**4. The OP-1 implant: BMP-7**

There is a third drug-device combination spinal bone graft product, which deserves some discussion: the OP-1 implant formerly commercialized by Stryker Biotech under FDA humanitarian device exemptions (HDE) OP-1 was bone morphogenetic protein (BMP)-7 on a collagen delivery carrier. The BMP-7 was bound to the collagen prior to packaging and terminal sterilization. Following study in long bone nonunions, the OP-1 implant was studied as an autograft replacement for primary posterolateral spinal fusion (PLF) under an IDE (IDE G990028).

After failing to meet the primary outcomes of the study to qualify for a PMA approval [rejection at the FDA advisory panel meeting in November, 2007], Stryker Biotech filed an HDE for revision PLF, which was granted in 2004. The Humanitarian Device Exemption (HDE) pathway is a method of gaining very limited FDA approval for a medical device. The device has to be intended to benefit patients in the treatment or diagnosis of a disease or condition that affects or is manifested in not more than 8000 individuals in the United States per year. Although the application is similar to a premarket approval (PMA) application, the product is exempt from effectiveness requirements and, therefore, does not require a wellcontrolled Level I clinical trial. The application is required to only provide sufficient technical information to demonstrate that the device will not expose patients to an unreasonable or significant risk of illness or injury and the probable benefit to health from the use of the device outweighs the risk of injury or illness from its uses.

The OP-1 device was commercialized by Stryker in the United States until 2010 and then, subsequently sold to Olympus. OP-1 was later removed from the market worldwide.

## **5. Conclusions**

Nonstructural allograft and cellular allograft products marketed as HCT/Ps do not require any FDA review for safety or efficacy. Synthetic bone grafts and DBM's require a 510(k) for clearance on the basis of animal studies, and most of these technologies have little to no meaningful clinical data. Currently, there are only two PMA-supported Class III drug-device bone graft substitutes available with Level I data that demonstrate equivalence in safety and effectiveness to autograft in the spine: Infuse® (rhBMP-2) and i-FACTOR bone graft (P-15 peptide). Both of these technologies have multiple peer-reviewed clinical studies that can be used to evaluate their effectiveness and make a clinical use decision.
