 
11 Contains Nonbinding Recommendations 
Submissions that use methods that rely on clinical studies or animal data to support SE are not 
typically appropriate for the Special 510(k) Program because the methodologies and endpoints 
vary, are often dependent on the condition(s) being studied, and cannot be appropriately 
summarized. The use of clinical specimens to conduct IVD verification and validation does not 
necessarily mean that a well-established method does not exist to evaluate the change. When 
FDA does not agree that a well-established method exists to evaluate the change, FDA intends to 
convert the Special 510(k) to a Traditional 510(k). In that case, FDA intends to explain to the 
submitter why the method to evaluate the change is not well-established. 
D.  Can the data be reviewed in a summary or risk analysis 
format? 
To be appropriate for a Special 510(k), the results from verification and validation associated 
with design or labeling changes should be able to be placed in a summary or risk analysis format 
without losing information necessary to support SE. Complete test reports should not be 
submitted in a Special 510(k). If complete test reports are submitted, FDA intends to assess 
whether the information can be reviewed in a summary format before converting to a Traditional 
510(k). This assessment should occur during FDAs acceptance review in accordance with the 
510(k) Refuse to Accept (RTA) policy. Given the shorter timeframe for review of Special 
510(k)s, if the submitter cannot provide summary information within the timeframe identified 
during interactive RTA review, FDA intends to convert the submission to a Traditional 510(k). 
FDA does not believe that data can be summarized when the SE determination will depend on 
the Agencys interpretation of the underlying data, such as images, raw graphs, or line item data. 
For example, FDA does not believe that data can be placed in a summary format when fatigue to 
failure testing involves the review of graphical images to interpret the failure modes observed. In 
limited circumstances where a small number of representative images for non-clinical 
performance are submitted, such would be appropriate for a Special 510(k). For example, 
representative images used to demonstrate radiopacity for guidewires or devices with radiopaque 
markers may be included in a Special 510(k). FDA has included anticipated common scenarios 
for when data may be unable to be summarized without loss of information in section III.E. 
FDA believes that the results from risk management activities, including relevant verification 
and validation information, produced under design controls procedures can be used to support a 
SE determination of the Special 510(k) under the conditions described in this guidance. As 
described in Appendix A, this information should include a concise summary of design control 
activities and verification and validation testing required to comply with 21 CFR 820.30 based 
on a manufacturers procedures. To have sufficient information to establish SE under a Special 
510(k), your summary or table should describe, for each change that required a 510(k), the 
specific verification and validation activities, how the methods applied are appropriate for the 
change, acceptance criteria, any changes or deviations from testing methods in previous 510(k) 
submissions, and a summary of the results. When FDA does not agree that the performance data 
can be summarized, FDA intends to convert the submission to a Traditional 510(k). This should 
typically occur during the RTA review. In this case, FDA intends to explain to the submitter why 
the performance data could not be provided in a summary or risk analysis format. 
12 Contains Nonbinding Recommendations 
In accordance with the flexibility of the QS Regulation, there can be different approaches to the 
summary of design control activities and verification and validation that can be included in a 
Special 510(k). This can include redlined software requirements specification (SRS) and design 
documentation that clearly documents the changes that were made, consistent with well-
established methods. Manufacturers can include their risk management documentation, such as a 
Design Failure Modes and Effects Analysis (DFMEA), along with a separate summary of 
supporting verification and validation. Manufacturers could also summarize their risk 
management activities with the specifics of verification and validation that provide information 
necessary for FDAs SE determination process. To facilitate FDA review, the summary of design 
control activities and verification and validation should highlight and focus on the information 
that is relevant to the changes under review. FDA has provided examples in Appendix C of this 
guidance. 
E.  Additional considerations 
Because FDA intends to review a Special 510(k) within 30 days, FDA believes there are some 
circumstances when it is not appropriate to submit a Special 510(k), including: 
  When evaluation of the change(s) to the device generally involve greater than three 
scientific disciplines (e.g., biocompatibility, sterility, electromagnetic compatibility); 
  For multiple devices with unrelated changes as described in the FDA guidance Bundling 
Multiple Devices or Multiple Indications in a Single Submission;17
  When a recent QS inspection has resulted in the issuance of a violative inspection report 
identifying observations related to design controls that are relevant to the design changes 
under review in the 510(k). If a manufacturer believes such violations are unrelated to the 
subject 510(k), they should provide a rationale for why the 510(k) should still be 
appropriate for review under the Special 510(k) Program; 
  When Special 510(k)s are submitted for common scenarios that FDA anticipates a review 
of complete test reports will be necessary to establish SE, such as: 
  Changes to the indications for use that are supported by clinical, animal,18 or 
cadaver data; 
  Use of novel sterilization methods as described in the FDA guidance Submission 
and Review of Sterility Information in Premarket Notification (510(k)) 
Submissions for Devices Labeled as Sterile;19
                                                
17 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/bundling-multiple-devices-or-
multiple-indications-single-submission. 
18 FDA supports the principles of the 3Rs, to reduce, refine, and replace animal use in testing when feasible. We 
encourage sponsors to consult with us if it they wish to use a non-animal testing method they believe is suitable, 
adequate, validated, and feasible. We will consider if such an alternative method could be assessed for equivalency 
to an animal test method.  
19 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/submission-and-review-sterility-
information-premarket-notification-510k-submissions-devices-labeled. 
13 Contains Nonbinding Recommendations 
  Changes to introduce initial MR Conditional labeling, or significant deviations 
from the test methods used to establish MR Conditional labeling in the original 
510(k); 
  Change from single-use to reusable when reprocessing validation or human 
factors data should be provided; and 
  Use of analytical chemistry testing using International Organization for 
Standardization (ISO) 10993-1820 and/or toxicological risk assessment using ISO 
10993-1721 to address biocompatibility.22
  For a reprocessed single-use device (SUD) that requires the submission of cleaning, 
sterilization, and functional performance validation data under section 510(o) of the 
FD&C Act and in FDAs Federal Register notice published in 70 FR 5691123 requiring 
the submission of SUD validation data. Consistent with the FDA guidance Medical 
Device User Fee and Modernization Act of 2002, Validation Data in Premarket 
Notification Submissions (510(k)s) for Reprocessed Single-Use Medical Devices,24 if the 
reprocessed SUD does not require validation data, and is otherwise appropriate for a 
Special 510(k) submission, the reprocessor may submit a Special 510(k); and 
  For changes that could affect the reprocessing of reusable devices required by section 
510(q) of the FD&C Act to include reprocessing validation in 510(k) submissions. These 
devices are identified in FDAs Federal Register notice published in 82 FR 2680725 and 
Appendix E of the Reprocessing Guidance.26
                                                
20 ISO 10993-18 Biological evaluation of medical devices  Part 18: Chemical characterization of materials. 
21 ISO 10993-17 Biological evaluation of medical devices  Part 17: Establishment of allowable limits for leachable 
substances. 
22 We recognize that chemical information may be used to support another part of your biocompatibility evaluation 
(e.g., a rationale for why a specific biocompatibility test is not needed). Use of chemical information (e.g., literature, 
Safety Data Sheet (SDS)) that does not involve a toxicological risk assessment may be acceptable. For more 
information, see Example C.2. 
23 This notice was published on September 29, 2005.  
24 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/medical-device-user-fee-and-
modernization-act-2002-validation-data-premarket-notification. 
25 This notice was published on June 9, 2017. 
26 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/reprocessing-medical-devices-
health-care-settings-validation-methods-and-labeling. 
14 Contains Nonbinding Recommendations 
Appendix A.  Recommended content of a Special 510(k) 
A Special 510(k) should include: 
  A coversheet clearly identifying the submission as a Special 510(k): Device 
Modification; 
  The name of the manufacturers legally marketed (existing) device and the 510(k) 
number under which it was cleared; 
  Information required under 21 CFR 807.87, including a description of the modified 
device, a comparison to the cleared device, the indications for use of the device, and the 
proposed labeling for the device. To help ensure that FDA has a complete understanding 
of the device under review, this should include: 
  A detailed description of the change(s) made to the device that resulted in the 
submission of a new 510(k). When labeling or specific technological 
characteristics (e.g., materials, dimensions) are unchanged in comparison to the 
predicate, the submission should clearly state that no changes were made; 
  A comparison of the modified device to the cleared device in a tabular format; 
  Clean and redlined copies of documents that were updated from what was 
submitted in the predicate devices submission because of the device change (e.g., 
labeling, risk analysis); and 
  Other changes to labeling or design 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 original 510(k), in accordance with the 
recommendations in the FDA guidance Deciding When to Submit a 510(k) for a 
Change to an Existing Device.27
  If the Special 510(k) includes reference(s) or a declaration of conformity to a recognized 
voluntary consensus standard, we recommend that you consult the FDA guidance 
Appropriate Use of Voluntary Consensus Standards in Premarket Submissions for 
Medical Devices;28
  A concise summary of the design control activities. Appendix C provides examples of 
narratives and a table of this information that has been historically provided. FDA 
considers the information generated from the design control activities to be appropriate 
supporting data within the meaning of 21 CFR 807.87(g). Your risk management file 
may already contain some of the design control activities in a risk analysis format. In lieu 
of creating a new table that addresses all recommended content, you may instead submit 
your risk analysis as an attachment or appendix to your submission. This summary should 
include the following: 
  Identification of the risk analysis method(s) used to assess the impact of the 
change on the device and the results of the analysis; 
  Identification of the device change(s); 
                                                
27 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/deciding-when-submit-510k-change-
existing-device. 
28 hhttps://www.fda.gov/regulatory-information/search-fda-guidance-documents/appropriate-use-voluntary-
consensus-standards-premarket-submissions-medical-devices. 
15 Contains Nonbinding Recommendations 
  Identification of all risks associated with each device change, including 
identification of risks that are considered new because of the change; and 
  Risk control measures to mitigate identified risks (e.g., labeling, verification). 
  Based on the risk analysis, an identification of the verification and/or validation activities 
required to comply with 21 CFR 820.30. This identification should include a summary of 
test methods, acceptance criteria, and results, and why each is adequate to establish SE. If 
unchanged from a previous premarket submission, the manufacturer can reference the 
location of protocols and acceptance criteria by providing a submission and section 
numbers. When the results are quantitative in nature, the submission should include basic 
descriptive statistics, such as the mean, standard deviation, and range of the data. 
Protocol deviations observed during testing should be provided and justified, if 
applicable. When appropriate, the summary of verification and validation should include: 
  For non-standardized test methods only: 
  A reference to the protocol used for the existing device with an 
identification of any differences (e.g., protocol, test conditions, pre-
defined acceptance criteria, sample size) from the previous 510(k). If 
protocol changes were made, the results summary should describe why the 
test methods, acceptance criteria, and results support SE. 
  For test methods described in an FDA-recognized standard: 
  Cross-reference to the relevant section of the Special 510(k) where a 
declaration of conformity (DOC) was submitted under section 514(c) of 
the FD&C Act. This should also include or cross-reference applicable 
supplemental documentation per ISO/IEC 17050-229 to support the DOC; 
or 
  If a DOC is not submitted, the basis for general use of a consensus 
standard should include underlying information or data that supports how 
the standard was used. For Special 510(k)s, submitters that rely on general 
use of a consensus standard should provide a description of methods with 
deviations, selected options and the reasons for their selection, acceptance 
criteria, and a results summary. See the FDA guidance Appropriate Use of 
Voluntary Consensus Standards in Premarket Submissions for Medical 
Devices30 for more information about the use of voluntary consensus 
standards. 
  Indications for Use form (Form FDA 3881);31 and 
  A signed statement by the manufacturers designated individual(s) responsible for design 
control activities that includes: 
  A statement that, as required by the risk analysis, all design verification and 
validation activities were performed by the designated individual(s) and the 
results demonstrated that the predetermined acceptance criteria were met; and 
                                                
29 ISO 17050-2 Conformity assessment  Part 2: Supporting documentation for the general requirements and 
supporting documentation. 
30 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/appropriate-use-voluntary-
consensus-standards-premarket-submissions-medical-devices. 
31 https://www.fda.gov/media/86323/download. 
16 Contains Nonbinding Recommendations 
  A statement that the submitter has complied and is not currently in violation of the 
design control procedure requirements as specified in 21 CFR 820.30 and the 
records are available for review, upon request. 
17 Contains Nonbinding Recommendations 
Appendix B.  Examples of changes 
These examples are for illustrative purposes and may not include all details for each change. The 
examples are intended to help FDA staff and industry determine which changes can be submitted 
as a Special 510(k). 
Example B.1
Change: The submitter wants to change their 2-D chest x-ray image processing software to 
add a feature that highlights nodules in the lung. The submitter is also requesting to modify 
their indications for use to describe this new software feature that now quantifies and 
characterizes information about the nodules. 
Relevant Questions: 
A - Is it a change to the manufacturers own device? 
Yes, the submitter is the manufacturer of the predicate device. 
B - Are performance data needed to evaluate the change? 
Yes. Clinical testing should be provided to support marketing clearance for such a change in 
the indications for use to assess the performance of the software on patients with and without 
nodules in the lung. This clinical testing should support that the software can successfully 
quantify and characterize information about the nodules. 
C - Is there a well-established method to evaluate the change? 
No. There are no well-established methods identified in the predicates submission for the 
evaluation of lung nodules, consensus standards, or widely available and accepted methods 
published in the public domain to address the change in the indications for use. 
D - Can the data be reviewed in a summary or risk analysis format?  
N/A. 
Decision: Change cannot be reviewed in a Special 510(k). 
Example B.2
Change: The submitter wants to add wireless control capabilities to their bilevel positive 
airway pressure (BiPAP) device intended to treat patients with obstructive sleep apnea. 
Relevant Questions: 
A - Is it a change to the manufacturers own device? 
Yes, the submitter is the manufacturer of the predicate device. 
B - Are performance data needed to evaluate the change? 
Yes. The predicate device did not contain and was not tested for wireless functionality. 
Verification and validation should be conducted to ensure that the BiPAP has acceptable 
wireless quality of service, coexistence, cybersecurity, and maintains EMC in its intended 
18 Contains Nonbinding Recommendations 
environment of use, as described in the FDA guidance Radio Frequency Wireless 
Technology in Medical Devices.32
C - Is there a well-established method to evaluate the change? 
No. International Electrotechnical Commission (IEC) 60601-1-233 and Association for the 
Advancement of Medical Instrumentation (AAMI) Technical Information Report (TIR) 6934
can be used to support EMC and wireless coexistence. However, there are not well-
established methods in an FDA-recognized voluntary consensus standard or in the 
manufacturers previous 510(k) that address the methods to evaluate the addition of wireless 
control for this BiPAP. The test methods vary depending on the wireless quality of service 
necessary for the devices intended use and environment of use. 
D - Can the data be reviewed in a summary or risk analysis format? 
N/A. 
Decision: Change cannot be reviewed in a Special 510(k). 
Example B.3
Change: The submitter wants to modify their general indications for delivering illumination 
and laser energy for photocoagulation to include specific clinical applications for treatment 
of retinopathy. 
Relevant Questions: 
A - Is it a change to the manufacturers own device? 
Yes, the submitter is the manufacturer of the predicate device. 
B - Are performance data needed to evaluate the change? 
Yes. Clinical testing is typically provided to support marketing clearance for such a change 
in the indications for use. The requested change in the indications for use now identify a 
specific disease condition. The clinical outputs have changed from general coagulation of 
blood vessels to treatment of retinopathy. Clinical testing should be conducted to assess new 
outcomes such as decrease in vision impairment, whereas the predicate assessed the general 
outcome of successful vessel coagulation. 
C - Is there a well-established method to evaluate the change? 
No. There is no well-established method identified in the predicates submission or a 
consensus standard to evaluate clinical endpoints for this device. The SE determination rests 
on a review of the underlying clinical performance data. 
D - Can the data be reviewed in a summary or risk analysis format? 
N/A. 
                                                
32 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/radio-frequency-wireless-
technology-medical-devices-guidance-industry-and-fda-staff. 
33 IEC 60601-1-2 Medical electrical equipment - Part 1-2: General requirements for basic safety and essential 
performance - Collateral Standard: Electromagnetic disturbances - Requirements and tests. 
34 AAMI TIR69 Risk management of radio-frequency wireless coexistence for medical devices and systems. 
19 Contains Nonbinding Recommendations 
Decision: Change cannot be reviewed in a Special 510(k). 
Example B.4
Change: The submitter currently markets a cardiac output monitor that is cleared for use 
with their endotracheal tube. The submitter is requesting clearance to modify the indications 
for use so that the submitters cardiac output monitor can be used with their 510(k)-cleared 
endobronchial tube that also includes integrated electrodes for sensing. 
Relevant Questions: 
A - Is it a change to the manufacturers own device? 
Yes, the submitter is the manufacturer of the predicate device. 
B - Are performance data needed to evaluate the change? 
Yes. Verification should be completed to demonstrate that the newly identified tube can be 
used for cardiac output by impedance cardiography as safely and effectively with the monitor 
as the endotracheal tube does with the monitor, and that the monitor and endobronchial tube 
both continue to function as intended. 
C - Is there a well-established method to evaluate the change? 
Yes. Because the bench testing to verify the change uses the same protocol as the predicate 
device, and the methods and acceptance criteria have not changed, the protocol is considered 
a well-established method. In addition, this type of connection for the specified tube and 
monitor has been included in other cleared 510(k) submissions for this device, and the 
submitter referenced these devices in their submission. 
D - Can the data be reviewed in a summary or risk analysis format? 
Yes. The protocol, methods and acceptance criteria were not modified from those used in the 
predicate submission to evaluate the change. The existing methods were appropriate to 
evaluate the change because the same cardiac output parameters are intended to be monitored 
and displayed. The acceptance criteria and a summary of the results were provided for each 
test. The results can be summarized because the SE determination does not depend on the 
Agencys interpretation of the underlying data, such as images, raw graphs, or line item data. 
Decision: Change can be reviewed in a Special 510(k). 
Example B.5
Change: The company is requesting clearance to change the environment of use identified in 
their labeling for their transcutaneous electrical nerve stimulation (TENS) device from a 
professional healthcare facility only to both professional healthcare facility and home use. 
The device is still intended to be used under the direction and supervision of a healthcare 
professional. 
Relevant Questions: 
A - Is it a change to the manufacturers own device? 
Yes, the submitter is the manufacturer of the predicate device. 
20 Contains Nonbinding Recommendations 
B - Are performance data needed to evaluate the change? 
Yes. There are different acceptance criteria for electrical safety and electromagnetic 
compatibility (EMC) to address home use. 
C - Is there a well-established method to evaluate the change? 
Yes. For example, the FDA-recognized standard methods American National Standards 
Institute (ANSI)/AAMI  ES60601-135 and IEC 60601-2-1036 address basic safety and 
essential performance, EMC (IEC 60601-1-237), and basic safety for home use devices 
(ANSI/AAMI HA60601-1-1138 or IEC 60601-1-1139), along with the International Special 
Committee on Radio Interference (CISPR) 1140 emission limits for Group 1 and Class B. The 
manufacturer provided their statement of essential performance and associated device-
specific acceptance criteria. 
D - Can the data be reviewed in a summary or risk analysis format? 
Yes. The particular standard used was identified. The acceptance criteria and results were 
summarized in a tabular format. A justification was provided for all results that were outside 
the bounds of an acceptance range or differed from the predicate. The results can be 
summarized because the SE determination does not depend on the Agencys interpretation of 
the underlying data, such as images, raw graphs, or line item data. 
Decision: Change can be reviewed in a Special 510(k). 
Example B.6
Change: The submitter is requesting clearance to market metal bone screws terminally 
sterilized via gamma irradiation that were previously only supplied non-sterile and sterilized 
by the end user. The indications for use and materials of construction remain unchanged from 
the clearance for the manufacturers existing device. 
Relevant Questions: 
A - Is it a change to the manufacturers own device? 
Yes, the submitter is the manufacturer of the predicate device. 
                                                
35 ANSI/AAMI ES60601-1 Medical electrical equipment - Part 1: General requirements for basic safety and 
essential performance. 
36 IEC 60601-2-10 Medical electrical equipment - Part 2-10: Particular requirements for the basic safety and 
essential performance of nerve and muscle stimulators.  
37 IEC 60601-1-2 Medical electrical equipment - Part 1-2: General requirements for basic safety and essential 
performance - Collateral Standard: Electromagnetic disturbances - Requirements and tests. 
38 ANSI/AAMI HA60601-1-11 Medical electrical equipment Part 1-11: General requirements for basic safety and 
essential performance - Collateral Standard: Requirements for medical electrical equipment and medical electrical 
systems used in the home healthcare environment. 
39 IEC 60601-1-11 Medical electrical equipment - Part 1-11: General requirements for basic safety and essential 
performance - Collateral Standard: Requirements for medical electrical equipment and medical electrical systems 
used in the home healthcare environment. 
40 CISPR 11 Industrial, scientific and medical equipment  Radio-frequency disturbance characteristics  Limits and 
methods of measurement. 
21 Contains Nonbinding Recommendations 
B - Are performance data needed to evaluate the change? 
Yes. The submitter should include an evaluation of biocompatibility, sterility, pyrogenicity, 
package integrity, and shelf-life to support the proposed change. Non-clinical testing to 
address performance of the device outside of biocompatibility, sterility, packaging, and shelf-
life is not necessary based on a scientifically-based rationale from the submitter that gamma 
irradiation does not impact the material composition or properties of this metallic device. 
Based on the recommendations in the FDA guidance Use of International Standard ISO 
10993-1, Biological evaluation of medical devices - Part 1: Evaluation and testing within a 
risk management process,41 the submitter provided a valid scientifically-based rationale 
supporting the decision that no further biocompatibility testing was necessary to address this 
change. 
C - Is there a well-established method to evaluate the change? 
Yes. The FDA guidance Submission and Review of Sterility Information in Premarket 
Notification (510(k)) Submissions for Devices Labeled as Sterile42 indicates that gamma 
irradiation is an Established Sterilization Method, Established Category A. The FDA-
recognized standards ISO 11137-143 and ISO 11137-244 can be used to support the 
sterilization validation. Pyrogenicity can be assessed using the recommendations discussed in 
the FDA guidance documents Submission and Review of Sterility Information in Premarket 
Notification (510(k)) Submissions for Devices Labeled as Sterile45 and Pyrogen and 
Endotoxins Testing: Questions and Answers,46 and the methods described in the FDA-
recognized versions of ANSI/AAMI ST7247 and United States Pharmacopeia (USP) <161>.48
Package integrity and shelf-life for this change can be evaluated through accelerated aging 
using American Society for Testing and Materials (ASTM) F198049 and package integrity 
testing for visual integrity, seal integrity, and seal strength using the methods identified in 
ASTM F1886/F1886M,50 ASTM F2096,51 and ASTM F88/F88M,52 respectively. 
                                                
41 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/use-international-standard-iso-
10993-1-biological-evaluation-medical-devices-part-1-evaluation-and. 
42 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/submission-and-review-sterility-
information-premarket-notification-510k-submissions-devices-labeled. 
43 ISO 11137-1 Sterilization of health care products - Radiation - Part 1: Requirements for development, validation 
and routine control of a sterilization process for medical devices. 
44 ISO 11137-2 Sterilization of health care products - Radiation - Part 2: Establishing the sterilization dose. 
45 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/submission-and-review-sterility-
information-premarket-notification-510k-submissions-devices-labeled. 
46 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/pyrogen-and-endotoxins-testing-
questions-and-answers. 
47 ANSI/AAMI ST72 Bacterial endotoxins - Test methods, routine monitoring, and alternatives to batch testing. 
48 USP <161> Medical Devices - Bacterial Endotoxin and Pyrogen Tests. 
49 ASTM F1980 Standard guide for accelerated aging of sterile barrier systems for medical devices. 
50 ASTM F1886/F1886M Standard test method for determining integrity of seals for flexible packaging by visual 
inspection. 
51 ASTM F2096 Standard test method for detecting gross leaks in packaging by internal pressurization (bubble test). 
52 ASTM F88/F88M Standard test method for seal strength of flexible barrier materials. 
22 Contains Nonbinding Recommendations 
D - Can the data be reviewed in a summary or risk analysis format? 
Yes. The methods are standardized, and the results can be summarized because the SE 
determination does not depend on the Agencys interpretation of the underlying data, such as 
images, raw graphs, or line item data. The FDA guidance Submission and Review of Sterility 
Information in Premarket Notification (510(k)) Submissions for Devices Labeled as Sterile53
discusses how sterilization validation, package integrity, and pyrogenicity information can be 
summarized in 510(k) submissions. 
Decision: Change can be reviewed in a Special 510(k). 
Example B.7
Change: The submitter wants to increase the number of channels for their receive-only 
magnetic resonance (MR) coil. 
Relevant Questions: 
A - Is it a change to the manufacturers own device? 
Yes, the submitter is the manufacturer of the predicate device. 
B - Are performance data needed to evaluate the change? 
Yes. Consistent with the FDA guidance Submission of Premarket Notifications  
for Magnetic Resonance Diagnostic Devices,54 performance testing should be provided for 
the increased number of coils to address image quality metrics and patient safety from 
surface heating. For a receive-only coil, this should include signal-to-noise ratio, image 
uniformity, and coil surface heating assessments. 
C - Is there a well-established method to evaluate the change? 
Yes. There are standard test methods for MR devices such as FDA-recognized consensus 
standards National Electrical Manufacturers Association (NEMA) MS 955 and NEMA MS 
6.56 The predicate device used the same standards, protocols, and acceptance criteria. 
D - Can the data be reviewed in a summary or risk analysis format? 
Yes. The methods can be summarized and the results can be placed into a summary format 
for each test conducted because the SE determination does not depend on the Agencys 
interpretation of the underlying data, such as images, raw graphs, or line item data. While a 
small, representative subset of sample images were included, the manufacturer did not 
include a complete dataset of images that would be necessary for FDA to evaluate SE. 
Instead, the manufacturer provided a statement from a U.S. Board Certified radiologist 
attesting that images produced by the device are of sufficient quality for diagnostic use. 
                                                
53 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/submission-and-review-sterility-
information-premarket-notification-510k-submissions-devices-labeled. 
54 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/submission-premarket-notifications-
magnetic-resonance-diagnostic-devices. 
55 NEMA MS 9 Standards Publication Characterization of Phased Array Coils for Diagnostic Magnetic Resonance 
Images. 
56 NEMA MS 6 Determination of Signal-to-Noise Ratio and Image Uniformity for Single-Channel Non-Volume 
Coils in Diagnostic MR Imaging. 
23 Contains Nonbinding Recommendations 
Decision: Change can be reviewed in a Special 510(k). 
Example B.8
Change: The submitter wants to add analytical sensitivity data for the new H7N9 influenza 
strain to their diagnostic test. 
Relevant Questions: 
A - Is it a change to the manufacturers own device? 
Yes, the submitter is the manufacturer of the predicate device. 
B - Are performance data needed to evaluate the change? 
Yes. Analytical reactivity testing should be provided to address the addition of analytical 
sensitivity data for the new strain into the labeling. 
C - Is there a well-established method to evaluate the change? 
Yes. The same protocol as the original submission was used for collecting and assessing the 
data. The acceptance criteria were not altered from those used for the original device. No 
additional types of evaluation are needed. 
D - Can the data be reviewed in a summary or risk analysis format? 
Yes. The results can be summarized because the SE determination does not depend on the 
Agencys interpretation of the underlying data, such as images, raw graphs, or line item data. 
In addition, the methods and acceptance criteria are unmodified from the predicate testing. 
Decision: Change can be reviewed in a Special 510(k). 
Example B.9
Change: The submitter wants to change the labeling of their blade-form endosseous dental 
implant from Safety in MRI Not Evaluated to MR Conditional. 
Relevant Questions: 
A - Is it a change to the manufacturers own device? 
Yes, the submitter is the manufacturer of the predicate device. 
B - Are performance data needed to evaluate the change? 
Yes. Non-clinical performance testing to support SE should be provided by manufacturers 
seeking MR Conditional labeling for a device that contains metallic components. The FDA 
guidance document Establishing Safety and Compatibility of Passive Implants in the 
Magnetic Resonance (MR) Environment57 provides recommendations for such testing. 
                                                
57 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/establishing-safety-and-
compatibility-passive-implants-magnetic-resonance-mr-environment. 
24 Contains Nonbinding Recommendations 
C - Is there a well-established method to evaluate the change? 
Yes. There are FDA-recognized voluntary consensus standards such as ASTM F2503,58
ASTM F2052,59 ASTM F2213,60 ASTM F2182,61 and ASTM F211962 for MR compatibility 
testing of passive implants. 
D - Can the data be reviewed in a summary or risk analysis format? 
No. Although there are consensus standards for all test methods, FDA does not believe this 
data can be summarized because the SE determination will depend on FDAs interpretation 
of the underlying data to support the MR Conditional label. This includes interpretation of 
device-specific pass/fail criteria and results that are not addressed in the standard. This is 
referenced in section III.E as an anticipated common scenario for when data may be unable 
to be summarized. 
Decision: Change cannot be reviewed in a Special 510(k). 
Example B.10
Change: The submitter wants to increase the size of their MR Conditional blade-form 
endosseous dental implant from 4mm long to 5mm long. 
Relevant Questions: 
A - Is it a change to the manufacturers own device? 
Yes, the submitter is the manufacturer of the predicate device. 
B - Are performance data needed to evaluate the change? 
Yes. FDA has designated special controls for blade-form endosseous dental implants in 21 
CFR 872.3640(b)(2)(i)-(ix) that must be addressed, including performance testing for fatigue, 
corrosion, biocompatibility evaluation, sterility, and evaluation of the device in the MR 
environment. The FDA guidance document Establishing Safety and Compatibility of Passive 
Implants in the Magnetic Resonance (MR) Environment63 recommends that manufacturers 
seeking MR Conditional labeling for a device that contains metallic components provide 
non-clinical performance testing to support SE. The manufacturer also submitted a 
biocompatibility evaluation based on a scientific justification. 
                                                
58 ASTM F2503 Standard Practice for Marking Medical Devices and Other Items for Safety in the Magnetic 
Resonance Environment. 
59 ASTM F2052 Standard Test Method for Measurement of Magnetically Induced Displacement Force on Medical 
Devices in the Magnetic Resonance Environment. 
60 ASTM F2213 Standard Test Method for Measurement of Magnetically Induced Torque on Medical Devices in the 
Magnetic Resonance Environment. 
61 ASTM F2182 Standard Test Method for Measurement of Radio Frequency Induced Heating On or Near Passive 
Implants During Magnetic Resonance Imaging. 
62 ASTM F2119 Standard Test Method for Evaluation of MR Image Artifacts from Passive Implants. 
63 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/establishing-safety-and-
compatibility-passive-implants-magnetic-resonance-mr-environment. 
25 Contains Nonbinding Recommendations 
C - Is there a well-established method to evaluate the change? 
There are FDA-recognized voluntary consensus standards such as ASTM F2503,64 ASTM 
F2052,65 ASTM F2213,66 ASTM F2182,67 and ASTM F211968 for MR compatibility testing 
of passive implants. There are also FDA-recognized voluntary consensus standards for 
fatigue testing of endosseous dental implants, such as ANSI/American Dental Association 
(ANSI/ADA) Standard No. 12769 and ISO 1480170 to address the performance of the device. 
In addition, ISO 14801 and ANSI/ADA Standard No. 127 are applicable to all dental 
implants. 
D - Can the data be reviewed in a summary or risk analysis format? 
Yes. There are consensus standards for test methods, and guidance documents for reference. 
The fatigue testing can be placed into a summary format because the size change does not 
necessitate protocol or acceptance criteria deviations. In addition, the size change (4mm to 
5mm) does not necessitate clinical or animal data. Because there has been no material 
change, and the 1 mm size change is not expected to alter the safety of the device with 
respect to MR compatibility, and the protocol and acceptance criteria has not changed, the 
MR testing results can be placed into a summary format because the SE determination does 
not depend on the Agencys interpretation of the underlying data, such as images, raw 
graphs, or line item data. 
Decision: Change can be reviewed in a Special 510(k). 
Example B.11
Change: The submitter proposes to change the shape of the test cassette for a lateral flow 
immunoassay for fecal occult blood. The new test cassette has a longer and slimmer housing 
design in comparison to the predicate device. 
Relevant Questions: 
A - Is it a change to the manufacturers own device? 
Yes, the submitter is the manufacturer of the predicate device. 
B - Are performance data needed to evaluate the change? 
Yes. A method comparison study should be conducted using the predicate device and 
candidate device to measure patient samples from the intended use population. 
                                                
64 ASTM F2503 Standard Practice for Marking Medical Devices and Other Items for Safety in the Magnetic 
Resonance Environment. 
65 ASTM F2052 Standard Test Method for Measurement of Magnetically Induced Displacement Force on Medical 
Devices in the Magnetic Resonance Environment. 
66 ASTM F2213 Standard Test Method for Measurement of Magnetically Induced Torque on Medical Devices in the 
Magnetic Resonance Environment. 
67 ASTM F2182 Standard Test Method for Measurement of Radio Frequency Induced Heating On or Near Passive 
Implants During Magnetic Resonance Imaging. 
68 ASTM F2119 Standard Test Method for Evaluation of MR Image Artifacts from Passive Implants. 
69 ANSI/ADA Standard No. 127 Fatigue Testing for Endosseous Dental Implants. 
70 ISO 14801 Dentistry - Implants - Dynamic fatigue test for endosseous dental implants. 
26 Contains Nonbinding Recommendations 
C - Is there a well-established method to evaluate the change? 
Yes. The submitter stated in their submission that the test method used is the same as that 
used for assessment of the predicate device. 
D - Can the data be reviewed in a summary or risk analysis format? 
Yes. Given that the test method used is the same for this submission as used for the predicate, 
a risk analysis was used to assess the impact of the change on the device and its components. 
The results of the method comparison study can be reviewed in terms of meeting the 
predefined acceptance criteria and a summary of study results that includes the observed 
false positive and false negative rates. 
Decision: Change can be reviewed in a Special 510(k). 
Example B.12
Change: The submitter wants to change their over-the-counter (OTC) human chorionic 
gonadotropin (hCG) urine pregnancy test device to add an absorbent sample application tip 
and change the instructions for use to specify that the results should be read between three 
and ten minutes after use, instead of at five minutes. 
Relevant Questions: 
A - Is it a change to the manufacturers own device? 
Yes, the submitter is the manufacturer of the predicate device. 
B - Are performance data needed to evaluate the change? 
Yes. Analytical validation studies and a clinical lay user study should be provided to 
demonstrate that device performance is substantially equivalent to the predicate. 
C - Is there a well-established method to evaluate the change? 
Yes. The protocols used for the analytical validation and clinical studies (method comparison 
study and lay user study) were consistent with protocols that have been found acceptable by 
FDA in the submitters own 510(k) submission for the predicate device. 
D - Can the data be reviewed in a summary or risk analysis format? 
Yes. For the analytical and clinical validation studies, the Agencys determination of 
substantial equivalence relies on well-defined acceptance criteria that are specific enough to 
assess whether the device has substantially equivalent performance to its predicate. For the 
analytical method comparison study, results can be reviewed as a summary of false positive 
and false negative rates. For the clinical lay user study, the patient population information 
can be adequately described in the study protocol and the results can be reviewed as a 
summary of agreement rate between the subject and predicate devices. These assessments do 
not require review of study line item data. 
Decision: Change can be reviewed in a Special 510(k). 
27 Contains Nonbinding Recommendations 
Example B.13
Change: The submitter wants to widen the hematocrit range for blood samples that their 
OTC blood glucose meter can measure and change the design and materials used in the 
external housing of their device. 
Relevant Questions: 
A - Is it a change to the manufacturers own device? 
Yes, the submitter is the manufacturer of the predicate device. 
B - Are performance data needed to evaluate the change? 
Yes. Analytical validation should be conducted to assess the effect of the wider hematocrit 
range on device performance. Disinfection efficacy studies and a cleaning and disinfection 
robustness study should assess whether the new external case design and materials can be 
adequately cleaned and disinfected. 
C - Is there a well-established method to evaluate the change? 
Yes. The FDA guidance documents Self-Monitoring Blood Glucose Test Systems for Over-
the-Counter Use71 and Blood Glucose Monitoring Test Systems for Prescription Point-of-
Care Use72 include recommendations for hematocrit range evaluation, disinfection efficacy, 
and cleaning and disinfection robustness testing methods. 
D - Can the data be reviewed in a summary or risk analysis format? 
Yes. For these analytical validation studies, the Agencys determination of substantial 
equivalence relies on well-defined acceptance criteria that are specific enough to assess 
whether the device has substantially equivalent performance to its predicate. For the 
hematocrit and cleaning and disinfection robustness studies, summary results of the 
measurement bias can be reviewed. For the disinfection efficacy study, results can be 
reviewed as a pass/fail summary compared to predefined acceptance criteria for viral 
inactivation. These assessments do not require review of study line data. 
Decision: Change can be reviewed in a Special 510(k). 
Example B.14
Change: The submitter wants to change the Reference Range section in the package insert 
for an immunoglobulin light chain specific assay by adding the normal range of the kappa 
lambda free light chain ratio. The submitter is not proposing to change their indications for 
use or device design. 
Relevant Questions: 
A - Is it a change to the manufacturers own device? 
Yes. The submitter is the manufacturer of the predicate device. 
                                                
71 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/self-monitoring-blood-glucose-test-
systems-over-counter-use-0. 
72 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/blood-glucose-monitoring-test-
systems-prescription-point-care-use. 
28 Contains Nonbinding Recommendations 
B - Are performance data needed to evaluate the change? 
Yes. Testing with relevant samples should be completed to determine the normal range of the 
test results. 
C - Is there a well-established method to evaluate the change? 
Yes. The reference range study may be conducted based on the FDA-recognized version of 
Clinical and Laboratory Standards Institute (CLSI) EP28-A3c.73  
D - Can the data be reviewed in a summary or risk analysis format? 
Yes. A summary of subject demographic information and summary statistics (e.g., mean, 
median, and range) can be reviewed for the samples used in the new reference range study. 
Decision: Change can be reviewed in a Special 510(k). 
Example B.15
Change: The submitter wants to change the threshold for the deoxyribonucleic acid (DNA) 
probe of a specific bacterial pathogen to address customer feedback. The threshold change 
increases the stringency for determining if a test result is positive to reduce potential false 
positives and as a preventative measure to mitigate against variability at customers sites. No 
changes were made to the assay reagents or procedure. 
Relevant Questions: 
A - Is it a change to the manufacturers own device? 
Yes. The submitter is the manufacturer of the predicate device. 
B - Are performance data needed to evaluate the change? 
Yes. Analytical testing, including both reanalysis of existing data and new performance 
wet testing, should be conducted to demonstrate that the assay performance is not 
negatively impacted by the change. 
C - Is there a well-established method to evaluate the change? 
Yes. The analytical testing methods and acceptance criteria are the same as the predicate 
devices submission. 
D - Can the data be reviewed in a summary or risk analysis format? 
Yes. Summary review of limited analytical performance testing are sufficient to determine 
the assay performance is not adversely affected by the change. 
Decision: Change can be reviewed in a Special 510(k). 
                                                
73 CLSI EP28-A3c Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory. 
29 Contains Nonbinding Recommendations 
Appendix C.  Examples of the summary of design control 
activities 
This section provides sample design control activities summaries that can be used to support a 
Special 510(k). Because of the inherent flexibility of design controls and the QS regulation, this 
summary may differ depending on a manufacturers internal procedures. The examples are 
intended to show different formats that have been used in previously cleared Special 510(k) 
submissions. 
Example C.1
In the subject 510(k), the manufacturer requested clearance to change their lacrimal stent to 
remove a metal ring, change the shape of the stents duct tube, and alter the surface area of a 
hydrophilic coating. The manufacturers design controls narrative described that a risk analysis 
was conducted to assess the impact of the changes on the subject device using internal design 
control procedures and a fault tree analysis described in the FDA-recognized version of ISO 
14971.74 The manufacturer included their fault tree analysis specific to this design change in an 
attachment for the Special 510(k) to identify the hazardous situations, causes, risk control 
measures, and acceptability before and after risk control measures. The manufacturer explained 
that the protocol, test methods, and acceptance criteria used were the same as those used in the 
predicate submission and provided references to the applicable sections in the previous 
submission. The risk analysis identified the verification and validation activities necessary to 
establish SE, and summarized that information in the following table: 
Table 1. Example design control activities summary for a hypothetical lacrimal stent 
Device Change  Risks  Verification/Validation  Acceptance Criteria  Summary of 
Method(s)  Results 
 Damaged  Penetration test performed  Breaking load shall be  Pass (12/12) 
tissue  with bougie  greater than 9N 
 Damage to  Mean: 15.0 
device during  (Protocol and acceptance  Standard 
Removal of 
insertion with  criteria same as Kxxxxxx  deviation: 0.39 
ring 
bougie causes  without any deviations)  Range: 14.4-15.6 
delay in patient 
treatment 
 Damaged   Simulated insertion test with  For both tests, visual  Pass (20/20) for 
tissue  bougie  inspection shall  both tests 
 Damage to   Bending test with bougie  demonstrate that the 
device causes  device can be inserted 
Shape change  delay in patient  (Protocol and acceptance  without damage. 
treatment  criteria same as Kxxxxxx 
without any deviations) 
                                                
74 ANSI/AAMI/ISO 14971 Medical devices - Application of risk management to medical devices. 
30 Contains Nonbinding Recommendations 
Device Change  Risks  Verification/Validation  Acceptance Criteria  Summary of 
Method(s)  Results 
 Difficulty   Insertion test with simulated   No visual damage    Pass (15/15) 
inserting  lacrimal duct  after simulated    Pass (10/10) 
causes delay in   Visual inspection  insertion 
Change in 
patient   No droplets, 
hydrophilic 
treatment  (Protocol and acceptance  extraneous matter, or 
coating surface 
 Abnormalities  criteria same as Kxxxxxx  abnormalities are 
area 
on catheter  without any deviations)  visualized under a 
causes damage  microscope 
to tissue 
Adverse tissue  Biocompatibility evaluation in  Materials of  Biocompatibility 
reaction from  agreement with  construction and  testing is not 
material coating  recommendations in Use of  manufacturing  needed because 
area and  International Standard ISO   materials do not  device does not 
geometric  10993-1, Biological  introduce chemicals  introduce a 
changes.  evaluation of   that raise a  biocompatibility 
medical devices - Part 1:  biocompatibility  risk. 
Evaluation   concern. 
and testing within a risk 
management process  Materials of  Material-
(CDRHs Biocompatibility  construction and  mediated 
Guidance).75 manufacturing  pyrogenicity 
materials do not  testing is not 
Leveraged all biocompatibility  introduce chemicals  needed because 
testing from another device  that raise a material- device does not 
with similar type and duration  mediated pyrogenicity  introduce a 
of contact, greater surface  concern.  material-
area, and same formulation  mediated 
and processing by the same  pyrogenicity 
device manufacturer.  risk. 
                                                
75 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/use-international-standard-iso-
10993-1-biological-evaluation-medical-devices-part-1-evaluation-and. 
31 Contains Nonbinding Recommendations 
Example C.2
In the subject 510(k), the manufacturer requested clearance to modify the geometric design and constructive materials of the single-
use sheath used in a self-retaining retractor for neurosurgery. The manufacturers design controls narrative described that a design 
failure modes and effects analysis (DFMEA) was included in the submission. In accordance with their risk management procedures, 
the manufacturer identified their design inputs, identified risks with their evaluation, risk control measures, and residual risk. The risk 
analysis identified the verification and validation activities and summarized them in this table: 
Table 2. Example design control activities summary for a hypothetical sheath 
Device Change  Risks  Verification/Validation Method(s)  Acceptance Criteria  Summary of Results 
Cytotoxicity (ISO 10993-5)77 Reactivity grade shall  There was no evidence of the test 
using the ISO minimum  be 0, which is the same  extract causing cell lysis or toxicity 
essential medium (MEM)  as for the predicate  (Grade = 0) for three replicates at 
Elution method.  device.  48 hours. 
The protocol used the same  Latex Positive Control = Grade 3 
Biocompatibility 
test article preparation and  High Density Polyethylene 
evaluation in 
extraction conditions as the  Negative Control = Grade 0 
Adverse  agreement with 
predicate (MEM with 10% 
tissue  recommendations in 
serum, 37 oC, 24 hours, at a  The test article is non-cytotoxic. 
reaction  CDRHs 
surface area/volume ratio of 6 
from  Biocompatibility 
Material change  cm2/ml), appropriate controls, 
material  Guidance.76Based on 
to polyethylene  extracts were not stored for 
change  our risk management 
more than 24 hours, and were 
procedures, 
not altered (e.g., filtered or pH 
biocompatibility 
adjusted). These testing 
testing was repeated 
conditions are the same as the 
for some endpoints. 
predicate device, the extracts 
did not change color, appear 
turbid or have particulates, and 
there were no 
deviations/amendments from 
the protocol. 
                                                
76 Use of International Standard ISO 10993-1, Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process, 
available at: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/use-international-standard-iso-10993-1-biological-evaluation-medical-
devices-part-1-evaluation-and. 
77 ISO 10993-5 Biological evaluation of medical devices - Part 5: Tests for in vitro cytotoxicity. 
32 Contains Nonbinding Recommendations 
Device Change  Risks  Verification/Validation Method(s)  Acceptance Criteria  Summary of Results 
Irritation (ISO 10993-10)78 The difference between  The polar extract showed no 
using the intracutaneous  the mean reaction score  irritation (Grade 0) and the non-
reactivity method.  for the test article and  polar extract showed minimal 
control shall be 1.0,  irritation (Grade 0/1) at 24, 48 and 
The protocol used the same  which is the same as the  72 hours, which was consistent 
test article preparation and  predicate device.  with the negative vehicle control 
extraction conditions as the  results. 
predicate (saline and sesame 
seed oil extract solvents,   50  Saline Vehicle Control = Grade 0 
oC, 72 hours, at a surface  at all timepoints 
area/volume ratio of 6  Sesame Vehicle Control = Grade 
cm2/ml), appropriate controls,  0/1 at all timepoints 
extracts were not stored for 
more than 24 hours, and  No adverse in vivo findings were 
extracts were not altered (e.g.,  noted in any of the test or control 
filtered or pH adjusted). These  animals. 
testing conditions are the same 
as the predicate device, the  The test article is a non-irritant. 
extracts did not change color, 
appear turbid, or have 
particulates, and there were no 
deviations/amendments from 
the protocol. 
                                                
78 ISO 10993-10 Biological evaluation of medical devices - Part 10: Tests for irritation and skin sensitization. 
33 Contains Nonbinding Recommendations 
Device Change  Risks  Verification/Validation Method(s)  Acceptance Criteria  Summary of Results 
Sensitization (ISO 10993- Grade 0 in both test and  Both the polar and non-polar 
10)79using the guinea pig  control animals, which  extracts scored 0 at 24 and 48 
maximization test.  is the same as the  hours for all test subjects, which 
predicate device.  was consistent with the negative 
The protocol used the same  control. The extracts did not 
test article preparation and  change color or have particulates. 
extraction conditions as the 
predicate (saline and sesame  The test article is a non-sensitizer. 
oil extract solvents, 50 oC, 72 
hours, at a surface 
area/volume ratio of 6 
cm2/ml), appropriate controls, 
extracts were not stored for 
more than 24 hours, and 
extracts were not altered (e.g., 
filtered or pH adjusted). These 
testing conditions are the same 
as the predicate device, the 
extracts did not change color, 
appear turbid or have 
particulates, and there were no 
deviations/amendments from 
the protocol. 
Acute systemic toxicity  Materials of  Acute systemic toxicity testing is 
construction and  not needed because device does 
Reviewed:  manufacturing  not introduce an acute systemic 
1) Literature; and  materials do not  toxicity risk. Neither analytical 
2) SDS that are in accordance  introduce chemicals  chemistry testing nor a 
with Appendix D of 29 CFR  that elicit acute  toxicological risk assessment were 
1910.1200.80 systemic toxicity.  used to support this rationale. 
SDS meets 29 CFR 
1910.1200 content. 
                                                
79 ISO 10993-10 Biological evaluation of medical devices - Part 10: Tests for irritation and skin sensitization. 
80 For more information about Safety Data Sheets, see 77 FR 17574. 
34 Contains Nonbinding Recommendations 
Device Change  Risks  Verification/Validation Method(s)  Acceptance Criteria  Summary of Results 
Material-mediated  Materials of  Material-mediated pyrogenicity 
pyrogenicity  construction and  testing is not needed because 
manufacturing  device does not introduce a 
Leveraged material-mediated  materials do not  material-mediated pyrogenicity 
pyrogenicity testing from  introduce chemicals  risk. Neither analytical chemistry 
another polyethylene device  that raise a material- testing nor a toxicological risk 
with similar type and duration  mediated pyrogenicity  assessment were used to support 
of contact, greater surface  concern.  this rationale. 
area, and same formulation 
and processing by the same 
device owner. 
 Patient  Sterilization validation was completed using an  Devices shall maintain  Package integrity testing results all 
infection  established method (gamma irradiation) in conformity  package integrity and  passed (n=30 each). 
 Device  with ISO 11137-1 without deviation.81 have SAL of 10-6. 
failure  Bioburden studies passed. 
causes  The sterilization validation approach was Verification 
patient  Dose Maximum (VDmax) for a Sterility Assurance Level  Sterilization validation established 
injury or  (SAL) of 10-6 in accordance with AAMI TIR33.82 SAL of 10-6. 
delay in  Package integrity testing was also conducted using 
procedure.  methods consistent with the predicate device (seal 
integrity, dye penetration, and visual inspection). 
 Damage to  Specification review and dimensional analysis.  Dimensional  Pass (n=20) 
devices  verification shall 
Geometric 
causes  demonstrate that the 
design change 
patient  sheath geometric 
injury or  change does not 
interfere with obturator. 
                                                
81 ISO 11137-1 Sterilization of health care products  Radiation  Part 1: Requirements for the development, validation and routine control of a sterilization 
process for medical devices. 
82 AAMI TIR33 Sterilization of health care products  Radiation  Substantiation of a selected sterilization dose  Method VDmax. 
35 Contains Nonbinding Recommendations 
Device Change  Risks  Verification/Validation Method(s)  Acceptance Criteria  Summary of Results 
delay in  Design validation to confirm that the sheath continues to  The sheath shall be able  Pass 
procedure. meet manufacturer-defined user requirements.  to be used with third-
 Adverse  Simulated-use testing was conducted with a prospective  party accessories and 
tissue  user to confirm that the device can achieve its intended  provide access to the 
reaction  use.  tissue identified in 
from  labeling. 
geometric  (Protocol and acceptance criteria same as Kxxxxxx 
shape  without any deviations) 
change. 
Implantation and thrombogenicity  For externally  Additional biocompatibility 
communicating devices  evaluation to assess the impact of 
Reviewed geometric changes per CDRHs  in contact with tissue or  the geometric change on the 
Biocompatibility Guidance83(Attachment A, Table A.1)  bone for < 24 hours,  biological response is not needed. 
to determine whether implantation or thrombogenicity  Table A.1 indicates that 
(which can be impacted by geometry) are recommended  implantation and 
for this device type/duration of contact.  thrombogenicity 
assessments are not 
necessary. 
                                                
83 Use of International Standard ISO 10993-1, Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process, 
available at: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/use-international-standard-iso-10993-1-biological-evaluation-medical-
devices-part-1-evaluation-and. 
36