In what may be a trend, the FDA has again addressed material specifications, this time in a draft guidance document titled Characterization of Ultrahigh Molecular Weight Polyethylene (UHMWPE) Used in Orthopedic Devices.
As with previous FDA comments on ventilator tubing, and as expressed in a guidance document on dialysis access devices, the issue here is that not all UHMWPE is the same and therefore just using the acronym UHMWPE is not an adequate description. For example, the draft guidance document notes that conventional UHMWPE, highly cross-linked UHMWPE, and highly cross-linked UHMWPE containing vitamin E are all being used—as well as “unconventional” versions. Highly cross-linked materials may also differ by the method by which they are thermally annealed and the use of antioxidants.
Because of the potential for significant variability, the FDA is recommending that the material description include the resin manufacturers catalog number, the concentration and identification of antioxidant or other additives, resin consolidation method, radiation dose and type, time and temperature of all post-consolidation thermal anneals, the compression ratio of all mechanical anneals, and the terminal sterilization method. Additional characterization may be covered by compliance with ASTM standard F648, which addresses these materials. For general properties of a non-F648 compliance material, a similarity argument to a material already used may be acceptable. The FDA document does not specify the degree of similarity. Note that even a supplier’s identification number may not adequately address variability of the resin and its constituents.
For biocompatibility, the draft guidance document distinguishes between materials that are “identical” to those used previously and those that are not identical. Identical is one of those words that might not allow a modifier, although this is often done anyway, i.e., nearly identical or almost identical violate the actual meaning of identical. At best, identical means with respect to a particular set of specifications, but since specifications often have ranges even materials meeting the same specs might not actually be identical. The FDA further notes that radiation-induced degradation products and the addition of antioxidants can raise new biocompatibility concerns. Tissue response to wear debris also is mentioned, illustrating the principle that true biocompatibility is application specific.
As always, a draft guidance document shows only what FDA is considering about a topic because it is the final guidance document that shows what they are actually thinking. It is not clear if the FDA would cite a draft guidance document as showing its expectations, although even a final guidance document does not officially create regulations or requirements, and the term “recommends” is commonly used.
In principle, one could choose not to comply with a final guidance document, although this would likely trigger considerable FDA scrutiny and resistance. However, this draft guidance document, along with other recent expressions of FDA expectations in the area of materials characterization, may reflect a more thorough approach to material characterization and movement away from accepting generic material names as definitive. It also might be worth noting that the FDA is not the only arbiter of the right thing to do.
William Hyman, ScD, is professor emeritus of biomedical engineering at Texas A&M University. He now lives in New York where he is a consultant and adjunct professor of biomedical engineering at The Cooper Union.