Off-label-use of Bone Morphogenetic Proteins (BMPs)
|rhBMP-2 on collagen sponge
Since 2002 both rhBMP-2 and rhBMP-7 are registered medicine and available on the market. BMPs are restricted to certain surgical fields which differ in varies countries. As far as we know restrictions and deviations of registration are based on economical reasons of the manufacturers. Until recently rhBMP-2 was permitted for the use in spine surgery in the USA, while in Europe it was only allowed to use in open tibial fractures. Just recently the use of BMPs in spine surgery has been permitted in Europe as well.
The use of BMPs in oral surgery is described to be off-labelled. Within the scope of medical freedom of action only individual medical treatments are allowed on the surgeon's own responsibility. These treatments basically differ from controlled clinical studies based on "Good Clinical Practice (GCP)" whose legal principles are "ICH Guideline For Good Clinical Practice", "the Guideline 2001/20/EG of European Parliament and Council of the European Union", "the 12th act to amend the law governing the manufacture and prescription of drugs" and "The Guidelines for Good Clinical Practice of the Federal Ministry For Health and Social Welfare"of 9. August 2004. Studies which have to take into consideration the ethical principles for medical research involving human subjects require the permission and surpervision of the ethical commissions.
(Reference: International Conference on Harmonisation, www.ich.org; Official Journal of the EU, 1.May.2001; Bundesgesetzblatt Jahrgang 2004 Partl I No.42, published in Bonn, 12. August 2004; World Medical Association Declaration of Helsinki; 52. General Assembly October 2000)
It is intended for the near future to conduct clinical studies for the use of rhBMP-2 in oral surgery. A possible type of conduction could be the concept of multicentre trials in cooperation with a university hospital.
Based on the scientific and legal background Schuckert and Jopp carried out single medical treatments with rhBMP-2 on different indications and published them. Each patient met one of the following criteria:
- the previous standard treatment was not successful
- the therapy to preserve some teeth or implants was impossible with present general technology
- an obviously higher osteoinductive potency for vertical augmentation was neccessary that could not have been achieved by all previously known methods
- the prospect of preserving teeth, implants, soft and hard tissue was low and not promising
Beforehand each patient was detailed medically examined by an internist and informed of the peculiarity of the off-label use. The operations were carried out under monitoring by an anesthesist.