**Abstract**

This chapter is focused on the USFDA regulation and the related efficacy evidence of bone graft materials, especially Class III drug-device combination products for use in the spine. Nonstructural allograft and cellular allograft products that do not rely on the metabolic activity of living cells are HCT/P products, which require no premarket review for safety and efficacy. Synthetic bone grafts and demineralized bone matrices (DBMs) fall under Class II and require a 510(k) for market clearance, generally on the basis of an animal study. Drug-device combination bone grafts are Class III and require an investigational device exemption (IDE) clinical trial followed by a premarket approval (PMA) application with the FDA to review safety and effectiveness. Currently, there are only two PMA-supported Class III drug-device bone graft substitutes with Level I data that demonstrate equivalence to autograft for safety and effectiveness in spine: Infuse® (rhBMP-2) and i-FACTOR (P-15 peptide). Both of these products have been shown to be effective autograft replacement options, vs. the other technologies, which are autograft extenders. The OP-1 Implant (rhBMP-7) was marketed for a period of time, but it has been removed from the market. This chapter will discuss these products along with their supporting clinical data.

**Keywords:** spine, bone graft, regulatory approval, clinical evidence, BMP, P-15, infuse
