Contains Nonbinding Recommendations 
 
Draft  Not for Implementation 
 
Medical Devices with Indications 
Associated with Weight Loss -  
Non-Clinical Recommendations 
 
Draft Guidance for Industry and  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DRAFT GUIDANCE 
 
This draft guidance document is being distributed for comment purposes 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 15, 2023. 
 
You should submit comments and suggestions regarding this draft document within 60 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publication in the Federal Register of the notice announcing the availability of the draft 
guidance.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. Identify all comments with the docket number 
listed in the notice of availability that publishes in the Federal Register. 
 
For questions about this document, contact OHT3: Office of Gastro-Renal, ObGyn, General 
Hospital, and Urology Devices/DHT3A: Division of Renal, Gastrointestinal, Obesity, and 
Transplant Devices at (301) 796-7030. 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Devices and Radiological Health  
  Contains Nonbinding Recommendations 
 
Draft  Not for Implementation 
 
Preface 
 
Additional Copies 
 
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 
GUI00019046 and complete title of the guidance in the request. 
  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
Table of Contents
I. Introduction ............................................................................................................................. 1 
II. Scope ....................................................................................................................................... 2 
III. Premarket Submission Recommendations .............................................................................. 3 
Device Description.............................................................................................................. 3 
Labeling .............................................................................................................................. 4 
(1) Warnings ..................................................................................................................... 4 
(2) MR Safety Information ............................................................................................... 4 
(3) Overview of Clinical Studies ...................................................................................... 4 
(4) Adverse Events ........................................................................................................... 5 
(5) Patient Labeling (including patient implant card, if applicable) ................................ 6 
Sterility ................................................................................................................................ 6 
(1) Sterile Devices ............................................................................................................ 6 
(2) Non-Sterile Devices .................................................................................................... 7 
Pyrogenicity ........................................................................................................................ 8 
Shelf Life and Packaging .................................................................................................... 9 
Biocompatibility ............................................................................................................... 10 
Software  ........................................................................................................................... 11 
Electrical Safety and Electromagnetic Compatibility (EMC) .......................................... 13 
Wireless Technology ........................................................................................................ 14 
Magnetic Resonance (MR) Compatibility for Implants ................................................... 14 
Non-Clinical Bench Performance Testing ........................................................................ 15 
(1) Corrosion Resistance ................................................................................................ 15 
(2) Dimensional Verification .......................................................................................... 17 
(3) Strength ..................................................................................................................... 17 
(4) Durability and Fatigue .............................................................................................. 17 
(5) Delivery/Removal System Testing ........................................................................... 19 
(6) Interactions with Other Devices ................................................................................ 20 
(7) Microorganism Susceptibility ................................................................................... 20 
Animal Studies.................................................................................................................. 21 
(1) Animal Model ........................................................................................................... 22 
(2) Study Endpoint Considerations................................................................................. 22 
(3) Animal Study Protocol .............................................................................................. 22  Contains Nonbinding Recommendations 
 
Draft  Not for Implementation 
 
Medical Devices with Indications 
1 
Associated with Weight Loss -  
2 
Non-Clinical Recommendations 
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   
15  I.  Introduction 
16  This draft guidance document provides recommendations for the non-clinical testing to support 
17  premarket submissions (e.g., Premarket Approval (PMA) Applications, Investigational Device 
18  Exemption (IDE) Applications, Premarket Notifications (510(k)s), and De Novo classification 
19  requests) for medical devices with indications for use associated with weight loss. Examples of 
20  indications associated with weight loss include indications for weight loss, weight reduction, 
21  weight management, or obesity treatment in patients who are overweight or have obesity. Due to 
22  the wide variety of device designs, among other things, there can be variability in the 
23  demonstrated weight loss and risk associated with these devices, as well as variability in the 
24  applicability of some of the recommended testing. The recommendations reflect current review 
25  practices of premarket submissions for these devices and are intended to promote consistency 
26  and facilitate efficient review of these submissions. 
27   
28  For the current edition of the FDA-recognized consensus standard(s) referenced in this 
29  document, see the FDA Recognized Consensus Standards Database.1 For more information 
30  regarding use of consensus standards in regulatory submissions, please refer to the FDA 
31  guidance titled Appropriate Use of Voluntary Consensus Standards in Premarket Submissions 
32  for Medical Devices.2 
 
1 Available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm. 
2 Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/appropriate-use-
voluntary-consensus-standards-premarket-submissions-medical-devices. 
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33   
34  In general, FDAs guidance documents do not establish legally enforceable responsibilities. 
35  Instead, guidances describe the Agencys current thinking on a topic and should be viewed only 
36  as recommendations, unless specific regulatory or statutory requirements are cited. The use of 
37  the word should in Agency guidances means that something is suggested or recommended, but  
38  not required. 
39   
40  II.  Scope 
41  The scope of this document is limited to devices with indications for use associated with weight 
42  loss, including weight loss, weight reduction, weight management, or obesity treatment in 
43  patients who are overweight or have obesity. This includes the existing product codes listed in 
44  Table 1 below: 
45   
46  Table 1. Existing product codes within the scope of this guidance 
Product  Product Code Name  Regulation Number 
Code 
LTI  Intragastric implant for morbid  Not applicable3 
obesity 
OYF  Aspiration therapy system  Not applicable4 
PIM  Neuromodulator for obesity  Not applicable5 
ONY  Oral removable retainer for  21 CFR 876.59816 
weight management 
QFQ  Ingested, Transient, Space  21 CFR 876.59827 
Occupying Device For Weight 
Management And/Or Weight 
Loss 
QTD  Endoscopic Suturing Device For  21 CFR 876.59838 
Altering Gastric Anatomy For 
Weight Loss 
47   
48  Although the product codes listed above are current as of the date of issuance of this guidance, 
49  new product codes or classification regulations may be created over time and could fall within 
50  the scope of this guidance.  We recommend that you reference the product code database 
51  (http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPCD/classification.cfm) or contact OHT3: 
52  Office of Gastro-Renal, ObGyn, General Hospital, and Urology Devices if you are uncertain 
 
3 This is a postamendments class III device. 
4 Ibid. 
5 Ibid. 
6 This classification regulation includes special controls. See 21 CFR 876.5981(b). 
7 This classification regulation includes special controls. See 21 CFR 876.5982(b). 
8 This classification regulation includes special controls established in the reclassification order, available at 
https://www.accessdata.fda.gov/cdrh_docs/pdf21/DEN210045.pdf. The publication of this classification in the 
Federal Register and codification in the Code of Federal Regulations are currently pending. 
2  Contains Nonbinding Recommendations 
 
Draft  Not for Implementation 
 
53  whether this guidance applies to your device and the product code for your device is not already 
54  captured in this guidance. 
55   
56  Some of the recommendations in this guidance may assist in complying with some of the special 
57  controls for devices with indications associated with weight loss. For information regarding 
58  special controls for oral removable retainers for weight management, see 21 CFR 876.5981(b).  
59  For information regarding special controls for ingested, transient, space occupying devices for 
60  weight management and/or weight loss, see 21 CFR 876.5982(b). For information regarding 
61  special controls for endoscopic suturing devices for altering gastric anatomy for weight loss, see 
62  FDAs website.9 
63   
64  This draft guidance should be viewed as a complement to FDAs draft guidance entitled, 
65  Medical Devices with Indications Associated with Weight Loss - Clinical Study and Benefit-
66  Risk Considerations,10 which, once finalized, will provide recommendations regarding clinical 
67  study design for these devices and also includes discussion on how FDA considers the benefit-
68  risk analysis to support such indications. 
69   
70  III.  Premarket Submission Recommendations 
71    Device Description 
72  We recommend submitters identify their device by the applicable regulation number and product 
73  code indicated in Section II above and include the information described below.  
74   
75    An explanation of how the device functions, the scientific concepts that form the 
76  basis for the device, and the significant physical and performance characteristics of 
77  the device, such as device design, material(s) used, and physical properties.  
78    A complete description of the device, which may be facilitated by the submission of 
79  engineering schematics or other figures. If the device consists of multiple 
80  components, a diagram identifying how the different components of the device 
81  system work together, a video, and/or animation, could be beneficial.  
82    A discussion of the physical specifications and/or tolerances of the device. 
83    If the device includes nitinol, submitters should include the General Information 
84  recommended in the FDA guidance document Technical Considerations for Non-
85  Clinical Assessment of Medical Devices Containing Nitinol.11 
86     
 
9 See reclassification order, available at https://www.accessdata.fda.gov/cdrh_docs/pdf21/DEN210045.pdf. 
10 When final, this guidance will represent FDAs current thinking on clinical study and benefit-risk considerations 
for medical devices with indications associated with weight loss. Available at https://www.fda.gov/regulatory-
information/search-fda-guidance-documents/medical-devices-indications-associated-weight-loss-clinical-study-and-
benefit-risk-considerations.  
11 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/technical-considerations-non-
clinical-assessment-medical-devices-containing-nitinol. 
3  Contains Nonbinding Recommendations 
 
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87   
88    Labeling 
89  For a premarket approval application (PMA), submitters must submit all proposed labeling. (21 
90  CFR 814.20(b)(10)).  Additionally, a 510(k) submission must include proposed labeling in 
91  sufficient detail to satisfy the requirements of 21 CFR 807.87(e). Proposed labels and labeling, 
92  sufficient to describe the device, its intended use, and the directions for use must be provided. 
93  Lastly, for De Novo requests, submitters must provide labeling sufficient to describe the device, 
94  its intended use, and the directions for its use. (21 CFR 860.220(a)(18)).   
95   
96  As prescription devices, devices with indications associated with weight loss are exempt from 
97  having adequate directions for lay use required under section 502(f)(1) of the Federal Food, 
98  Drug, and Cosmetic Act (FD&C Act) as long as the conditions in 21 CFR 801.109 are met. For 
99  instance, labeling must include adequate information for the intended user of the device, 
100  including indications, effects, routes, methods, frequency and duration of administration and any 
101  relevant hazards, contraindications, side effects, and precautions (21 CFR 801.109(d)). The 
102  following section does not detail all of the elements of proposed labeling that are required within 
103  a marketing submission, but instead outlines recommendations for specific content for inclusion 
104  in the user manual that may apply specifically to devices with indications associated with weight 
105  loss. 
106   
107  (1)  Warnings 
108  If the device includes nitinol and has prolonged or permanent contact with the body, we 
109  recommend inclusion of the warning regarding nickel allergy as described in FDA guidance 
110  Technical Considerations for Non-Clinical Assessment of Medical Devices Containing 
111  Nitinol.12 
112   
113  (2)  MR Safety Information 
114  We recommend submitters follow the labeling guidance in Testing and Labeling Medical 
115  Devices for Safety in the Magnetic Resonance (MR) Environment.13 We also recommend that 
116  submitters use the standardized terminology and icons specified in the currently recognized 
117  version of ASTM F2503: Standard Practice for Marking Medical Devices and Other Items for 
118  Safety in the Magnetic Resonance Environment. 
119   
120  (3)  Overview of Clinical Studies 
121  Submitters should provide a narrative description of the study(ies) relevant to the device. For 
122  information regarding clinical study considerations for these devices, we recommend submitters 
 
12 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/technical-considerations-non-
clinical-assessment-medical-devices-containing-nitinol. 
13 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/testing-and-labeling-medical-
devices-safety-magnetic-resonance-mr-environment. 
4  Contains Nonbinding Recommendations 
 
Draft  Not for Implementation 
 
123  follow FDAs draft guidance, Medical Devices with Indications Associated with Weight Loss- 
124  Clinical Study and Benefit-Risk Considerations.14 The narrative should be brief, and for each 
125  study, it should include a description of the following: 
126   
127    design of the study, including any randomization, blinding, and the control or controls 
128  used; 
129    number of patients enrolled; 
130    number of investigational sites both inside the United States (U.S.) and outside the 
131  United States (O.U.S.); 
132    primary study endpoints; 
133    results of the study (e.g., adverse events, endpoint data, statistical analysis); and 
134    amount of available follow-up. 
135   
136  Data on the changes in the major weight-related comorbidities (e.g., type 2 diabetes mellitus, 
137  hypertension) are important to describe the overall benefit-risk profile of a new device with an 
138  indication associated with weight loss and could be included in the Clinical Studies section of the 
139  device labeling. Any labeling associated with secondary effectiveness endpoints should be based 
140  on results that are both clinically and statistically significant. If any of the secondary endpoint 
141  analyses are intended to support the indications for use or to describe device performance in the 
142  labeling (e.g., comparing treatment and control groups using p-values and confidence intervals), 
143  we recommend that submitters pre-specify this intention in the study protocol and provide a 
144  detailed description of the statistical methods submitters plan to follow. To support inclusion in 
145  labeling, the overall type I error rate should be controlled. The clinical significance and 
146  consistency across studies of any observed differences will be important in determining whether 
147  the secondary effectiveness data are appropriate for inclusion in the Clinical Studies section of 
148  the labeling. 
149   
150  (4)  Adverse Events 
151  In addition to the adverse event information from the clinical study described in Section IV.H of 
152  FDAs draft guidance, Medical Devices with Indications Associated with Weight Loss - 
153  Clinical Study and Benefit-Risk Considerations,15 submitters should also include potential risks 
154  associated with the device. 
155   
 
14 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/medical-devices-indications-
associated-weight-loss-clinical-study-and-benefit-risk-considerations. 
15 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/medical-devices-indications-
associated-weight-loss-clinical-study-and-benefit-risk-considerations. 
5  Contains Nonbinding Recommendations 
 
Draft  Not for Implementation 
 
156  FDA has alerted health care providers about potential risks with liquid-filled intragastric 
157  balloons.16 If the device is a liquid-filled intragastric balloon, we recommend that the specific 
158  risks identified in these safety communications be included in the labeling, and occurrence rates 
159  be separated by occurrence in the U.S. and globally, if applicable. These risks include, but may 
160  not be limited to: spontaneous hyperinflation in patients stomachs, acute pancreatitis, 
161  esophageal perforation, gastric perforation, aspiration, and death. 
162   
163  (5)  Patient Labeling (including patient implant card, if 
164  applicable) 
165  Submitters should provide examples of all patient labeling, including the patient guide and 
166  implant card, that are intended to be provided to patients. When preparing patient labeling, we 
167  recommend use of the FDA guidance Guidance on Medical Device Patient Labeling.17 
168   
169  For MR Conditional devices, we recommend submitters include in the patient labeling and on 
170  the patient implant card all conditions for safe MR use as specified in Testing and Labeling 
171  Medical Devices for Safety in the Magnetic Resonance (MR) Environment18 as well as the MR 
172  Conditional icon from the currently recognized version of ASTM F2503: Standard Practice for 
173  Marking Medical Devices and Other Items for Safety in the Magnetic Resonance Environment. 
174   
175    Sterility 
176  Devices with indications for use associated with weight loss can be sterile or provided non-
177  sterile. 
178  (1)  Sterile Devices 
179  Significance: Devices with indications for use associated with weight loss can be implanted 
180  devices or come in contact with breached or compromised tissue and/or the blood path. Such 
181  devices should be adequately sterilized to minimize infections and related complications. 
182   
183  Recommendation: For devices labeled as sterile, we recommend submitters provide the 
184  information outlined below.19  
185   
 
16 See The FDA alerts health care providers about potential risks with liquid-filled intragastric balloons, available 
at https://www.fda.gov/medical-devices/letters-health-care-providers/fda-alerts-health-care-providers-about-
potential-risks-liquid-filled-intragastric-balloons. 
17 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/guidance-medical-device-patient-
labeling. 
18 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/testing-and-labeling-medical-
devices-safety-magnetic-resonance-mr-environment.  
19 For 510(k) submissions, we recommend that submitters provide information for the final sterile device in 
accordance with FDAs guidance Submission and Review of Sterility Information in Premarket Notification 
(510(k)) Submissions for Devices Labeled as Sterile (available at https://www.fda.gov/regulatory-
information/search-fda-guidance-documents/submission-and-review-sterility-information-premarket-notification-
510k-submissions-devices-labeled).  
6  Contains Nonbinding Recommendations 
 
Draft  Not for Implementation 
 
186  1.  For the sterilization method, submitters should provide the following:  
187  a.  a comprehensive description of the sterilization method/process;  
188  b.  a description of the sterilization chamber if not rigid, fixed (e.g., flexible bag); 
189  c.  the sterilization site; 
190  d.  in the case of radiation sterilization, the radiation dose; and  
191  e.  for chemical sterilants (e.g., ethylene oxide (EO), hydrogen peroxide (H O )), the 
2 2
192  maximum levels of sterilant residuals that remain on the device, and an explanation of 
193  why those levels are acceptable for the device type and the expected duration of 
194  patient contact. 
195  In the case of EO sterilization, CDRH has accepted EO residuals information based 
196  on the currently recognized version of the standard, AAMI/ANSI/ISO 10993-7, 
197  Biological Evaluation of Medical Devices  Part 7: Ethylene Oxide Sterilization 
198  Residuals. 
199  2.  For the sterilization method, submitters should provide a description of the method used 
200  to validate the sterilization cycle (e.g., the half-cycle method) as well as the sterilization 
201  validation data. The submission should also identify all relevant consensus standards used 
202  and identify any aspects of the standards that were not met. In the absence of a 
203  recognized standard, a comprehensive description of the process and the complete 
204  validation protocol should be submitted and reviewed.  
205  3.  Submitters should state the sterility assurance level (SAL) of 10-6 for devices labeled as 
206  sterile unless the device is intended only for contact with intact skin. FDA recommends a 
207  SAL of 10-3 for devices intended only for contact with intact skin. 
208   
209  (2)  Non-Sterile Devices 
210  Significance: If the single-patient use device makes contact with only non-sterile areas of the 
211  body (e.g., intact gastrointestinal tract) and will not breach mucosal tissues, it may be acceptable 
212  to be provided to the user and used as non-sterile. However, the use of a non-sterile device in the 
213  gastrointestinal tract can introduce microbes that can cause illness, introduce antibiotic-resistant 
214  organisms, and/or alter the gut microflora. Therefore, it is important to monitor microbial levels 
215  during the manufacturing process to minimize these risks. 
216   
217  Recommendation: Submitters should describe the type and frequency of microbial monitoring 
218  that is conducted to ensure that the types of microbes and the levels of bioburden on any 
219  gastrointestinal tract-contacting components of the device will, within reason, not negatively 
220  impact human health in regard to the risk of infection. 
221   
222  Submitters should provide test reports and protocols with the following information for devices 
223  intended to be provided non-sterile: 
224   
7  Contains Nonbinding Recommendations 
 
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225  1.  Description of the microbiological controls in the manufacturing process, which should 
226  include processes to maintain low bioburden levels and the absence of pathogens (e.g., 
227  Escherichia coli, Salmonella spp., Clostridium spp.) on the device; 
228  2.  Description and justification of the type and frequency of microbial monitoring 
229  conducted; 
230  3.  The level of bioburden on the device and the historical data and scientific justification 
231  used to determine alert and action levels; 
232  4.  Bioburden recovery efficiency validation and bioburden culture methods; and 
233  5.  The identities of predominant bioburden species and a justification for how the types of 
234  microorganisms and the levels of bioburden on the device do not negatively impact 
235  human health. 
236   
237  For intragastric devices filled with liquid (e.g., balloons), FDA recommends that the fill fluid for 
238  the device is provided sterile. The presence of microorganisms in the fill fluid of these devices 
239  may lead to hyperinflation of the device beyond the intended maximum fill volume described in 
240  the labeling, which could lead to patient complications and/or device failure.  
241  a.  Clean Devices 
242  If the device is intended to be labeled as clean, non-sterile, we recommend that submitters 
243  describe the method of cleaning conducted to support that the device is clean, and include the 
244  cleaning methods, assays to assess cleanliness, and acceptance criteria used. Submitters should 
245  consider the FDA-recognized version of ASTM F3127: Standard Guide for Validating Cleaning 
246  Processes Used during the Manufacture of Medical Devices for further recommendations related 
247  to the validation of critical cleaning processes to reduce manufacturing contaminants on medical 
248  devices to acceptable levels prior to packaging. 
249   
250    Pyrogenicity 
251  Significance: Pyrogenicity testing is used to help protect patients from the risk of febrile reaction 
252  due to gram-negative bacterial endotoxins and/or chemicals that can leach from a medical device 
253  (e.g., material-mediated pyrogens). 
254   
255  Recommendation: To address the risks associated with the presence of bacterial endotoxins, if 
256  applicable, the device should meet applicable pyrogen limit specifications.20 Submitters should 
257  also follow the recommendations in Pyrogen and Endotoxins Testing: Questions and 
258  Answers.21 To address the risks associated with material-mediated endotoxins, follow the 
 
20 For 510(k) submissions, submitters should meet pyrogen limit specifications by following the recommendations 
outlined in FDAs guidance Submission and Review of Sterility Information in Premarket Notification (510(k)) 
Submissions for Devices Labeled as Sterile (available at https://www.fda.gov/regulatory-information/search-fda-
guidance-documents/submission-and-review-sterility-information-premarket-notification-510k-submissions-
devices-labeled). 
21 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/pyrogen-and-endotoxins-testing-
questions-and-answers. 
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259  recommendations in FDAs guidance Use of International Standard ISO 10993-1, Biological 
260  evaluation of medical devices - Part 1: Evaluation and testing within a risk management 
261  process.22 
262   
263  For devices intended to be labeled as non-pyrogenic, we recommend that both bacterial 
264  endotoxins and material-mediated pyrogens be addressed. As discussed in Section III.F, 
265  material-mediated pyrogenicity assessment can be evaluated as part of a non-clinical animal 
266  study. 
267   
268    Shelf Life and Packaging  
269  Significance: Shelf life testing is conducted to support the proposed expiration date through 
270  evaluation of the package integrity for maintaining device sterility, bioburden, or cleanliness and 
271  evaluation of changes to device performance or functionality. 
272   
273  Recommendation: With respect to package integrity, submitters should provide a description of 
274  the packaging, including how it will maintain the devices sterility, bioburden, or cleanliness, the 
275  protocol(s) used for package integrity testing, the results of the testing, and the conclusions 
276  drawn from results.23 We recommend that a package validation study include simulated 
277  distribution and associated package integrity testing, as well as an aging process (accelerated 
278  and/or real-time) and associated seal strength testing, to validate package integrity and shelf life 
279  claims. We recommend following the methods described in the FDA-recognized series of 
280  consensus standards AAMI/ANSI/ISO 11607-1: Packaging for terminally sterilized medical 
281  devices  Part 1: Requirements for materials, sterile barrier systems and packaging and 
282  AAMI/ANSI/ISO 11607-2: Packaging for terminally sterilized medical devices  Part 2: 
283  Validation requirements for forming, sealing and assembly processes. 
284   
285  With respect to evaluating the effects of aging on device performance or functionality, shelf life 
286  studies should evaluate the critical device properties to ensure it will perform adequately and 
287  consistently during the entire proposed shelf life. To evaluate device functionality, we 
288  recommend submitters assess each of the bench tests described in Section III.K and repeat all 
289  tests that evaluate design components or characteristics that are potentially affected by aging 
290  using aged devices. 
291   
292  For non-sterile devices that contact only non-sterile areas of the body (e.g., intact gastrointestinal 
293  tract, intact skin), a risk assessment should be performed to identify if the device or device 
294  component has the potential to support microbial growth during the shelf life (e.g., lubricants, 
295  oils, organic substances). Non-sterile devices with a high risk of supporting microbial growth 
296  should undergo bioburden testing at the end of the proposed shelf life to ensure that the device 
297  does not exceed microbial action levels at the end of the proposed shelf life. If the device is 
 
22 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/use-international-standard-iso-
10993-1-biological-evaluation-medical-devices-part-1-evaluation-and. 
23 For 510(k) submissions, submitters should provide a description of the packaging, including how it will maintain 
the devices sterility, and a description of the package integrity test methods, but not the package test data. 
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298  determined to have a low risk of microbial growth during shelf life, then the microbiological 
299  testing at the end of the proposed shelf life may not be necessary. 
300   
301  We recommend submitters provide the protocol(s) used for shelf life testing, the results of the 
302  testing, and the conclusions drawn from results.24 In the context of a PMA, if the submitter 
303  intends to extend the shelf life of the device after initial approval, we recommend they provide 
304  the protocol(s) to support the extension in the original submission per 21 CFR 814.39(a)(7). We 
305  recommend all test samples undergo real-time aging to assess the effects of aging on the 
306  maintenance of sterility and device performance.  
307   
308  If devices subjected to accelerated aging are used, we recommend submitters specify the way in 
309  which the device was aged and provide a rationale to explain how the results of shelf life testing 
310  based on accelerated aging are representative of the results if the device were aged in real time. 
311  We recommend submitters age the devices as per the currently FDA-recognized version of 
312  ASTM F1980: Standard Guide for Accelerated Aging of Sterile Barrier Systems for Medical 
313  Devices and specify the environmental parameters established to attain the expiration date. For 
314  devices or components containing polymeric materials or coatings, submitters should conduct 
315  testing on real-time aged samples to confirm the results of the accelerated aging study. This 
316  testing should be conducted in parallel with FDA review and results documented to file in the 
317  design history file (i.e., complete test reports do not need to be submitted to FDA). 
318   
319    Biocompatibility 
320  Significance: Devices with indications associated with weight loss contain patient-contacting 
321  materials, which, when used for their intended purpose, may induce a harmful biological 
322  response.  
323   
324  Recommendation: Submitters should determine the biocompatibility of all patient-contacting 
325  components present in the device. If the device is identical in chemical composition and 
326  processing methods to a device with a history of successful use, submitters can reference 
327  previous testing experience or the literature, if appropriate. For some device materials, it may be 
328  appropriate to provide a reference to either a recognized consensus standard, or to a Letter of 
329  Authorization (LOA) for a device Master File (MAF). Submitters should refer to the following 
330  FDA webpage for additional information on using device MAFs: https://www.fda.gov/medical-
331  devices/premarket-approval-pma/master-files. 
332   
333  If submitters are unable to identify a legally marketed device with the same nature of contact and 
334  contact duration that uses the same materials and manufacturing process as used in the subject 
335  device, we recommend conducting the biocompatibility evaluation as recommended in FDAs 
336  guidance Use of International Standard ISO 10993-1, Biological evaluation of medical devices 
337  - Part 1: Evaluation and testing within a risk management process.25 The evaluation should 
 
24 For 510(k) submissions, we recommend submitters provide a summary of the test methods used for shelf life 
testing, results, and the conclusions drawn from your results. 
25 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/use-international-standard-iso-
10993-1-biological-evaluation-medical-devices-part-1-evaluation-and. 
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338  explain the relationship between the identified biocompatibility risks, the information available 
339  to mitigate the identified risks, and any knowledge gaps that remain. Submitters should then 
340  identify any biocompatibility testing or other evaluations that were conducted to mitigate any 
341  remaining risks. We recommend that submitters consider the recommendations in this guidance, 
342  which identifies the types of biocompatibility assessments that should be considered and 
343  recommendations regarding how to conduct related tests. 
344   
345  Data from a non-clinical animal study26 that uses the device in its final finished form could be 
346  used in lieu of some biocompatibility tests, if the study is designed to include assessments for 
347  those biocompatibility endpoints. For example, an implantation study could be used to evaluate 
348  local tissue responses, material-mediated pyrogenicity, and acute, subacute/subchronic, and 
349  chronic systemic toxicity evaluation, by including the parameters of clinical biochemistry, 
350  hematology, gross pathology, and organ histopathology examinations. 
351   
352  For an intragastric device filled with gas or liquid, submitters should provide: 
353    Information to describe the source, chemical name, composition, purity, and 
354  amount/dose of the filling gas or liquid.  
355    A toxicological risk assessment on the gas or liquid when it is expelled into the 
356  stomach, upon emptying or rupture of the device.  
357    Information or test data (e.g., chemical leachable/extractable analysis) to evaluate the 
358  potential chemical reaction of the filling gas or liquid with the device and assess the 
359  toxicological risks to patients if any compounds leach out of the device.  
360   
361  If the device includes nitinol, we recommend that submitters consider the biocompatibility 
362  recommendations in the FDA guidance Technical Considerations for Non-Clinical Assessment 
363  of Medical Devices Containing Nitinol.27 
364   
365    Software  
366  Significance: When the device contains software, adequate software performance testing 
367  provides assurance that the device is operating within safe parameters and that adequate alarms 
368  are provided to the user if warranted. Software should conform to user needs and the intended 
369  use(s) of the device. 
370   
371  Recommendation: Refer to the FDA software guidance Content of Premarket Submissions for 
372  Device Software Functions28 for a discussion of the software documentation that submitters 
 
26 FDA supports the principles of the 3Rs, to replace, reduce, and/or refine animal use in testing when feasible. 
We encourage sponsors to consult with us if they wish to use a non-animal testing method they believe is suitable, 
adequate, validated, and feasible. We will consider if such an alternative method could be assessed for equivalency 
to an animal study. 
27 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/technical-considerations-non-
clinical-assessment-medical-devices-containing-nitinol.  
28 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/content-premarket-submissions-
device-software-functions. 
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373  should provide in the marketing submission. The software guidance outlines the recommended 
374  information to be provided based on the Documentation Level associated with the device. If a 
375  submitter believes that the device warrants a Basic Documentation Level as defined in this 
376  software guidance, the submitter should provide a scientific justification that supports the 
377  rationale of the Documentation Level based on the possible consequences of software failure. 
378   
379  We recommend submitters provide a full description of the software/firmware supporting the 
380  operation of the subject device following this software guidance, commensurate with the 
381  appropriate Documentation Level. This recommendation applies to original devices/systems as 
382  well as to any software/firmware changes made to already-marketed devices. Changes to 
383  software must be revalidated and reverified in accordance with Design Controls, 21 CFR 
384  820.30(g)(i),29 and documented in the Design History File, 21 CFR 820.30(j).30  
385   
386  If the device meets the definition of a cyber device under section 524B(c) of the FD&C Act, 
387  cybersecurity documentation under section 524B(b) of the FD&C Act is required as part of the 
388  premarket submission. For more information on this topic, see FDAs guidance Content of 
389  Premarket Submissions for Management of Cybersecurity in Medical Devices.31 
390   
391  If the device includes off-the-shelf software, submitters should provide the additional 
392  information as recommended in the FDA guidance documents Off-the-Shelf Software Use in 
393  Medical Devices32 and Cybersecurity for Networked Medical Devices Containing Off-The-
394  Shelf (OTS) Software,33 which provide additional information regarding medical devices 
395  utilizing off-the-shelf software. 
396   
 
29 On 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. 
30 For 510(k) submissions, some software changes may warrant the submission of a new 510(k). For further 
information on this topic, refer to Deciding When to Submit a 510(k) for a Software Change to an Existing Device 
(available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/deciding-when-submit-
510k-software-change-existing-device). 
31 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/content-premarket-submissions-
management-cybersecurity-medical-devices-0. 
32 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/shelf-software-use-medical-devices. 
33 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/cybersecurity-networked-medical-
devices-containing-shelf-ots-software. 
 
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397  Overall, the documentation related to the software contained in the medical device should 
398  provide sufficient evidence to describe the role of the software included in the device, and 
399  performance testing to demonstrate that the software functions as designed.  
400   
401    Electrical Safety and Electromagnetic Compatibility 
402  (EMC) 
403  Significance: If the device or device system is electrical, it may expose the operator and patient 
404  to hazards associated with the use of electrical energy or may fail to operate properly in the 
405  presence of electromagnetic disturbance. 
406  Recommendation: These devices should be tested to demonstrate that they perform as anticipated 
407  in their intended use environment. We recommend that this testing be performed as described in 
408  the currently FDA-recognized versions of the following standards for medical electrical 
409  equipment safety and electromagnetic compatibility: 
410    AAMI/ANSI ES60601-1: Medical electrical equipment - Part 1: General 
411  requirements for basic safety and essential performance. 
412    AAMI/ANSI/IEC 60601-1-2: Medical electrical equipment - Part 1-2: General 
413  requirements for basic safety and essential performance - Collateral standard: 
414  Electromagnetic disturbances - Requirements and tests. 
415    If the device is an implanted electrical stimulator, we also recommend that submitters 
416  conduct the specific tests for electrical safety and EMC that are described in the 
417  currently FDA-recognized version of ISO 14708-3: Implants for Surgery  Active 
418  implantable medical devices  Part 3: Implantable neurostimulators. 
419   
420  If submitting a declaration of conformity to the above standards, we recommend that appropriate 
421  supplemental documentation such as an assessment of the results and how conformity was 
422  determined, and information regarding test methods used should be provided, because this series 
423  of standards includes general methods with multiple options and, in some cases, does not include 
424  specific acceptance criteria or address assessment of results. For additional information on 
425  providing electromagnetic compatibility information in a premarket submission, see FDAs 
426  guidance Electromagnetic Compatibility (EMC) of Medical Devices.34 
427   
428  Additionally, implanted devices that use a battery should remain functional through the battery 
429  life to limit the need for unplanned surgical intervention. 
430     
 
34https://www.fda.gov/regulatory-information/search-fda-guidance-documents/electromagnetic-compatibility-emc-
medical-devices.  
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431   
432    Wireless Technology 
433  Significance: In the design, testing, and use of wireless medical devices, the correct, timely, and 
434  secure transmission of medical data and information is essential for the safe and effective use of 
435  medical devices and systems.  
436   
437  Recommendation: If the device incorporates radiofrequency wireless technology such as 
438  Bluetooth, IEEE 802.11 (Wi-Fi), or RFID (radio frequency identification) technology; testing 
439  beyond what is specified in the IEC 60601 standards is recommended to demonstrate that the 
440  wireless device functions will perform as intended in environments with other wireless products. 
441  For additional recommendations for home use devices with wireless technology, if applicable, 
442  refer to FDAs guidance Design Considerations for Devices Intended for Home Use.35  
443   
444  We recommend submitters consult FDAs guidance Radio Frequency Wireless Technology in 
445  Medical Devices36 for additional recommendations on this topic. 
446   
447    Magnetic Resonance (MR) Compatibility for Implants 
448  Significance: MR imaging of patients with implanted devices poses the following potential 
449  hazards:  
450   
451    Movement of the implant, resulting in tissue damage or displacement of the device; 
452  heating of the tissue surrounding the implant and subsequent tissue damage; image 
453  artifacts that may render the MR images uninterpretable or misleading; and/or 
454    Malfunction of electrically active devices or induce voltages in leads or other long 
455  conductive portions of the device which can result in a failure of the device to deliver 
456  the intended therapy.  
457   
458  Recommendation: We recommend submitters address the safety and compatibility of the device 
459  in the MR environment as described in the FDA guidance Testing and Labeling Medical 
460  Devices for Safety in the Magnetic Resonance (MR) Environment.37  
461   
462  If the submitter would like to market devices of various sizes and shapes, then we recommend 
463  following the recommendations in the FDA guidance Assessment of Radiofrequency-Induced 
 
35 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/design-considerations-devices-
intended-home-use.  
36 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/radio-frequency-wireless-
technology-medical-devices-guidance-industry-and-fda-staff. 
37 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/testing-and-labeling-medical-
devices-safety-magnetic-resonance-mr-environment.  
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464  Heating in the Magnetic Resonance (MR) Environment for Multi-Configuration Passive Medical 
465  Devices.38 
466   
467    Non-Clinical Bench Performance Testing 
468  Non-clinical performance bench testing supports device usability, device safety, and device 
469  performance. Typical bench performance testing should demonstrate that the device functions as 
470  intended. To assist in determining the appropriate non-clinical bench performance testing for 
471  their device, submitters can seek input from the Agency via the Q-Submission Program. For 
472  details on the Q-Submission Program, refer to the guidance Requests for Feedback and 
473  Meetings for Medical Device Submissions: The Q-Submission Program.39 
474   
475  For information on recommended content and format of test reports for the testing described in 
476  this section, refer to FDAs guidance Recommended Content and Format of Test Reports for 
477  Non-Clinical Bench Performance Testing in Premarket Submissions.40 
478   
479  The non-clinical bench performance tests referenced in this section are intended to be general 
480  recommendations. They are not an exhaustive list due to the variety of device technologies with 
481  indications associated with weight loss. 
482   
483  (1)  Corrosion Resistance 
484  Significance: When made of metallic materials, device corrosion can cause or contribute to 
485  premature device failure. In addition, corrosion byproducts may be toxic or cause other adverse 
486  biological and tissue responses. 
487  Recommendation: If the device includes nitinol, we recommend characterizing the corrosion 
488  potential of the device as described in the FDA guidance Technical Considerations for Non-
489  Clinical Assessment of Medical Devices Containing Nitinol.41  
490   
491  If the device includes metallic materials other than nitinol, we recommend that the submitter 
492  assess corrosion susceptibility as described below. Note that corrosion testing is generally not 
493  warranted for limited contact devices; however, such testing may be requested in situations such 
494  as devices with an electrically active component, a dissimilar metal couple, or a degradable 
495  metal/polymer component where these features could accelerate metal corrosion. In these cases, 
496  we recommend that submitters seek more detailed feedback via the Q-Submission Program. 
497   
 
38 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/assessment-radiofrequency-induced-
heating-magnetic-resonance-mr-environment-multi-configuration. 
39 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/requests-feedback-and-meetings-
medical-device-submissions-q-submission-program.  
40 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/recommended-content-and-format-
non-clinical-bench-performance-testing-information-premarket. 
41 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/technical-considerations-non-
clinical-assessment-medical-devices-containing-nitinol.  
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498  a.  Pitting Corrosion 
499  We recommend conducting pitting corrosion testing on the as-manufactured device according to 
500  the currently recognized version of ASTM F2129: Standard test method for conducting cyclic 
501  potentiodynamic polarization measurements to determine the corrosion susceptibility of small 
502  implant devices (or an equivalent method with justification). Testing should be performed after 
503  subjecting the device to simulated use testing that mimics in vivo anatomic conditions.. This 
504  device conditioning is intended to simulate the clinical conditions of the device at the time of 
505  implantation. Appropriate simulated fluid (e.g., gastric or intestinal) should be used as the 
506  standard test solution. 
507   
508  On the test report, when practical, we recommend plotting all polarization curves in one graph. 
509  Results should be assessed against acceptance criteria. ASTM F2129 does not include 
510  acceptance criteria. While there is limited data directly linking in vitro corrosion testing to in 
511  vivo corrosion outcomes, there is published data that could be used to establish acceptance 
512  criteria.42 The criteria should be justified based on pitting and crevice corrosion performance as 
513  well as risk of metal leaching for the device. If breakdown occurred, submitters should include 
514  results of the visual inspection of the device before and after testing to assess evidence of pitting 
515  and location of pits. Images of sufficient magnification should be provided to support the 
516  assessment. Literature or previous performance data may support the pitting susceptibility 
517  assessment of the device. However, the materials, design, and fabrication processes specific to 
518  the device may reduce or eliminate the applicability of literature or previous experience with the 
519  device.  
520   
521  b.  Galvanic Corrosion 
522  Similar to pitting corrosion, galvanic corrosion may lead to higher than anticipated rates of metal 
523  ion release or compromised mechanical integrity. If the device consists of contacting dissimilar 
524  metals, galvanic corrosion testing should be considered. We recommend the methods described 
525  in the currently recognized version of ASTM F3044: Standard Test Method for Evaluating the 
526  Potential for Galvanic Corrosion for Medical Implants. As an alternative to using devices for 
527  galvanic corrosion testing, coupons representing an expected worst-case galvanic coupling that 
528  are subjected to identical manufacturing processes could be used. In addition, a scientific 
529  justification may be provided, in lieu of testing, if the expected worst-case potential shift due to 
530  galvanic coupling is small and if the relative surface ratios of the cathodic to anodic materials are 
531  low. 
532   
533  c.  Metal Ion Release 
534  If a metal device does not meet the submitters pre-specified acceptance criteria for corrosion 
535  resistance or does not employ an established surface finishing process or if your device has an 
536  electrically active component, we recommend metal ion release testing be performed per the 
537  currently recognized version of ASTM F3306: Standard Test Method for Ion Release Evaluation 
 
42 Corbett, R. A. (2004). Laboratory corrosion testing of medical implants. In Proceedings of Materials and 
Processes for Medical Devices Conference (pp. 166-171). ASM International, Materials Park, OH. 
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538  of Medical Implants. A risk assessment should be performed to compare the amount of metal 
539  ion(s) released from the device to a Tolerable Intake (TI) value for the metal(s). A TI value is 
540  defined in the currently recognized version of ISO 10993-17: Biological evaluation of medical 
541  devices  Part 17: Establishment of allowable limits for leachable substances as an estimate of 
542  the average daily intake of a substance over a specified time period, on the basis of body mass, 
543  that is considered to be without appreciable harm to health. 
544   
545  (2)  Dimensional Verification 
546  Significance: Accurate device dimensions help the user to achieve proper device sizing and 
547  accurate placement in the body. They also affect the functional behavior of a device.  
548   
549  Recommendation: FDA recommends submitters include in the submission verification of 
550  dimensional specifications for the device. 
551   
552  (3)  Strength 
553  Significance: Failure of bonds between materials used in the device can lead to device failure 
554  and clinical complications. 
555   
556  Recommendation: We recommend that tensile strength testing be performed for any device 
557  system that includes materials that are bonded, welded, or susceptible to fatigue. We recommend 
558  that submitters test until failure or provide a justification why acceptance criteria are clinically 
559  appropriate with a margin of safety. 
560   
561  (4)  Durability and Fatigue 
562  Significance: Failure of a device to maintain its integrity throughout the duration of use can 
563  result in adverse clinical consequences or loss of therapy. For liquid-filled intragastric balloons, 
564  susceptibility to leakage is believed to increase the risk of hyperinflation.  
565   
566  Additionally, exposure to the gastrointestinal environment can cause or contribute to degradation 
567  of material coatings, which could expose patients to materials that are not intended to contact 
568  body tissue. In addition to causing potential device failure, exposure of coated materials may 
569  release chemicals that may be toxic or cause other adverse biological and tissue responses.  
570   
571  Recommendation: If the device can burst (e.g., an intragastric balloon) or leak, is subjected to 
572  peristaltic forces, consists of material(s) that may be degraded by the gastrointestinal 
573  environment, and/or consists of a protective plastic or polymer coating, then submitters should 
574  demonstrate that the device will function as intended throughout its intended use life. As 
575  applicable, we recommend conducting the following testing: 
576    Mechanical integrity and fatigue; 
577    Leak susceptibility; 
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578    Coating integrity; and 
579    Burst strength. 
580   
581  If the device includes nitinol, we recommend following the recommendations for mechanical 
582  testing in the FDA guidance Technical Considerations for Non-Clinical Assessment of Medical 
583  Devices Containing Nitinol.43 
584   
585  a.  Mechanical Integrity and Fatigue 
586  If the device is left indwelling in the body, the device should function as intended continuously 
587  throughout the implant period under clinically relevant worst-case conditions. Testing submitted 
588  should support that the device can withstand the implant environment and, if in the 
589  gastrointestinal tract, simulated gastrointestinal motion (including simulated vomiting conditions, 
590  if appropriate) while maintaining integrity and functionality. Devices should be aged to the 
591  labeled shelf life prior to testing (See Section III.E). 
592   
593  We recommend that the device be in contact with simulated fluid (e.g., gastric, intestinal) at 37oC 
594  for a time that is representative of the implantation time of the device plus a safety factor. The 
595  safety factor should account for a reasonable worst-case scenario in the event that the device 
596  remains in the body longer than intended. If applicable, the device should be subjected to 
597  simulated gastrointestinal motion (i.e., peristalsis) during this period. An elevated temperature 
598  can be used for accelerated testing over a shorter period of time, as supported by valid kinetic 
599  calculations for impact of temperature and actual clinical use conditions. 
600   
601  The model for simulated gastric motion should be based on current literature on gastric motion 
602  dynamics.44, 45 Submitters should consider that a gastric implant will be exposed to 
603  circumferential pressures of variable intensity specifically during and following eating. The 
604  amount of pressure used should be justified based on current literature and be representative of a 
605  worst-case scenario. The number of pressure events (squeezes) that the device is subjected to 
606  should consider the number of anticipated pressure events per minute using conservative 
607  assumptions (e.g., assuming 100 minutes per meal and six meals per day).  
608   
609  An example calculation for a six-month gastric implant is: 
610   
611   
3 events 100 minutes 6 meals
612   
  180 days  = 324,000 events (or squeezes)
minute meal day
 
43 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/technical-considerations-non-
clinical-assessment-medical-devices-containing-nitinol. 
44 Bortolotti, M., Annese, V., and Coccia, G. (2000). Twenty-four hour ambulatory antroduodenal manometry in 
normal subjects (co-operative study). Neurogastroenterol Motil 12(3): 231-238. 
45 Marciani, L., Gowland, P. A., Fillery-Travis, A., Manoj, P., Wright, J., Smith, A., Young, P., Moore, R., and 
Spiller, R. C. (2001). Assessment of antral grinding of a model solid meal with echo-planar imaging. Am J Physiol 
Gastrointest Liver Physiol 280(5): G844-849. 
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613  Testing should include appropriate acceptance criteria considering the device design, and 
614  analyses of device integrity should be performed after exposure to the implant environment as 
615  described above. Appropriate analyses should include burst strength testing and strength testing 
616  if applicable to the device design.  
617   
618  b.  Leak Susceptibility 
619  We recommend that leak susceptibility testing be incorporated into mechanical integrity and 
620  fatigue testing. If the device is inflated and has an inflation/deflation valve, or other design 
621  component(s) that may leak, then we recommend that the integrity of the device throughout the 
622  implantation period be assessed for its ability to prevent deflation and prevent ingress of 
623  surrounding contents (e.g., stomach contents). The amount of leakage recorded should be 
624  justified considering the clinical use of the device (e.g., risks of hyperinflation, infection, and 
625  gastric and/or intestinal obstruction due to deflation).  
626   
627  c.  Coating Integrity 
628  This testing could be incorporated into the testing protocol for mechanical integrity and fatigue. 
629  If the device consists of a protective plastic or polymer coating intended to eliminate patient 
630  contact with a certain material, then we recommend submitters assess the device for coating 
631  degradation potential in the implant environment as described above for mechanical integrity and 
632  fatigue testing. After exposure to the simulated fluid, the tensile strength of the device material 
633  should be measured and compared to an untreated device. Visual inspection of the device using 
634  optical microscopy should also be performed.  
635   
636  d.  Burst Strength 
637  If the device has a balloon, or is an intragastric balloon, then we recommend assessing the 
638  volume at which the balloon will burst. The purpose of this test is to evaluate the ability of the 
639  balloon to withstand rupture under a worst-case clinically anticipated scenario. We recommend 
640  that balloons not burst at least at a volume of X times the maximum labeled volume, where 
641  X represents a worst-case scenario supported by a clinical justification considering the 
642  likelihood of over inflation during device placement and/or hyperinflation during device use.  
643   
644  (5)  Delivery/Removal System Testing 
645  Significance: The device should be able to be safely and reliably delivered to, and removed from 
646  (if applicable), the intended location in the patient according to the instructions for use, without 
647  device failure and patient injury. 
648   
649  Recommendation: Simulated use testing, as part of bench testing, can be useful to ensure that a 
650  device can be placed in and/or removed from the intended location in the patient without 
651  complication. We recommend utilizing a simulated use test model that is representative of a 
652  clinically relevant worst-case tortuous anatomy that the device is anticipated to encounter  when 
653  used as intended. Forces associated with deployment of the device should be measured against 
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654  pre-defined acceptance criteria. Additionally, if the device is intended to be filled with gas or 
655  liquid once placed inside the body (e.g., an intragastric balloon), then submitters should measure 
656  the inflation/deflation time against pre-defined acceptance criteria. Submitters should provide a 
657  clinically relevant justification for all acceptance criteria. 
658   
659  (6)  Interactions with Other Devices 
660  Significance: Interactions between an implanted device and other implants or external medical 
661  devices may impact the performance of the device. 
662   
663  Recommendation: If the device is implanted and may interact with other implants, or external 
664  medical devices, in particular, implanted pumps, implanted neurostimulators, external pumps 
665  like insulin pumps, other products that contain magnets, or devices such as pacemakers that may 
666  contain magnetically operated switches, then we recommend the following: 
667    If the device includes magnets, then submitters should provide data confirming the 
668  magnetic strength specification, and provide data showing the magnetic field strength 
669  of the device at its surface and as a function of distance from the device. 
670    Submitters should analyze how the device might interact with other devices like those 
671  listed above, and determine if additional warnings in labeling are warranted. 
672   
673  (7)  Microorganism Susceptibility 
674  Significance: Devices that are left indwelling in the gastric environment can become 
675  contaminated with microorganisms (e.g., fungi, bacteria). This is especially of concern when 
676  stomach pH is increased due to concurrent use of proton pump inhibitors (PPIs), creating a 
677  favorable growth environment. Microorganisms that colonize a device can degrade the device 
678  material(s) and compromise the functionality of the device. Hyperinflation of intragastric 
679  balloons could be associated with microbial contamination.46 FDA is also aware of published 
680  cases of fungal and bacterial colonization of intragastric balloons.47 This may lead to adverse 
681  events and/or loss of effectiveness. For example, a compromised intragastric balloon may deflate 
682  and move into the bowels, potentially causing an obstruction. 
683   
684  Recommendation: If the device is an intragastric implant, we recommend conducting a risk 
685  assessment to assess susceptibility to microorganism colonization on the device and subsequent 
686  material breakdown. The risk assessment should include, at a minimum: 
687    Device geometry: The devices geometry may contribute to capturing gut 
688  microorganisms. For example, a smooth spherical shape may not allow colonization 
 
46 See The FDA alerts health care providers about potential risks with liquid-filled intragastric balloons, available 
at: https://www.fda.gov/medical-devices/letters-health-care-providers/fda-alerts-health-care-providers-about-
potential-risks-liquid-filled-intragastric-balloons. 
47 For example, see Coskun, H., & Bozkurt, S. (2009). A case of asymptomatic fungal and bacterial colonization of 
an intragastric balloon. World journal of gastroenterology, 15(45), 57515753. 
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689  to occur as easily as a device design that includes external appendages (e.g., external 
690  valve). 
691    Impact on device material: Colonizing microorganisms may impact material 
692  properties; for example, change of elasticity could result in increased risk of material 
693  rupture.  
694    Gastric environment: Gastric pH may be altered during device indwelling (e.g., via 
695  concomitant use of PPIs). Additionally, if the device causes delayed gastric emptying, 
696  increased exposure times to microorganisms in the stomach may increase the 
697  likelihood of colonization. 
698    Clinical experience: If the device is already marketed in other countries, submitters 
699  should provide an evaluation of known microorganism contamination issues. An 
700  example of this evaluation could include an analysis of complaint data from 
701  marketing the device in other countries. 
702    Colonization testing: As appropriate, submitters should conduct an assessment of the 
703  affinity for anticipated microorganisms to colonize the device under anticipated use 
704  conditions. The assessment should evaluate fungal and bacterial species, as 
705  applicable.  
706   
707    Animal Studies 
708  Significance: Due to limitations of bench models, animal studies may be warranted to support 
709  medical device premarket submissions. The in vivo setting generally provides an initial 
710  assessment of how a medical device interacts with biological systems, including physiological, 
711  pathological, and toxicological effects of the device, and how the biological system may affect 
712  the device.  
713   
714  Recommendation: We recommend submitters assess whether an animal study(ies) is warranted 
715  in the non-clinical testing plan. Study in an animal model should address factors that cannot be 
716  evaluated through bench tests alone. The study design and endpoints should be based upon the 
717  intended use of the device and clinical risk assessment. We recognize that there is no single best 
718  animal study design; however, we have the following recommendations for designing an animal 
719  study.  
720   
721  FDA supports the principles of the 3Rs, replace, reduce and/or refine animal use in testing 
722  when feasible. We encourage submitters to consult with us if they wish to use a non-animal 
723  testing method they believe is suitable, adequate, validated, and feasible. We will consider if 
724  such an alternative method could be assessed for equivalency to an animal study. 
725   
726  We encourage submitters to take advantage of the Q-Submission Program to ensure that the 
727  animal study protocol addresses safety concerns and contains elements that are appropriate for a 
728  regulatory submission. Additionally, for information and recommendations regarding animal 
729  studies used to support medical device submissions, refer to the guidance General 
21  Contains Nonbinding Recommendations 
 
Draft  Not for Implementation 
 
730  Considerations for Animal Studies Intended to Evaluate Medical Devices.48 If the submitter is 
731  proposing to use a non-animal testing method in lieu of an animal study, we recommend 
732  discussing the proposal using the Q-Submission Program. For details on the Q-Submission 
733  Program, refer to the guidance Requests for Feedback and Meetings for Medical Device 
734  Submissions: The Q-Submission Program.49 
735   
736  (1)  Animal Model 
737  Large animal models are typically chosen for device safety evaluations, because they simulate 
738  human gastrointestinal anatomy and size. Submitters should consider relevant comparative 
739  anatomy and physiology when choosing the animal model for device safety testing. Porcine and 
740  canine models are common choices because of similarities in gastrointestinal anatomy and 
741  physiology to humans. FDA recognizes that device safety testing in an animal may be limited in 
742  some cases by model anatomy or physiology. For example, quadruped animal models may 
743  present a different anatomical device orientation in vivo given their stance versus the human 
744  biped. Nevertheless, the chosen animal model should be scientifically justified and able to 
745  address the safety characteristics that will be evaluated with an animal study.  
746   
747  (2)  Study Endpoint Considerations 
748  The primary objective of animal studies performed to support a submission to FDA is typically 
749  to evaluate safety. Animal safety studies must be performed under the Good Laboratory Practice 
750  for Nonclinical Laboratory Studies (GLP) regulation (21 CFR part 58) to help ensure the quality 
751  and integrity of the safety data submitted to the Agency. Though the objectives of some animal 
752  studies may also include usability or effectiveness, effectiveness can be challenging to 
753  meaningfully assess in animal studies for devices with indications associated with weight loss. 
754  Proof-of-concept studies, such as those evaluating device-related endocrine effects in an animal 
755  model may provide valuable data to support a future FDA submission. However, animal models 
756  of disease often present study confounders that complicate data interpretation. Therefore, 
757  effectiveness can be more difficult to interpret in an animal model, particularly if animals are still 
758  growing. FDA recognizes these limitations and believes that demonstration of effectiveness via 
759  animal testing may not be appropriate for some devices with indications associated with weight 
760  loss. 
761   
762  (3)  Animal Study Protocol 
763  We recommend that the animal study protocol address identified safety concerns via pre-defined 
764  objectives and acceptance criteria. Study procedures should follow the planned clinical use as 
765  closely as possible to help ensure applicability of data to device safety when used in humans. 
766  The protocol should mimic the intended device deployment, implant location, treatment 
 
48 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/general-considerations-animal-
studies-medical-devices. 
49 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/requests-feedback-and-meetings-
medical-device-submissions-q-submission-program. 
22  Contains Nonbinding Recommendations 
 
Draft  Not for Implementation 
 
767  procedures and duration, as well as device retrieval/explant, while considering the limitations 
768  inherent to the animal model.  
769   
770  Animal model limitations can sometimes be managed by protocol modifications. For example, 
771  altering device deployment procedures in animal testing may help address anatomic differences 
772  between species. In such cases, we recommend that submitters consider how clinical deployment 
773  procedures could be evaluated in other testing. Including a control or sham arm can also help to 
774  differentiate device- from animal model-related adverse events, which could otherwise confound 
775  the study data. We recommend that submitters include a scientific justification if they believe 
776  observed adverse events are related to the animal model.  
777   
778  Whenever possible, animal testing should evaluate the final finished version of the device 
779  intended for commercial distribution. This helps ensure applicability of the animal studies data to 
780  clinical use in humans. FDA recognizes that some animal studies are performed to help support 
781  safety while a device is still in development. In these cases, we recommend that submitters 
782  include a description of any differences between the tested and final finished version of the 
783  device and an explanation of why these differences would not be expected to affect data 
784  interpretation in the submission.  
785   
786  In some cases, biocompatibility testing recommendations may also be addressed as part of other 
787  animal studies, such as to assess device safety (See Section III.F). In these cases, we also 
788  recommend that submitters  use the Q-Submission Program to obtain feedback on the feasibility 
789  of this approach and how best to design the animal study protocol. 
790   
23