Animal Studies for Dental Bone Grafting Material Devices

Dental bone grafting material devices that fill, augment, or reconstruct periodontal or bony defects of the jaw and maxillofacial region require in vivo performance studies under physiologically relevant conditions. To supplement existing guidance and address the special controls requirements for this class of medical devices, the FDA recently published animal testing recommendations for bone grafting materials (Synthetic, LYC; Animal Source, NPM; and Human Source, NUN). In addition, the guidance supports implementing strategies to minimize animal use when possible and promote the 3Rs (replace, refine, and reduce) framework,https://www.fda.gov/regulatory-information/search-fda-guidance-documents/animal-studies-dental-bone-grafting-material-devices-premarket-notification-510k-submissions.

The FDA recommends skeletally mature canine or porcine models incorporating a critical size defect* with a minimum of three (3) animals per treatment and control group per evaluation timepoint. However, if the proposed indications for use will be for use “only in extraction sockets,” a critical size defect model may not be necessary. Sample groups include test article, predicate control**, and negative control (sham) tested concurrently for a minimum of three (3) timepoints (e.g. four (4), eight (8), and twelve (12) weeks). Design considerations include uniform control of the absence or presence of periosteum across all experimental groups. Additional timepoints for grafting material devices with components that resorb faster than native bone growth (or elicit early healing response (2 weeks)) or components with slow resorption kinetics (26 weeks) should be considered. “For most bone grafting material devices, FDA understands that the final timepoint may not allow for complete device resorption, but instead, the final timepoint should demonstrate a trend towards complete device resorption.”. For defect models that include teeth extraction, a three (3) to six (6) month healing period is recommended prior to defect creation, see representative timeline.

*Critical size defect is the smallest bone wound that doesn’t allow spontaneous healing. **Predicate device, reference, or autogenous graft with similar physical and chemical characteristics.

In vivo performance is assessed with qualitative and quantitative radiography, histology, and histomorphometry. Data on bone formation, device resorption, presence of residual device material, and degradation byproducts can demonstrate the ability of newly formed bone to support biomechanical loading for the intended use of the device under physiologically relevant conditions. 

While the animal study described within the new guidance is intended to evaluate the in vivo performance of dental bone grafting material, it’s possible to incorporate in vivo safety elements typically assessed separately under ISO 10993-6 Biological evaluation of medical devices – Part 6: Tests for local effects after implantation under a single study to help refine animal usage. Study design and reporting will require careful consideration with explicitly defined endpoints to satisfy both performance and safety requirements.