Contains Nonbinding Recommendations
Draft  Not for Implementation
Evidentiary Expectations for
510(k) Implant Devices
____________________________________________________________________________
Draft Guidance for Industry and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DRAFT GUIDANCE
This draft guidance document is being distributed for comment purposes 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publication in the Federal Register of the notice announcing the availability of the draft 
guidance.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Draft Not for Implementation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 
GUI00020017 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Draft Not for Implementation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 ....................................................................................................................................... 4
IV.  Recommendations for 510(k) Implants .................................................................................. 5
General Considerations .................................................................................................... 5 
(1) What are the indications for use of the device? ............................................................ 5 
(2) What is the intended duration of implantation? ............................................................ 6 
(3) What is the anticipated patient and physician experience with the implant? ............... 7 
  Non-Clinical Recommendations ...................................................................................... 7 
(1)  Biocompatibility ........................................................................................................... 8 
(2) Sterility and Shelf Life ................................................................................................. 9 
(3) Reprocessing and Cleaning ........................................................................................ 11 
(4) Software and Cybersecurity........................................................................................ 11 
(5) Electrical Safety and Electromagnetic Compatibility ................................................ 12 
(6) Magnetic Resonance (MR) Compatibility .................................................................. 13 
(7) Other Non-Clinical Performance Testing ................................................................... 14 
(8) Animal Testing ........................................................................................................... 17 
(9) Implant Device Design Considerations ...................................................................... 18 
  Human Factors/Usability................................................................................................ 19 
  Clinical Performance Testing ......................................................................................... 20 
  Patient Experience Information ...................................................................................... 21 
  Labeling and Other Recommendations .......................................................................... 22 
(1) Instructions for Use .................................................................................................... 22 
(2) Implant Cards and Other Patient Information ............................................................ 22 
 
   
  Contains Nonbinding Recommendations
Draft Not for Implementation
Evidentiary Expectations for 
1 
510(k) Implant Devices
2 
3  ______________________________________________________________________________
Draft Guidance for Industry and
4 
Food and Drug Administration Staff
5 
6   
7  This draft guidance, when finalized, will represent the current thinking of the Food and Drug 
8  Administration (FDA or Agency) on this topic.  It does not establish any rights for any person 
9  and is not binding on FDA or the public.  You can use an alternative approach if it satisfies 
10  the requirements of the applicable statutes and regulations.  To discuss an alternative 
11  approach, contact the FDA staff or Office responsible for this guidance as listed on the title 
12  page.  
13   
I.  Introduction 
14 
15  As part of FDAs Medical Device Safety Action Plan: Protecting Patients, Promoting Public 
16  Health (herein referred to as the Safety Action Plan),1 FDA committed to strengthen and 
17  modernize the premarket notification [510(k)] Program. To enhance the predictability, 
18  consistency, and transparency of the 510(k) Program, FDA is issuing this guidance to provide 
19  our current thinking on 510(k) submissions for implant devices. This guidance is intended to 
20  serve as a primary resource on general recommendations for all implant devices for which a 
21  510(k) is required (510(k) Implants), while device-specific guidances may provide further 
22  specificity for a given device type. This document is intended to clarify our evidentiary 
23  expectations for 510(k) Implants. By evidentiary expectations, we mean that this document is 
24  intended to assist industry in design and execution of appropriate performance testing that may 
25  be necessary to support 510(k) submissions for implants. It also provides general 
26  recommendations for other content, including proposed labeling, to include in these submissions. 
27  In addition, some of the recommendations in the guidance, such as those related to identification 
28  and mitigation of certain risks associated with implants, may be relevant beyond the context of 
29  preparing a 510(k) submission and helpful to consider throughout the total product lifecycle. For 
30  purposes of this guidance, a submitter is the entity that submits the 510(k) to FDA for review. 
31   
32 For the current edition of the FDA-recognized consensus standards referenced in this document, 
33 see the FDA Recognized Consensus Standards Database.2 For more information regarding use of 
34 consensus standards in regulatory submissions, refer to the FDA guidance titled Appropriate 
1Available at https://www.fda.gov/about-fda/cdrh-reports/medical-device-safety-action-plan-protecting-patients-
promoting-public-health.
2Available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm.
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35  Use of Voluntary Consensus Standards in Premarket Submissions for Medical Devices3 and 
36  Standards Development and the Use of Standards in Regulatory Submissions Reviewed in the 
37  Center for Biologics Evaluation and Research.4 
38   
39  In general, FDAs guidance documents do not establish legally enforceable responsibilities. 
40  Instead, guidances describe the Agencys current thinking on a topic and should be viewed only 
41  as recommendations, unless specific regulatory or statutory requirements are cited. The use of 
42  the word should in Agency guidances means that something is suggested or recommended, but 
43  not required.  
44   
II.  Background 
45 
46  In April 2018, CDRH issued the Safety Action Plan to communicate CDRHs vision for 
47  modernizing measures to improve the safety of medical devices while continuing to create more 
48  efficient pathways to bring critical devices to patients. The Safety Action Plandescribes efforts 
49  underway to modernize the 510(k) Program. 
50   
51  In November 2018, FDA announced transformative new steps to modernize FDAs 510(k) 
52  Program to advance the review of the safety and effectiveness of medical devices.5 In connection 
53  with this announcement, FDA also requested public feedback on these steps to continue to 
54  modernize the framework for 510(k) review while promoting innovation and patient safety, and 
55  posed other questions that could inform regulatory policy development.6 One area identified by 
56  the public comments where additional clarity and transparency would be helpful related to 
57  recommendations specific to 510(k) submissions for implants.  
58   
59  Under section 510(k) of the Federal Food, Drug, and Cosmetic (FD&C) Act, a premarket 
60  notification submission (often referred to as a 510(k)) must be submitted to FDA at least 90 days 
61  before introducing, or delivering for introduction, a device into interstate commerce for 
62 commercial distribution.7 A 510(k) is required for devices intended for human use, for which a 
63 premarket approval application (PMA) is not required, unless the device is exempt from the 
64 510(k) requirements of the FD&C Act and does not exceed therelevant limitations of 
65 exemptions in the device classification regulations. Through review of the 510(k), FDA
3Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/appropriate-use-
voluntary-consensus-standards-premarket-submissions-medical-devices.
4Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/standards-development-
and-use-standards-regulatory-submissions-reviewed-center-biologics-evaluation.
5Please 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.
6Please 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.
7See sections 510(k) and (n) of the FD&C Act (21 U.S.C.  360(k) & (n)).
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66  determines whether the new device8 is substantially equivalent9 (SE) to a predicate device.10
67  For additional information on how FDA evaluates SE in the 510(k) premarket review process, 
68  please see the FDA guidance entitled The 510(k) Program: Evaluating Substantial Equivalence 
69  in Premarket Notifications [510(k)], 11 hereafter called the 510(k) Program Guidance.  
70   
71  For FDA to find a new device SE to a predicate device, FDA must first find that the new device 
72  and predicate device have the same intended use. FDA must then find that the new device and 
73  predicate device have the same technological characteristics, or if they do not, that the different 
74  technological characteristics12 of the new device do not raise different questions of safety and 
75  effectiveness and that the new device is as safe and effective as a predicate device.  
76   
77  To determine the safety and effectiveness of a device, FDA weighs if there is any probable 
78  benefit to health from the use of the device against any probable risk of injury or illness from 
79  such use,13 among other relevant factors. Under the 510(k) paradigm, the benefit-risk profile of 
80  the new device is determined in the context of a comparison to the benefit-risk profile of a 
81  predicate device; the benefit-risk profile of a new device with different technological 
82  characteristics does not need to be identical to that of its predicate device in order to determine if 
83  the new device is as safe and effective as a predicate device. The FDA guidance Benefit-Risk 
84  Factors to Consider When Determining Substantial Equivalence in Premarket Notifications 
85  (510(k)) with Different Technological Characteristics14 describes considerations for evaluating 
86  benefit-risk profile of a device in comparison to a predicate device for purposes of SE 
87  determinations. 
88   
89  FDA expects that submitters will typically provide a variety of non-clinical and/or clinical data 
90 to support that an implant is as safe and effective as a predicate device, given thescientific and 
91 clinical considerations that implants often raise. In addition, if FDA has established special 
92 controls applicable to the device type, the information in the 510(k) submission would need to 
93 demonstrate that the proposed device meetsthe relevant special controls for the device to be 
8For 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).
9The standard for a substantial equivalence determination for a 510(k) submission is set out in section 513(i) of the 
FD&C Act. 
10A predicate device is a legally marketed device. For 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 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.
11Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/510k-program-
evaluating-substantial-equivalence-premarket-notifications-510k.
12For 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)(1)(B) of the FD&C Act. 
13See 21 CFR 860.7(b).
14Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/benefit-risk-factors-
consider-when-determining-substantial-equivalence-premarket-notifications-510k.
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94  classified into class II, which may require, among other things, submission of certain 
95  performance data for the device.15
96   
97  As with all devices reviewed through the 510(k) process, to reach a scientifically justified 
98  determination regarding SE for an implant, FDA conducts a robust and comprehensive 
99  evaluation of information included in a submission. If necessary to reach a determination 
100  regarding SE, FDA will request additional information.16 FDA may rely on descriptive 
101  information, non-clinical data and/or clinical data, including postmarket data, to support SE 
102  determinations for implants.  
103   
104  In order to enhance transparency, consistency, and predictability of the review process and to 
105  promote the development of safe and effective 510(k) Implants, this guidance discusses 
106  considerations that are generally relevant to all types of implants subject to 510(k) requirements. 
107  It is intended to serve as a primary resource, used in conjunction with other guidances, to provide 
108  clarity and facilitate discussions regarding expectations for performance data that may be 
109  necessary to establish SE for implants. However, the type and quantity of performance data 
110  needed to support an SE determination for a particular device will vary depending on the device 
111  and/or device type, and on the differences from the predicate device. As noted above, the 
112  guidance also includes recommendations, such as those related to implant labeling, that are 
113  important to consider for any 510(k) Implant. 
114   
115  To help guide submitters, this guidance also refers to a wide variety of guidances and voluntary 
116  consensus standards that might apply to a particular submission. While this document discusses 
117  recommendations for implants generally, device-specific guidances may provide further 
118  specificity for a given device type.17 
119   
III.  Scope 
120 
121  This guidance applies to implants for which a 510(k) is required. Implants subject to premarket 
122 approval, including those that may be eligible for the De Novo classificationprocess, and 
123  implants that are exempt from the 510(k) requirements of the FD&C Act are outside the scope of 
124  this document.18 An implant is defined in 21 CFR 860.3(d) as a device that is placed into a 
125  surgically or naturally formed cavity of the human body. The regulation further specifies that 
126 [a] device is regarded as an implant for the purpose of this part only if it is intended to remain 
127 implanted continuously for a period of 30 days or more, unless the Commissioner determines 
15See section 513(a)(1)(B) of the FD&C Act.
16See 21 CFR 807.87(m). For more information on FDAs policies regarding requests for additional information, 
please see the FDA guidance, Developing and Responding to Deficiencies in Accordance with the Least 
Burdensome Provisions, available at https://www.fda.gov/regulatory-information/search-fda-guidance-
documents/developing-and-responding-deficiencies-accordance-least-burdensome-provisions.
17To search for guidance documents, please see the database at https://www.fda.gov/regulatory-information/search-
fda-guidance-documents. Device-specific guidance documents can also be identified by searching for the relevant 
product code at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPCD/classification.cfm.
18The De Novo classification process provides a pathway for certain new types of devices to obtain marketing 
authorization as class I or class II devices, rather than remaining automatically designated as a class III device, 
which would require premarket approval under section 513(f)(1) of the FD&C Act.
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128  otherwise in order to protect human health. Therefore, the term implant in this guidance refers 
129  to devices intended to be implanted continuously for 30 days or more. However, FDA believes 
130  that many of the review considerations and associated recommendations in this guidance are also 
131  applicable to devices that are intended to remain implanted continuously for fewer than 30 days. 
132  For example, while a single catheter may only be used for a few days, a patient may routinely 
133  replace catheters as part of living with a chronic condition, and so cumulative patient exposure to 
134  a catheter may be significantly longer than 30 days and potentially lifelong. Therefore, we 
135  recommend that submitters of 510(k)s for devices intended to be implanted continuously for 
136  fewer than 30 days also consider the recommendations in this guidance. We note, however, that 
137  the amount and type of non-clinical and/or clinical data needed to support an SE determination 
138  may vary depending on the intended duration of implantation.  
139   
140  We recommend that submitters consider the general recommendations in this document and 
141  discuss specific questions with the appropriate review division associated with their device by 
142  submitting a pre-submission. Additional information on the pre-submission program is available 
143  in the FDA guidance, Requests for Feedback and Meetings for Medical Device Submissions: 
144  The Q-Submission Program.19 
145   
IV.  Recommendations for 510(k) Implants 
146 
  General Considerations 
147 
148  We recommend that submitters consider the following questions regarding the evidence and 
149  information that may be necessary to support an SE determination for a 510(k) Implant. 
150  (1)  What are the indications for use of the device? 
151  FDA recommends that submitters carefully consider the indications for use of the device, taking 
152  into account the specific intended patient population, disease state, and conditions of use, when 
153  designing and conducting performance testing. For example, some 510(k) Implants may be 
154  indicated for palliative use in patients with limited mobility in a hospice care setting. Testing 
155  appropriate for these implants may be different than testing appropriate for implants indicated to 
156  remain permanently within an ambulating patient (e.g., a hip implant designed to accommodate 
157  repetitive mechanical loading). Similarly, FDA recommends that submitters provide 
158  performance data that are representative of the way in which the device is indicated to be used, 
159  including the anatomical location(s) for which it is indicated. For example, although orthopedic 
160  devices and dental devices may both interface with bone, the biochemical and biomechanical 
161  environment differ between dental and orthopedic devices and therefore data generated for an 
162  orthopedic device may not apply to a dental device.  
163   
164 510(k) Implants specifically indicated for use in pediatricpopulations may haveunique 
165 considerations compared to implants indicated for use in adults. For purposes of this guidance,
166 FDA considers pediatric patients to beindividuals who are 21 years of age or younger (that is, 
19Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/requests-feedback-and-
meetings-medical-device-submissions-q-submission-program.
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167  from birth through the 21st year of life, up to but not including the 22nd birthday).20 Designing 
168  pediatric implants can be challenging: pediatric individuals are often smaller and more active 
169  than adults; body structures and functions may change throughout development; and pediatric 
170  individuals may be long-term device users, which raises additional concerns about device 
171  longevity and long-term exposure to implanted materials. FDA recommends that for 510(k) 
172  Implants indicated for use in pediatric patients, submitters follow the recommendations in FDAs 
173  guidance Premarket Assessment of Pediatric Medical Devices21 (hereafter called the 
174  Pediatrics Guidance). Additionally, submitters should consider whether it is appropriate to 
175  extrapolate adult data for pediatric use. For example, certain orthopedic devices should be 
176  evaluated differently for pediatric patients versus adults due to differences in skeletal maturity. 
177  See FDAs guidance Leveraging Existing Clinical Data for Extrapolation to Pediatric Uses of 
178  Medical Devices22 for more information. Clinical studies with pediatric patients must comply 
179  with applicable requirements to protect the rights, safety, and welfare of children23 involved as 
180  study participants, including FDA regulations at 21 CFR Part 50, Subpart D. FDAs Pediatrics 
181  Guidance discusses these issues in more detail. 
182  (2)  What is the intended duration of implantation? 
183  FDA recommends that submitters consider the intended duration of implantation or of patient 
184  exposure to the device when designing and conducting performance testing. While many 
185  implants are intended for permanent implantation, others are intended to be implanted for a 
186  period of time and then removed; still other implants are implanted and intended to degrade or 
187  resorb over time. Testing appropriate for a device that is intended to degrade over 30 days may 
188  be different than for a device that is intended to degrade over a year, or one that is not intended 
189  to degrade at all but is still subject to wear over its lifetime. In keeping with the least burdensome 
190  provisions,24 in certain cases, FDA may consider whether results from shorter duration testing 
191 can be extrapolated to provide information about long-term performance. There may be implants 
192 for which non-clinical testing is suitably predictive of longer-term clinical performance, or for 
193 which 1-year performance is suitably predictive of 5-year performance. For devices expected to 
20See section 520(m)(6)(E) of the FD&C Act (21 U.S.C.  360j(m)(6)(E)(i)), which defines pediatric patients for 
purposes of a Humanitarian Device Exemption as age 21 years or younger at the time of diagnosis or treatment and 
specifies categories of pediatric subpopulations; see also 21 CFR 814.3(s).
21Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/premarket-assessment-
pediatric-medical-devices.
22Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/leveraging-existing-
clinical-data-extrapolation-pediatric-uses-medical-devices. The principles discussed in this guidance may be helpful 
regarding data considerations to support an indication for use of an implant in a pediatric population. We note, 
however, that if a change in the indications for use to add a pediatric indication constitutes a change in the intended 
use of the 510(k) Implant, the submitter would need to identify an appropriate predicate device with this same 
intended use in order to obtain clearance to market the device for the pediatric indication through the 510(k) process.
23FDAs human subject protection regulations define children as persons who have not attained the legal age for 
consent to treatments or procedures involved in clinical investigations, under the applicable law of the jurisdiction in 
which the clinical investigation will be conducted. See 21 CFR 50.3(o). Therefore, some pediatric patients, as 
that term is used in this guidance, may not meet the definition of children. 
24Please see the FDA guidance, The Least Burdensome Provisions: Concept and Principles, available at 
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/least-burdensome-provisions-concept-
and-principles, for additional discussion of FDAs policies and implementation of the least burdensome provisions 
in the FD&C Act.
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194  be replaced repeatedly, we recommend that submitters consider testing reflective of the 
195  aggregate patient exposure.  
196   
197  FDA recommends that submitters consider whether testing should be provided to address safety 
198  and effectiveness questions associated with wear or degradation, whether intended or 
199  unintended. Depending on the device and/or device type and its differences from the predicate, a 
200  combination of bench performance testing (e.g., wear testing and characterization of wear debris) 
201  and biological evaluation (e.g., in vivo testing) may be needed to demonstrate SE. Information 
202  related to wear and degradation provided in a 510(k) should consider the expected lifespan of the 
203  implant and take into account the implant location, potential local and systemic biological 
204  responses to the implant, and potential degradation products. When designing and conducting 
205  performance testing, we recommend accounting for worst-case implantation conditions. 
206  (3)  What is the anticipated patient and physician experience 
207  with the implant? 
208  FDA recommends that submitters consider both the patient and the physician experience with the 
209  implant in performing risk analysis and identifying performance testing that may be needed to 
210  demonstrate SE. Submitters should consider whether risks such as the following are relevant to 
211  their devices and are adequately addressed in their 510(k) submission. For example, the 
212  submitter should consider if certain features of its device could increase the risks identified 
213  below relative to the predicate: 
214    Risks associated with everyday activities (e.g., the effect to the implant during airport 
215  security screening or exposure to magnetic fields); 
216    Risks associated with ongoing or future medical care (e.g., magnetic resonance or 
217  interaction with other implants); 
218    Risks associated with reoperation or revision associated with the implant; 
219    Risks that may vary between different patient populations based on patient 
220  demographics;  
221    Risks associated with duration of use (e.g., physical discomfort or other adverse 
222  events); 
223    Risks associated with user interaction with the implant, including considerations 
224  regarding user training and instructions for ongoing maintenance of the device and/or 
225  device updates (e.g., software or firmware updates); 
226   Risks associated with device design/ergonomics and human factors issues related to 
227  use by a physician; and 
228    Risks associated with the implantation procedure, including shorter or longer 
229  operating time, infection, tissue damage caused by implantation, associated operative 
230  imaging radiation exposure, etc. 
231   
  NonClinical Recommendations 
232 
233 This section highlights non-clinical issues that are generally relevant across 510(k) Implants and 
234 provides recommendations for related performance testing and information to include in a 510(k) 
235 submission. We recommend that submitters consider the non-clinical issues outlinedbelow. We 
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236  believe this will lead to higher quality submissions and a more efficient review process. In 
237  addition, we believe that considering the risks identified below and related mitigation strategies 
238  during the design process is an important part of efforts to continuously improve the safety of 
239  510(k) Implants. For information on recommended content and format of complete test reports 
240  for non-clinical bench performance testing in premarket submissions, generally, refer to FDAs 
241  guidance, Recommended Content and Format of Non-Clinical Bench Performance Testing 
242  Information in Premarket Submissions,25 hereafter called the Non-Clinical Bench Testing 
243  Guidance.  
244   
245  As explained above, the type and quantity of performance data needed to support an SE 
246  determination for a particular device will vary depending on the device and/or device type, and 
247  on the differences from the predicate device. Accordingly, it may not be necessary to provide all 
248  the information or conduct all the performance testing described below for a particular 510(k) 
249  submission. In cases where the submitter believes the information or testing described in this 
250  guidance does not apply to their device, we recommend that the submitter provides a rationale 
251  explaining why they believe the recommended information or testing is not applicable in the 
252  510(k) submission. 
253  (1)  Biocompatibility 
254  We recommend that a biocompatibility evaluation for an implant be performed in accordance 
255  with the FDA guidance, Use of International Standard ISO 10993-1, Biological evaluation of 
256  medical devices - Part 1: Evaluation and testing within a risk management process,26 hereafter 
257  called the Biocompatibility Guidance. In general, FDAs recommendations in the guidance 
258  align with the framework established in ISO 10993-1 for identification of the nature and duration 
259  of contact (e.g., cumulative effects with repeat use).27 However, FDAs recommendations 
260  include several modifications to the evaluations identified in that standard. Attachment A of the 
261  Biocompatibility Guidance identifies a framework for developing a biocompatibility evaluation 
262  of a medical device, including an implant. For implants within the scope of this guidance (see 
263 Section III), regardless of the natureof body contact, we recommend that the following 
264 endpoints be considered, at a minimum, as part of abiocompatability evaluation:
265  Cytotoxicity
266  Sensitization
267  Irritation or intracutaneous reactivity
268  Acute systemic toxicity
25Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/recommended-content-
and-format-non-clinical-bench-performance-testing-information-premarket. Note that the Non-Clinical Bench 
Testing Guidance does not apply to test reports for biocompatibility evaluation, reprocessing or sterilization 
validation, human factors, software verification and validation, and computational modeling. Information on those 
assessments is detailed in different guidances. Test reports for clinical studies, animal studies, and studies evaluating 
the performance characteristics of in vitro diagnostic devices are also excluded from the scope of the Non-Clinical 
Bench Testing Guidance.
26Available 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.
27See ISO 10993-1:2009, Clause 5.2 Categorization by nature of body contact and Clause 5.3 Categorization by 
duration of contact.
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269   Material-mediated pyrogenicity
270   
271  Additional endpoints are recommended based on the particular nature of body contact: 
272    Subacute/subchronic toxicity 
273    Genotoxicity
274    Implantation 
275    Hemocompatibility 
276    Chronic toxicity 
277    Carcinogenicity 
278    Reproductive/developmental toxicity 
279    Degradation 
280   
281  Note that FDAs Biocompatibility Guidance recommends that biocompatibility endpoints, such 
282  as neurotoxicity and immunotoxicity, should be considered for devices where local or end organ 
283  toxicity assessments relevant to the implant location or toxicity issues of concern would not be 
284  assessed in a traditional biocompatibility study.  
285 (2)  Sterility and Shelf Life 
286  a.  Sterility and Pyrogenicity 
287  FDA expects most implants to be sterilized prior to implantation for patient safety. We 
288  recommend that submitters consider FDAs guidance Submission and Review of Sterility 
289  Information in Premarket Notification (510(k)) Submissions for Devices Labeled as Sterile,28 
290  hereafter called the Sterility Guidance, when preparing their 510(k) submission. 
291   
292  As stated in the Sterility Guidance, implants should also meet pyrogen limit specifications. 
293  Pyrogenicity testing is used to help protect patients from the risk of febrile reaction due to either 
294  gram-negative bacterial endotoxins or other sources of pyrogens (e.g., material-mediated 
295  pyrogens). Unless the complete removal of pyrogens can be established, devices should be 
296  labeled as non-pyrogenic or meets pyrogen limit specifications instead of pyrogen free to 
297 more accurately communicate the devices pyrogenicity risk to patients.
298 
299  Note that the Sterility Guidance excludes from its scope sterilization processes for certain 
300 medical devices, including devices that incorporate materials of animal origin (i.e., human or 
301 animal tissues). For devices containing animal-derived materials, submitters should consider 
302 additional safety issues associated with disease transmission from the biological source. Please 
303 see FDAs guidance Medical Devices Containing Materials Derived from Animal Sources 
304 (Except for In Vitro Diagnostic Devices)29 for additional information concerning the sourcing of 
305 animal tissues, viral inactivation, sterilization, and risk management for these devices.
28Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/submission-and-review-
sterility-information-premarket-notification-510k-submissions-devices-labeled.
29Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/medical-devices-
containing-materials-derived-animal-sources-except-vitro-diagnostic-devices.
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306 b. Shelf Life and Packaging 
307  Shelf life testing is typically conducted to support the proposed expiration date of a device 
308  through evaluation of the package integrity for maintaining device sterility and/or evaluation of 
309  any changes to implant device performance or functionality over time.  
310   
311  With respect to evaluating package integrity for maintaining device sterility, submitters should 
312  provide in their 510(k) submissions a description of the packaging, including how it will 
313  maintain the devices sterility, and a description of the package integrity test methods, but it 
314  generally is not necessary to include the package test data. We recommend that a package 
315  validation study include simulated distribution and associated package integrity testing, as well 
316  as an aging process (accelerated and/or real-time) and associated seal strength testing, to support 
317  package integrity and shelf life claims. We recommend submitters follow the methods described 
318  in the FDA-recognized series of consensus standards ANSI/AAMI/ISO 11607-1: Packaging for 
319  terminally sterilized medical devices  Part 1: Requirements for materials, sterile barrier 
320  systems and packaging systems and ANSI/AAMI/ISO 11607-2: Packaging for terminally 
321  sterilized medical devices  Part 2: Validation requirements for forming, sealing and assembly 
322  processes, or request FDA feedback on appropriate package validation study methods through 
323  the Q-Submission Program30 for packaging that falls outside of the scope of these standards. 
324   
325  With respect to evaluating the effects of aging on device performance or functionality, shelf life 
326  studies should evaluate the critical device properties and specifications to ensure the device will 
327  perform adequately and consistently during the entire proposed shelf life. To evaluate device 
328  functionality, we recommend that relevant bench tests are conducted. We further recommend 
329  that all tests that evaluate design components or characteristics that are potentially affected by 
330  aging are repeated using aged devices as the test article. 
331   
332  We recommend that submitters provide in their 510(k) submissions a summary of the test 
333  methods used for their shelf life testing, the results, and the conclusions drawn from their results. 
334  If submitters use accelerated aging of devices to conduct shelf life testing, we recommend that 
335  submitters specify the way in which the device was aged and provide a rationale to explain how 
336  the results of shelf life testing based on accelerated aging are representative of results based on a 
337  device aged in real time. In general, the stability testing results should demonstrate that device 
338  performance is comparable at both standard and elevated temperatures, and should demonstrate a 
339  linear correlation of accelerated aging data and real-time aging data. We recommend that 
340  accelerated aging of implants for shelf life/stability testing be conducted in accordance with the 
341  currently FDA-recognized version of ASTM F1980: Standard Guide for Accelerated Aging of 
342  Sterile Barrier Systems for Medical Devices and that submitters specify the environmental 
343 parameters established to attain the proposed device expiration date. 
344
345 For devices or components containing polymeric materials or coatings, testing on real-time,aged 
346 samples should be conducted to confirm the results of anaccelerated aging study. This 
30For details on the Q-Submission Program, please refer to the FDA guidance Requests for Feedback and Meetings 
for Medical Device Submissions: The Q-Submission Program, available at https://www.fda.gov/regulatory-
information/search-fda-guidance-documents/requests-feedback-and-meetings-medical-device-submissions-q-
submission-program.
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347  confirmatory testing can generally be conducted in parallel with 510(k) review, with results 
348  documented to file in the design history file (i.e., complete test reports typically would not need 
349  to be submitted to FDA). FDA recommends that submitters contact the relevant review division 
350  for more information regarding suitable aging protocols based on the device and materials 
351  composition, as some material properties of implants (e.g., animal-derived components) may not 
352  be appropriate for acceleratedaging testing. 
353  (3)  Reprocessing and Cleaning 
354  While implants are generally single-use, sterile devices, there may be implants that are 
355  reprocessed prior to implantation. For example, certain orthopedic devices may be provided non-
356  sterile, but sterilized in a healthcare facility just prior to implantation (e.g., intervertebral body 
357  fusion devices). To ensure that the device is sterile, as intended, prior to implantation, the 
358  instructions provided for device reprocessing should be validated for the device. For devices 
359  intended to be reprocessed in this way, submitters should follow the recommendations in FDAs 
360  guidance Reprocessing Medical Devices in Health Care Settings: Validation Methods and 
361  Labeling.31 
362  (4)  Software and Cybersecurity 
363  Implants raise specific concerns associated with the duration of use and risks related to implant 
364  removal. Patients may live with an implant for years, or even permanently; therefore, long-
365  lasting implants promote patient safety by minimizing the need for removal due to outdated 
366  software or other related vulnerabilities or failures.  
367   
368  For implants containing software, or devices containing software that communicate with 
369  implants, FDA recommends that submitters provide information in their 510(k) submission 
370  consistent with the recommendations in FDAs guidance, Content of Premarket Submissions for 
371  Device Software Functions.32 
372   
373  We also recommend that submitters provide in their 510(k) submissions information regarding 
374 thedevices cybersecurity risks and related controls to assure device functionality and safety, 
375 consistent with FDAs guidance entitled, Content of Premarket Submissions for Management of 
376 Cybersecurity in Medical Devices.33 Additionally, cybersecurityrisk should continue to be 
377 addressed throughout the total product lifecycle of these devices using the recommendations in 
378 theFDAguidance entitled, Postmarket Management of Cybersecurity in Medical Devices.34
31Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/reprocessing-medical-
devices-health-care-settings-validation-methods-and-labeling.
32Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/content-premarket-
submissions-device-software-functions. 
33Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/content-premarket-
submissions-management-cybersecurity-medical-devices.
34Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/postmarket-
management-cybersecurity-medical-devices.
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379  Consideration of cybersecurity information is often necessary as part of a premarket submission 
380  and as part of an adequate software validation and risk analysis required by 21 CFR 820.30(g).35 
381   
382  The 510(k) premarket review process for implants containing software or devices containing 
383  software that communicate with implants will consider cybersecurity-related risks, including 
384  those that might necessitate the need for implant removal, in the context of comparing the new 
385  device to a predicate device. Specific consideration of cybersecurity risks early in the design 
386  process can significantly reduce or mitigate these risks (e.g., design with sufficient excess 
387  memory to allow for significant architecture updates that may be needed to maintain or 
388  reestablish security, or consideration for management of implants when End of Service and/or 
389  End of Life are reached). 
390  (5)  Electrical Safety and Electromagnetic Compatibility 
391  FDA recommends that submitters of 510(k)s for implants with electrical components consider 
392  risks related to those electrical components, including the risks of electrical shock and 
393  electromagnetic interference with other devices, and provide information to support that those 
394  risks have been adequately mitigated. As an initial approach, FDA recommends that the 
395  electrical safety and electromagnetic compatibility (EMC) of implants with electrical 
396  components demonstrate conformity with consensus standards for electrical safety.  
397   
398  510(k) submissions for electrically-powered medical devices often reference FDA-recognized 
399  consensus national or international standards for EMC. For medical electrical equipment or 
400  medical electrical systems (as defined in the International Electrotechnical Commission (IEC) 
401  60601-1 Medical Electrical Equipment  Part 1: General Requirements For Basic Safety and 
402  Essential Performance), submissions primarily reference the IEC 60601-1-2 standard or the 
403 equivalent United States (US) version.36 In addition, there are device-specific consensus 
404 standards, or particular standards, under the IEC 60601-1 family (e.g., IEC 60601-2-X, where 
35On February 23, 2022, FDA proposed to amend the device Quality System Regulation, 21 CFR Part 820, to align 
more closely with international consensus standards for devices (87 FR 10119; available at 
https://www.federalregister.gov/documents/2022/02/23/2022-03227/medical-devices-quality-system-regulation-
amendments). Specifically, FDA proposed to withdraw the majority of the current requirements in Part 820 and 
instead incorporate by reference the 2016 edition of the International Organization for Standardization (ISO) 13485, 
Medical devices  Quality management systems for regulatory purposes, in Part 820. As stated in that proposed rule, 
the requirements in ISO 13485 are, when taken in totality, substantially similar to the requirements of the current 
Part 820, providing a similar level of assurance in a firms quality management system and ability to consistently 
manufacture devices that are safe and effective and otherwise in compliance with the FD&C Act. FDA intends to 
finalize this proposed rule expeditiously. When the final rule takes effect, FDA will also update the references to 
provisions in 21 CFR Part 820 in this guidance to be consistent with that rule.
36IEC 60601-1-2 Edition 3: 2007: Medical Electrical Equipment - Part 1-2: General Requirements for Safety - 
Collateral Standard: Electromagnetic Compatibility - Requirements and Tests, IEC 60601-1-2 Edition 4.0:2014: 
Medical Electrical Equipment, Part 1-2: General Requirements for Basic Safety and Essential Performance  
Collateral Standard: Electromagnetic Disturbances  Requirements and Tests, AAMI/ANSI/IEC 60601-1-2: 
2007/(R)2012: Medical Electrical Equipment - Part 1-2: General Requirements for Safety - Collateral Standard: 
Electromagnetic Compatibility - Requirements and Tests, and AAMI/ANSI/IEC 60601-1-2: 2014: Medical 
Electrical Equipment - Part 1-2: General Requirements for Safety - Collateral Standard: Electromagnetic 
Disturbances - Requirements and Tests.
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405  X denotes a particular device standard). These particular standards may augment or supersede 
406  the specifications in the IEC 60601-1-2 standard.  
407   
408  Note that the IEC 60601-1 series of medical electrical equipment standards excludes implants. 
409  However, some implants are used with external devices, where the external device transmits 
410  energy to the implant; IEC 60601-1 may therefore apply to the external device and should be 
411  considered, if applicable. There are also consensus standards for certain active implantable 
412  medical devices that include information on EMC. One example is ISO 14708 Implants for 
413  surgery  Active implantable medical devices  Part 3: Implantable neurostimulators. 
414   
415  In cases where an implant may include radio frequency (RF) wireless technology, the 
416  recommendations in FDAs guidance, Radio Frequency Wireless Technology in Medical 
417  Devices,37 should be considered.  
418   
419 In some cases, additional electrical safety and EMC testing may be needed to demonstrate SE, 
420  depending on the device and/or device type and the differences from the predicate device.  
421  (6)  Magnetic Resonance (MR) Compatibility 
422  All implants have risks associated with exposure to an MR environment. FDA recommends that 
423  submitters consider the risks associated with their device when exposed to an MR environment 
424 and provide information to support that those risks have been adequately mitigated. FDA has 
425  provided recommendations on testing and labeling for implants for safety and compatibility in 
426  the MR environment in the FDA guidance Testing and Labeling Medical Devices for Safety in 
427  the Magnetic Resonance (MR) Environment.38 FDA recognizes that implants are subject to 
428  various magnetic resonance-related hazards, including the following, and recommends that 
429  submitters consider how to mitigate these hazards and other relevant hazards, as applicable, 
430  when designing their devices: 
431    Magnetically induced displacement forcesor torque, leading to unwanted movement 
432  of the medical device and tissue damage; 
433    Heating of the medical device itself and/or tissue adjacent to the medical device from 
434  RF and switching gradient fields (dB/dt) of the MR system; 
435   Vibrations or electric potential induction due to an MR systems pulsed gradient 
436 magnetic fields;
437  Unintended tissue stimulation caused by rectified voltages generated by implants 
438 subject to RFexposure;
439  Medical device malfunctions, either temporary or permanent, caused by exposure to 
440 an MR environment; and
441  Corruption of MR images, including image artifacts, caused by the presence of 
442 metallic implants.
37Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/radio-frequency-
wireless-technology-medical-devices-guidance-industry-and-fda-staff.
38Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/testing-and-labeling-
medical-devices-safety-magnetic-resonance-mr-environment.
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443 (7) Other Non-Clinical Performance Testing 
444  Additional kinds of non-clinical performance testing are often needed to demonstrate SE of a 
445  510(k) Implant to a predicate device. For example, materials used in implants can cause adverse 
446  biological responses depending on the material, implant duration, and implant location, that may 
447  not be identified in standard biocompatibility evaluations. Beyond the non-clinical evaluations 
448  discussed above, FDA recommends that submitters consider whether additional performance 
449  testing should be conducted to evaluate safety and effectiveness issues raised by differences 
450  between the new device and the predicate to demonstrate SE and help ensure that the device will 
451  perform safely and effectively across its expected lifespan. We recommend that all testing be 
452  conducted on final, finished devices. The amount and types of additional testing that should be 
453  considered can vary widely with the device or device type (e.g., testing considerations may vary 
454  based on the intended use of the device, implant duration, materials used, various failure modes 
455  related to implant geometry, manufacturing procedures and tolerances, and other unique implant 
456  characteristics) and with the differences between the new device and the predicate. Depending on 
457  these factors, some or all of the following testing may be applicable and needed to demonstrate 
458  SE, and the issues below should be considered when evaluating the risks associated with a 
459  510(k) Implant: 
460   
461    Corrosion: Corrosion is the deterioration of a metal due to electrochemical reactions 
462  with its environment. Multiple corrosion mechanisms (pitting, fretting, galvanic) can 
463  result in the release of metal ions or other byproducts. Most device alloys form a 
464  protective oxide layer that reduces corrosion, but the biochemical and mechanical 
465  stresses of the implant environment can damage the protective layer and increase 
466  corrosion. Given sufficient time, corrosion can weaken the structural integrity of a 
467  medical device to the point of device collapse and failure. To help understand how 
468  the host body responds to metal devices, FDA recommends a combination of non-
469  clinical studies on corrosion, the release of metal ions, and device-specific fatigue 
470  testing as well as animal and clinical studies, in some cases, to assess biological 
471  responses. FDA uses this information to evaluate biocompatibility issues, such as risk 
472  of immunological response, tissue destruction or overgrowth, and other adverse 
473  reactions. For recommendations related to corrosion testing of implants or materials, 
474  please see the FDA guidance Technical Considerations for Non-Clinical Assessment 
475  of Medical Devices Containing Nitinol.39 
476   
477    Fatigue: Devices that are subject to repetitive stresses may fail and break. Implants 
478  should demonstrate adequate fatigue life under conditions simulating in vivo use to 
479 mitigate the risk of device breakage and failure during the expected lifespan of the 
480 device. FDA recognizes a variety of voluntary consensus standards to support
481 mechanical fatigue testsfor certain device types.40
39Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/technical-
considerations-non-clinical-assessment-medical-devices-containing-nitinol. The submitter may consider whether the 
recommendations regarding performance testing in this guidance may be informative for implants containing other 
metals.
40See the FDA-Recognized Consensus Standards Databaseavailable at
https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm.
14 Contains Nonbinding Recommendations
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482 
483    Degradation: Devices that are intended to degrade or resorb over time, or for which 
484  the technological characteristics are such that the device inevitably degrades after 
485  implantation, may lead to the release of degradation products into the local or 
486  systemic biological environment, causing inflammation or other biological reactions. 
487  An evaluation of the degradation profile of the device should be conducted under 
488  anticipated conditions of use, including worst-case scenario conditions, to understand 
489  the degradation profile over time and any conditions that may accelerate or modulate 
490  device degradation. 
491   
492    Particulate Characterization: For implants subject to wear or degradation under 
493  repetitive motion or other processes, the characterization of particulates can be an 
494  important consideration. Therefore, the bodys response to any associated degradation 
495  products, including those leached from wear debris, should be assessed. This may be 
496  accomplished via injecting degradation products from non-clinical testing or other 
497  representative particles into an appropriate animal model.41 Alternatively, it may be 
498  possible to demonstrate that the particulates generated have similar 
499  size/number/shape of particles as other similar, legally marketed devices, and that the 
500  degradation products are not bioavailable. Finally, devices may introduce particulates 
501  outside of wear or degradation scenarios (e.g., particulates left over from 
502  manufacturing) that should be characterized. For example, infusion pump systems 
503  may introduce particulates in the solutions they infuse. 
504   
505    Coating Characterization: The surfaces of implants may have a coating (e.g., in the 
506  case of orthopedic or dental devices, to improve joint fixation through a porous rough 
507  surface texture). Although coatings may represent a small portion of an implant by 
508  volume, coatings can have a significant impact on safety and effectiveness. For 
509  implants with coatings, FDA recommends that submitters provide in their 510(k), at a 
510  minimum, information on the intended function of the coating, as well as detailed 
511  information regarding the materials used in the coating or its generation, bond method 
512  and bond strength between a coating and its substrate, and salient material or 
513  biochemical properties of the coating, including thickness, pore size, and overall 
514  volume of porous coatings. Note that there may be other FDA guidances related to 
515 coatings that apply to your device. For example, for detailed information regarding 
516 coatings for orthopedic implants, seeFDAs Guidance Documentfor Testing 
517 Orthopedic Implants With Modified Metallic Surfaces Apposing Bone Or Bone 
518 Cement.42
519
41FDA supports the principles of the 3Rs to replace, reduce, and/or refine animal use in testing, when 
feasible. We encourage submitters to consult with FDA if they wish to use a non-animal testing method that they 
believe is suitable, adequate, validated, and feasible. We will consider if a proposed alternative method could be 
assessed for equivalency to an animal test method. FDA also encourages the use of the Q-Submission Program to 
obtain feedback on the design of an animal study if an animal study is warranted.
42Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/guidance-document-
testing-orthopedic-implants-modified-metallic-surfaces-apposing-bone-or-bone.
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520   Imaging Compatibility and Radiotherapy Compatibility: After implantation, 
521  implants may need to be visualized by various imaging techniques to identify their 
522  position or orientation, including X-ray based techniques such as fluoroscopy or 
523  computed tomography (CT). Over their lifetime, many patients will also undergo 
524  imaging exams for other medical reasons. We recommend that implants be evaluated 
525  to determine whether the presence of the device impacts the image quality (e.g., 
526  image artifacts). For devices where detection via imaging is necessary to support 
527  future device removal or to support the safety of future surgical procedures, FDA 
528  recommends that you conduct radiopacity testing or other suitable imaging 
529  compatibility testing to demonstrate the device can be located. Additionally, as with 
530  MR, discussed above, other imaging exams and radiation therapy may also interact 
531  with implants. Even if the probability of an adverse event is low, we recommend that 
532  submitters assess the risks associated with exposure of the implant to other imaging 
533  exams and radiotherapy devices, including electronic component failure. FDA 
534  recommends that submitters consider the risks associated with their device when 
535  exposed to other types of imaging exams and radiation therapy and provide 
536  information to support that those risks have been adequately mitigated, such as by the 
537  devices technical design, inclusion of appropriate information in the labeling, or a 
538  combination of these mitigation strategies. We recommend that manufacturers 
539  provide evidence-based recommendations for patients and physicians in the implant 
540  labeling on what to do if a patient needs to undergo an imaging exam. Since it is not 
541  feasible to evaluate all imaging protocols that may be considered for patients after 
542  they receive an implant, FDA recommends that manufacturers specify in the implant 
543  labeling the methods and results of imaging safety testing that has been performed 
544  and other safety information relevant to an imaging exam that should be considered to 
545  help inform physicians. 
546   
547    Engineering Analysis: It may be appropriate to evaluate some 510(k) Implants based 
548  on a combination of material specifications, finite element analysis (FEA), and/or 
549  other computational modeling approaches. A combination of engineering analyses 
550  and non-clinical testing may, in some cases, be sufficient to support SE, especially in 
551  circumstances where such analyses and testing have been validated to represent 
552 clinically-relevant failure modes. For more information on submitting computational 
553  modeling studies to support a device marketing submission, see the FDA guidance 
554  Reporting of Computational Modeling Studies in Medical Device Submissions.43 
555   
556    Bench Model Testing: While analyses of components and possible failure modes are 
557  important to a comprehensive understanding of device performance, in some cases, it 
558  may be necessary for submitters to provide the results of testing using model systems 
559 with representative materials, geometries, and/or other simulated use parameters to 
560 evaluate the implant and demonstrate SE. In such cases, FDA recommends that 
561 submitters provide a rationale for the test set up and a discussion of how testing with 
43Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/reporting-
computational-modeling-studies-medical-device-submissions.
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562  a bench model represents device performance under the anticipated conditions of use, 
563  considering worst-case scenarios, as appropriate. 
564   
565  Given the variety of implant types and unique considerations that different implants may raise, 
566  this guidance cannot provide recommendations regarding all bench-based performance tests that 
567  may be relevant for a specific implant. When considering performance testing to support an SE 
568  determination, submitters should consider the total product lifecycle experience with the implant 
569  type, available information on performance testing conducted for relevant predicate devices, 
570  device-specific guidance, and voluntary consensus standards applicable to a given device type. 
571  (8)  Animal Testing 
572  In many cases, non-clinical bench performance testing alone may not be adequate to demonstrate 
573  SE. For example, engineering analyses and mechanical tests may provide objective 
574  measurements for comparing an implants technological characteristics to those of a predicate 
575  device, but may not fully capture complexities related to clinical use to allow for a full 
576  assessment of how differences in technological characteristics affect safety and effectiveness. In 
577  these cases, evaluating in vivo performance may be the least burdensome way to demonstrate 
578  that an implant is SE to the predicate. While FDAs primary purpose in recommending an animal 
579  study is often to generate safety information, these studies are frequently used to provide insight 
580  into other performance measures that can impact effectiveness as well.  
581   
582  Below are some representative examples of situations where FDA may recommend animal 
583  testing: 
584    For implants that degrade, wear, or otherwise introduce foreign material into the local 
585  environment that is not intended to be removed (e.g., an implant that may abrade or 
586  damage tissue it contacts or against which it articulates); 
587    For implants where in vivo device migration or behavior is not well characterized in a 
588  bench model; 
589    To evaluate safety concerns where histological analysis is needed and human tissue 
590  biopsy is not feasible (e.g., local inflammation around the implant, or 
591  thrombogenicity/embolic effects in downstream tissues);  
592    To evaluate an anatomically similar clinical procedure/technique, where healthcare 
593  practitioner (HCP) training (e.g., knowledge and refinement of surgical technique, 
594  expertise in specialized procedures) is important for the device to be used safely; and 
595    To assess functional outcomes, including outcomes for devices intended to mitigate 
596 symptoms of injury or disease, where an animal model can be suitably extrapolated to 
597 human clinical performance.
598
599 Whenconsidering the appropriate number of animals to use and amount of data, FDA 
600 recommends considering the ethical principles of replacement, reduction, and refinement, as well 
601 as the least burdensome principles,44 with the goal of using the minimum number of animals 
44Please see the FDA guidance, The Least Burdensome Provisions: Concept and Principles, available at 
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/least-burdensome-provisions-concept-
17 Contains Nonbinding Recommendations
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602  necessary to generate valid scientific evidence sufficient to demonstrate SE. We encourage 
603  submitters to take advantage of the Q-Submission Program45 to ensure that their animal study 
604  protocol addresses relevant safety issues and contains elements that are appropriate for studies 
605  intended to support a regulatory submission (e.g., is consistent with applicable Good Laboratory 
606  Practice (GLP) regulations in 21 CFR Part 58).  
607   
608  FDA supports the principles of the 3Rs46 to replace, reduce, and/or refine animal use in testing, 
609  when feasible. We encourage submitters to consult with FDA if they wish to use a non-animal 
610  testing method that they believe is suitable, adequate, validated, and feasible. We will consider if 
611  a proposed alternative method could be assessed for equivalency to an animal test method. FDA 
612  also encourages the use of the Q-Submission Program47 to obtain feedback on the design of an 
613  animal study if an animal study is warranted. 
614  (9)  Implant Device Design Considerations 
615  Medical devices are manufactured from a wide variety of materials, using a variety of 
616  manufacturing processes. For certain implants, information regarding raw materials and critical 
617  aspects of manufacturing and processing steps, and how these impact device design and 
618  specifications, may be important to understanding the safety and effectiveness of the final, 
619  finished device relative to a predicate device. Examples where this information may be 
620  particularly important include: 
621    Implants composed of nitinol, as nitinol may release different amounts of nickel 
622  under fatigue (for more information, please see the FDA guidance Technical 
623  Considerations for Non-Clinical Assessment of Medical Devices Containing 
624 Nitinol48); 
625   Implants that may have different wear characteristics in vivo (e.g., please see the 
626  recommendations in the FDA guidance Characterization of Ultrahigh Molecular 
627  Weight Polyethylene (UHMWPE) Used in Orthopedic Devices49);  
628    Implants composed of degradable polymers, hydrogels, or other materials that may 
629 undergo material changes (e.g., form changes, degradation, in situ polymerization) in 
630 vivo;
631  Implants for which residuals and impurities from manufacturing processes may 
632 remain in the packaged final finished form(e.g., animal derived materials following 
633 viral inactivation); 
and-principles, for additional discussion of FDAs policies and implementation of the least burdensome provisions 
in the FD&C Act. 
45 For details on the Q-Submission Program, please refer to the FDA guidance Requests for Feedback and Meetings 
for Medical Device Submissions: The Q-Submission Program, available at https://www.fda.gov/regulatory-
information/search-fda-guidance-documents/requests-feedback-and-meetings-medical-device-submissions-q-
submission-program. 
46 Animal Use Alternatives (3Rs), available at https://www.nal.usda.gov/animal-health-and-welfare/animal-use-
alternatives. 
47 See footnote 45. 
48 Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/technical-
considerations-non-clinical-assessment-medical-devices-containing-nitinol.
49Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/characterization-
ultrahigh-molecular-weight-polyethylene-uhmwpe-used-orthopedic-devices.
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634   Implants manufactured using additive manufacturing processes, as they may have 
635  different mechanical properties compared to devices made using traditional 
636  manufacturing methods; and 
637    Implants with biologically-derived materials, because information regarding animal 
638  husbandry and materials processing may be necessary to evaluate risks of disease 
639  transmission and the adequacy of viral inactivation. 
640   
641  We recommend that submitters consider providing certain information regarding materials, 
642  specifications, and design for such implants. Specifically, submitters should consider providing 
643  information regarding materials and their sourcing and critical processing information, such as 
644  reaction parameters and/or solvents used in processing or cleaning. This information may allow 
645  FDA to better understand the final, finished form of the implant and its similarities to and 
646  differences from the predicate device, for purposes of determining if the new device is SE to the 
647  predicate device. This information may also be particularly important when evaluating the effect 
648  of changes to the manufacturing process (e.g., for uses of novel manufacturing processes) or for 
649  changes to device design (e.g., incorporation of a new surface treatment for a metal implant) on 
650  the safety and effectiveness of a previously cleared device.50  
651   
  Human Factors/Usability 
652 
653  Human factors information may be needed to demonstrate SE for certain 510(k) Implant devices. 
654  For example, as part of an SE determination, FDA may need to evaluate the impact of 
655  differences between the user interfaces of the new device and the predicate device on safety and 
656  effectiveness. In addition, differences between the new device and predicate device could affect 
657  how the device may be used (e.g., by additional users or in different use environments) in a way 
658  that raises safety and effectiveness issues. 
659   
660  As part of their design controls, manufacturers should conduct a use-related risk analysis that 
661  includes the risks specific to the device use and the measures implemented to reduce those 
662  risks.51 ANSI/AAMI/ISO 14971, Medical Devices  Application of risk management to medical 
663  devices, defines risk as the combination of the probability of occurrence of harm and the severity 
664  of that harm. However, because probability is generally difficult to determine accurately for use 
665  errors, and in fact many use errors cannot be anticipated until device use is simulated or 
666  observed, the severity of the potential harm is more meaningful for determining the need to 
667 eliminate (design out) or reduce resulting harm. If the results of the use-related risk analysis 
668 indicate that use errors could cause serious harm to the patient or the device user, then we 
669 recommend that appropriate human factors/usability (HF/U) engineering processes are applied 
50See 21 CFR 807.81(a)(3). For more information on evaluating changes to a previously cleared device, and 
whether such changes require the submission of a new 510(k), see the FDA guidance, Deciding When to Submit a 
510(k) for a Change to an Existing Device, available at: https://www.fda.gov/regulatory-information/search-fda-
guidance-documents/deciding-when-submit-510k-change-existing-device. 
51Under 21 CFR 820.30(g), design validation must ensure that devices conform to defined user needs and intended 
uses and shall include testing of production units under actual or simulated use conditions. It must also include 
software validation and risk analysis, where appropriate.
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670  according to the FDA guidance Applying Human Factors and Usability Engineering to Medical 
671  Devices.52 
672   
673  FDA recommends that HF/U engineering processes are followed during 510(k) Implant 
674  development, focusing specifically on the user interface, where the user interface includes all 
675  points of interaction between the product and the user(s), including elements such as displays, 
676  controls, packaging, product labels, and directions for use. The goal is to ensure that the device 
677  user interface has been designed such that use errors that could cause harm, including by 
678  compromising medical care, are either eliminated or reduced to the furthest extent possible. This 
679  is particularly important to consider for devices with complex interfaces designed to be 
680  implanted by HCPs and implants that involve post-implantation management by the patient 
681  and/or HCP (e.g., programming, monitoring, maintenance). FDA recommends that you consider 
682  the workflow and interactions between different user groups and with the device throughout the 
683  overall lifecycle of the device (including maintenance and removal). In general, HF/U testing 
684  should capture all critical tasks, including those related to the relevant workflows and expected 
685  lifespan of your device. As an example, you should consider whether there are any surgical 
686  implantation completion time endpoints that, if not met, could potentially result in serious patient 
687  harm or death; if so, this endpoint should be included as a critical task to be tested in HF/U 
688  validation testing. 
689   
690  510(k) Implants may have specialized implantation instructions. Instructions and any training the 
691  manufacturer offers for the implanting physician should take into account how the device user 
692  interface and implantation technique(s) differ from similar device user interfaces and current 
693  standard of care, respectively. In any summative evaluation, the training provided to the human 
694  factors validation test participants should approximate the training that actual users would 
695  receive. 
696   
  Clinical Performance Testing 
697 
698  While clinical data is not generally necessary to demonstrate SE in most 510(k) submissions, 
699  there are scenarios where clinical data may be needed to support an SE determination. The most 
700 common scenarios of when clinical data may be necessary in a 510(k) are discussed in the 510(k) 
701 Program Guidance53 and the draft guidance, Recommendations for the Use of Clinical Data in 
702  Premarket Notification [510(k)] Submissions,54 which, when final, will represent FDAs current 
703  thinking on that topic. FDAs draft guidance on Recommendations for the Use of Clinical Data 
704  in Premarket Notification [510(k)] Submissions is intended to clarify and provide additional 
705 context for situations when clinical data may be necessaryto support SE. It discusses when such 
706 data may beneededin the context of abenefit-risk assessment conducted as part of determining 
707 if a new device with different technological characteristics that do not raise different questions of 
52Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/applying-human-
factors-and-usability-engineering-medical-devices.
53Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/510k-program-
evaluating-substantial-equivalence-premarket-notifications-510k.
54Available athttps://www.fda.gov/regulatory-information/search-fda-guidance-documents/recommendations-use-
clinical-data-premarket-notification-510k-submissions.
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708  safety and effectiveness is as safe and effective as a legally marketed device, as well as other 
709  decision points in the 510(k) decision-making process. 
710   
  Patient Experience Information 
711 
712  Where relevant to determinations of SE, FDA encourages the collection, analysis, and 
713  integration of patient experience data for implants. Patient experience data includes patient 
714  preference information (PPI) and patient-reported outcomes. Patients perspectives on living 
715  with implants are most useful when they are relevant to the regulatory decision and reliably 
716  measured. Patient-reported outcome instruments facilitate the systematic collection of how 
717  patients feel, function, and survive as valid scientific evidence to support the regulatory and 
718  healthcare decision-making process. These instruments can be used to capture endpoints in 
719  clinical studies. 
720   
721  We recommend that submitters consider the FDA guidance entitled Patient-Reported Outcome 
722  Measures: Use in Medical Product Development to Support Labeling Claims55 and the FDA 
723  guidance entitled Principles for Selecting, Developing, Modifying, and Adapting Patient-
724  Reported Outcome Instruments for Use in Medical Device Evaluation.56 
725   
726  CDRH has been a leader in incorporating PPI into regulatory decision-making. PPI may be used 
727  to help understand the relative value or the tradeoffs patients are willing to make among different 
728  benefits and risks associated with their condition and its diagnosis or management. PPI may be 
729  considered with the totality of evidence to inform an SE determination when evaluating the 
730  overall benefit-risk profile of an implant and whether that implant is as safe and effective as a 
731  predicate device.57 For example, in the context of a 510(k), PPI has been used as valid scientific 
732  evidence to support clearance of expanded indications for use. We recommend that submitters 
733 considering use of PPI in a 510(k) Implant submission consult the FDA guidance entitled 
734  Patient Preference Information  Voluntary Submission, Review in Premarket Approval 
735  Applications, Humanitarian Device Exemption Applications, and De Novo Requests, and 
736  Inclusion in Decision Summaries and Device Labeling.58 Though the aforementioned guidance 
737 is not intended to cover510(k) submissions, the content and recommendations regardingfeatures 
738 of well-designed and -conducted patient preference studies may be helpful for submitters who 
739 are planning to include PPIstudies in510(k) submissions as well.
740
55Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/patient-reported-
outcome-measures-use-medical-product-development-support-labeling-claims.
56Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/principles-selecting-
developing-modifying-and-adapting-patient-reported-outcome-instruments-use.
57See the FDA guidance, Benefit-Risk Factors to Consider When Determining Substantial Equivalence in 
Premarket Notifications (510(k)) with Different Technological Characteristics, available at 
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/benefit-risk-factors-consider-when-
determining-substantial-equivalence-premarket-notifications-510k.
58Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/patient-preference-
information-voluntary-submission-review-premarket-approval-applications.
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Labeling and Other Recommendations 
741
742 (1) Instructions for Use 
743  A 510(k) submission must include proposed labeling in sufficient detail to satisfy the 
744  requirements of 21 CFR 807.87(e), which requires a 510(k) to contain proposed labels, labeling, 
745  and advertisements sufficient to describe the device, its intended use, and the directions for use. 
746  Given the nature of implants, they are generally prescription devices and are exempt from having 
747  adequate directions for lay use required under section 502(f)(1) of the FD&C Act (21 U.S.C.  
748  352(f)(1)) as long as the conditions in 21 CFR 801.109 are met. For instance, any labeling 
749  distributed by or on behalf of the manufacturer, packer, or distributor of the device that provides 
750  information for use of the device must include adequate information for the use of the device, 
751  including indications, effects, routes, methods, frequency and duration of administration, and any 
752  relevant hazards, contraindications, side effects, and precautions, under which practitioners 
753  licensed by law to employ the device can use the device safely and for the purposes for which it 
754  is intended, including all purposes for which it is advertised or represented (21 CFR 801.109(d)).  
755   
756  Recognizing that implants are generally intended to remain with a patient for a long time, FDA 
757  expects that the physician would typically provide information to the patient about the 
758  implantation procedure and the benefits and risks of the device after implantation. FDA 
759  considers it important for manufacturers to provide information for the practitioner and also for 
760  patients about the risks of the device  including, but not limited to, information that can mitigate 
761  risks to health associated with layperson use errors after device implantation. This information is 
762  important to ensuring that implants are used safely and effectively across their expected lifespan. 
763  It is also important for practitioners to know how to educate their patients about risks that might 
764  arise throughout the implants expected lifespan. As such, we recommend that manufacturers 
765  provide patient information in a format that the practitioner could easily convey directly to the 
766  patient (e.g., separate patient labeling), which will help to ensure the implant is used safely and 
767  effectively. In particular, permanent implants may have risks for which labeling is especially 
768  important for safety during everyday activities or other medical procedures, such as during a 
769  magnetic resonance imaging (MRI) procedure, radiation exposure, or security screening. 
770  Labeling submitted in a 510(k) for an implant should take into account these risks.  
771   
772  To the extent not already required under 21 CFR Part 801 or by applicable special controls, FDA 
773  recommends that all implants be accompanied by labeling that includes information on device 
774  operation, implantation instructions, and implant removal, if the device is intended to be 
775  removed. 
776  (2)  Implant Cards and Other Patient Information 
777  As noted above, to help ensure continued safety over the expected lifespan of the implant, FDA 
778  considers it important for manufacturers to provide patients with 510(k) Implants information 
779  regarding their device. Certain information may be appropriate for inclusion in the form of an 
780 implant ID card for the patient or caregiver, while other information may be more appropriate for 
781 other forms of labeling.The choice to use a particular implant is often made by aphysician or 
782 other licensed HCP based on their clinical experience and expertise. However, patients may not 
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783  always know which implants they have, how to best manage their implants, or if there are 
784  adverse events reported for that implant model. Implant information is also important for parents 
785  or other caregivers responsible for patient care outside of a healthcare facility. FDA recommends 
786  including the information listed below on an implant ID card or other labeling that can be 
787  provided to patients or their caregivers for a 510(k) Implant:  
788    Implant identifying information, including model name and manufacturer, and 
789  implant location; 
790    Salient details regarding device composition and patient contacting materials, 
791  including pertinent information related to any known allergic reactions;  
792    Information regarding how to report malfunctions or other adverse events to the 
793  manufacturer; and 
794    For MR conditional implants, all conditions for safe MR use as described in the FDA 
795  guidance Testing and Labeling Medical Devices for Safety in the Magnetic 
796  Resonance (MR) Environment,59 as well as the MR Conditional icon from the 
797  currently recognized version of ASTM F2503: Standard Practice for Marking 
798 Medical Devices and Other Items for Safety in the Magnetic Resonance Environment.
799
800 FDA recommends that manufacturers provide such information in a format that can be easily 
801 conveyed to patients. We encourage submitters to discuss patient labeling for 510(k) Implants 
802 with the appropriate FDA review division.
59Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/testing-and-labeling-
medical-devices-safety-magnetic-resonance-mr-environment.
23