ADDENDUM

TO

CITIZEN PETITION 2006P-0151/PSA 1

September 29, 2006

Dockets Management Branch

Food and Drug Administration

Department of Health and Human Services, Rm 1061

5630 Fishers Lane

Rockvillle, MD 20852

FAX 301/827-6870

The undersigned submits this addendum to citizen petition 2006P-015/PSA 1 filed 4/10/2006 to request that the Commissioner of the Food and Drug Administration (FDA) stay the current approvable letters with conditions of any and all Premarket Applications (PMAs) for silicone gel-filled breast implants (SGFBIs) for an indefinite time. This addendum will address the FDA’s recently released backgrounder on platinum in silicone breast implants and letters to the editor of Analytical Chemistry by Lane and Brook. This addendum also provides a manuscript by Lykissa and Maharaj in response to the Lane and Brook letters.

• The FDA quotes the Institute of Medicine (IOM) 1999 report on platinum in silicone breast implants.

• Some of the biases in the oft quoted IOM 1999 report include the following:

1. The conclusion of the IOM report regarding platinum related health problems in women with silicone breast implants misleads the non-scientific reader, as it suggests that appropriate studies have been conducted and were reviewed, when in fact, if evidence is lacking for an association between platinum and health problems in women with silicone breast implants as the report states, it is because no such studies have been performed.
2. With respect to the amount of platinum in breast implants, the ‘data’ cited in the IOM report consists almost entirely of manufacturer’s non-peer-reviewed company documents, or personal communications by individuals employed by breast implant manufacturers. The one scientific publication (El-Jammal and Templeton 1995) that it did review was deemed questionable by the IOM because it showed a much higher amount of platinum in silicone gel than the ‘data’ reported by the manufacturers and state "the higher measured value is confusing". Why? Because it differed from the ‘data’ in the internal company documents, and personal communications by individuals employed by manufacturers.
3. The bias of the IOM report is evident in the outright error it makes on page 82 where it refers to Appendix B stating that allergies and asthma are not prominent in lists of problems with breast implant patients. Table B-1 in Appendix B lists symptoms reported by individual women or consumer groups (not in order of prevalence or severity). Included in this table are breathing difficulties, allergic reactions, asthma, chemical and environmental sensitivities (among many other symptoms). Many of the symptoms listed in Appendix B are common to those side effects reported in patients treated with Cisplatin.

• The IOM report is now out of date with the publication of independent peer-reviewed published research by Flassbeck, et.al. (2003), Maharaj (2004), and Lykissa and Maharaj (2006). It is no longer scientifically valid to continue citing this document with respect to the amount of platinum in implant gels or shells.

• The FDA scientists (Arepalli, et.al. 2002) simply reviewed the available studies from the medical literature on platinum and breast implants and reported they did not find evidence that platinum in silicone gel breast implants causes illness. The FDA’s bias in quoting this study to imply safety is obvious when one considers that if no studies looking for platinum hypersensitivity or toxicity are conducted or published, then a review of the literature finds no evidence of a link to disease.

• The FDA’s bias is evident when they do not require the manufacturers of implants to follow the health of women who have their implants removed perhaps because of health concerns and do not require the manufacturers to test for platinum levels in breast milk or follow the health of any children born to women with implants while enrolled in a clinical study.

• All women who received silicone gel-filled implants after 1992 had to enroll in a clinical study. It has been reported by a hospital ethics board to the FDA that it appeared these poorly designed clinical studies were simply a "political means" to keep gel-filled implants on the market. Consumers should have 14 years of data on "third-generation" implants at this point. Why does the FDA allow the manufacturers to present only one, two, and three years of data to determine safety?

• In a review of the Flassbeck, et.al. research, the FDA notes that a larger study is needed to establish the significance of these results. Since the year 2003 when this research was published, why has the FDA taken no action to require the manufacturers of breast implants to conduct this larger study on platinum levels in the fat tissue of women who have their implants removed?

• In a review of the Maharaj (2004) research, FDA declares the study seriously flawed. We strongly object to the term "seriously flawed" in reference to peer-reviewed papers published by scientists not associated with manufacturers and published in high quality analytical chemistry journals. For example, Maharaj (2004) is the most comprehensive peer-reviewed scientific publication to date regarding the amount of platinum in silicone breast implants. Also, for the first time in a peer-reviewed journal publication, Maharaj (2004) provided platinum values for some of the shell types. However, the FDA suggested the entire study was "seriously flawed", when in fact, it had limitations (like all studies), and in this case it was regarding the use of control tissue samples. The use of such language by the FDA is another example of bias and intentionally misleads the consumer. This statement should be removed. Since this research was published in 2004, why has the FDA not required studies by the manufacturers of removed silicone gel-filled breast implants or the surrounding breast/scar tissue for platinum content?

• Limited funding did not provide for a large number of control samples from women without implants in the Lykissa and Maharaj (2006) peer-reviewed published research. Of the five control samples that were provided, the FDA has apparently dismissed the significance that the platinum was in the zero (0) oxidation state while all nine silicone gel-filled implanted women’s samples reported had up to a +4 oxidation state. The editorial in Analytical Chemistry on 8/1/06 state, "Perhaps the speciation results of this paper are correct – even though the data are startling." The data are "startling" because oxidized platinum is capable of crossing the placental and brain barrier and carry second-generation risks.

• Raymond E. Biagini, a research toxicologist with CDC/NIOSH who has done a lot of research on platinum salts and allergy in the work place stated in 2001 "In discussion with Dow and other companies which made silicone implants, I’m relatively satisfied that they used chloroplatinic acid as a catalyst. Recent discussions with them lead to much double talk regarding the species of platinum that was used. By definition, catalysts are not changed during chemical reactions, so there is some basic problem in the chemical explanation of silicone catalysis."

• In 1995 a protective "gag" order regarding platinum discovery on breast implants was granted to Bristol-Myers Squibb Company (BMS) by Judge Sam C. Pointer. This order covered discovery related to platinum-containing substances and BMS’s testing of platinum-containing substances. All women with leaking or ruptured implants but especially women with BMS implants and their children born after implantation need to know if they might be sensitized to platinum should they develop cancer and consider treatment with a platinum containing chemotherapy drug.

• The FDA further shows their bias by quoting Brook (2006), a paid breast implant manufacturer consultant, whose published review contains no new scientific data and grossly deviates from the scientifically accepted norm. The paper cites as evidence: information from web sites, internal company documents from litigation and patents, non-peer-reviewed book chapters, and many other such substandard materials, even a book review. The FDA appears to be using this paper by Brook to dismiss the peer-reviewed published data on oxidized platinum being released from breast implants, and to perpetuate non-peer-reviewed data in the field, under the disguise of a peer-reviewed work.

• Brook in his 2006 review states that previous studies have analyzed silicone for the various species. However, no such peer-reviewed study ever analyzed an actual explant for the various forms of platinum after it came out of the human body. Lykissa and Maharaj 2006 was the first (and only) study to do so. It is suspected that the platinum used in the manufacture of the gel and shell of silicone breast implants which is reported to be neutralized with a vinyl binding, over time in the human body detaches from the binding and is leaked to all parts of the body via the lymphatic and blood systems in an oxidized state.

• Peer-reviewed papers with new scientific evidence in scholarly journals have long been the cornerstone of acceptable standards for excellence in science. The research by Flassbeck, et.al., Maharaj, and Lykissa and Maharaj, satisfy this requirement yet the FDA chooses to dismiss or ignore this important research. Lykissa and Maharaj welcome the opportunity to respond to the letters sent to Analytical Chemistry by the Dow employee Lane and the breast implant consultant Brook. Enclosed in this addendum is the Lykissa and Maharaj response titled "Response to Comments on Total Platinum Concentration and Platinum Oxidation States in Body Fluids, Tissue, and Explants from Women Exposed to Silicone and Saline Breast Implants by IC-ICPMS" which provides further clarification on experimental details that will permit the work to be reproduced. Additional work on a large number of exposed women, their children born after implantation, and an equal number of control subjects is needed to corroborate and extend the results of this important study.

• By posting the FDA Backgrounder on Platinum in Silicone Breast Implants on their website, the FDA has committed a great disservice to the public, to consumers, and to women who trust the FDA for unbiased information regarding the safety of medical devices.

• The FDA seems to choose to ignore or dismiss the following:

1. Dow notified the EPA on 12/27/96 of substantial risk to their platinum catalyst used in making breast implants. Manufacturing proprietary documents list chloroplatinic acid as an ingredient in mammary implant material formulation.
2. Oxidized platinum is one of the most allergenic substances and potent sensitizers known to man.
3. Given the hypersensitivity, toxicity, and biological reactivity of oxidized forms of platinum, any amount may be too much.
4. With oxidized platinum a major toxicologic issue is immunogenicity, where absolute amounts have little significance in the development of allergic and immune disorders.
5. A "safe" dose of oxidized platinum is unknown.
6. Both Mentor and Inamed (now Allergan) submitted unpublished data regarding platinum at the 2005 FDA advisory meeting on brand new implants never implanted in the human body.
7. Significant amounts of platinum are now being found in the urine of children born to women with silicone gel-filled breast implants (abstract submitted to the American Chemical Society Meeting, 2005). Platinum was found in the breast milk of six samples from breast implanted women. Cisplatin research has found platinum in breast milk from chemotherapy patients and it is known to cross the blood brain barrier.

In conclusion, the FDA should stay the approvable letters for silicone gel-filled breast implants, for the above reasons, until a well controlled scientific study measuring platinum levels in implants removed from the human body, fluids (including breast milk), and tissues is completed by the manufacturers of implants or by government agencies. FDA admits that implants contain platinum and before approval is given, the toxicological significance of this platinum must be determined to the developing fetus.

Women can never make an informed decision on the amount of risk they are willing to take to their health and that of their unborn children, unless the research is done. Why is the FDA considering approving a non life-saving device that has the potential to leak significant amounts of a heavy metal into their bodies, brain, and fluids without adequate research? Could the influence of this billion dollar breast implant industry be more important than the health of women and children?

The undersigned certifies that, to the best knowledge and belief of the undersigned, this petition includes all information and views on which the petition relies, and that it includes representative data and information known to the petitioner that are unfavorable to the petition.

 

 

 

Marlene Keeling, President

Chemically Associated Neurological Disorders

P. O. Box 682633

Houston, Texas 77268-2633

281/444-0662

281/444-5468 FAX

keeling.m@worldnet.att.net

Exhibits

Exhibit A:

Lykissa ED, Maharaj SVM. Response to Comments on Total Platinum Concentration and Platinum Oxidation States in Body Fluids, Tissue, and Explants from Women Exposed to Silicone and Saline Breast Implants by IC-ICPMS. Submitted for publication

Exhibit B:

United States District Court Northern District of Alabama "Protective Order Regarding Platinum Discovery" Silicone Gel Breast Implant Products Liability. February 1995.