Comment on FDA’s Draft Guidance for Orthopedic Implant Coatings

A new draft guidance issued by FDA calls for medical device manufacturers to submit additional data in premarket submissions for class II and class III orthopedic devices that contain metallic or calcium phosphate coatings.

FDA said that the recommendations reflect current review practices and are intended to promote consistency and facilitate efficient review of submissions for orthopedic devices that contain certain coatings.

The guidance applies to the following types of coatings:

• Metallic coatings that can be manufactured using thermal spray, sintering, vapor deposition/infiltration, physical vapor deposition and additive manufacturing.
• Calcium phosphate coatings that can be manufactured by plasma spray, solution precipitation and electrochemical deposition.
• Metallic and calcium phosphate dual coatings manufactured using one or more of the above methods.

FDA proposed that premarket submissions for devices that contain these coatings include the following information:

• Coating Description. Note the name of the coating and coating type (titanium, hydroxyapatite, titanium/hydroxyapatite dual coating, etc.). For coatings applied by a contract manufacturer (CM), refer to the CM’s Master File for information regarding the coating. Include this information — along with a Letter of Authorization from the CM that specifies where information relevant to your implant is located within the MAF — in premarket submissions. Also, document the method used to apply the coating (including pre- and post-processing), the starting materials used to produce the coating, the physical structure of the coating and the location and total coverage of the coating on the device. 

• Sterility. FDA recommends that you sterilize all coated devices to maintain the coating’s integrity upon delivery to sites of care. Describe the method used to validate the sterilization method, include the validation data and identify relevant consensus standards used — and those that are not met. Gamma radiation should be used to sterilize devices coated with calcium phosphate to maintain the properties of the coating, according to FDA. 

• Pyrogenicity. Document that devices meet applicable pyrogen limit specifications to protect patients from the risk of febrile reactions caused by gram-negative bacterial endotoxins and chemicals that can leach from applied coatings. 

• Shelf Life and Packaging. Describe the packaging system and note how it will maintain the device’s sterility. Include a description of the package integrity test method, protocols used for testing and the results and conclusions of the tests. Validation studies should include simulated distribution and integrity testing, accelerated or real-time aging performance and seal strength testing to validate shelf-life claims. 

• Biocompatibility. All patient-contacting materials in the substrate and coating must undergo biocompatibility testing. You can reference coatings on a legally marketed device with a history of successful use if the processing methods and composition are identical to the coating on your device. When an identical marketed device is unavailable, biocompatibility testing should follow FDA guidance and explain the relationship between identified biocompatibility risks, what’s been done to mitigate the risks and remaining knowledge gaps. Biocompatibility testing for metallic and calcium phosphate coatings should include assessments of starting materials, subsequent processing of the materials and cleaning and sterilization steps. 

• Non-clinical Bench Testing. Inadequate coating integrity could cause device failure and complications such as poor fixation, so the draft guidance recommends the use of non-clinical tests that characterize various types of metallic and calcium phosphate coatings. Final sterilized devices from multiple lots should be used for testing, and characterization or rationale should be provided to justify why a test sample is equivalent to the final device. Describe the alternative testing approach you use and its scientific rationale if you think the guidance’s recommended tests do not apply to your coating. 

• Non-clinical Animal Testing. Animal studies must be conducted to provide initial assessments of how coated medical devices interact with biological systems and how the biological systems impact the performance of the devices. Base a study’s design and endpoints on the intended use of the device and mitigation of its risks. Animal testing can be replaced, reduced or refined in some cases. Take advantage of the Q-Submission Program and consult with FDA to ensure that non-animal methods are suitable, adequate, validated and feasible, and that they address safety concerns and factors that are suitable for regulatory submissions. FDA said it will work with device manufacturers to determine whether non-animal testing alternative methods are equivalent to animal studies. 

• Clinical Performance Testing. Clinical studies are often unnecessary for metallic and calcium phosphate-coated devices, but might be appropriate if novel materials and compositions are used in the coatings or when bench and animal testing raise issues, such as concerning mechanical properties or low shear fatigue strength, that require further evaluation. Real-world Data (RWD) can be used in some cases instead of traditional clinical data. FDA’s additional guidance on this topic provides information on when RWD is appropriate. 

• Labeling. Joint replacement devices coated with calcium phosphate material should be implanted using only a cementless method, because calcium phosphate coatings can adversely affect the longevity of cemented fixation. FDA recommends specifying this information in a device’s Indications for Use Statement and labeling. Devices with porous coatings that generally align with descriptions in 741 21 CFR 888.3358 and 21 CFR 888.3670 can be labeled for biological fixation. Additionally, provide the “nano” characteristics for devices that will be labeled as such in the premarket submission. 

• Modifications. 21 CFR 807.81(a)(3) outlines when changes or modifications to a device could significantly affect its safety or effectiveness or represents a major alteration in the intended use that requires a new 510(k) clearance. Modifications that require a new clearance include changes to the coating method or use of a different coating vendor, the addition of coating layers or changes in the coating’s thickness or porosity, and changes to another substrate material. Changing from one supplier to another for the starting material of a plasma-sprayed metallic coating that conforms to an FDA-recognized consensus standard or reducing the number of coatings or thickness of a metallic coating on a previously cleared device generally do not require a new clearance.

Comments on the draft guidance must be submitted by March 22. The final document will supersede two pieces of guidance: 510(k) Information Needed for Hydroxyapatite Coated Orthopedic Implants and Guidance for Industry on the Testing of Metallic Plasma Sprayed Coatings on Orthopedic Implants to Support Reconsideration of Postmarket Surveillance Requirements.

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