The Centers for Medicare and Medicaid Services (CMS) has called this meeting to consider the currently available evidence regarding the clinical benefits and harms of on-label and off -label use of BMPs. More than 20 BMPs have been identified, but only BMPs -2, -4, -6 and -7 have been shown to have significant osteogenic properties. The main physiologic role of BMP is to promote differentiation of mesenchymal cells into chrondrocytes and osteoblasts, to promote differentiation of osteoprogenitors into osteoblasts, and to influence skeletal pattern formation.
Human BMPs are now produced using recombinant DNA technology. Currently, two recombinant BMPs have some form of FDA approval and are commercially available in the United States: rhBMP-2 and rhBMP-7. The on-label and off -label use of BMPs has rapidly grown since becoming clinically available in 2001. There are reports stating that up to 85% of BMP use is for off-label indications, mostly in the spine. There have also been a number of reports of adverse events associated with the use of BMPs.
For all voting questions, the clinically meaningful health outcomes of interest for CMS are pain, patient function and adverse events related to use of BMPs.
For explanation of premarket approval (PMA) and humanitarian device exemption (HDE) on-label use of BMPs, see the attached appendix that summarizes the FDA actions and public health notification on BMPs.
Off-label use is defined as any use for other than the manner or specific indications in the FDA approval. Some examples of off-label use in the lumbar spine would be:
For the voting questions, use the following scale identifying level of confidence - with 1 being the lowest or no confidence and 5 representing a high level of confidence.
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Summary of FDA Actions on BMPs
*Stryker submitted an application with the FDA for OP-1 Putty spinal product and hoped for approval by late 2007. FDA requested additional data which significantly delayed the company’s expectation for approval. FDA convened an advisory committee to review this issue and did not recommend approval (2009). No further action by FDA.