Contains Nonbinding Recommendations 
 
Draft  Not for Implementation 
 
 
Patient-Matched Guides to 
Orthopedic Implants 
 
Draft Guidance for Industry and 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DRAFT GUIDANCE 
 
This draft guidance document is being distributed for comment purposes 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 June 28, 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of publication in the Federal Register of the notice announcing the availability of the draft 
guidance.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, Rm. 1061, (HFA-305), Rockville, MD 20852-1740. Identify all comments with the 
docket number listed in the notice of availability that publishes in the Federal Register. 
 
For questions about this document, contact the OPEQ: Office of Product Evaluation and Quality, 
OHT6: Office of Orthopedic Devices at (301) 796-5650. 
 
 
 
 
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Draft  Not for Implementation 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 include the 
document number GUI01400006 and complete title of the guidance in the request. 
   Contains Nonbinding Recommendations 
 
Draft  Not for Implementation 
 
 
Table of Contents
 
 
I.  Introduction ...................................................................................................................... 1 
II.  Background ...................................................................................................................... 2 
III.  Scope ................................................................................................................................ 2 
IV.  Submission and Design Recommendations ..................................................................... 3 
  Indications for Use ................................................................................................... 3 
  Device Description ................................................................................................... 3 
1.  Patient-Matched Guide Description ...................................................................... 4 
2.  General Design Process Description ..................................................................... 5 
3.  Patient Image Acquisition Description ................................................................. 5 
4.  Image Quality Control, Segmentation, and Anatomical Definitions Description 5 
5.  Pre-operative Planning and Healthcare Professional Concurrence Description ... 6 
6.  Guide Design and Patient-Matched Features Definition Description ................... 7 
7.  Guide Construction Description ........................................................................... 7 
8.  Surgical Technique Description ............................................................................ 8 
  Software .................................................................................................................... 8 
  Biocompatibility ....................................................................................................... 9 
  Sterility ................................................................................................................... 10 
1.  Devices provided sterile ...................................................................................... 10 
2.  Single-use devices provided non-sterile and intended for sterile processing ..... 11 
  Shelf Life and Packaging ....................................................................................... 12 
  Non-Clinical Performance Testing ......................................................................... 13 
1.  Intra- and Inter-Designer Variability .................................................................. 13 
2.  Mechanical Integrity (Post-Processing) .............................................................. 13 
3.  Debris Generation ............................................................................................... 14 
4.  Implant Alignment Accuracy and Guide Usability ............................................ 14 
  Clinical Performance Testing ................................................................................. 15 
  Labeling .................................................................................................................. 16 
  Modifications (Devices subject to 510(k)) ............................................................. 16 
   Contains Nonbinding Recommendations 
 
Draft  Not for Implementation 
 
 Patient-Matched  
1 
Guides to Orthopedic Implants  
2 
3   
Draft Guidance for Industry and  
4 
Food and Drug Administration Staff 
5 
6   
7  This draft guidance, when finalized, will represent the current thinking of the Food and Drug 
8  Administration (FDA or Agency) on this topic. It does not establish any rights for any person 
9  and is not binding on FDA or the public. You can use an alternative approach if it satisfies the 
10  requirements of the applicable statutes and regulations. To discuss an alternative approach, 
11  contact the FDA staff or Office responsible for this guidance as listed on the title page.  
12   
13  I.  Introduction 
14   
15  This draft guidance document provides recommendations regarding information that should be 
16  included in regulatory submissions for patient-matched guides to orthopedic implants. This 
17  document also provides recommendations that manufacturers should consider when developing 
18  their design process for these device types. Patient-matched guides are intended to assist in the 
19  execution of a pre-surgical plan concurred upon by the patients healthcare professional to 
20  position an orthopedic implant in a way consistent with the implants indicated use.  
21  While this guidance includes considerations related to design aspects, it is not intended to 
22  comprehensively address all considerations or regulatory requirements to ensure your device is 
23  manufactured in accordance with quality system regulation requirements (21 CFR 820). For 
24  class II and class III devices such as identified in the scope of this guidance, manufacturers must 
25  establish and maintain procedures to control the design of the device to ensure that specified 
26  design requirements are met per 21 CFR 820.30, Design controls.  Manufacturers must also 
27  establish and maintain procedures for monitoring and control of process parameters for validated 
28  processes to ensure that the specified requirements continue to be met.1 Where the results of a 
29  process cannot be fully verified by subsequent inspection and testing, the process must be 
30  validated with a high degree of assurance and approved according to established procedures.2 
31  FDA interprets these regulations to require manufacturers to establish procedures including 
32  process validation of patient-matched guides to ensure that the device can perform as intended. 
 
1 21 CFR 820.75(b). 
2 21 CFR 820.75(a). 
1   Contains Nonbinding Recommendations 
 
Draft  Not for Implementation 
 
33  For the current edition of the FDA-recognized consensus standard(s) referenced in this 
34  document, see the FDA Recognized Consensus Standards Database.3  For more information 
35  regarding use of consensus standards in regulatory submissions, please refer to the FDA 
36  guidance titled Appropriate Use of Voluntary Consensus Standards in Premarket Submissions 
37  for Medical Devices.4   
38  In general, FDA's guidance documents do not establish legally enforceable responsibilities. 
39  Instead, guidances describe the Agency's current thinking on a topic and should be viewed only 
40  as recommendations, unless specific regulatory or statutory requirements are cited. The use of 
41  the word should in Agency guidance means that something is suggested or recommended, but 
42  not required.  
43   
44  II.  Background 
45   
46  Patient-matched guides5 are designed to implement, in part or in whole, the pre-operative plan 
47  concurred upon by the patients healthcare professional. The plan is based upon clearly 
48  identifiable landmarks on pre-operative patient images and within accordance to the implant 
49  systems indicated use.  
50  As the designs of the patient-matched guides differ slightly between each patient, it is important 
51  to establish a design template and a range of pre-specified allowable design parameters to ensure 
52  a consistent and accurate guide. In general, the design process includes 1) patient image 
53  acquisition, 2) image quality control, segmentation, and anatomical definitions, 3) pre-operative 
54  planning and healthcare provider concurrence, 4) guide design and patient-matched features 
55  definition, and 5) guide construction. In addition to the design process, the preparation 
56  (cleaning/sterilization) and actual surgical use of the guide (surgical technique) are also critical 
57  to patient-matched guide performance.  
58  III.  Scope 
59   
60  The scope of this document is limited to patient-matched guides intended for use with legally 
61  marketed orthopedic implant systems that include recommended alignment parameters relative to 
62  rigid anatomical structures that can be identified on pre-operative imaging.   
63  This guidance is intended to promote clarity and transparency as to expectations regarding 
64  submission recommendations for orthopedic patient-matched guides.  Following such 
 
3 https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm.  
4 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/appropriate-use-voluntary-consensus-
standards-premarket-submissions-medical-devices.  
5 Patient-matched guides as discussed in this guidance are also commonly referred to as patient-specific guides.  
These are distinct from custom devices, as described in FDAs guidance entitled Custom Device Exemption, 
available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/custom-device-exemption. 
2   Contains Nonbinding Recommendations 
 
Draft  Not for Implementation 
 
65  recommendations may increase efficiency and consistency in review.  Additionally, this 
66  guidance provides recommended best practices regarding certain elements of the design process.   
67  IV.  Submission and Design Recommendations 
68   Indications for Use 
69   
70  The term indications for use, as defined in 21 CFR 814.20(b)(3)(i), describes the disease or 
71  condition the device will diagnose, treat, prevent, cure or mitigate, including a description of the 
72  patient population for which the device is intended. To identify appropriate technical 
73  performance testing parameters, it is necessary to identify the indications for use of the patient-
74  matched guide. For example, consistent with 21 CFR 801.6, the technical performance 
75  assessment for an orthopedic patient-matched guide that is indicated to support a specific implant 
76  system should evaluate the performance of the guide within that implant systems recommended 
77  surgical technique. Hence, it is important to consider any conflicts that may arise from the 
78  orthopedic patient-matched guides indications for use and the implant systems cleared or 
79  approved indications/contraindications, which may translate into possible misbranding.6  FDA 
80  considers the indications for use of an orthopedic patient-matched guide to include (but not be 
81  limited to) the following: 
82    The surgical approach and the procedure supported (e.g., total knee replacement, total hip 
83  replacement  Posterior-lateral surgical approach),  
84    The specific implant system(s) that the guide is intended to support,  
85    The patient population for which the guide is indicated and whether this is a subset of the 
86  implant systems indicated patient population, and 
87    The types of imaging modalities necessary for designing the guides (e.g., magnetic 
88  resonance imaging (MRI), computed tomography (CT)). 
89    The anatomic landmarks necessary for pre-operative planning that, at a minimum, should 
90  be clearly identified on the patients pre-operative radiographic images. 
91    Device Description  
92   
93  As the designs of the patient-matched guides differ slightly between each patient, it is important 
94  to establish and document the design process used to define a range of pre-specified allowable 
95  design parameters to ensure a consistent and accurate guide that correlates to the patient-matched 
96  guides performance. As noted above, to ensure that specified design requirements are met per 
97  21 CFR 820.30, manufacturers must establish and maintain procedures to control the design of 
98  the device. Therefore, the device description should encompass the patient-matched guide design 
99  as well as the design process and surgical use. This descriptive information is necessary to 
100  develop the appropriate technical performance testing parameters that are necessary to support a 
 
6 Per 21 CFR 801.6, Among representations in the labeling of a device which render such device misbranded is a 
false or misleading representation with respect to another device or a drug or food or cosmetic. See also section  
201(n) of the Federal Food, Drug, and Cosmetic Act. 
3   Contains Nonbinding Recommendations 
 
Draft  Not for Implementation 
 
101  regulatory submission. A complete device description should include (but not necessarily be 
102  limited to) the information outlined in each section below. 
103   
104  1.  Patient-Matched Guide Description 
105   
106  Your submission should include the following information:  
107   
108    A list of all guide components and available sizes, including information regarding the 
109  design envelope. If multiple guide designs are to be offered, a full description of each 
110  design should identify when each design is utilized.  For example, if there are two 
111  different overall guide designs depending on surgical approach, an explanation of when 
112  each design is recommended should be provided. 
113    Fully dimensioned engineering drawings, including nominal dimensions with tolerances, 
114  of sample guides noting which critical-to-quality regions of the guides are fixed and 
115  which are variable based on patient anatomy. The drawings should also identify the limits 
116  associated with all variable dimensional aspects.  For example, if the guide has a 
117  structural member that requires a minimum thickness to maintain structural integrity, this 
118  minimum thickness should be defined. 
119    A list of the specific implants that can be implanted using the guides, along with the 
120  implant systems 510(k), De Novo, or PMA number.  
121    A list of any ancillary components that may be included with the system. These 
122  components may include drop rods, pins, etc. 
123    A list of all accessories that are not included with the system, but are necessary to use the 
124  guide, listed with adequate specificity to allow for their acquisition by the end user. These 
125  accessories may include cut blocks, saw blades, etc.  
126    A list of all materials of construction (for both guides and provided accessories, if any) 
127  and method of manufacture.7 This list should also include an identification of any color 
128  additives or coatings used.  
129    A description of the specific function of each guide design feature (e.g., hole for pin 
130  placement, slot for saw-blade guidance).  
131    A list of all software used with the device and a description of the specific function of the 
132  software (e.g., pre-surgical planning, image segmentation, guide design). Please see 
133  Section IV.C. for additional software recommendations. 
134   
 
7 If you intend to use additive manufacturing methods for your device, please see FDAs guidance 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.  
4   Contains Nonbinding Recommendations 
 
Draft  Not for Implementation 
 
135  2.  General Design Process Description 
136   
137  To assist in the characterization of the device and its performance, your submission should 
138  include the following information:  
139   
140    A description of the overall process, such as a flowchart, that details the involved parties 
141  and the steps involved in designing and creating the guides.  This should include an 
142  explanation of how such processes will be utilized to match the patient anatomy with 
143  adequate fit and fidelity to achieve the intended effect. 
144   
145  In designing and developing your guide, you should consider the following: 
146   
147    Establishing a mechanism to ensure that the patients pre-operative plan is maintained 
148  throughout the guides design and manufacturing process.  For example, you should 
149  develop a method for patient case identification (e.g., marking with UDI or other patient 
150  identification method) on the guide itself.  
151    Identifying any qualifications and training pertaining to the end user and persons 
152  involved in the design process. 
153    Developing a process to ensure that compatibility of the patient-matched guide will be 
154  monitored and maintained for the indicated implants, including from third party 
155  manufacturers . Establishing an agreement with such a third party implant manufacturer 
156  to communicate implantation or dimensional modifications would be one method to 
157  accomplish this.  
158   
159  3.  Patient Image Acquisition Description 
160   
161  To identify appropriate performance testing considerations, your submission should include a 
162  summary of an imaging protocol(s) for obtaining the patient pre-operative images that are used 
163  for guide design. Please note that the minimum imaging specifications from this protocol should 
164  be considered when identifying worst-case technical performance testing (see Section IV.G.). 
165  Your imaging protocol should be developed considering the image modalitys accuracy and 
166  limitations, the parameters necessary for surgical planning and guide design, the surgical 
167  procedure, the presence of deformity that may impact subject device performance, patient 
168  disease level (e.g., large defects), and any additional hardware that may already exist in the 
169  anatomical location. These factors can affect image acquisition and mitigation measures should 
170  be adequately described. 
171   
172  4.  Image Quality Control, Segmentation, and Anatomical 
173  Definitions Description 
174   
175  To ensure reproducibility of performance testing results, your submission should include the 
176  following information:  
177   
5   Contains Nonbinding Recommendations 
 
Draft  Not for Implementation 
 
178    A summary description of your image processing methods to illustrate how the patient 
179  image(s) is received and manipulated prior to pre-operative planning. 
180    A description of any software used for manual or automatic segmentation. If automation 
181  is utilized, appropriate software verification/validation should be provided to support 
182  regulatory evaluation. For automated segmentation processes, the same datasets should 
183  not be used for verification/validation as was used for software development.  
184    The necessary anatomical landmarks for designing the guide. The necessary anatomical 
185  landmarks should be clearly defined to allow for reproducible identification and 
186  transparency to the end user.  
187    A description of any software algorithms that are used to automate the definition of 
188  anatomic landmarks, axes, and planes and quality control measures associated with this 
189  process. For automated anatomical landmark identification, the same datasets should not 
190  be used for verification/validation as was used for software development.  
191   
192  For more information on software recommendations for these devices, please see Section IV.C. 
193   
194  In developing your patient image processing methods, you should consider the following: 
195   
196    Establishing a patient image quality check, including critical parameter checks and an 
197  identification of the responsible party. The patient image quality check should clearly 
198  identify how incoming images are analyzed for compliance with the radiographic 
199  protocol(s). 
200    Developing a segmentation protocol(s) for processing the patient images. The 
201  segmentation protocol should clearly instruct the responsible persons on how to address 
202  abnormalities within segmented volumes and identify any conditions that may prevent 
203  development of an adequate patient model.  
204   
205  5.  Pre-operative Planning and Healthcare Professional 
206  Concurrence Description 
207   
208  To develop instructions for use allowing for the device to be used safely and for the purpose for 
209  which it is intended,8 your submission should include the following information:  
210   
211    Implant planning and alignment methods and goals. The planning process description 
212  should identify implant alignment methods and goals consistent with those specified by 
213  the implant manufacturer for each implant system with which the guide is intended to be 
214  compatible.  
215    A description of the healthcare professionals involvement in the guide design process, 
216  including an identification of the parameters that can be modified, and at which steps the 
217  healthcare professional provides input and concurrence. If the healthcare professional has 
218  access to pre-operative planning images and/or software, the quality and resolution of 
219  these images should be described to the healthcare professional within the images and/or 
 
8 21 CFR 801.109(c). 
6   Contains Nonbinding Recommendations 
 
Draft  Not for Implementation 
 
220  software. When the original patient image quality or resolution is altered by the 
221  manufacturer, we recommend that the manufacturer indicate within the image(s) and/or 
222  software that the image(s) are intended for pre-operative planning only and are not 
223  intended for diagnostic purposes.  
224    A description of how requests for plan (e.g., surgical, guide design) modifications and the 
225  final plan concurrence are processed and documented by the guide manufacturer and the 
226  healthcare professional.  
227    An example of any surgical proposal(s) or final report(s) that are communicated to the 
228  healthcare professional. These proposals/reports should include adequate information and 
229  image definition to inform the healthcare professional of the proposed surgical plan to 
230  ensure knowledgeable concurrence. 
231   
232  6.  Guide Design and Patient-Matched Features Definition 
233  Description 
234   
235  To assist in the characterization of the device and its performance, your submission should 
236  include the following information:  
237   
238    A summary description of the guide design process to illustrate how the generic guide 
239  model is modified to yield a patient-matched guide, including the targeted bone/guide 
240  interface location.  The description should also identify how the resulting guide features 
241  (e.g., pin location, cut slot location) correlate with the implant systems alignment 
242  recommendations. 
243   
244  In developing your guide design and patient-matched feature definitions methods, you should 
245  consider the following: 
246   
247    Establishing a process for modifying generic guide models to allow for patient specific 
248  features. The process should identify critical structures, such as cut slots, drill guides, 
249  etc., whose positioning is crucial for proper guide function. The process should also 
250  specify how these structures are positioned and controlled throughout the design process. 
251    Identifying default values with upper and lower limits for each planning parameter (e.g., 
252  pin location, resection angle, implant position). 
253   
254  7.  Guide Construction Description 
255   
256  In developing your guide construction methods, you should consider the following:  
257   
258    Determining how, during the manufacturing process, quality control in regard to the 
259  dimensional characteristics is maintained for the manufactured guide.9 You should 
 
9 For specific considerations regarding additively-manufactured devices, please see 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 
7   Contains Nonbinding Recommendations 
 
Draft  Not for Implementation 
 
260  identify pre-determined dimensional specifications and tolerances for accepting the final 
261  guide such that the technical performance testing can be considered representative of the 
262  predefined manufacturing tolerances.  
263   
264  8.  Surgical Technique Description 
265   
266  To develop instructions for use allowing for the device to be used safely and for the purpose for 
267  which it is intended,10 your submission should include the following information:  
 
268   
269    A description of how the guides recommended surgical technique is compatible with the 
270  implantation technique recommended by the implant manufacturer. 
271    A description of any methods available for converting to traditional manual implantation 
272  techniques (if appropriate) and at which surgical steps this conversion is possible. 
273    A description of how the healthcare professional would detect and remedy an incorrect 
274  guide alignment or surgical outcome. 
275    A description of any additional considerations that may be necessary due to anatomical 
276  variation in the indicated patient population (e.g., patient size, bone condition). 
277    Software  
278   
279  Significance:  Software used in the development of patient-matched guides may use proprietary 
280  and/or off-the-shelf software to support pre-operative planning and guide design. This software 
281  ensures that a pre-operative plan is developed and correctly implemented within the guide design 
282  parameters. Adequate software performance testing provides assurance that the software operates 
283  as intended to ensure accurate and reproducible results for the compatible implant system(s).  
284   
285  Recommendation:  As a reference for developing, performing, and documenting software 
286  performance testing, refer to the FDA software guidance, Content of Premarket Submissions for 
287  Device Software Functions11 for a discussion of the software documentation that you should 
288  provide in your submission.  
289   
290  To assess the adequacy of your performance testing, we recommend that you provide a full 
291  description of the software/firmware supporting pre-operative planning and guide design 
292  following the software guidance, commensurate with the appropriate Documentation Level as 
293  described in the guidance. This recommendation applies to original device/systems as well as to 
294  any software/firmware changes made to already-marketed systems. Changes to software must be 
295  revalidated and reverified in accordance with Design Controls, 21 CFR 820.30(g)(i), and 
296  documented in the Design History File, 21 CFR 820.30(j). Some software changes may warrant 
297  the submission of a new marketing submission. For additional information regarding software 
298  modifications, please see FDA guidances Deciding When to Submit a 510(k) for a Software 
 
10 21 CFR 801.109(c). 
11 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/content-premarket-submissions-
device-software-functions. 
8   Contains Nonbinding Recommendations 
 
Draft  Not for Implementation 
 
299  Change to an Existing Device and Modification to Devices Subject to Premarket Approval 
300  (PMA)  The PMA Supplement Decision-Making Process.12 
301   
302  The design process may use third-party software to aid in guide design. If the device includes 
303  off-the-shelf software, you should provide the additional information as recommended in the 
304  FDA documents titled Off-the-Shelf Software Use in Medical Devices13 and Cybersecurity 
305  for Networked Medical Devices Containing Off-The-Shelf (OTS) Software.14 
306   
307  As appropriate, you should also provide information on the Cybersecurity aspects of your device. 
308  For more information on this topic, please see FDAs guidance Content of Premarket 
309  Submissions for Management of Cybersecurity in Medical Devices.15  
310   
311  Overall, the documentation related to the software should provide sufficient evidence to describe 
312  the role of the software used to develop the device, and functions to produce a guide that 
313  performs as intended. 
314    Biocompatibility 
315   
316  Significance:  Patient-matched guides contain patient-contacting materials, which, when used for 
317  their intended purpose, i.e., contact type and duration, may induce a harmful biological response.  
318   
319  Recommendation:  You should determine the biocompatibility of all patient-contacting materials 
320  present in your device. If your device is identical in composition and processing methods to 
321  patient-matched guides with a history of successful use, you can reference previous testing 
322  experience or the literature, if appropriate. For some device materials, it may be appropriate to 
323  reference to either a recognized consensus standard, or to a Letter of Authorization (LOA) for a 
324  device Master File (MAF). You should refer to the following FDA webpage for additional 
325  information on using device MAFs: https://www.fda.gov/medical-devices/premarket-approval-
326  pma/master-files. 
327   
328  If you are unable to identify a legally marketed device with similar location/duration of contact 
329  and intended use that uses the same materials and processing methods as used in your device, we 
330  recommend you conduct and provide a biocompatibility risk assessment. The assessment should 
331  explain the relationship between the identified biocompatibility risks, the information available 
332  to mitigate the identified risks, and any knowledge gaps that remain. You should then identify 
333  any biocompatibility testing or other evaluations that were conducted to mitigate any remaining 
334  risks.  
 
12 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/deciding-when-submit-510k-
software-change-existing-device and https://www.fda.gov/regulatory-information/search-fda-guidance-
documents/modifications-devices-subject-premarket-approval-pma-pma-supplement-decision-making-process.  
13 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/shelf-software-use-medical-devices.  
14 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/cybersecurity-networked-medical-
devices-containing-shelf-ots-software.  
15 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/content-premarket-submissions-
management-cybersecurity-medical-devices.  
9   Contains Nonbinding Recommendations 
 
Draft  Not for Implementation 
 
335   
336  We recommend that you follow FDAs guidance Use of International Standard ISO 10993-1, 
337  Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk 
338  management process, 16 which identifies the types of biocompatibility assessments that should 
339  be considered and recommendations regarding how to conduct related tests. 
340   
341  Per ISO 10993-1: Biological evaluation of medical devices  Part 1: Evaluation and testing 
342  within a risk management process and Attachment A of FDAs guidance on ISO-10993-1, 
343  patient-matched guides are external-communicating devices in contact with tissue/bone/blood for 
344  a limited contact duration. Therefore, the following endpoints should be addressed in your 
345  biocompatibility evaluation: 
346   
347    cytotoxicity; 
348    sensitization; 
349    irritation or intracutaneous reactivity; 
350    acute systemic toxicity; 
351    material-mediated pyrogenicity. 
352   
353  As patient-matched guides often utilize additive manufacturing techniques, it is important to 
354  consider the impact of the manufacturing process on the biocompatibility of the patient-
355  contacting materials. Additive manufacturing should utilize quality controls to ensure that 
356  foreign material or re-used material does not influence guide biocompatibility. Refer to the FDA 
357  guidance, Technical Considerations for Additive Manufactured Medical Devices,17 for 
358  additional information regarding the possible impact of additive manufacturing on material 
359  biocompatibility.  
360    Sterility  
361   
362  Significance:  Patient-matched guides come in contact with blood and bone and should be 
363  adequately sterilized to minimize infections and related complications.  They are either provided 
364  sterile to the user or are single-use end-user sterilized devices. 
365   
366  1.  Devices provided sterile 
367   
368  Recommendation:  For patient-matched guides labeled as sterile, we recommend that you 
369  develop information outlined below: 
370   
371  1.  For the sterilization method:  
372  a.  a comprehensive description of the sterilization method/process;  
373  b.  a description of the sterilization chamber if not rigid, fixed (e.g., flexible bag); 
 
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.  
17
 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/technical-considerations-additive-
manufactured-medical-devices-guidance-industry-and-food-and-drug.  
10   Contains Nonbinding Recommendations 
 
Draft  Not for Implementation 
 
374  c.  the sterilization site; 
375  d.  in the case of radiation sterilization, the radiation dose;  
376  e.  for chemical sterilants (e.g., EO, H O ), the maximum levels of sterilant residuals that 
2 2
377  remain on the device, and an explanation of why those levels are acceptable for the 
378  device type and the expected duration of patient contact. 
379   
380  In the case of EO sterilization, CDRH has accepted EO residuals information based on 
381  the currently recognized version of the standard, AAMI/ANSI/ISO 10993-7: Biological 
382  Evaluation of Medical Devices  Part 7: Ethylene Oxide Sterilization Residuals.  
383   
384  2.  For the sterilization method, a description of the method used to validate the sterilization 
385  cycle as well as the sterilization validation data.18 A premarket submission should also 
386  identify all relevant consensus standards19 used and identify any aspects of the standards that 
387  were not met. In the absence of a recognized standard, a comprehensive description of the 
388  process and the complete validation protocol should be submitted and reviewed.   
389   
390  3.  You should state the sterility assurance level (SAL) of 10-6 for devices labeled as sterile 
391  unless the device is intended only for contact with intact skin.  
392    
393  As patient-matched guides rely upon a specific geometrical configuration to establish a unique 
394  alignment to the patients anatomy, it is important to consider the impact of the sterilization 
395  process on the guides geometrical configuration. During development of the sterilization 
396  process, manufacturers should ensure that guides do not deform unacceptably during the final 
397  recommended sterilization process.  
398   
399  2.  Single-use devices provided non-sterile and intended for sterile 
400  processing 
401   
402  Recommendation: Instructions on how to reprocess a single-use device that is provided non-
403  sterile to the user are critical to ensure that a device is appropriately prepared for its use. For 
404  recommendations regarding the development and validation of reprocessing instructions, refer to 
405  the guidance Reprocessing Medical Devices in Health Care Settings: Validation Methods and 
406  Labeling.20   
407   
 
18 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)s, 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. 
19 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.  
20
 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/reprocessing-medical-devices-
health-care-settings-validation-methods-and-labeling.  
11   Contains Nonbinding Recommendations 
 
Draft  Not for Implementation 
 
408  As patient-matched guides rely upon a specific geometrical configuration to establish a unique 
409  alignment to the patients anatomy, it is important to consider the impact of the cleaning and 
410  sterilization process on the guides geometrical configuration. During development of the 
411  cleaning and sterilization processes, manufacturers should ensure that guides do not deform 
412  unacceptably during the final recommended cleaning and sterilization processes.  
413    Shelf Life and Packaging  
414   
415  Significance:  If the patient-matched guide is provided non-sterile, shelf life should reflect an 
416  appropriate duration between the acquisition of patient imaging and the planned surgical 
417  intervention to ensure that the anatomical situation has not changed such that guide performance 
418  can be affected. If the patient-matched guide is provided sterile, shelf life testing should 
419  additionally be conducted to support the proposed expiration date through evaluation of the 
420  package integrity for maintaining device sterility and/or evaluation of any changes to device 
421  performance or functionality.  
422   
423  Recommendation:  With respect to package integrity for maintaining device sterility, you should 
424  develop a description of the packaging, including how it will maintain the devices sterility. You 
425  should also maintain the protocol(s) used for your package integrity testing, the results of the 
426  testing, and the conclusions drawn from your results. We recommend that a package validation 
427  study include simulated distribution and associated package integrity testing, as well as an aging 
428  process (accelerated and/or real-time) and associated seal strength testing, to validate package 
429  integrity and shelf life claims. We recommend you follow the methods described in the FDA-
430  recognized series of consensus standards ANSI/AAMI/ISO 11607-1: Packaging for terminally 
431  sterilized medical devices  Part 1: Requirements for materials, sterile barrier systems and 
432  packaging and ANSI/AAMI/ISO 11607-2: Packaging for terminally sterilized medical devices  
433  Part 2: Validation requirements for forming, sealing and assembly processes. 
434   
435  We recommend devices undergo real-time aging to determine the effects of aging on the 
436  maintenance of sterility.  If you use devices subjected to accelerated aging, we recommend that 
437  you specify the way in which the device was aged and develop a rationale to explain how the 
438  results of shelf life testing based on accelerated aging are representative of the results if the 
439  device were aged in real time. We recommend that you age your devices as per the currently 
440  FDA-recognized version of ASTM F1980: Standard Guide for Accelerated Aging of Sterile 
441  Barrier Systems for Medical Devices and specify the environmental parameters established to 
442  attain the expiration date. Testing of real-time aged devices can be conducted in parallel with 
443  submission review, with results documented to file in the design history file (i.e., complete test 
444  reports do not need to be submitted to FDA). 
445   
446  With respect to patient-matched guides provided non-sterile, the maximum time between the 
447  acquisition of patients images and planned surgical intervention should be specified. The shelf 
448  life should be based upon the indicated patient pathology and sensitivity of the patient-matched 
449  regions to continued disease progression.  The shelf life for guides provided sterile should not 
450  exceed the duration for which the anatomical situation may change.   
451   
12   Contains Nonbinding Recommendations 
 
Draft  Not for Implementation 
 
452  As patient-matched guides rely upon a specific geometrical configuration to establish a unique 
453  alignment onto the patients anatomy, we also recommend that guide deformation as a result of 
454  shipping be considered. Additional dimensional testing should demonstrate that guides do not 
455  deform following simulated distribution testing. For additional information, please see Section 
456  IV.G.2. 
457    Non-Clinical Performance Testing 
458   
459  For information on recommended content and format of test reports for non-clinical bench 
460  performance testing described in this section, refer to FDAs final guidance, Recommended 
461  Content and Format of  Non-Clinical Bench Performance Testing Information in Premarket 
462  Submissions.21 
463   
464  1.  Intra- and Inter-Designer Variability  
465   
466  Significance:  The patient-matched guide design process should yield reproducible results for 
467  patient data sets within individual designers and across multiple designers. High designer 
468  variability may cause patient-matched guides to misalign implants. Variability testing provides 
469  assurance that the design process reliably outputs adequate specifications to yield reproducible 
470  clinical results.  
471   
472  Recommendation:  We recommend that you investigate intra- and inter-designer variability 
473  across representative patient data sets and designers. Variability in segmentation, patient 
474  modeling, anatomical landmark definition, preoperative planning, and guide creation should be 
475  addressed by your testing. We recommend you utilize established work instructions to evaluate 
476  the ability of multiple designers to follow the provided instructions. We recommend that the 
477  selected data sets represent the anticipated patient population, and that the selected designers 
478  represent different experience levels with the work instructions. We recommend that any 
479  observed variability be analyzed regarding the impact on the planned implant position. 
480   
481  2.  Mechanical Integrity (Post-Processing) 
482   
483  Significance:  Patient-matched guides rely upon geometrical specifications to align implants to 
484  the patients anatomy. Shipment, processing (e.g., cleaning and sterilization), and clinical use in 
485  the surgical environment can cause patient-matched guides to mechanically distort or fail, 
486  potentially yielding inaccurate implant alignment. Mechanical analysis following shipping, 
487  processing, and anticipated clinical loading provides assurance that the guide design is of 
488  sufficient strength and functions effectively.  
489   
490  Recommendation:  We recommend that you conduct dimensional and mechanical evaluations to 
491  assess that guide stability and strength is adequate to withstand forces associated with worst-case 
 
21 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/recommended-content-and-format-
non-clinical-bench-performance-testing-information-premarket. 
13   Contains Nonbinding Recommendations 
 
Draft  Not for Implementation 
 
492  conditions relative to transit, cleaning/sterilization, and use in the surgical environment. If you 
493  label your device for cleaning/sterilization and use after an accidental impact (dropping), we 
494  recommend drop testing to validate dimensional stability and validation of additional 
495  sterilization cycles. Justification should be documented for the selected worst-case conditions 
496  including the selected worst-case guide design.  
497   
498  3.  Debris Generation  
499   
500  Significance:  Interaction between polymeric patient-matched guides and the specified surgical 
501  instruments can generate debris that can be implanted. The generated debris can cause 
502  biocompatibility and/or mechanical concerns to the patient and/or implant system. Debris 
503  generation testing quantifies the magnitude and type of debris that may be generated during use.  
504   
505  Recommendation:  We recommend that you conduct simulated use testing utilizing the specified 
506  surgical instruments under worst-case contact conditions to measure the amount, size and shape 
507  of debris generated per ASTM F1877: Standard Practice for Characterization of Particles. The 
508  biocompatibility ramifications of the generated debris should be evaluated. We recommend the 
509  magnitude and size of debris generated should be less than or equal to a similar, legally marketed 
510  device with the same intended use, or should meet or exceed clinically justified acceptance 
511  criteria. 
512   
513  4.  Implant Alignment Accuracy and Guide Usability 
514       
515  Significance:  Patient-matched guides are intended for aligning orthopedic implants relative to 
516  anatomical landmarks identified on pre-operative images as recommended by the orthopedic 
517  implant manufacturer. Implant misalignment can cause premature implant failure and impact 
518  patient outcomes.  
519   
520  Recommendation:  We recommend that you conduct objective, clinically relevant evaluations to 
521  assess the usability and accuracy with which the patient-matched guides recreate the pre-surgical 
522  plan.  
523   
524  While benchtop evaluations may be useful in early verification activities, validation of the 
525  system performance including bone and soft tissue interaction should be performed in a 
526  cadaveric model to test the fit, feasibility, and accuracy of the guide within the surgical 
527  workflow. Soft tissue interaction is also critical in establishing the feasibility in preparing the 
528  surgical site when removal of cartilage and/or osteophytes is appropriate. 
529   
530  We recommend cadaveric testing of the worst-case guide configuration by multiple independent 
531  healthcare professionals with varied experience (3 levels: novice, intermediate, expert) in the 
532  surgeries associated with anatomical location using patient-matched guides, with a statistically 
533  and/or clinically supported sample size for each general guide design and for each proposed 
534  surgical technique. (Note that additional samples may be requested if error variability is large or 
535  if other unanticipated observations occur.) A worst-case scenario justification should be 
536  provided. The justification should consider various parameters such as guide configuration, 
14   Contains Nonbinding Recommendations 
 
Draft  Not for Implementation 
 
537  cleaning, sterilization, guide fit, anatomical positioning, surgical approach, implantation 
538  technique, pathological conditions for the intended patient population, and cadaveric anatomical 
539  conditions. We also recommend that these activities document the usability of the guide within 
540  the implant surgical technique(s) and assess the guides unique and stable fit to the anatomy. 
541   
542  The final implant alignment and/or bone preparation should be quantitatively compared to the 
543  pre-surgical plan. Descriptive statistics (including mean absolute error, standard deviation, and 
544  maximum error of the measured parameters) should be provided and demonstrated to be less 
545  than or equal to a legally marketed device with the same intended use and/or clinically justified 
546  acceptance criteria. If justifying acceptance criteria with a clinical rationale, the acceptance 
547  criteria should be established to include consideration for the sensitivity of the surrounding 
548  anatomy and impact on implant performance due to malalignment. Clinically justified 
549  acceptance criteria should not exceed that applied to a legally marketed device with the same 
550  intended use (if available), unless an equivalent benefit-risk profile is demonstrated. An analysis 
551  of performance testing results should be conducted to describe the expected clinical accuracy. 
552  The complete data set may be requested to perform further analysis. In addition, a healthcare 
553  professional should document any observations and indicate that the prosthesis can be implanted 
554  using the guides to their satisfaction.  
555    Clinical Performance Testing 
556   
557  Clinical performance testing is generally not necessary to support regulatory evaluation of 
558  orthopedic patient-matched guides. However, clinical performance testing may be requested to 
559  address certain situations that cannot be adequately addressed through bench testing alone, such 
560  as:  
561 
 
562    indications for use dissimilar from legally marketed devices of the same type; 
563    significantly different technological characteristics;  
564    cases where engineering and/or cadaveric testing raise issues that warrant further 
565  evaluation with clinical evidence; 
566    labeling claims about improved patient outcomes or reduced surgical time; and/or 
567    a surgical approach, implant alignment specifications, or indications for use other than 
568  that recommended by the implant manufacturer.  
569   
570  We will consider alternatives to clinical testing when the proposed alternatives are supported by 
571  an adequate scientific rationale. If a clinical study is needed to support marketing authorization, 
572  the study must be conducted under the Investigational Device Exemptions (IDE) regulation, 21 
573  CFR 812. Generally, we believe patient-matched guides addressed by this guidance document 
574  are significant risk devices subject to the requirements in 21 CFR 812. See the FDA Guidance 
575  titled, Significant Risk and Nonsignificant Risk Medical Device Studies.22  In addition to the 
576  requirements in 21 CFR 812, sponsors of such trials must comply with the regulations governing 
577  institutional review boards (21 CFR 56) and informed consent (21 CFR 50). 
 
22 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/significant-risk-and-nonsignificant-
risk-medical-device-studies.  
15   Contains Nonbinding Recommendations 
 
Draft  Not for Implementation 
 
578  In some cases, real-world data (RWD) may be used in lieu of traditionally-collected clinical 
579  data. Whether the collection of RWD for a legally marketed device requires an IDE depends on 
580  the particular facts of the situation. Specifically, if a device is being used in the normal course of 
581  medical practice, an IDE would likely not be required. For additional information regarding this 
582  topic, please refer to the FDA Guidance entitled Use of Real-World Evidence to Support 
583  Regulatory Decision-Making for Medical Devices. 23 
584    Labeling 
585   
586  As prescription devices, patient-matched guides are exempt from having adequate directions for 
587  lay use required under section 502(f)(1) of the Federal Food, Drug and Cosmetic Act as long as 
588  the conditions in 21 CFR 801.109 are met. For instance, labeling must include adequate 
589  information for the intended user of the device, including indications, effects, routes, methods, 
590  frequency and duration of administration and any relevant hazards, contraindications, side 
591  effects, and precautions (21 CFR 801.109(d)).  
592   
593  The inclusion of the following additional information unique to this device type is also 
594  recommended:  
595   
596    information regarding the implant systems for which the device has been designed and 
597  tested to be compatible; 
598    instructions regarding how the user should assess proper guide alignment; 
599    instructions regarding conversion to a traditional implantation technique if the user is 
600  unable or unwilling to use the patient-matched guides; 
601    instructions to irrigate the region during situations where polymeric debris is being 
602  generated; 
603    graphical illustrations of key steps that may otherwise be unclear; and 
604    a description of the convention used to ensure that the user can map the pre-operative 
605  plan to the final guide.  
606    a means of identifying the patient for which the guide was created. This identification is 
607  recommended to reduce the potential for using a guide on an incorrect patient and should 
608  be placed directly on the guide (for example, by marking with UDI or other patient 
609  identification method). 
610   Modifications (Devices subject to 510(k))  
611    
612  In accordance with 21 CFR 807.81(a)(3), a device change or modification that could 
613  significantly affect the safety or effectiveness of the device or represents a major change or 
 
23
 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/use-real-world-evidence-support-
regulatory-decision-making-medical-devices.  
16   Contains Nonbinding Recommendations 
 
Draft  Not for Implementation 
 
614  modification in the intended use of the device requires a new 510(k).24  The changes or 
615  modifications listed below are examples of changes that may require submission of a new 
616  510(k). Note that this list is not exhaustive but provides examples of modifications that are likely 
617  to require submission of a new 510(k).  For additional details, please see FDA guidances 
618  Deciding When to Submit a 510(k) for a Change to an Existing Device25 and Deciding When 
619  to Submit a 510(k) for a Software Change to an Existing Device.26 
620   
621  Such changes or modifications include: 
622   
623    Design of the patient contacting regions, guiding slots/holes, or critical guide 
624  structure. FDA considers the modification to the design of the patient contacting regions 
625  of the guide to be a significant change, which could significantly affect the use of the 
626  device, including both safety and effectiveness, by impacting final device alignment, 
627  resulting bone preparation, and guide integrity.  
628    Planning process - automate a manual segmentation step. A modification in the 
629  planning process such as automating a manual segmentation step may be a significant 
630  change which could significantly affect both safety and effectiveness of the device by 
631  producing an inaccurate patient-matched guide that does not correspond to the patients 
632  anatomy due to an error in the segmentation process, which could lead to implant 
633  malalignment. 
634    Patient imaging modality. FDA considers a modification in the patient imaging 
635  modality such as changing from MRI to CT to be a significant design change, which 
636  could significantly affect both safety and effectiveness of the device by impacting final 
637  device alignment due to an inaccurate patient-matched guide that does not reflect the 
638  limitations of the new imaging modality. 
639    Anatomic contact location. Modifications to the anatomic contact location for a patient-
640  matched guide may pose significant changes to the guides stability and fit which could 
 
24 Section 3308 of the Food and Drug Omnibus Reform Act of 2022, Title III of Division FF of the Consolidated 
Appropriations Act, 2023, Pub. L. No. 117-328 (FDORA), enacted on December 29, 2022, added section 515C 
Predetermined Change Control Plans for Devices to the FD&C Act (section 515C). Under section 515C, FDA can 
approve or clear a predetermined change control plan (PCCP) for a device that describes planned changes that may 
be made to the device and that would otherwise require a supplemental premarket approval application or premarket 
notification. For example, section 515C provides that a supplemental premarket approval application (section 
515C(a)) or a premarket notification (section 515C(b)) is not required for a change to a device if the change is 
consistent with a PCCP that is 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 as such device changes pursuant to such plan, 
notification requirements if the device does not function 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. 
25https://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDoc
uments/ucm514771.pdf https://www.fda.gov/regulatory-information/search-fda-guidance-documents/deciding-
when-submit-510k-change-existing-device.  
26 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/deciding-when-submit-510k-
software-change-existing-device.  
17   Contains Nonbinding Recommendations 
 
Draft  Not for Implementation 
 
641  significantly affect safety and effectiveness by misaligning the implant compared to the 
642  pre-operative planning.  
643     
644  FDA believes that the following modifications would likely not require submission of a new 
645  510(k): 
646   
647    Software update to off-the-shelf segmentation software. This modification does not 
648  introduce new risks that would significantly affect safety or effectiveness. 
649    Format of the Pre-operative Planning Report. Modifications to improve usability of 
650  the pre-operative planning report that do not alter the informational content. 
651    Non-patient contacting and non-critical guide structure. Modifications to the non-
652  patient contacting and non-critical guide structures to increase intra-operative usability 
653  that do not impact upon the guides structural integrity (i.e., rounding an external edge, 
654  placing an external divot to indicate recommended user finger placement during 
655  alignment) would likely not require submission of a new 510(k).  
656   
657   
18