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In March, FDA released draft guidance on the information that must be included in premarket submissions for non-resorbable, non-spinal bone plates, screws and washers. The draft guidance is an important update for orthopedic device companies.
Devices that fall within the scope of the guidance document are comprised of metallic or polymeric components, including titanium, stainless steel, cobalt chrome and polyetheretherketone. The document does not pertain to nitinol devices, coated devices and devices with surface modifications, complex or unique geometries and differing modularities. It also does not specifically address additively manufactured or resorbable devices, or plates and screws in certain craniomaxillofacial and foot and ankle applications.
Importantly, the draft guidance stated that premarket submissions should include the biocompatibility of patient-contacting materials in subject devices. Previous biocompatibility tests can be referenced if the final form of devices is identical in chemical composition, manufacturing process and processing methods to currently marketed devices with a history of successful use.
Orthopedic manufacturers that can’t identify an established predicate device should provide a biocompatibility evaluation in accordance with FDA’s ISO-10993-1 guidance, which includes information regarding biocompatibility risk assessments and how to conduct relevant tests.
“It is often questioned whether FDA uses a risk-based approach for biocompatibility, which involves conducting a biological evaluation plan as an initial risk assessment to determine which endpoints can be justified and which require testing — and whether FDA accepts justifications,” said Thor Rollins, Vice President, Global Market Segment Leader of Medical Devices at Nelson Labs, a toxicology and E&L expert. “This new draft reinforces the fact that FDA recommends a risk-based approach to biocompatibility.”
As Rollins pointed out, the guidance states that if a subject device’s chemical composition, manufacturing and processing methods, and any differences in geometry or surface properties, of a subject device are not expected to have an adverse impact on the biological response compared to legally marketed bone plates, screws, washers, or instruments with a history of successful use, you may reference previous testing experience or the literature.
“These materials are well-categorized and have an extensive history of passing biocompatibility tests, so checkbox testing does not provide added value if an appropriate evaluation and justification can be performed,” he said.
The draft guidance outlined several other important aspects of premarket submissions, including the following categories.
Indications for use. Premarket submissions for devices should include intended uses and indications, and a comparison of both to at least one legally marketed predicate device. Vague language should be avoided to ensure that indication for use statements clearly state appropriate uses of submitted devices.
Submissions for devices that are intended for use in osteopenic bone must be compared to one or more predicate devices that are used in the same anatomical location and with similar indications. FDA might require additional information that demonstrates the simulated performance of the implant in bone conditions noted in the indications for use.
Submissions for plates or screws intended for use in pediatric patients should include mention of the subpopulations the devices are designed to treat.
Device description. FDA recommends that orthopedic companies identify their devices with applicable regulation numbers and product codes.
Manufacturers should also include the following information about subject devices in a table format: intended use, product code, target population, anatomical site(s) of use, packaging status (sterile or non-sterile), sterilization method, shelf life, packaging type if provided sterile and system components that can be reprocessed.
Predicate Comparison. Manufacturers should compare new devices reviewed under the 510(k) process to a similar legally marketed predicate device to support its substantial equivalence, according to FDA. The comparison should include how the subject device is similar and different, and include applicable side-by-side comparisons of key characteristics in a table form.
Labeling. Device labeling should include enough detail to satisfy the requirements of 21 CFR 807.87(e), according to FDA. Label descriptions must note intended use and patient population; contraindications; applicable warnings; MR safety information (more on that below); cleaning and sterilization instructions; and removal instructions, especially for devices intended for pediatric use.
The guidance document also recommends that manufacturers include instructions for proper construct selection in labeling for plating systems.
Sterility. Manufacturers should provide the information outlined in FDA’s sterility information guidance for plates, screws, washers and instruments labeled as sterile.
Shelf life and packaging. Applications for devices that are provided sterile should include a description of the packaging and how it will maintain a device’s sterility, including the testing methods used to test package integrity. FDA recommends the use of simulated distribution and associated package integrity testing and simulated or real-time aging and associated seal strength testing to validate integrity and shelf-life claims in accordance with methods outlined in ISO 409 11607-1 and ISO 409 11607-2.
Shelf-life studies should evaluate the critical physical and mechanical properties of the device to ensure that it will perform adequately and consistently during the entire proposed shelf life, according to FDA.
Magnetic resonance (MR) compatibility. MR imaging of bone plates, screws and washers could cause the implanted materials to move or retain heat, resulting in tissue damage or device displacement. Image artifacts could also result in imaging results that are uninterpretable or misleading.
FDA, therefore, suggests manufacturers follow recommendations outlined in section VIII.D of the agency’s guidance for the testing and labeling of medical devices in the MR environment.
Non-clinical testing. Submissions should include information that the subject device provides substantially equivalent fixation of fractures, according to FDA. Relevant testing should involve evaluating the material and performance data of the worst-case device in its final form. These evaluations might require more than one worst-case device for plates, screws and washers that are indicated for use in multiple anatomical locations.
FDA will accept comments and suggestions about the draft guidance until May 30, 2023.
