Andrew von Eschenbach, M.D., Acting Commissioner
U.S. Food and Drug Administration
Food and Drug Administration
5600 Fishers Lane
Rockville, MD 20857
Dear Dr. von Eschenbach:
I have recently obtained a copy of a June 22, 2006 letter sent to the FDA by a former senior scientist from Mentor-one of the two companies seeking FDA approval of silicone gel breast implants-accusing the company of withholding from the FDA important new safety information concerning dangerous physical and chemical properties of their implants. Prior to sending the letter, the scientist had raised all of the serious concerns mentioned in the letter within the company; he had urged Mentor to submit the withheld data, but they had refused. The scientist sent the information to the FDA only after his employment was terminated after 15 years with the company.
Several weeks ago, the former Mentor scientist was called by the FDA staff member to whom the letter was sent. The scientist was told that because:
(1) the withheld test data demonstrating dangers of the implants referred to in the letter were not required in FDA’s request to Mentor (and Inamed, the other breast implant manufacturer) for more studies (referred to as the “deficiency response”); and (2) since the submitted data from both Mentor and Inamed (the other silicone gel breast implant manufacturer) were similar, that he had no other comment on the new information, implying that the agency would take no action.
This new information is compelling enough to warrant a reassessment of FDA’s position. At the very least it should clearly stop any FDA final approval of either device until the withheld data has been submitted, evaluated by the FDA staff, and made available to the public. This new evidence that information has been illegally withheld from the FDA should prompt a new criminal investigation into the Mentor’s failure to promptly send the agency all new information bearing on the safety of silicone gel implants.
In discussions with the scientist, he has explained to me the details and significance of the information. This is summarized below, under five subheadings that correspond to the five points made in the letter to the FDA:
Tests/data concerning gel leakage, composition
1. Diffusion Testing Validation: The gel bleed (diffusion out of the implant and into the body) chemical test data submitted to the FDA is invalid and has been fraudulently represented. A new procedure to correct this problem was successfully tested but the data from this more valid method was never submitted to the FDA. The importance of this is that the submitted data might understate the amount of low molecular weight siloxanes (the more toxic component of silicone gel) that is seeping out from the implant into the body.
2. Explant Semivolatile Extractable Testing: In tests of explanted silicone gel implants, the company found that there were very large amounts of the above-mentioned low molecular weight siloxanes compared to the amounts in devices that had not yet been implanted, implying that the larger molecular weight siloxanes were continually being degraded in the body to low molecular weight siloxanes. This suggests that a continual degradation of higher molecular weight gel to lower molecular weight siloxanes and bleeding of this may subject women to a constant source of the more dangerous low molecular weight siloxanes. These data were not submitted to the FDA.
Tests related to mechanical properties of the implant
3. Explant Mechanical Testing: The company found a significant decrease in some of the mechanical properties of explanted devices in comparison to unimplanted control devices from the same manufacturing lot. In their submission to the FDA, however, these comparisons with unimplanted devices were not explicitly made, thus obscuring as much as a 50% decrease in some of these mechanical properties. This magnitude of weakening of the implant shell is extremely relevant to the issue of implant rupture.
4. Device Projection Fatigue Testing: Device projection refers to the distance from the front of the implant to the back (the anterior-posterior distance). A Mentor investigation of the relationship between device projection and fatigue lifetime (the time until the implant ruptures) found an inverse relationship, i.e., as the device projection increased, the estimated lifetime of the device decreased. This information was also not sent to the FDA.
More toxic form of platinum in the implant shell
5. Platinum Valence: As noted in the letter, Mentor studies showed that in the silicone rubber envelope of the implant, Platinum existed in the +2 oxidation state (Pt (II). This previously unknown finding is of potential importance since this oxidation state is thought to be more toxic than the Pt (0) oxidation state of the metal. Again, this information was not sent to the FDA.
In summary, this former Mentor scientist has made the FDA aware of previously undisclosed information based on company files. These include considerable test data showing safety problems with silicone gel breast implants. Although some of these studies were not “required “ to be done in the Guidance among the studies the FDA asked Mentor to do, their results directly address important issues of safety that are of relevance and concern. The fact that they were done and that they found some serious problems with the safety of the implants is reason enough for the FDA to take them into account and demand that Mentor provide the actual data from the studies.
As mentioned above, no approval decision on either the Mentor or Inamed implants can be made until the FDA is in possession of and has evaluated these new studies. Unless the FDA opens a criminal investigation into Mentor’s failure to submit the studies, it will encourage Mentor and other device manufacturers to selectively send the agency only those studies that put their products in the most favorable light. Please note that in his letter to the FDA, the former employee identified the specific Mentor staff files containing the withheld information.
I look forward to a prompt response concerning this serious matter.
Sidney M. Wolfe, M.D.
Director, Public Citizen’s Health Research Group