Contains  Nonbinding  Recommendations  
 
Draft    Not  for  Implementation  
 
 
Characterization of Metallic  
Coatings and/or  Calcium  Phosphate  
Coatings on Orthopedic  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Draft Guidance  for Industry and 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DRAFT GUIDANCE  
 
This  draft guidance document is being distributed for comment purposes  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 January 23, 2024  
 
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of publication in the  Federal Register of the notice announcing the availability of  the  draft  
guidance.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 regarding this document, contact  OHT6: Office of Orthopedics/DHT6A: 
Division of Joint Arthroplasty Devices at 301-796-5650. 
 
When final, this document will supersede  510(k) Information Needed for  
Hydroxyapatite Coated Orthopedic Implants, dated March 10, 1995  
(revised February 20, 1997);  and Guidance  for Industry on the Testing of 
Metallic Plasma Sprayed Coatings on Orthopedic Implants to Support 
Reconsideration of Postmarket Surveillance Requirements  dated February 
2, 2000.   
 
 
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Draft    Not  for  Implementation  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 e-mail request to  
CDRH-Guidance@fda.hhs.gov to receive a  copy of the guidance. Please use the document  
number GUI00020051 and complete title of  the guidance  in the request.  
   
 
  Contains  Nonbinding  Recommendations  
 
Draft    Not  for  Implementation  
 
 
Table of Contents  
   
I.   Introduction  ........................................................................................................................  4  
II.   Scope  ..................................................................................................................................  5  
III.  Premarket Submission Recommendations .........................................................................  6  
  Coating Description  .......................................................................................................  6  
  Sterility   ..........................................................................................................................  7  
  Pyrogenicity   ..................................................................................................................  8  
  Shelf Life and Packaging  ...............................................................................................  9  
  Biocompatibility  ..........................................................................................................  10  
  Non-Clinical Bench Testing  ........................................................................................  11  
(1)   General Recommendations  ......................................................................................  11  
(2)   Testing of Metallic Coatings ....................................................................................  13  
(3)   Testing of Calcium Phosphate Coatings  ..................................................................  16  
(4)   Testing of Metallic and Calcium Phosphate Dual Coatings  ....................................  19  
(5)   Coated Substrate/Device Testing  .............................................................................  20  
  Non-Clinical Animal Testing .......................................................................................  21  
  Clinical Performance Testing  ......................................................................................  21  
  Labeling  .......................................................................................................................  23  
IV.  Modifications (Devices  subject to 510(k)) .......................................................................  23  
   
 
  Contains  Nonbinding  Recommendations  
 
Draft    Not  for  Implementation  
 
 
Characterization of Metallic  
1  
Coatings and/or  Calcium Phosphate  
2  
Coatings on Orthopedic  Devices   
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  
9   Drug Administration (FDA or Agency) on this  topic. It does not establish any rights for  
10   any person and is not binding on FDA or the public. You can use an alternative approach  
11   if it satisfies the requirements of the applicable statutes and  regulations. To discuss  an  
12   alternative  approach, contact the FDA staff  or Office  responsible for this guidance as 
13   listed on the title page.  
14    
I.   Introduction   
15  
16   This draft guidance document  provides recommendations for premarket submissions  for 
17   orthopedic devices that  contain metallic coatings  and/or calcium phosphate coatings on the  
18   surface. The recommendations reflect current  review practices and are intended to promote 
19   consistency  and facilitate efficient review of these submissions. In this document, the terms 
20   you and your refer  to members  of industry, sometimes referred to  as sponsors, 
21   submitters, or  applicants; and the terms we,  us, and our refer  to FDA.  
22    
23   For the current edition of the FDA-recognized standards referenced in this document, see the 
24   FDA Recognized Consensus Standards Database. 1  For more information regarding  use of 
25   consensus standards in  regulatory submissions, please refer to the FDA guidance titled  
26   Appropriate Use of Voluntary Consensus Standards in Premarket Submissions for Medical  
27   Devices.2    
28    
29   In general, FDAs guidance documents do not establish legally enforceable responsibilities.  
30   Instead, guidances describe the Agencys current  thinking on a topic  and should be viewed 
31   only as recommendations, unless specific regulatory or statutory requirements are cited.  The  
 
 
1  https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm  
2  https://www.fda.gov/regulatory-information/search-fda-guidance-documents/appropriate-use-voluntary-
consensus-standards-premarket-submissions-medical-devices  
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Draft    Not  for  Implementation  
 
 
32   use of the word should in Agency guidance  means that something is suggested or  
33   recommended, but not  required.  
34    
II.   Scope  
35  
36   The recommendations in this document are  applicable to class II and  class III  devices  that  
37   contain  metallic and/or  calcium phosphate coatings, intended for orthopedic applications. 
38   Specifically, this guidance addresses the characterization of  the  following coatings on 
39   orthopedic  devices:  
40    
41   1.   a metallic coating, which can be manufactured using thermal spray  (e.g., plasma 
42   spray), sintering (e.g., sintering of powders, beads, or  fiber mesh  pad), chemical 
43   vapor deposition/infiltration, physical vapor deposition (e.g., ionic plasma  
44   deposition), additive manufacturing3 (e.g., electron beam manufacturing, selective 
45   laser sintering) or other  methods;4  
46    
47   2.   a calcium phosphate coating, which can be manufactured by plasma spray,  
48   solution precipitation, electrochemical deposition or  other methods4; and  
49    
50   3.   a metallic and  calcium phosphate dual coating, which can be manufactured using 
51   one or more  of the above methods.  
52    
53   Other types  of coatings (e.g., other  calcium-based coatings, other ceramic coatings) or  
54   surface modifications (e.g., surface etching, surface anodizing)  are not within the scope of  
55   this guidance document.  For  a coating containing a drug or  a biologic, this guidance does  
56   not  discuss drug or biologic  characterization  recommendations.  
57    
58   This guidance  does not  address device-specific functional  testing, such as  system  
59   component  fatigue testing. For additional information on device-specific performance  
60   testing, refer to the  recommendations in any  applicable device-specific guidance  
61   document, if available, or contact the appropriate review  division. 
62    
63   Some of the  recommendations  in this guidance  may assist in complying with some of the  
64   special controls for devices within the scope of this guidance. For information regarding 
65   special controls, refer to the appropriate classification regulation and the following 
66   special controls documents, as applicable:  
 
 
3  Please refer  to  FDAs  guidance document  entitled  Technical  Considerations  for  Additive  Manufactured 
Medical  Devices,  available  at  https://www.fda.gov/regulatory-information/search-fda-guidance-
documents/technical-considerations-additive-manufactured-medical-devices  for  additional  information  on  this  
topic.  
4  See ISO 17327-1 Non-active  surgical  implants    Implant coating   Part  1:  General  requirements.  
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67      Class II Special Controls Guidance  Document: Knee Joint Patellofemorotibial and  
68   Femorotibial Metal/Polymer Porous-Coated Uncemented Prostheses; Guidance for  
69   Industry and  FDA5  
70      Class II Special Controls Guidance:  Shoulder  Joint Metal/Polymer/Metal  
71   Nonconstrained or Semi-Constrained Porous-Coated Uncemented Prosthesis - 
72   Guidance for Industry and FDA Staff6  
73      Class II Special Controls Guidance  Document: Hip Joint Metal/Polymer  
74   Constrained  Cemented or Uncemented Prosthesis7  
75    
76   Where  consensus standards are included in a  special  control for devices within the scope  
77   of this guidance, FDA believes conformance to the currently FDA-recognized version of  
78   the standard would provide the same  level of or  improved protection of  the public health 
79   and safety  as conformance to other versions of these standards included in a special  
80   control,  and that  conformance  to the currently FDA-recognized standard would meet  any 
81   such consensus standards included in a special control.  Therefore,  firms may  choose to  
82   submit a declaration of conformity  to the currently FDA-recognized standard.8 
83    
III.   Premarket Submission Recommendations  
84  
  Coating Description  
85  
86   We recommend that you provide  the  following information  in your submission to describe  a 
87   metallic and/or calcium phosphate coating on orthopedic devices.  
88    
89   1.   Name of the coating including the coating type (e.g., titanium  coating, hydroxyapatite  
90   coating, titanium/hydroxyapatite dual coating). If a coating is applied by a third party  
91   (i.e., a coating vendor), you can  reference  the third partys master file (MAF) for 
92   specific  information regarding the coating. In your premarket  submission, you should 
93   include  a letter of authorization (LOA) from the  MAF holder, which specifies the 
94   location of  the information relevant to your submission within the master file. The  
95   LOA allows the Agency to reference  information included within the MAF and to 
96   discuss concerns applicable to your submission with the MAF holder. For  additional 
97   information  on master files, see FDAs website on  Master Files. 9  
98    
99   2.   Coating method including a description of the process, and pre- and post-processing.  
100    
 
 
5  https://www.fda.gov/medical-devices/guidance-documents-medical-devices-and-radiation-emitting-
products/knee-joint-patellofemorotibial-and-femorotibial-metalpolymer-porous-coated-uncemented-prostheses  
6  https://www.fda.gov/medical-devices/guidance-documents-medical-devices-and-radiation-emitting-
products/shoulder-joint-metalpolymermetal-nonconstrained-or-semi-constrained-porous-coated-uncemented  
7  https://www.fda.gov/medical-devices/guidance-documents-medical-devices-and-radiation-emitting-
products/hip-joint-metalpolymer-constrained-cemented-or-uncemented-prosthesis-class-ii-special-controls   
8  See section  514(c) of  the  Federal  Food,  Drug  and  Cosmetic Act  (FD&C  Act).  
9  https://www.fda.gov/medical-devices/premarket-approval-pma/master-files  
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101   3.   Starting materials (e.g.,  a description of the  materials and  their chemical  
102   compositions) used for both the coating and the substrate and any standards to which 
103   they conform; note that the starting  materials are not necessarily the same as  the  
104   materials  of the final coating (e.g., calcium and phosphate salts are generally used  as 
105   the  starting materials  for a solution precipitated calcium phosphate coating). 
106    
107   4.   Physical structure of the coating  including number of  layers with  different physical or 
108   chemical properties, thickness of the coating and  each layer, and whether  the coating  
109   is a porous  coating (see Section F.(2).b  below for  a description of porous coating  
110   as specified  in certain device classification  regulations); including interconnecting 
111   porosity, volume porosity percentage, and pore size. 
112    
113   5.   Location of  the coating and its coverage of the device (e.g., provide device  
114   engineering drawings showing the location of the coating and the total coverage 
115   area).  
  Sterility   
116  
117   Significance: Metallic and/or calcium phosphate coated orthopedic devices are implanted  
118   devices  and should be adequately sterilized to minimize infections and related complications.  
119    
120   Recommendation: We recommend  that manufacturers sterilize  all coated  orthopedic devices  
121   as it  is unclear how processing (cleaning and sterilization) by the end user may affect the 
122   integrity of a coating (e.g., if the cleaning and sterilization method by the end user will affect  
123   the chemical properties of the coating), or if a porous coating can be adequately cleaned. 
124   Therefore, if you are intending to provide a coated device non-sterile,  a rationale  based on  
125   testing  data or scientific literature  should be provided to justify  that the proposed 
126   reprocessing  instructions  will not  affect the integrity of the  coating  and/or the cleanliness of  
127   the device. For recommendations regarding the  development and validation of reprocessing 
128   instructions  in your proposed device  labeling, refer to the guidance Reprocessing Medical  
129   Devices in Health Care  Settings: Validation Methods and Labeling.10 
130    
131   For metallic and/or calcium phosphate coated orthopedic devices labeled  as sterile, we 
132   recommend that  you provide information outlined below:  
133    
134   1.   For the sterilization method11:  
135   a.  a comprehensive  description  of the sterilization method/process;  
136   b.   a description of the sterilization chamber if not rigid and fixed (e.g., flexible bag);  
137   c.   the sterilization site;  
138   d.   in the case of radiation sterilization, the radiation dose;   
 
 
10  https://www.fda.gov/regulatory-information/search-fda-guidance-documents/reprocessing-medical-devices-
health-care-settings-validation-methods-and-labeling  
11  Please refer  to  FDAs  recognized  standards  database  FDA  Recognized  Consensus  Standards  Database,  
available at  https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm  for  applicable 
consensus  standards depending on  the  type  of  sterilization method chosen  for  your  device.   
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139   e.   for chemical sterilants (e.g., ethylene oxide (EO), H2O2), the  maximum levels of 
140   sterilant residuals that remain on the  device, and an explanation of why those levels  
141   are acceptable for  the device type and the expected duration  of patient contact.  
142    
143   In the case of EO sterilization, CDRH  has accepted EO residuals information based  
144   on the currently recognized version of the standard, ISO 10993-7 Biological 
145   Evaluation of  Medical Devices   Part 7: Ethylene Oxide Sterilization  Residuals.   
146    
147   2.   For the sterilization method  used, a description of the method used to validate the  
148   sterilization cycle (e.g.,  the half-cycle method), as well as  the sterilization validation  
149   data.12  A premarket submission should also identify all  relevant consensus standards used 
150   and identify any aspects  of the standards  that were not met. In the absence of a 
151   recognized consensus standard, a comprehensive description of the  sterilization  process 
152   and the complete validation protocol  should be submitted for review.   
153    
154   3.   You should state the  sterility assurance level (SAL) of 10-6  for devices labeled as sterile.   
155    
156   We recommend that  all  calcium phosphate coated  devices be  sterilized using gamma  
157   radiation based on a long history of  clinical use  of orthopedic devices with such coatings that  
158   have been sterilized using this method and non-clinical data demonstrating that gamma 
159   radiation does not negatively impact  the coating properties. If any other sterilization method 
160   is used, supporting data  or scientific  rationale  should be provided to  demonstrate  that the 
161   sterilization method  will not affect the  properties  of calcium phosphate coatings  (e.g., phase 
162   composition  and chemical structure)  and the  resulting  clinical outcomes.  
  Pyrogenicity   
163  
164   Significance: Pyrogenicity testing is  used to help protect patients from the  risk of febrile  
165   reaction due to gram-negative bacterial endotoxins and/or chemicals that can leach  from a  
166   medical device (e.g., material-mediated pyrogens).  
167    
168   Recommendation: To address the risks associated with the presence of bacterial endotoxins, 
169   metallic and/or calcium  phosphate coated orthopedic devices  should meet applicable pyrogen 
170   limit specifications.13 You should also follow the recommendations in FDAs guidance  
 
 
12  Submission  of  validation protocols  and data  is  only recommended  for  certain premarket submission  types and  
sterilization  methods.  For  additional  information  regarding  submission  recommendations  for  sterility  
information  in 510(k),  please see 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  
13  For devices  subject  to  510(k) requirements, please also  see 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  
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171   Pyrogen and Endotoxins Testing: Questions  and Answers.14  To address the risks associated  
172   with material-mediated pyrogens, you should follow the recommendations in FDAs  
173   guidance Use of International Standard ISO 10993-1, Biological  evaluation of medical  
174   devices - Part 1: Evaluation and testing within a  risk management process.15   
175    
176   For devices  intended to be labeled as non-pyrogenic, we recommend that both bacterial  
177   endotoxins  and material-mediated pyrogens be  addressed.  
  Shelf Life  and Packaging  
178  
179   Significance: Shelf-life  testing is conducted to support the proposed expiration date  through 
180   evaluation of the package integrity for  maintaining device sterility  and/or evaluation of any 
181   changes to device performance or functionality.  
182    
183   Recommendation: With respect to package integrity for maintaining  device sterility, you 
184   should provide a description of the packaging, including how it will maintain the devices  
185   sterility,  and a description of the package integrity test  methods. Depending  
186   on submission type, you should also provide  the  protocol(s)  used for your package  integrity  
187   testing, the  results of the  testing, and the conclusions drawn from your results. We 
188   recommend that  a package validation study include simulated distribution and associated 
189   package integrity  testing, as well as  an aging process  (accelerated  and/or real-time) and  
190   associated seal strength  testing, to validate package integrity and shelf-life claims. We 
191   recommend you follow the methods  described in the FDA-recognized series of consensus 
192   standards ISO 11607-1 Packaging for terminally sterilized  medical devices  Part 1: 
193   Requirements for materials, sterile barrier systems and packaging and ISO 11607-2  
194   Packaging for terminally sterilized  medical devices  Part 2: Validation requirements for  
195   forming, sealing and assembly processes.  
196    
197   With  respect to evaluating the effects of aging on  performance or functionality of a metallic  
198   and/or calcium phosphate coated device, shelf-life  studies should evaluate the critical  
199   physical, chemical and  mechanical  properties of the metallic and/or calcium phosphate  
200   coating to ensure the  coated device  will perform adequately and consistently during the entire  
201   proposed shelf  life.  To evaluate coating performance, we recommend  that  you assess each of  
202   the bench tests described in Section F.(2).  for metallic coatings and Section F.(3).  for 
203   calcium phosphate coatings  and repeat all tests  that evaluate  critical coating characteristics  
204   that are potentially affected by aging using aged devices.  
205    
206   We recommend that you provide  the protocol(s) used for  your  shelf-life  testing, results, and 
207   the conclusions drawn from your results. If you use  coated  devices or  specific test samples  
208   (coupons)  subject  to accelerated aging for shelf-life testing, we recommend that you  specify  
209   the way in which the  devices  or coupons  were aged  and provide a rationale to explain how  
 
 
14  https://www.fda.gov/regulatory-information/search-fda-guidance-documents/pyrogen-and-endotoxins-testing-
questions-and-answers  
15  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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210   the results of shelf-life  testing based on accelerated aging are representative of the results if  
211   the device were aged  in real time. We recommend that you age your devices as per  the  
212   currently FDA-recognized version of ASTM F1980 Standard Guide for Accelerated Aging of  
213   Sterile Barrier Systems for Medical Devices  and specify the  environmental  parameters  
214   established  to attain the  expiration date.  For resorbable calcium  phosphate  coatings, you 
215   should conduct testing on real-time aged samples to confirm the results of  the accelerated  
216   aging study. This testing  should be conducted in parallel with submission review, with results  
217   documented to file in the design history file (i.e., complete test reports do not need to be  
218   submitted to  FDA).  
  Biocompatibility  
219  
220   Significance: Both the  metallic  coatings and calcium phosphate coatings  on orthopedic  
221   devices are patient-contacting, which, when used for their  intended purpose (i.e., contact  type  
222   and duration), may induce a  harmful biological response.  
223    
224   Recommendation: You should determine  the biocompatibility of  all patient-contacting  
225   materials present in your device,  including both the device  substrate as well as the coating. If 
226   your coating is identical  in composition and processing methods  to a coating on a legally  
227   marketed device  with  a history of successful use, you can  reference previous testing 
228   experience or literature, if appropriate. For some  device  materials, it may  be appropriate to  
229   provide a  reference  to either a recognized consensus standard, or to a LOA for a device  
230   MAF.   
231    
232   If you are unable to  identify  a legally marketed  device with  similar location/duration of 
233   contact and intended use that uses the same coating (i.e., materials and  manufacturing  
234   process)  as used  on your device, we recommend you conduct and provide a biocompatibility  
235   evaluation as recommended in FDAs guidance  Use of International Standard ISO 10993-1, 
236   Biological evaluation of medical devices  - Part 1: Evaluation and testing within a  risk  
237   management process.  16  The  evaluation should explain the  relationship between the  
238   identified biocompatibility  risks,  the information available to mitigate  the identified  risks,  
239   and any knowledge gaps that  remain. You should then identify any biocompatibility testing  
240   or  other evaluations that were conducted to mitigate any remaining risks. We recommend  
241   that you consider  the recommendations in this guidance, which identifies the types of  
242   biocompatibility assessments that should be considered and recommendations regarding how  
243   to conduct  related tests.  
244    
245   Per ISO 10993-1 Biological evaluation of medical devices   Part 1: Evaluation and testing 
246   within a risk management process  and Attachment A of FDAs guidance  on ISO 10993-1, 
247   orthopedic  implants  are considered implant devices in contact with  tissue/bone for a long-
248   term contact duration. Therefore, the following  endpoints should be addressed in your  
249   biocompatibility evaluation:  
 
 
16  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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250   
251      cytotoxicity;   
252      sensitization;   
253      irritation or intracutaneous reactivity;  
254      acute systemic  toxicity;   
255     material-mediated pyrogenicity;  
256      subchronic toxicity (sub-acute toxicity);  
257      genotoxicity;   
258      implantation;   
259      chronic  toxicity; and  
260     carcinogenicity.  
261    
262   We recommend consideration of the  following for metallic  and/or calcium phosphate  
263   coatings:  
264    
265     Your  biocompatibility assessment should consider  not  only the  starting materials used  
266   for  the coating and the device, but also the subsequent processing of the  materials, the  
267   manufacturing methods  (including coating process and pre- and post-coating 
268   processes), cleaning,  and sterilization steps, and any residuals  from  manufacturing 
269   aids used during the  process to ensure the  biocompatibility  assessment  reflects the  
270  final sterilized device.   
271    
272      Differences in  formulation, processing, sterilization, device surface properties (e.g., a 
273   coating containing nano characteristics) compared  to legally  marketed devices that 
274   could affect biocompatibility of the final device  may warrant additional 
275  biocompatibility testing.   
276    
277      For new formulations of  degradable or resorbable calcium phosphate coatings, in 
278   addition to the testing described above, we recommend you address the  
279   biocompatibility  of the  coating over the life of  the device  and discuss the  starting, 
280  intermediate, and final degradation products present over  the  course of degradation.  
  Non-Clinical  Bench Testing  
281  
282   (1)   General  Recommendations  
283   This section identifies general  recommendations  to consider  when conducting non-clinical  
284   tests to  characterize coatings.  Section F.(2)  and Section F.(3) below  list  recommended non-
285  clinical tests for evaluating the  integrity of metallic coatings and calcium  phosphate coatings, 
286   respectively. Inadequate coating integrity could cause  device failure  and clinical  
287   complications such as poor fixation.   
288    
289   For information on the  recommended content and format of test reports  for the testing  
290  described in this section, refer to FDAs guidance, Recommended Content and Format of  
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291   Non-Clinical Bench Performance Testing Information  in Premarket Submissions.17  
292    
293   Unless a coupon is described in the  consensus standard used, we  recommend that you use  
294   final sterilized  devices  from multiple lots  for testing and characterization. Alternatively, a 
295   rationale  should be provided to  justify that the test sample is equivalent to  the final device in 
296   terms of  manufacturing process  including variability between lots, geometry (e.g., radius of  
297   curvature), cleaning and sterilization.  Also, whenever applicable, you should include  a  
298   description of the test sample,  such as the test sample is a coating with substrate, a coating 
299   peeled off from a substrate, or powder that has been pulverized from a  coating.  A  minimum 
300   sample size has been recommended  for each  test  below  unless it is specified in the associated  
301   material/testing consensus standards. Unexpected test results (e.g., a large variability  in  
302   results) or device design may suggest a larger  sample size should be utilized.  
303    
304   The specifications  (a range of values  to be achieved) for a specific coating property, if 
305   applicable, must  meet  the established acceptance criteria  from required  special controls, if 
306   any, and should follow any other applicable recommendations arising out of guidance  
307   documents, or  consensus standards, or be supported by clinical justifications. The range of  
308   the specifications defined  for each coating property should be  assessed and  justified  both 
309   individually and as an aggregate  with  the other properties to demonstrate that the worst-case  
310   scenario  is acceptable. For example,  a coating with  a thickness (or porosity or  pore size)  at  
311   the highest end of the specifications  should demonstrate acceptable mechanical properties. 
312   The  test  results should be expressed quantitatively including average, standard deviation, and 
313   range whenever applicable. You should provide a  discussion of the conclusions drawn from  
314   your test results.  
315    
316   If you believe some of  the recommended tests described below  are not applicable to your 
317   coating, or  if  you are using an alternative  testing standard/method, you should describe your  
318   approach (e.g., providing  a scientific rationale  to  explain the tests that you have conducted 
319   and decided not to conduct).  
320    
321   Note that the tests specified in  Section F.(2)  and Section F.(3)  are not all inclusive. Thus, it  
322   is important  to ensure  that unique attributes specific to your coating or your device are  
323   adequately evaluated. Also note that  some orthopedic devices have device-specific 
324   recommendations  for certain coating properties  and/or testing methods,  and some devices are 
325   subject to special controls.  Refer to FDAs  website regarding  Guidance Documents (Medical  
326   Devices and Radiation-Emitting Products)18  for additional guidance documents or  class II  
327   special controls documents19 that  may pertain to your device type.    
328    
 
 
17  https://www.fda.gov/regulatory-information/search-fda-guidance-documents/recommended-content-and-
format-non-clinical-bench-performance-testing-information-premarket  
18  https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/guidance-
documents-medical-devices-and-radiation-emitting-products  
19  https://www.fda.gov/medical-devices/guidance-documents-medical-devices-and-radiation-emitting-
products/class-ii-special-controls-documents   
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329   For feedback regarding your specific coating, we recommend submitting a Pre-Submission to 
330  obtain Agency feedback.  For  further information regarding  the  Q-Submission Program, refer 
331   to the guidance Requests for Feedback  and Meetings for  Medical Device Submissions: The 
332   Q-Submission Program.20  
333   (2)   Testing of Metallic  Coatings  
334   This section lists recommended bench tests for characterizing metallic coatings.  Three types 
335  of metallic  coatings with  significant clinical experience  may be  sufficiently  evaluated with  a 
336   subset of  these tests (see Section F.(2).d  below).  
337   a.   Coating Chemical Analysis  
338   Significance:  Chemical composition of a metallic coating affects the stability and  the  
339   patients  biological response to  the coated device.  
340   
341   Recommendation:  We recommend providing a  chemical composition  analysis of the 
342   metallic coating on the final device  with a minimum sample size of three. The test results 
343   should be expressed quantitatively and compared to specifications identified in  relevant 
344   consensus standards (e.g.,  for plasma-sprayed coatings derived from unalloyed titanium and 
345  TiAl6V4 powders, see  ISO  13179-1 Implants for surgery   Coating on metallic surgical  
346   implants    Part 1:  Plasma-sprayed  coatings derived from  titanium and titanium-6 
347   aluminum-4 vanadium alloy powders). 
348   b.   Coating Microstructural Characterization  
349   Significance:  The microstructure of a metallic coating affects the implant fixation  since the  
350  coating directly  interfaces the bone/tissue. These tests provide elementary quantifications of 
351   the microstructural characteristics of the coating  on the device. For a porous-coated  device, 
352   the characteristics of the porous coating are  indicators of the  ability of the coating  to allow  
353   for biological fixation.  
354    
355  Recommendation:  You should specify in your premarket submission  if you intend to label  
356   your device  as porous coated for biological  fixation. Per 21 CFR 888.3358(a)  and 21 CFR  
357   888.3670(a), the porous  coating of  a hip joint metal/polymer/metal semi-constrained porous-
358   coated uncemented prosthesis  and a  shoulder joint  metal/polymer/metal nonconstrained or  
359   semi-constrained porous-coated uncemented prosthesis  has a volume porosity between 30 
360  and 70 percent, an average pore size  between 100 and 1,000 microns, interconnecting 
361   porosity, and a porous coating thickness between 500 and 1,500 microns. Such devices are 
362   designed to achieve biological  fixation to bone  without the  use of bone  cement (21 CFR 
363   888.3358(a)  and 21 CFR  888.3670(a)). While the  description  is included in the  
364   aforementioned regulations only, FDA recommends that other orthopedic device types that  
365  include porous coatings for biological fixation that are discussed in this guidance generally 
366   have those characteristics as well.  
 
 
20  https://www.fda.gov/regulatory-information/search-fda-guidance-documents/requests-feedback-and-
meetings-medical-device-submissions-q-submission-program  
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367   Regardless of  whether the  device is labeled  for biological fixation, we recommend providing 
368   the following microstructural evaluation of the coating on the  final device  with a minimum 
369   sample size of three.  
370   
371   1)   Surface and  cross-sectional photomicrographs of the coating should be provided to 
372   show all microstructural features of the coating such as physically or chemically  
373   distinct  layers, interconnecting porosity, and coating-substrate  interface. The  
374   magnification should be  identified on each image.  
375   
376   2)   Thickness, average pore size, and overall porosity of the coating and/or  each layer  
377   should be reported.  
378      We recommend using ASTM F1854 Standard test method for stereological  
379   evaluation of porous coatings on medical  implants  to evaluate the mean coating 
380  thickness,  average pore size (mean void intercept length), and porosity  (volume  
381   percent void)  of  the coating and each distinct layer, if applicable.  
382      For some device types (e.g., knee femoral and tibial components;  anatomic 
383   shoulder glenoid components), the  Tissue Interface Gradients method per  ASTM  
384   F1854-15 sections on Tissue Interface Gradients  and Tissue Interface Gradient  
385  Method  should be used to evaluate the porous coating. In this case,  the volume  
386   percent void and the mean void intercept length should be  evaluated in three  
387   200-m-thick zones below the tissue  interface. The results should demonstrate  
388   that the mean void content and intercept length in all three  zones  generally align 
389   with the porous coating description  in  21 CFR 888.3358(a) and 21 CFR  
390  888.3670(a).  
391      For some devices, coatings with a higher volume porosity (i.e., > 70%), larger  
392   average pore size  (>1000 m) or greater  thickness (i.e., > 1500 m) than those  
393   described in 21 CFR 888.3358 and 21 CFR 888.3670 may be desired. These 
394   coatings may have low  rigidity;  therefore, we recommend additional mechanical 
395  testing pertaining to their application, e.g., a test on plastic deformation of  
396   porosity (see  Section F.(2).c, below).
397   c.   Coating Mechanical Testing  
398   Significance:  Mechanical properties of a metallic coating impact the integrity  (e.g., coating  
399   delamination, spallation, abrasion) of the coated  device. These tests evaluate the mechanical  
400  strength and abrasion  resistance of a  metallic coating due  to the implantation  of the device  
401   during surgery or micromotion/fatigue loading of the  implant over time.  
402    
403   Recommendation: All mechanical  tests should be performed  with a minimum sample size of 
404   six, using the  worst-case  sample, which is usually the thickest  coating  to be marketed.   
405  The following should be evaluated for any metallic coating:  
406    
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407   1)   Static tensile strength  per ASTM F1147 Standard test method for tension testing of  
408   calcium phosphate and metallic coatings. The static tensile  strength  should exceed 22  
409   MPa  (per ISO 13179-1).  
410   
411   2)   Shear fatigue strength per ASTM F1160 Standard test method for shear  and bending  
412   fatigue testing of calcium phosphate and metallic medical and composite  calcium  
413   phosphate/metallic coatings. Results from shear fatigue testing to 107  fatigue cycles 
414   should be provided with the inclusion of the photomicrographs  of the test samples  
415  before and after  each  test. The coating should withstand at least  107  cycles  with a  
416   shear fatigue maximum  stress  of at least 10 MPa without any failure  (per  ISO 13179-
417   1). 
418    
419   3)   Taber abrasion resistance test per ASTM F1978 Standard test method for measuring 
420  abrasion resistance of metallic  thermal spray coatings by using the Taber  Abraser.  
421   Results should include  the cumulative mass loss for each specimen  and the mean  
422   cumulative mass loss and standard deviations  for 2, 5, 10, and 100 cycles. The  
423   coatings should lose  less than a total  of 65 mg (by weight) when abraded for 100 
424   cycles (per  ISO 13179-1).  
425   
426   The following test should be conducted for metallic coatings  with low rigidity  (which  may  
427   include, but  is not limited to, a coating with a higher volume porosity (i.e., > 70%), larger  
428   average pore size (i.e., >1,000 m) or greater  thickness (i.e., > 1,500 m)).  See  Section  
429   F.(2).b, above. 
430   
431   Test for plastic deformation of the coating porosity. We  recommend reporting the  
432   amount of plastic deformation of the  porosity with a minimum sample size of six. The  
433   device should be loaded by a flat surface under  the worst case loading anticipated to  
434   occur during  and after  implantation. The test method and test sample used should be  
435  defined and appropriately justified given the  device type. Test results including an  
436   evaluation of post-testing pore structure of the coating should be provided and 
437   justified.  
438   d.   Testing recommendations for three  specific  types of metallic  
439   coatings  
440  Three  types of metallic coatings  with a long history of  clinical use, specifically:  
441    
442   a)   beaded, sintered cobalt-chrome  coatings on a cobalt-chrome substrate,  
443   b)   beaded, vacuum-sintered  titanium coatings  on a titanium substrate,  and  
444   c)   vacuum-sintered titanium fiber mesh pads on a titanium substrate,  
445   
446   may be  sufficiently  evaluated  with  the  descriptive information and testing outlined in items  
447   1-3) below:  
448    
449   1)   Identify the  materials used for both the metallic coating and the substrate  and any 
450  consensus standards to which they conform.  
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451    
452   2)   Evaluate  the static shear  strength of  the coating to the substrate per ASTM F1044 
453   Standard test method for shear testing of calcium phosphate coatings and metallic  
454   coatings.  
455   
456   3)   Provide the average bead size and number of bead layers for beaded coatings;  and 
457   evaluate average pore size, overall pore volume, and thickness of the coating per  
458   ASTM F1854.     
459   i.   If you intend to label the device  as  porous coated for biological fixation, the  
460  coating characteristics generally  should align with the porous coating 
461   description referenced  in Section F.(2).b. 
462   ii.   The Tissue Interface Gradients  method per ASTM F1854-15 sections on 
463   Tissue Interface Gradients and Tissue Interface Gradient  Method should be  
464   used for certain orthopedic devices (see Section F.(2).b, above).  
465  (3)   Testing of Calcium  Phosphate Coatings  
466   This section  lists recommended bench tests for  characterizing a calcium phosphate coating.  
467   a.   Coating Physicochemical Analysis   
468   Significance:  The physicochemical  properties  of a calcium phosphate coating affect the 
469   stability, dissolution and resorption in vivo, and other biological response  of the coated 
470  device. These tests evaluate if the calcium phosphate coating  has appropriate  
471   physicochemical properties  to ensure the safe use of the  coated device  in the human body.  
472    
473   Recommendation:  For any plasma-sprayed calcium phosphate (also known as  
474   hydroxyapatite or HA) coating, we  recommend providing the  following physicochemical  
475  properties  with a  minimum sample size of three  (see Additional Information  at the end of  
476   this section for the recommended physicochemical analysis for other  types of calcium  
477   phosphate coatings). Unless there are other types of control samples for a specific  test,  we  
478   recommend a control sample, e.g., National  Institute of Standards & Technology (NIST)  
479   Standard Reference Material (SRM)  2910B21  or a historical control be tested as a comparison 
480  for  the analyses.   
481    
482   We recommend  that the starting material  for plasma-sprayed HA  coatings be HA powder that  
483   conforms to one of the  following two consensus standards in  terms of trace elements,  phase 
484   composition /crystallinity, and Ca/P ratio:  
485     ASTM  F1185  Standard specification for composition of hydroxylapatite  for surgical  
486   implants or    
 
 
21  https://shop.nist.gov/ccrz__ProductDetails?sku=2910b&cclcl=en_US  
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487      ISO 13779-6  Implants for surgery   Hydroxyapatite  Part 6: Powders.  
488    
489   List of recommended  physicochemical analyses:  
490   
491   1)   Elemental  analysis  including  calcium and phosphorous, intentional additions, and 
492   manufacturing impurities per  ASTM F1609  Standard specification for calcium  
493   phosphate coatings for implantable  materials  or  ISO 13779-2 Implants for 
494   surgery  Hydroxyapatite   Part 2:  Thermally sprayed coatings of  
495  hydroxyapatite.  
496    
497   2)   Phase analysis per X-ray diffraction  X-ray diffraction patterns with  
498   crystallographic interpretations, including the  identification  and quantitative  
499   analysis of each crystalline phase (i.e., HA, -tricalcium phosphate or -TCP,  -
500  tricalcium phosphate or -TCP, tetracalcium phosphate or TTCP, calcium oxide  
501   or CaO) and amorphous  calcium phosphate (ACP), as well  as  crystallinity ratio. 
502   The  X-ray diffraction determination and phase analysis  should be performed with 
503   a copper  radiation and scanned from  4 to 60  and utilize one of the following two 
504   standards. The worst-case coating for this test, which is usually the thinnest  
505  coating, as a thinner coating generally contains more amorphous phase  compared  
506   to a  thicker coating, should be used.  
507    
508      ASTM F2024  Standard practice  for X-ray diffraction determination of phase  
509   content of plasma-sprayed hydroxyapatite coatings.     
510   
511      ISO 13779-3 Implants for surgery   Hydroxyapatite   Part 3: Chemical 
512   analysis and characterization of  crystallinity  ratio and phase purity.  
513    
514     If the phase composition determined  per each  standard is out  of the specified  
515  range in that standard, supporting data or scientific rationales  should be provided 
516   to justify  that  the coating is acceptable for  the intended clinical use.   
517    
518   3)   Ca/P ratio analysis using one of the  following two methods:   
519    
520     X-ray method per ISO 13779-3:  If the calculated  Ca/P ratio is outside the  range  
521   established  in  ISO 13779-2 Third Edition 2018-12  Clause 5.2 Calcium to  
522   phosphorus ratio (Ca:P)  (i.e., 1.61 to 1.76), supporting  data or a scientific 
523   rationale  should be provided to justify the  Ca/P  ratio, or  
524      A general wet chemistry method  such as inductively coupled plasma mass  
525  spectroscopy (ICP-MS)  or inductively coupled plasma atomic or optical  
526   emission  spectroscopy (ICP-AES or ICP-OES). 
527    
528   4)   Structural analysis  per infrared  analysis  Infrared spectra with detailed  molecular 
529   interpretations, including band assignments  for all phosphate  (HPO42- , PO43-) and 
530  hydroxyl (OH-) bands, crystallinity,  structural water, and carbonate. The infrared 
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531   spectra allow us to understand the chemical structure of  the coating, which cannot  
532   be obtained from X-ray diffraction.   
533    
534   5)   Dissolution rate  measured at 37oC in both pH 7.4 and pH 5.5 buffered solutions  
535   per ASTM F1926/F1926M Standard test method for  dissolution testing  of calcium  
536   phosphate granules, fabricated forms, and coatings. The pH changes of  the  
537   solution during measurement should be recorded. In addition,  we recommend the 
538   following:     
539   a.   Ratio of initial material mass (mg) to total dissolution media  volume  
540   (mL): ASTM F1926/F1926M-14 (Clause 6  Analytical Parameters)  
541   recommends a ratio of 1  to 4 mg/ml,  which is a wide range; a  justification  
542   should be provided for  the ratio used in your test.  
543    
544   Additional Considerations: If you are using a  coating method other  than plasma spray, or if  
545   the phase  composition of your coating is different from that of a typical plasma-sprayed 
546   calcium phosphate coating, for example, your coating is intended to contain one or  more  
547   other crystalline phases (e.g., dicalcium phosphate dihydrate (DCPD or Brushite), 
548   octacalcium phosphate (OCP) with or without  amorphous phase, the phase composition(s) of  
549   the coating should be determined against the corresponding crystalline phase(s), respectively. 
550   If the calcium phosphate phases formed in the coating are novel, animal or clinical data may  
551   be requested to ensure safe clinical use (see Sections  G  and H, below).  
552   b.   Coating Microstructural Characterization  
553   Significance: The microstructure of a calcium phosphate coating affects implant fixation as  
554   the coating  directly  interfaces the bone/tissue.  These tests provide elementary quantifications 
555   of the  microstructural characteristics  of the coating on the device.  
556     
557   Recommendation:  We recommend  providing  the following  microstructural evaluation of a  
558   calcium phosphate coating on the final device  with  a minimum sample size of three.  
559    
560   1.   Surface and  cross-sectional photomicrographs of the coating should be provided to 
561   demonstrate all microstructural features of the coating such as physically  or 
562   chemically distinct  layers, interconnecting porosity, and coating-substrate interface.  
563   The magnification bar should be identified on each image.  
564    
565   2.   Thickness, average pore size, and overall porosity of the coating and each layer  
566   should be provided.  
567    
568   You may use ASTM F1854 to determine  the thickness, average pore size, and 
569   porosity of the coating and each distinct layer or  an alternative standard/method.  
570    
571   If you intend to label the calcium phosphate coating as a nano coating (e.g., nano-
572   crystalline, nano-structured), you should provide additional microstructural characterization  
573   to demonstrate the nano characteristics (e.g., nano crystal size or other  nano features) and 
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574   address concerns related to  the biocompatibility  of the nano characteristics  (see Section  E. 
575  Biocompatibility).  
576   c.   Coating Mechanical  Testing  
577   Significance: Mechanical properties of a calcium phosphate coating  impact the integrity  
578   (e.g., coating delamination, spallation, abrasion)  of the coated device  itself. These tests 
579   evaluate the  mechanical strength of a metallic coating following  the implantation of the  
580  device during surgery or micromotion/fatigue  loading of the implant over time.  
581    
582   Recommendation:  All tests  should be performed  with a minimum sample size of six  using 
583   the  worst-case  sample,  which is usually  the thickest coating  to be marketed.   
584   1.   Static tensile strength per ASTM F1147  or  ISO 13779-4:  Implants for surgery   
585  Hydroxyapatite   Part  4: Determination of  coating adhesion strength, (see ISO  
586   13779-2 Third Edition 2018-12 Clause 5.7 Coating strength  for acceptance criteria,  
587   i.e., the  mean tensile coating adhesion strength should not be  less than 15 MPa and no 
588   individual result should be less than 10 MPa.).  
589    
590  2.   Static shear  strength per  ASTM F1044.  
591    
592   3.   Fatigue strength per ASTM F1160.  Results from shear fatigue testing for 107  cycles  
593   should be provided with inclusion of  the photomicrographs of the test samples before  
594   and after each test.  
595  (4)   Testing  of Metallic  and Calcium Phosphate Dual Coatings  
596   For  a metallic and  calcium phosphate dual coating, we recommend  that you provide  the  
597   following information:  
598    
599   1)   a description of any additional processing between the two coating processes in 
600  addition to the coating description recommended in Section A for both metallic  
601   coatings  and calcium phosphate coatings;  
602    
603   2)   testing  of the  metallic coating per  the  recommendations in Section F.(2);  
604    
605  3)   physicochemical properties of the  calcium phosphate coating per  the  
606   recommendations in Section F.(3).a; and 
607    
608   4)   microstructural  characterization  and mechanical testing of the dual coating per the  
609   recommendations in Section F.(2).b  and F.(2).c. The  underlying  metallic coating can 
610  be porous (intended for biological fixation) or nonporous (intended for  surface  
611   roughening and enhanced bonding between calcium phosphate coating and substrate). 
612   If the underlying metallic coating is  porous and you intend to label  the dual-coated  
613   device  for biological fixation, you should characterize the dual coating to  determine if  
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614   the dual  coating generally aligns with the previously discussed description of porous  
615   coating.22  
616   (5)   Coated Substrate/Device  Testing  
617   Significance: Some coating processes may affect the physical,  chemical  (e.g., changes in 
618   dimension, color, and chemical structure/ stability) or fatigue properties of the coated  device.   
619   This may include but not be limited to i)  when a coating is  significantly thicker than coatings  
620   of the same  type on legally marketed devices;  ii)  when a coating process  is novel; or  iii) 
621   when an implant  material  (e.g., polymer) or implant geometry (e.g., very thin)  could be  
622   impacted by the coating process. These tests evaluate the effect of  the coating process on  
623   performance of the coated device in these  situations. 
624    
625   Recommendation:  We recommend  conducting the following tests:  
626   1)   Comparative Physical and Chemical Testing of the Coated Substrate  Examination 
627   and testing of the substrate before and after coating with a minimum sample size of 
628   three  to demonstrate that the coating  process will not lead  to physical or chemical 
629   changes (e.g., changes in dimension, color, chemical structure/stability) of the coated 
630   substrate.  
631   2)   Comparative Fatigue Testing of the  Coated Substrate  This can  be evaluated using 
632   the bending fatigue testing recommendations outlined in ASTM F1160 or a similar  
633   method to assess  the substrate  material (i.e., axial, bending, or  rotating beam test with 
634   a minimum sample size  of six). Both the non-coated (i.e., substrate only)  and the  
635   coated specimens should be tested to quantify any  effect that the coating has on the 
636   substrate.  
637        Alternatively, the  effect of the coating process on the  fatigue property of the  coated  
638   device can be assessed using a fatigue test method specific to the final device if such  
639   a method exists. You should examine and describe  the coating integrity  and/or  failure  
640   mode after  the test  in the test report. If failure of the device is associated with the  
641   coating, rationales  or a benefit-risk analysis should be provided to justify the addition 
642   of the coating on the device.  
643   For some applications  (e.g., spinal devices), when performing a device-specific 
644   fatigue test, you should characterize  the  wear particulates  generated  from the metal 
645   coated device per ASTM F1877 Standard Practice for Characterization of  Particles. 
646   Please refer  to any applicable  device-specific guidance documents  and special  
647   controls  for your  device.  
648    
649    
 
 
22  See 21 CFR  888.3358 and  21  CFR  888.3670.  
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  Non-Clinical Animal  Studies  
650 
651   Significance:  Due to limitations of bench models, animal studies are often conducted to 
652   support medical device premarket submissions  for novel metallic and/or calcium phosphate  
653   coatings. The  in vivo setting generally provides an initial  assessment of how a medical  device 
654   interacts with biological  systems, including physiological, pathological, and toxicological  
655  effects of the device,  and how the biological system may  affect the device.    
656    
657   Recommendation:   Animal testing is  generally unnecessary for most metallic and  calcium 
658   phosphate coated devices; however, such testing may be appropriate  in situations such as  
659   novel technology (e.g., novel  materials, compositions and/or  phases in a calcium phosphate 
660  coating) that cannot be evaluated through bench tests or in a  clinical  study. The study design 
661   and endpoints should be  based upon the  intended use of the device and mitigation of risk. 
662    
663   FDA supports  the principles of the 3Rs, to replace, reduce,  and/or refine animal testing  
664   when feasible. We encourage sponsors to consult  with us if  they wish to use a non-animal  
665  testing method that  they  believe is suitable, adequate, validated, and feasible. We will  
666   consider if  such  an  alternative method  could  be assessed for equivalency to an animal study.  
667    
668   We encourage manufacturers to take advantage of the Q-Submission Program  to ensure that 
669   the animal  study protocol addresses safety  concerns and contains elements  that  are  
670  appropriate for  a regulatory submission. Additionally, for information  and recommendations  
671   regarding animal studies  used to support medical  device submissions, refer to the guidance  
672  General Considerations  for Animal Studies Intended to  Evaluate  Medical Devices.23 
673    If you are proposing to use a non-animal testing method  in lieu of an animal study, we  
674   recommend that you discuss the proposal using the Q-Submission Program. We will  consider  
675  if such an  alternative method could be assessed for equivalency to an animal  test method. For  
676   details on the Q-Submission Program, refer  to the guidance  Requests for Feedback and  
677   Meetings for Medical Device Submissions: The Q-Submission Program.24 
  Clinical Performance  Testing   
678  
679   Clinical studies are generally unnecessary for  metallic and calcium phosphate coated  
680  orthopedic  devices; however, such testing may be appropriate  in situations such as the 
681   following:  
682      Use of  novel  technology (e.g., materials, compositions and/or  phases in a calcium  
683   phosphate coating) different from that used  in legally  marketed devices of the same  
684   type; and/or  
685     Cases where  bench and/or animal  testing raise issues that warrant  further evaluation  
686   with clinical  studies  (e.g., devices with concerning  mechanical properties compared 
 
 
23  https://www.fda.gov/regulatory-information/search-fda-guidance-documents/general-considerations-animal-
studies-medical-devices  
24  https://www.fda.gov/regulatory-information/search-fda-guidance-documents/requests-feedback-and-
meetings-medical-device-submissions-q-submission-program  
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687   to legally  marketed devices of the same type  such as lower shear  fatigue strength, 
688   higher abrasion rate, or new types of  wear particulates).  
689    
690   We  will consider alternatives to  clinical studies  when the proposed alternatives are  supported 
691   by an adequate scientific rationale.  If a clinical investigation  involving one or more subjects  
692   is conducted  to determine  the  safety  or  effectiveness  of a device, the  Investigational Device 
693   Exemption (IDE)  regulation, 21 CFR  Part 812, applies  unless the  investigation  is excepted  
694   from the  IDE  requirements (see 21 CFR 812.3(a) and (c)). Generally, we  believe metallic  
695   and/or calcium phosphate coated orthopedic  devices addressed by this guidance document  
696   are significant risk  devices (see 21 CFR 812.3(m))  subject to all requirements  of  21 CFR  Part 
697   812 (the abbreviated requirements  referenced in 21 CFR 812.2(b) are generally not  
698   applicable to significant risk devices). See the FDA guidance titled, Significant Risk and 
699   Nonsignificant Risk Medical Device Studies.25 In addition to the requirements of 21 CFR  
700   Part 812, investigations to determine safety  and effectiveness of a device may also be subject  
701   to FDA regulations governing institutional review boards (21 CFR  Part 56) and the  
702   protection of human subjects (21 CFR Part 50), including informed consent (21 CFR Part 50, 
703   subpart B).  
704    
705   When data  from clinical  investigations conducted outside  the United States are submitted to 
706   FDA for  metallic and/or  calcium phosphate coated orthopedic devices, the requirements of  
707   21 CFR 812.28 may apply.26 21 CFR  812.28(a)  outlines  the conditions for FDA  acceptance 
708   of  data  from clinical investigations conducted outside  the United States to support an  IDE or 
709   a device marketing application or submission. For more  information, see the FDA guidance  
710   Acceptance of Clinical  Data to Support Medical Device Applications and Submissions:  
711   Frequently Asked Questions.27 
712    
713   In some cases, real-world data (RWD) may be used  in lieu  of traditionally collected  
714   clinical data.  Whether the collection  of RWD for  a legally marketed  device requires an IDE  
715   depends on the particular facts of the situation. Specifically,  if  a cleared device is being used  
716   in the normal course of medical practice, an IDE would likely not be  required. For additional 
717   information  regarding this topic, refer to the FDA Guidance entitled Use of  Real-World 
718   Evidence to Support Regulatory Decision-Making for Medical Devices.28 
719    
720    
721    
 
 
25  https://www.fda.gov/regulatory-information/search-fda-guidance-documents/significant-risk-and-
nonsignificant-risk-medical-device-studies.  
26  21 CFR  812.28 applies  to relevant  clinical  investigations  that  enroll  the  first  subject  on  or  after  February 21,  
2019,  and that  support  an IDE  or  a  device  marketing application or  submission to FDA.  
27  https://www.fda.gov/regulatory-information/search-fda-guidance-documents/acceptance-clinical-data-
support-medical-device-applications-and-submissions-frequently-asked.  
28https://www.fda.gov/regulatory-information/search-fda-guidance-documents/use-real-world-evidence-
support-regulatory-decision-making-medical-devices   
  22  Contains  Nonbinding  Recommendations  
 
Draft    Not  for  Implementation  
 
 
  Labeling  
722  
723   As  prescription devices, orthopedic devices with  coatings are exempt from  the requirement to  
724   have  adequate directions for use under  section 502(f)(1) of  the FD&C Act  as long as the 
725   conditions in 21 CFR 801.109 are  met. For  instance, to be  so  exempt, labeling that furnishes  
726   information  for use of the  prescription  device must, among other things,  contain adequate 
727   information for such use, including indications, effects, routes, methods, and frequency and 
728   duration of administration and any relevant hazards, contraindications, side effects, and 
729   precautions,  under which practitioners licensed by law to employ the device can use the 
730   device safely and for the purposes for which it is  intended. (21 CFR 801.109(d)).  
731    
732   Specific labeling  information  will vary depending on  the  device  on which the coating is used. 
733   The  following  should be considered for the  labeling of orthopedic devices with coatings:  
734    
735   1.   Calcium phosphate coated  joint arthroplasty  devices should only be implanted using a  
736   cementless method  because calcium phosphate coatings can adversely  affect the 
737   longevity of cemented  fixation; we recommend that this information  be clearly  
738   specified  in  the Indications for Use Statement  and labeling.  
739    
740   2.   A device with a porous coating  that generally  aligns with the  description  identified in 
741   21 CFR  888.3358 and 21 CFR 888.3670  may be labeled for biological  fixation.  FDA  
742   is currently  not aware of valid scientific means, including clinical,  animal,  or bench 
743   models,  to support  enhanced fixation claims  such as osseointegration, bone ingrowth 
744   or bone ongrowth in a clinical  setting.  
745    
746   3.   If you intend to label a coated device as nano  (e.g., nano-crystalline, nano-
747   structured), characterization  data  to demonstrate the nano characteristics of the 
748   coating should be provided  in  the submission  (see Section F.(3).b).  
749    
IV.   Modifications  (Devices  subject to  510(k))   
750  
751   21 CFR 807.81(a)(3)  provides that  a device change or  modification that could significantly 
752   affect the safety or  effectiveness of  the device or  represents [a]  major change or  
753   modification in the  intended use of the device requires  a new 510(k).29   The  changes or  
 
 
29  Section 3308 of  the  Food and Drug  Omnibus  Reform  Act  of  2022  (FDORA),  enacted as  part  of  the  
Consolidated  Appropriations  Act,  2023,  added section 515C  Predetermined  Change  Control  Plans  for  
Devices  to  the FD&C  Act  (Pub. L.  No.  117-328).  Section 515C  provides  FDA with express  authority  to  
approve  or  clear PCCPs  for  premarket  notification.  For  example,  section  515C  provides  that  supplemental  
applications  (section 515C(a))  and  new  premarket  notifications  (section 515C(b))  are  not  required for  a  change  
to a  device  that  would otherwise  require  a  premarket  approval  supplement  or  new  premarket  notification  if  the  
change is  consistent  with  a PCCP  approved or  cleared  by  FDA.  Section  515C  also  provides  that  FDA  may  
require that  a PCCP  include labeling  for  safe  and  effective use of  a device  devices  requiring  premarket  approval  
or  as  such device  changes  pursuant  to such plan,  notification requirements  if  the  device  does  not  function as  
 
 
  23  Contains  Nonbinding  Recommendations  
 
Draft    Not  for  Implementation  
 
 
754   modifications listed below  are examples of changes that may  require submission of a new  
755   510(k). Note that  this  list is not exhaustive but provides examples of modifications  that are 
756   likely to  require submission of a new 510(k). Also note this list does not address other  
757   modifications for your device but  is limited to the  modifications for coatings. For additional  
758   details, see FDA guidance Deciding When to Submit  a 510(k) for a Change to an Existing 
759   Device.30   
760    
761   Such changes  or modifications  include:  
762    
763      A change to a different coating method or to a  different coating  vendor (different 
764   coating vendors generally have  different specifications of coating  process parameters, 
765   e.g., spray power, distance, and environment for  a  plasma spray process) that lead to 
766   final coatings with different properties  FDA  generally  considers these changes to be  
767   significant changes  in material  and chemical composition, which could  significantly  
768   affect the  safety  and effectiveness of the coated device by adversely impacting  
769   biocompatibility or impacting coating integrity. Complete characterization  of the new  
770   coating should be provided in a new  510(k) submission.  
771    
772      Addition of coating layers, increasing  thickness, or modifying the  pore size or  
773   porosity  FDA generally considers these changes to be significant  changes in design, 
774   which  could significantly affect the safety  and effectiveness of the coated  device by 
775   introducing a new potential worst-case scenario for mechanical properties of the 
776   coating and the  risks associated with device failure.  
777    
778      A change to another  substrate material (e.g., from one metal to either another  metal  or  
779   a  polymer) or modifications of the surface treatment  that could result in a 
780   significantly different surface roughness   FDA generally considers these changes to  
781   be significant changes  in material or material processing, which could significantly 
782   affect the safety and  effectiveness of  the coated devices by introducing a  change in 
783   the risks associated with device strength and failure modes.  
784    
785   FDA believes that the  following  changes or  modifications  would likely  not require  
786   submission of a new 510(k):  
787    
788      A change to another supplier for the starting material for a  plasma-sprayed metallic  
789   coating (e.g., unalloyed titanium  powder)  where the material specifications such as 
 
 
intended pursuant  to such plan,  and performance  requirements  for  changes  made  under  the  plan.  If you  are 
interested in proposing  a  PCCP  in your  marketing submission,  we  encourage  you to submit  a  Pre-Submission  to 
engage  in further  discussion  with CDRH.  See FDAs  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  
30  https://www.fda.gov/regulatory-information/search-fda-guidance-documents/deciding-when-submit-510k-
change-existing-device  
  24  Contains  Nonbinding  Recommendations  
 
Draft    Not  for  Implementation  
 
 
790   chemical composition  conforming  with an FDA-recognized  consensus standard, 
791   particle  size  distribution, morphology and porosity are still within the  same material  
792   specifications. This  change  generally  is not expected to  impact  biocompatibility or  
793   change the risks associated with device failure.  
794    
795      Reduction of  number of  coating layers or  thickness of  a metallic coating  on a  
796   previously cleared device  while other microstructural characteristics (i.e., 
797   interconnecting porosity, pore size, volume porosity) are still within the  initial 
798   specifications  (in the case of a porous coating, the microstructural characteristics  
799   should still  generally align with the porous  coating description previously 
800   discussed31). Provided that the overall device dimensions still remain within  the  
801   tolerance of  the cleared device,  these  scenarios  generally  are not expected to  
802   introduce new or significantly  modified risks or a new worst-case for mechanical  
803   properties of the coating  and the  failure modes  of  the coated devices.  
804    
 
 
31  See 21 CFR  888.3358 and  21  CFR  888.3670.  
  25