The new draft addresses a number of elements of bone anchor design and testing. I will focus here on the Biocompatibility and Testing sections. Both the draft and final guidance documents use the terminology of “recommend,” “suggest,” and the somewhat ambiguous “should,” since guidance documents are not regulations and, in theory, are not required to be followed. The biocompatibility discussion begins with the general (and perhaps obvious) instruction that “You should determine the biocompatibility of all patient-contacting materials present in your device.” It goes on to say, “If your device is identical in composition and processing to bone anchors with a history of successful use, you may reference previous testing experience or literature, if appropriate.”
A key word here might be “identical.” While a plain English meaning might be exactly the same in all particulars, in implant materials, this has sometimes meant only of the same general type. This might be particularly at issue with respect to “processing,” especially if the predicate device comes from a different manufacturer—such that the processing may not be known in detail, or at all. The FDA further suggests a reference to a recognized consensus standard or device Master File, if available. However, as we know, materials meeting the same standard may not be identical.
In the absence of a suitable predicate for both the intended use and the materials, the FDA recommends that the manufacturer conduct and provide a biocompatibility risk assessment that includes risks, means to mitigate risks, and knowledge gaps. Based on this analysis, the manufacturer should provide whatever testing was done with regard to identified gaps. Following ISO 10993-1 is recommended.
Biocompatibility endpoints to be addressed include cytotoxicity; sensitization; irritation or intracutaneous reactivity; acute, sub-acute, and chronic toxicity; pyrogenicity; genotoxicity; carcinogenicity, and implantation effects. In addition, the FDA recommends attention to suture coatings, differences in formulation, and the effects of processing, cleaning, and sterilization. For degradable anchors, additional biocompatibility issues arise over the lifetime of the device, including healing effects and degradation products.
The discussion of performance testing begins with a recommendation to use the “final, worst-case, sterilized device.” What worst-case means here is not clear, but perhaps refers to known manufacturing variability. If so, this suggests the manufacturer knows it makes some devices better than others, even though all presumably meet the specifications. (Even so, I’d rather have a best-case than a worst-case implant.) Later, the term “worst-case clinical loading” is used, so maybe that is the meaning here as well.
The FDA makes a strong statement on resterilized suture components, asking for a “robust rationale” that addresses why resterilization is not expected to affect the performance of the suture component. This statement is presumably making an interesting distinction between an ordinary and a robust rationale. The elements of testing are to include suture characterization, insertion and pullout, component connection, fatigue, corrosion (for metals), and degradation where applicable. It is noted that clinical testing is generally unnecessary for bone anchors—except when there are different indications for use, different technology (including different materials), or lower mechanical properties than predicates, or when other testing suggests the need for additional evaluation. If clinical testing is necessary, the FDA “believes” that bone anchors should be treated as significant risk devices for IDE purposes.
Since the original draft was in existence for 20 years, perhaps manufacturers have already been doing all or most of these things, or at least those in the earlier draft. If not, the new draft may increase the effort level necessary to bring a bone anchor to market. However, remember that FDA’s perspective only sets a minimum expectation. Manufacturers still retain the responsibility to make their own judgments on what else might also be necessary and appropriate.