Contains Nonbinding Recommendations
Draft Not for Implementation
Recommendations for the Use of 
Clinical Data in Premarket 
Notification [510(k)] Submissions
Draft Guidance for Industry and
Food and Drug Administration Staff
DRAFT GUIDANCE
This draft guidance document is being distributed for comment purposes 
only.
Document issued on September 7, 2023.
You should submit comments and suggestions regarding this draft document within 90 days of 
publication in the Federal Register of the notice announcing the availability of the draft 
guidance. Submit electronic comments to https://www.regulations.gov. Submit written 
comments to the Dockets Management Staff, Food and Drug Administration, 5630 Fishers Lane, 
Room 1061, (HFA-305), Rockville, MD 20852-1740. Identify all comments with the docket 
number listed in the notice of availability that publishes in the Federal Register.
For questions about this document regarding CDRH-regulated devices, contact the Office of 
Product Evaluation and Quality, Office of Regulatory Programs, Division of Regulatory 
Programs 1 (Submission Support) 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, 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 Contains Nonbinding Recommendations
Draft Not for Implementation
Preface
Additional Copies
CDRH
Additional copies are available from the Internet. You may also send an email request to CDRH-
Guidance@fda.hhs.gov to receive a copy of the guidance. Please include the document number 
GUI00020016 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., 
Bldg. 71, Room 3128, Silver Spring, MD 20993-0002, 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. Contains Nonbinding Recommendations
Draft Not for Implementation
Table of Contents
I.  Introduction ............................................................................................................................. 1
II.  Background ............................................................................................................................. 2
III.  Scope ....................................................................................................................................... 5
IV.  Appropriate Use of Clinical Data in 510(k) Decision-Making ............................................... 6
V.  Scenarios When Clinical Data May be Necessary to Determine Substantial Equivalence .... 6
A.  Scenario #1  Differences in the indications for use ........................................................ 7
B.  Scenario #2  Differences in the technological characteristics ........................................ 8
C.  Scenario #3  SE cannot be determined by non-clinical testing .................................... 10
D.  Scenario #4  Newly identified or increased risk for the predicate device .................... 11 Contains Nonbinding Recommendations
Draft Not for Implementation
Recommendations for the Use of 
1 
Clinical Data in Premarket 
2 
Notification [510(k)] Submissions
3 
4 
 
Draft Guidance for Industry and 
5 
Food and Drug Administration Staff 
6 
7   
8  This draft guidance, when finalized, will represent the current thinking of the Food and Drug 
9  Administration (FDA or Agency) on this topic.  It does not establish any rights for any person 
10  and is not binding on FDA or the public.  You can use an alternative approach if it satisfies 
11  the requirements of the applicable statutes and regulations.  To discuss an alternative 
12  approach, contact the FDA staff or Office responsible for this guidance as listed on the title 
13  page.  
14   
I.  Introduction 
15 
16  As part of FDAs Medical Device Safety Action Plan: Protecting Patients, Promoting Public 
17  Health (herein referred to as the Safety Action Plan),1 FDA committed to strengthen and 
18  modernize the premarket notification [510(k)] Program. FDA is issuing this guidance to provide 
19  our current thinking on the use of clinical data in 510(k) submissions to enhance the 
20  predictability, consistency, and transparency of the 510(k) Program. The intent of this guidance 
21  is to clarify and provide additional context for situations when clinical data may be necessary to 
22  demonstrate substantial equivalence (SE), as initially described in The 510(k) Program: 
23  Evaluating Substantial Equivalence in Premarket Notifications [510(k)] guidance (herein 
24  referred to as the 510(k) Program Guidance).2 
25   
26  In that guidance, FDA described the most common scenarios for when clinical data may be 
27 necessary in a 510(k) submission. The scenarios are further described in this guidance, and FDA 
28 has described another scenario. In addition, FDA is providing additional examples to clarify 
29 these concepts, illustrating when clinical data may or may not be needed. Providing clarity and 
30 predictability about when clinical data may be necessary to include in a 510(k) submission to 
31 demonstrate SE will aid in protecting and promoting public health. 
32
1Available at https://www.fda.gov/about-fda/cdrh-reports/medical-device-safety-action-plan-protecting-patients-
promoting-public-health.
2Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/510k-program-
evaluating-substantial-equivalence-premarket-notifications-510k.
1 Contains Nonbinding Recommendations
Draft Not for Implementation
33  In general, FDAs guidance documents do not establish legally enforceable responsibilities. 
34  Instead, guidances describe the Agencys current thinking on a topic and should be viewed only 
35  as recommendations, unless specific regulatory or statutory requirements are cited. The use of 
36  the word should in Agency guidances means that something is suggested or recommended, but 
37 not required.  
38 
II.  Background 
39 
40  In April 2018, CDRH issued the Safety Action Plan to communicate CDRHs vision for 
41  modernizing measures to improve the safety of medical devices while continuing to create more 
42  efficient pathways to bring critical devices to patients. The Safety Action Plan describes efforts 
43  underway to enhance our programs to help improve device safety. 
44   
45  In November 2018, FDA announced transformative additional steps to modernize FDAs 510(k) 
46  Program to advance the review of the safety and effectiveness of medical devices.3 In connection 
47  with this announcement, FDA also requested public feedback on these steps to continue to 
48  modernize the framework for 510(k) review while promoting patient safety and posed other 
49  questions that could inform regulatory policy development.4 One area identified by the public 
50  comments where additional clarity and transparency would be helpful was the use of clinical data 
51  in 510(k) submissions.  
52   
53  Under section 510(k) of the Federal Food, Drug, and Cosmetic (FD&C) Act, a premarket 
54  notification submission (often referred to as a 510(k)) must be submitted to FDA at least 90 days 
55  before introducing, or delivering for introduction, a device into interstate commerce for 
56  commercial distribution.5 A 510(k) is required for devices intended for human use, for which a 
57 premarket approval application (PMA) is not required, unless the device is exempt from the 
58 510(k) requirements of the FD&C Act and does not exceed the relevant limitations of 
59 exemptions in the device classification regulations. Through review of the 510(k), FDA 
60 determines whether the new device6 is substantially equivalent7 (SE) to a predicate device.8
3Please see the Statement from then FDA Commissioner Scott Gottlieb, M.D., and Jeff Shuren, M.D., Director of 
the Center for Devices and Radiological Health, on November 26, 2018, available at https://www.fda.gov/news-
events/press-announcements/statement-fda-commissioner-scott-gottlieb-md-and-jeff-shuren-md-director-center-
devices-and.
4Please see Modernizing FDAs 510(k) Program; Establishment of a Public Docket; Request for Comments, 
Docket Number FDA-2018-N-4751, available at https://www.regulations.gov/docket/FDA-2018-N-4751.
5Under section 510(k) of the FD&C Act, a 510(k) is required for devices that are not subject to a premarket 
approval application, unless the device is exempt from the 510(k) requirements of the FD&C Act and does not 
exceed the limitations of exemptions for each of the device classification regulations (see 21 CFR Parts 862-892). 
See sections 510(k) and (n) of the FD&C Act (21 U.S.C.  360(k) & (n)).
6For purposes of this guidance, a new device means a device within the meaning of section 201(h) of the FD&C 
Act that is not legally marketed. It can be either a completely new device or a modification of a legally marketed 
device that would require a new 510(k).
7The standard for a substantial equivalence determination for a 510(k) submission is set out in section 513(i) of the 
FD&C Act. 
8For purposes of an SE determination, a predicate device is (1) a device that was legally marketed prior to May 28, 
1976 (preamendments device) and for which a PMA is not required, or (2) a device that has been classified or 
2 Contains Nonbinding Recommendations
Draft Not for Implementation
61  For additional information on how FDA evaluates SE in the 510(k) review process, please see 
62  the 510(k) Program Guidance.  
63   
64  For FDA to find a new device SE to a predicate device, FDA must first find that the new device 
65  and predicate device have the same intended use. FDA must then find that the new device and 
66  predicate device have the same technological characteristics, or if they do not, that the different 
67  technological characteristics9 of the new device do not raise different questions of safety and 
68  effectiveness and that the new device is as safe and effective as a predicate device. 
69   
70  To determine the safety and effectiveness of a device, FDA also weighs if there is any probable 
71  benefit to health from the use of the device against any probable risk of injury or illness from 
72  such use,10 among other relevant factors. Under the 510(k) paradigm, the benefit-risk profile of 
73  the new device is determined in the context of a comparison to the benefit-risk profile of a 
74  predicate device; the benefit-risk profile of a new device with different technological 
75  characteristics does not need to be identical to that of its predicate device in order to determine if 
76  the new device is as safe and effective as a predicate device. The FDA guidance Benefit-Risk 
77  Factors to Consider When Determining Substantial Equivalence in Premarket Notifications 
78  (510(k)) with Different Technological Characteristics11 describes considerations for evaluating 
79  benefit-risk profile of a device in comparison to a predicate device for purposes of SE 
80  determinations. 
81   
82  In many cases, a new device that is subject to 510(k) requirements can demonstrate SE to a 
83  predicate device through robust non-clinical safety and performance data, without the need for 
84  clinical data, for example, because the intended use and technological characteristics of the new 
85  device is the same as, or sufficiently similar to, that of the predicate device. In such 
86 circumstance, clinical data would not be necessary to demonstrate SE to a predicate device, and 
87 requiring clinical data would be inconsistent with the least burdensome provisions of the FD&C 
88 Act.12 However, for certain devices subject to 510(k) requirements, obtaining clinical data may 
89 be necessary to demonstrate that a new device is SE to a predicate device. 
90
91 As described in the 510(k) Program Guidance, when analytical or non-clinical bench 
92 performance testing data or non-clinical animal13 and/or biocompatibility studies are insufficient, 
reclassified into Class II or I, or (3) a device that has been found to be SE through the 510(k) process. See 21 CFR 
807.92(a)(3) and section 513(f)(2) of the FD&C Act. 
9 A predicate device is a legally marketed device. For purposes of an SE determination, different technological 
characteristics means, with respect to a device being compared to a predicate device, that there is a significant 
change in the materials, design, energy source, or other features of the device from those of the predicate device. 
See section 513(i)(l)(B) of the FD&C Act. 
10 See 21 CFR 860.7(b). 
11 Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/benefit-risk-factors-
consider-when-determining-substantial-equivalence-premarket-notifications-510k. 
12 See section 513(i)(1)(D)(ii) of the FD&C Act, and The Least Burdensome Provisions: Concept and Principles 
guidance, available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/least-
burdensome-provisions-concept-and-principles. 
13 FDA supports the principles of the 3Rs to replace, reduce, and/or refine animal use in testing, when feasible. 
We encourage manufacturers to consult with FDAif they wish to use a non-animal testing method that they believe
3 Contains Nonbinding Recommendations
Draft Not for Implementation
93  or available scientific methods are not acceptable, e.g., the scientific methods are deemed 
94  unacceptable because they are not clinically validated or are not supported by a valid scientific 
95  rationale, FDA may request clinical performance data to support an SE determination. In such 
96  cases when clinical data are necessary, it may include, for example, data comparing the 
97  technological characteristics of the new device to the predicate device, data assessing whether a 
98  change in the indications for use results in a different intended use,14 or data supporting the 
99  assessment of the benefit-risk profile of a new device to demonstrate that the new device is as 
100  safe and effective as a predicate device. 
101   
102  Clinical data provided in support of any marketing submission, including a 510(k) submission, 
103  should constitute valid scientific evidence as defined in 21 CFR 860.7(c)(2).15 Clinical data may 
104  include, but are not limited to, results of pre- and post-market clinical investigation(s) of the 
105  device (i.e., traditional clinical trials); results of pre- and post-market clinical investigation(s) or 
106  other studies reported in the scientific literature of a comparable device; published and/or 
107  unpublished reports on clinical experience of either the device in question or a comparable 
108  device; and other sources of clinical experience such as registries, adverse event databases, and 
109  medical records (e.g., electronic health records, claims).16 Many of these sources constitute real-
110  world data,17 and the relevance and reliability of such data should be considered in evaluating 
111  whether the data constitutes valid scientific evidence sufficient to support the 510(k) submission. 
112  Additionally, when considering whether data collected on a comparable device, such as an 
113  earlier version of a device or a similar model of a device, may address certain questions of safety 
114  and effectiveness, an adequate justification regarding the applicability of such data should be 
115 provided demonstrating why such datawould be representative ofthe new device. In some cases, 
116 non-clinical data may also be needed to demonstrate that thedevices are comparable and that the 
117 clinical data from the comparable device are applicableto the new device. For purposes of this 
118 guidance, data obtained from human factors testing is not considered clinical data.
119
is suitable, adequate, validated, and feasible. We will consider if a proposed alternative method could be assessed for 
equivalency to an animal test method. 
14 As described in the 510(k) Program Guidance, for purposes of SE, the term intended use means the general 
purpose of the device or its function, and encompasses the indications for use. The term indications for use 
describes the disease or condition that the device will diagnose, treat, prevent, cure, or mitigate, including a 
description of the patient population for which the device is intended. 
15 21 CFR 860.7(c)(2) states that Valid scientific evidence is evidence from well-controlled investigations, partially 
controlled studies, studies and objective trials without matched controls, well-documented case histories conducted 
by qualified experts, and reports of significant human experience with a marketed device, from which it can fairly 
and responsibly be concluded by qualified experts that there is reasonable assurance of the safety and effectiveness 
of a device under its conditions of use. 
16 These example sources of clinical data are leveraged from theInternational Medical Device Regulators Forum 
Document, Clinical Evidence Key Definitions and Concepts, available at
http://www.imdrf.org/docs/imdrf/final/technical/imdrf-tech-191010-mdce-n55.pdf.
17For additional information regarding real world data, refer to FDAsguidance,Use of Real-World Evidence to 
Support Regulatory Decision-Making for Medical Devices, available athttps://www.fda.gov/regulatory-
information/search-fda-guidance-documents/use-real-world-evidence-support-regulatory-decision-making-medical-
devices.
4 Contains Nonbinding Recommendations
Draft Not for Implementation
III. Scope 
120 
121  This guidance provides recommendations for when clinical data may be needed to demonstrate 
122  that a device reviewed under the 510(k) Program is SE to a predicate device. The 
123  recommendations in this guidance are consistent with the 510(k) Program Guidance and expand 
124  on Section IV.F of that guidance. This guidance also provides additional detail on situations 
125  where providing clinical data may be the least burdensome18 means of demonstrating SE 
126  between a new device and a predicate device. FDA developed this guidance to improve the 
127  predictability, consistency, and transparency of the 510(k) premarket review process. 
128   
129  This guidance does not describe situations when postmarket collection of clinical data may be 
130  appropriate, such as when clinical data are required in a postmarket surveillance study.19 This 
131  guidance, and the concepts discussed herein, are not intended to propose any changes to 
132  applicable statutory and regulatory standards, such as how FDA evaluates SE, or the applicable 
133  requirements, including 510(k) content requirements and the requirement for valid scientific 
134  evidence.20 This guidance is intended to describe scenarios when clinical data may be necessary 
135  and is not intended to supersede applicable regulatory requirements of special controls that 
136  outline clinical data requirements for certain device types. 
137   
138  The principles in this guidance are applicable to devices that are subject to 510(k) review by 
139  CDRH and CBER; however, this guidance is not intended to supplant existing device-specific 
140  guidance. This guidance does not address review issues unique to combination products. For 
141  information on combination products, please refer to the Office of Combination Products 
142  webpage.21 
143   
144  If you have questions about how this guidance and a device-specific guidance apply to a 
145 particular issue, we recommend that you consider the general recommendations in this document 
146 and discuss specific questions with the appropriate review division associated with your device 
147 by submitting a pre-submission. Additional information on the pre-submission program is 
148 available in the FDA guidance, Requests for Feedback and Meetings for Medical Device 
149 Submissions: The Q-Submission Program.22
150
18See supra n. 13.
19Section 522 of the FD&C Act. For further information on postmarket surveillance studies, see FDAs guidance, 
Postmarket Surveillance Under Section 522 of the Federal Food, Drug, and Cosmetic Act, available at 
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/postmarket-surveillance-under-section-
522-federal-food-drug-and-cosmetic-act. 
20Sections 513(i) and 515 of the FD&C Act, 21 CFR Part 807 Subpart E, and 21 CFR 860.7(c)(2).
21Available at https://www.fda.gov/combination-products.
22Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/requests-feedback-and-
meetings-medical-device-submissions-q-submission-program.
5 Contains Nonbinding Recommendations
Draft Not for Implementation
IV. Appropriate Use of Clinical Data in 510(k) Decision
151 
Making 
152 
153  As described in the 510(k) Program Guidance, clinical data may be used during the 510(k) 
154  review process to support an SE determination at multiple points in the decision tree to address 
155  the critical questions in the 510(k) Decision-Making Flowchart.23 
156   
157  Typically, clinical data is reviewed after FDA finds that the intended use of the new device and 
158  the predicate device are the same, and that the devices have different technological 
159  characteristics that do not raise different questions of safety and effectiveness.24 In such cases, 
160  clinical data often is used to determine whether the new device is as safe and effective as a 
161  predicate device. However, clinical data may also be reviewed at other stages of the 510(k) 
162  review process. For example, in rare instances, FDA may rely upon clinical data to determine 
163  that new25 or modified indications for use fall within the same intended use as a predicate 
164  device.26 This guidance describes some of the more common scenarios where clinical data may 
165  be necessary to determine SE. 
166   
V.  Scenarios When Clinical Data May be Necessary to 
167 
Determine Substantial Equivalence 
168 
169  FDA initially described the most common scenarios for when clinical data may be necessary in a 
170  510(k) submission to demonstrate SE and provided illustrative examples in the 510(k) Program 
171  Guidance, Section IV.F, Requests for Performance Data.  
172   
173  In this guidance, FDA provides additional clarity on those scenarios (Scenarios 1  3 below), and 
174 describes another scenario (Scenario 4 below), to provide broad considerations to be used by 
175  industry and FDA to help determine whether clinical data may be necessary to demonstrate that a 
176  new device is SE to a predicate device:   
177   
178  1.  There are differences between the indications for use of the new device and the predicate 
179  device, and clinical data may be needed to determine SE. 
180 2.  There are differences between technological characteristics of the new device and the 
181 predicate device, and clinical data may be needed to determine SE.
182 3. SE between the new device and the predicate device cannot be determined by non-
183 clinical testing (analytical, bench, and/or animal).
184 4. A newly identified or increased risk for the predicate devicesuggests clinical data may be 
185 needed for the new devicein order to determine SE.
186
23See510(k) Program Guidance, Appendix A, Decision Points 1 through 4.
24See id. at Decision Points 5a and 5b.
25As used in this guidance, the term new in describing indications for use refers to an indication that is new or 
differs from that of the predicate device.
26See id. at Decision Point 2.
6 Contains Nonbinding Recommendations
Draft Not for Implementation
187  The information below provides additional descriptions of each of the scenarios for when clinical 
188  data may be necessary to determine SE, as well as illustrative examples. The applicability of 
189  these scenariosmay be determined based upon current knowledge, understanding, evidence, and 
 
190  experience available for the new device. Following the least burdensome provisions, the need for 
191  clinical data may also change as information on the device type is accrued. FDA acknowledges 
192  that there may be situations where one or more of these scenarios exist, but clinical data may not 
193  be needed depending on the specific circumstances surrounding the particular new device. 
194  Accordingly, for each scenario, FDA has provided examples where clinical data may be needed, 
195  as well as examples where clinical data are not typically needed, to determine SE. In addition, 
196  there may be other scenarios not described herein for which clinical data may be necessary to 
197  determine SE. Note, as described in the 510(k) Program Guidance, the examples provided below 
198  distinguish between examples that are only applicable to diagnostic devices, including in vitro 
199  diagnostics (IVDs), and therapeutic devices. This is because there are significant differences in 
200  the types of clinical data that may be needed to determine SE for these two categories of devices. 
201   
A.  Scenario #1  Differences in the indications for use 
202 
203  As described in the 510(k) Program Guidance, when the indications for use of a new device and 
204  predicate device differ, FDA must evaluate whether the indications for use of the new device fall 
205  within the same intended use as that of the predicate device. FDA determines the indications for 
206  use of the new device based on the proposed labeling27 and the indications for use statement in a 
207  510(k). Following review of the proposed labeling and indications for use statement, FDA may 
208  rely upon other clinical and/or scientific information submitted with the 510(k) in order to 
209  determine if the new device has the same intended use as the predicate device.  
210   
211  The following factors could impact when clinical data may be necessary to include in a 510(k) 
212 submission to demonstrate SE when there are differences between the indications for use of the 
213 new device and the predicate device, as shown in illustrative examples 1-A, 1-B, 1-C, and 1-D:
214
215  Differences in the patient population
216  Differences in the disease
217  Differences in the anatomical site, structure, or pathology
218  General to specific considerations28
219  Expansion of the new devices currently-cleared indications for use
220  Unknown or different benefit-risk profile for the proposed indications for use
221
222 Example1-A: A certain device typically does not require clinical data to be included in a 510(k) 
223 submission. However, if a new device is indicated for use in a higher risk population (e.g., 
27Pursuant to section 513(i)(1)(E)(i) of the FD&C Act, the proposed labeling in a 510(k) submission is used to 
determine a devices intended use. The intended use of a device encompasses the indications for use.
28See 21 CFR 807.92(a)(5); see also FDAs guidance General/Specific Intended Use, available at 
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/generalspecific-intended-use-guidance-
industry, which identifies the general principles that will be considered by FDA in determining when a specific 
indication for use is reasonably included within a general indication for use of a medical device for purposes of 
determining SE. 
7 Contains Nonbinding Recommendations
Draft Not for Implementation
224  different disease stage) than the predicate device, clinical data may be needed to demonstrate SE 
225  if there is increased risk for the use of the new device in the higher risk population due to 
226  differences in the benefit-risk profile of the new device for the proposed indications for use when 
227  compared to the predicate device. 
228   
229  Example 1-B: A certain device is indicated for use in a specific anatomic location that is in 
230  proximity to critical organs. The manufacturer intends to pursue an indication for use in a 
231  different anatomic location that does not represent a new intended use and does not pose 
232  additional or different risks. In this scenario, non-clinical data may suffice to demonstrate SE 
233  because the indication for use for the predicate device (i.e., the currently-marketed device) 
234  represents a higher risk or similar risk scenario than that of the new device. As a result, no 
235  additional clinical data are likely to be necessary to demonstrate SE because the benefit-risk 
236  profile of the new device with the expanded indications for use is comparable to that of the 
237  predicate device.  
238   
239  Example 1-C: A device is indicated for use in a specific anatomic location, and a manufacturer 
240  wants to expand the indications for use to a different anatomic location for the same intended 
241  use. There are no other changes to the device. Based on what is known for this device type in the 
242  literature and through clinical experience, using the device in this new anatomic location presents 
243  an increased risk (for example, due to increased proximity to critical organs or structures, or the 
244  indication includes a procedure that is technically more risky or complex). Clinical data may be 
245  necessary to demonstrate SE between the new device with the expanded indications for use and 
246  the predicate device (i.e., the currently-marketed device) due to the increased risk that may 
247  adversely affect the benefit-risk profile of the new device when compared to the predicate 
248  device. 
249   
250  Example 1-D: A predicate laser device is indicated for treatment of a certain skin condition. A 
251  new laser device is indicated for treatment of a different skin condition that is not a new intended 
252  use. This new laser device utilizes a lower energy wavelength than the predicate device for 
253  treatment. Although the lower energy wavelength is not expected to present increased risk 
254  compared to the predicate device, clinical data may be needed to demonstrate that the new device 
255  has an equivalent benefit-risk profile to the predicate device, given that the new device may 
256  result in a different degree of benefit for treatment compared to the predicate device due to both 
257  the lower energy wavelength and the difference in skin conditions.  
258   
B.  Scenario #2  Differences in the technological 
259 
characteristics 
260 
261  As discussed in the 510(k) Program Guidance, clinical data may be necessary to include in a 
262 510(k) submission when there are differences between the technological characteristics of the 
263 new device and the predicate device that do not raise different questions of safety and 
264 effectiveness in order to establish that a new device performs equivalent to the predicate device 
265 despite the differences in those characteristics.29
29Section 513(i)(1)(A)(ii) of the FD&C Act.
8 Contains Nonbinding Recommendations
Draft Not for Implementation
266 
267  The following factors should be considered in determining whether clinical data may be 
268  necessary to include in a 510(k) submission to demonstrate SE when there are differences 
269  between the technological characteristics30,31 of the new device and the predicate device, as 
270  illustrated in examples 2-A, 2-B, and 2-C: 
271   
272    Significant change in materials 
273    Significant change in device design 
274    Significant change in energy source 
275    Significant change in other device features  
276   
277  Example 2-A: An implanted device is used to provide anatomic support resulting in improved 
278  function. Most such devices are made of non-resorbable materials. Available performance data 
279  on such devices may not be applicable to a device comprised of resorbable material, which  
280  resorbs in vivo over time. For this difference in technology, assuming it does not raise different 
281  questions of safety and effectiveness, clinical data may be needed to support the SE 
282  determination. 
283   
284  Example 2-B: An IVD uses a monoclonal antibody as a critical reagent. If the manufacturer 
285  decides to change to a different clone from the previous antibody, clinical data may be needed to 
286  support the SE determination, as the differences in technological characteristics between the new 
287  IVD and the predicate IVD raise a question of whether the clinical performance of the new IVD 
288  can be expected to be equivalent to the clinical performance of the predicate IVD. 
289   
290  Example 2-C: A manufacturer chooses to add additional sizes of an implanted device to its 
291  existing line of cleared, implanted devices. No other changes are made to the design, materials, 
292  or other device features. The new sizes are within the minimum and maximum of the cleared, 
293  implanted devices of the device type. The new devices can likely be assessed using adequate 
294 non-clinical testing methods to determine SE to the predicate device. It is unlikely that clinical 
295 data would be necessary to evaluate this change in technological characteristic.
296
297 However, if the size of the new implanted device would become the new maximum or minimum 
298 size of all cleared, implanted devices of the device type, expanding the range of device sizes, 
299 provided that the intended use of the new device is the same as the predicate device, clinical data 
300 may be needed to support an SE determination.
301
30Differences in technological characteristics is defined in section 513(i)(1)(B) of the FD&C Act.
31The 510(k) Program Guidancedescribes overarching aspects for consideration regarding device design, materials, 
energy source, and other key technological features. For further information, please see Section IV.E of the 510(k) 
Program Guidance, available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/510k-
program-evaluating-substantial-equivalence-premarket-notifications-510k. 
9 Contains Nonbinding Recommendations
Draft Not for Implementation
C. Scenario #3  SE cannot be determined by nonclinical 
302 
testing
303 
304  Clinical data may be necessary to include in a 510(k) submission when non-clinical testing, such 
305  as analytical, bench, and/or animal testing, is not adequate to establish that the new device is SE 
306  to the predicate device.32 
307   
308  The following factors represent considerations for determining when clinical data may be 
309  necessary to demonstrate SE as non-clinical testing may not be appropriate for a particular 
310  device, because: 
311   
312    There is no model (e.g., analytical, bench, animal) available 
313    The available model(s) may not be adequate because the model has certain limitations 
314  that do not allow for an adequate assessment 
315    The model may not be predictive of clinical outcomes 
316    There are anatomical and/or pathophysiological species-specific questions that rely on 
317  clinical evidence 
318   
319  Example 3-A: For a new device with an intended use for treatment of schizophrenia, clinical data 
320  may be needed to demonstrate that the device is SE to the predicate device given the limited 
321  availability of non-clinical models and inadequate predictions of clinical outcomes for 
322  schizophrenia. 
323   
324  Example 3-B: A basic medical image management and processing system that adds a new organ-
325  specific processing, filtering, or enhancement feature may need to submit clinical data to 
326  demonstrate that the new device is SE to the predicate device. This may occur in scenarios where 
327  there is no phantom that accurately models the organ in that imaging modality, so we 
328  recommend using clinical images as part of the device evaluation. 
329   
330  Example 3-C: For a device intended for use to support hemostasis, clinical data may be 
331  necessary to demonstrate that the new device is SE to the predicate device given the inadequacy 
332  of current bench and animal models to be predictive and representative of human performance 
333  due to the differences in coagulation pathways between animals and humans. 
334   
335  Example 3-D: For a device intended for use in screening donors of blood and blood products for 
336  transfusion-transmitted infections, clinical data may be necessary to demonstrate that the new 
337 device is SE to the predicate device given the inability of analytical testing to evaluate the 
338 clinical performance of the assay and the risks to the blood supply associated with incorrect 
339 results.
340
341 Example 3-E: For IVDs, including for an IVD intended for point-of-care use where the predicate 
342 device is not intended for point-of-care use, clinical data may be necessaryto demonstrate that 
343 the new device performs equivalent and is SE to the predicate device. This is due to multiple 
32Section 513(i)(1)(A) of the FD&C Act.
10 Contains Nonbinding Recommendations
Draft Not for Implementation
344  factors, including the variety of clinical environments and the diverse populations with which the 
345  device is intended to be used, which can affect the performance of the device and cannot be 
346  evaluated solely through analytical data. 
347   
348  Example 3-F: For a device intended for an aesthetic purpose (e.g., to treat acne scars, or to 
349  reduce wrinkles), it may be difficult to demonstrate the effectiveness of the new device solely 
350  with non-clinical (e.g., animal) data to determine SE to a predicate device. This is because there 
351  are no appropriate animal models for device types intended for aesthetic purposes, and validated 
352  aesthetic measures of effectiveness and the translatability of such measures in humans have not 
353  been established. For this reason, in many scenarios, clinical data may be necessary to 
354  demonstrate that a new device intended for an aesthetic purpose is SE to the predicate device. 
355   
D.  Scenario #4  Newly identified or increased risk for the 
356 
predicate device 
357 
358  Although significant attention is applied to the design, testing, manufacturing, and evaluation of 
359  medical devices prior to their introduction into the marketplace, not all information regarding 
360  benefits and risks is available nor can be generally known at that time. New information about a 
361  devices safety, including unexpected adverse events, may become available once the device is 
362  more widely distributed and used in clinical practice. 
363   
364  In such cases, there may not be identified differences between the technological characteristics of 
365  new device and the predicate device that raise different questions of safety or effectiveness. 
366  However, there may be an awareness of new scientific information regarding a newly identified 
367  or increased risk of the predicate device, and clinical data may be needed to determine SE in 
368  light of the new scientific information.  
369   
370  As described in the 510(k) Program Guidance (Section IV.F), new scientific information may 
371  affect FDAs expectations concerning the type and level of performance data to be included in a 
372  510(k) submission. FDA may learn of these new or increased risks for a device (compared to 
373  what was known prior to introduction into the marketplace) from voluntarily-reported adverse 
374  events or literature, or from other sources of real-world data (e.g., 522 postmarket surveillance 
375 studies33,34 or recalls35), and incorporate that information into its review of premarket 
376 submissions and SE determinations. Information regarding new or increased risks for a device is 
377 often publicly communicated (e.g., via safety communication, guidance, advisory committee 
378 meeting) by FDA. When requesting clinical data during premarket review due to a new or 
33For further information on postmarket surveillance studies, see FDAs guidance, Postmarket Surveillance Under 
Section 522 of the Federal Food, Drug, and Cosmetic Act, available at https://www.fda.gov/regulatory-
information/search-fda-guidance-documents/postmarket-surveillance-under-section-522-federal-food-drug-and-
cosmetic-act.
34See FDAs webpage on the 522 Postmarket Surveillance Studies Program, available at 
https://www.fda.gov/medical-devices/postmarket-requirements-devices/522-postmarket-surveillance-studies.
35See FDAs webpage on Recalls, Market Withdrawals, & Safety Alerts available at 
https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts, as well as the Medical Device Recalls 
database, available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfRES/res.cfm. 
11 Contains Nonbinding Recommendations
Draft Not for Implementation
379  increased risk, FDA intends to provide an explanation of the reason(s) for the request and why 
380  such information is necessary to determine whether the new device is SE, consistent with the 
381  FDA guidance on Developing and Responding to Deficiencies in Accordance with the Least 
382  Burdensome Provisions.36 
383   
384  Whenever possible, FDA recommends that manufacturers should not use certain devices as 
385  predicate devices if they exhibit new or increased risks, especially if an alternative predicate 
386  device exists without the new or increased risk.37 However, in certain circumstances, there may 
387  not be an alternative predicate device available without the new or increased risk. Devices that 
388  exhibit new or increased risks may lead FDA to consider the need for additional data, such as 
389  clinical data, in the premarket submissions for such technology, as illustrated in examples 4-A, 
390  4-B, and 4-C. 
391   
392  Example 4-A: Through review of recalls, voluntarily-reported adverse events, and published 
393  scientific literature, FDA became aware of certain malfunctions for a particular device. However, 
394  based on FDAs assessment of the totality of clinical (e.g., published medical literature) and non-
395  clinical data (e.g., non-clinical bench performance testing), FDA determined that detailed non-
396  clinical testing, accompanied by appropriate instructions for use, could adequately demonstrate 
397  whether the risk for the new device was adequately mitigated by its design and technological 
398  features. FDA determined that additional clinical data was not necessary to demonstrate SE for 
399  new 510(k) submissions that may use this device as the predicate, provided that the appropriate 
400  non-clinical testing and certain labeling considerations are addressed in the 510(k) submission. 
401   
402  Example 4-B: A device was initially cleared by FDA without the inclusion of clinical data in the 
403  510(k). Following introduction of the device into the marketplace, recalls and other postmarket 
404  surveillance data reviewed by FDA suggested safety concerns related to component failure in the 
405  device. After a thorough review of the available data, FDA issued a class-wide postmarket 
406  surveillance study order under section 522 of the FD&C Act for currently marketed devices for 
407  this device type and began requesting that clinical data be included in 510(k) submissions for 
408  new devices seeking marketing clearance for this device type to ensure an adequate safety profile 
409  prior to marketing. 
410   
411  Example 4-C: There was a device issue reported that could lead to significant patient injury in 
412  surgical procedures. For this cleared device, the primary evidence demonstrating SE in 510(k) 
413 submissions had been non-clinical design verification and validation testing of the technological 
414 characteristics of the device. The manufacturer voluntarily recalled the device, submitted a new 
415 510(k) to address the issue, and included non-clinical and clinical performance data because the 
416 changes could significantly affect the safety or effectiveness of the device.38 FDA issued device-
36Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/developing-and-
responding-deficiencies-accordance-least-burdensome-provisions.
37Please see FDAs draft guidance, Best Practices for Selecting a Predicate Device to Support a Premarket 
Notification [510(k)] Submission, available at https://www.fda.gov/regulatory-information/search-fda-guidance-
documents/best-practices-selecting-predicate-device-support-premarket-notification-510k-submission. When final, 
that guidance will represent FDAs current thinking on that topic.
38See 21 CFR 807.81.
12 Contains Nonbinding Recommendations
Draft Not for Implementation
417  specific guidance to outline recommendations for non-clinical and clinical performance testing 
418 for this device type.
13