Melinda Barrow 6

FN123. Id.; Deposition of Lynch at 2482-94.

FN124. See Plaintiff's Exhibit 3.146 at 6, dated March 28, 1978; Deposition of Lynch at 2494-2501; Defendant's Exhibits 710 & 738.

Consequently, it is not known how much gel bleed occurs over the life of an implant [FN125] or the actual effect of such gel bleed. [FN126] MEC failed to conduct such tests, although Lynch himself noted the necessity for them and other experts testified that the standard for testing implantable devices at the time Plaintiff received her implants would require such tests. [FN127]

FN125. Lynch testified that when he first designed the silicone gel breast implant and knew that it would have gel bleed, he also knew that calculations could be made for the time it took for the gel "lites" to permeate the shell, the permeation coefficient or rate of transport through a material. Deposition of Lynch at 2724-25. Dr. Blais estimated that the actual released material for the duration of the implant would be 20 to 40 grams of gel bleed (or 10 to 20 grams per implant), but since the actual fill weight of the implant and the amount of material being absorbed back into the implant from the body is not known, the actual amount of gel bleed is undetermined. He weighed Plaintiff's implants in his laboratory after explant and found the right implant weighed 254.5 grams and the left implant weighed 251.6 grams. These implants were made from a 255 gram mold and had a fill weight of 253 grams for the left implant and 257 grams for the right. However, since the manufacturing protocol allowed the insertion of a needle to withdraw lint and gel, there might be additions to the gel to extend the expiration date, and there was no specific entry on the lot histories for Plaintiff's implants, he testified that the true manufacture weight is not known. Dr. Zeigler disputed the amount of gel bleed to which Dr. Blais testified, stating that the amount of gel bleed from Plaintiff's implants likely would not be as much as one gram based on the weight of the implants at fill as documented in the lot histories. However, Dr. Zeigler "made a conscious decision" not to weigh Plaintiff's explants, although he did weigh explants when he testified in other breast implant cases for Defendant. He explained that he did not weigh Plaintiff's implants because of "what was going on in vivo" and because he would be giving data that cannot be readily interpreted and might be misinterpreted. He offered the opinion that the maximum bleed from one implant would be four to five drops, or 0.25 grams. Dr. Zeigler theorized that the difference in weights of Plaintiff's implants noted by Dr. Blais and Dr. Puszkin was due to a difference their respective laboratories' balance calibrations.

FN126. Dr. Shons's testimony that by the 1980s silicone gel breast implants had a history of being clinically safe does not appear to be supported by evidence of any appropriate testing. Dr. McCarty, who has been an expert for Defendant BMS for several years, testified that he had reviewed MEC's documents and did not recall if tests on gel bleed or migration were reflected in such documents. Although MEC established the Scientific Affairs Committee in 1977, Dr. McCarty admitted that he saw no MEC study characterizing what occurred at the surface of the implant, analyzing extractants in animal and human capsules, or analyzing injection of radio labeled gel bleed materials.

FN127. For instance, Dr. Busch testified as to the "Van Winkler Rules," a guide for how a manufacturer should test drugs before putting them on the market, which was contained in an authoritative publication, "Rules for Drug Development and Toxicity," published in 1964. This advocated first testing for the safety and analysis of the efficacy of the product, then testing for the analysis of acute, sub-acute, and lifetime effects of the product. Under the Van Winkler Rules, a minimum of three primate animal studies for lifetime information on humans and one lifetime study should be done on any substance which will enter the body as a drug, such as silicone. These studies were not done by MEC. In 1985, the FDA did not require a new drug application for silicone gel breast implants which were treated as medical devices and not classified as drugs, and therefore, breast implants were regulated by the FDA as medical devices in a way different and distinct from drugs. There was no evidence presented to the Court as to when the FDA was apprised of gel bleed. Dr. Zeigler admitted that in 1971 and 1972 when MEC began marketing its silicone gel breast implants, the phenomenon of gel bleed was well-known, but he dismissed the significance of this by saying that silicone is in the body and everywhere, so there was no reason to think the product was not safe. On repeated questioning by Plaintiff's counsel, he conceded that this possibly could be an area of study.

Betty Lock, MEC's manager of regulatory affairs from 1980 until 1986 when she became director of regulatory affairs responsible for the content of control documents, labels, and package inserts, testified that the beagle studies done by both laboratories had the same flaw because numerous materials were implanted in the dogs, making the study invalid as clinical research, and because the cause of the adverse reactions could not be determined. [FN128] She noted that although low concentrations of silicon were found in the organs of certain dogs, no proper follow-up study was done by MEC. [FN129] Lock testified that MEC should have investigated the cause for silicone migration in the dogs' organs. While she told the FDA about the study, she did not disclose the finding of low amounts of silicon in the distant organs of the dogs. Instead she only advised the FDA that the dog study was not usable. [FN130] She admitted that the dog studies would not be reliable to show the safety of MEC's silicone gel breast implant, although that is what was represented by MEC on its package inserts for which she was responsible. [FN131]

FN128. Deposition of Lock at 106-107, 192, 214, & 1316.

FN129. Id. at 106-107 & 1316.

FN130. Id. at 1322. Lock testified that she knew in 1982 that if premarket approval was required by the FDA, she would need such things as laboratory data, animal and clinical study data, device characteristics, performance standards, labeling, and a bibliography of significant articles in preparation for the premarket approval process in 1988. Id. At 1674- 81. On February 2, 1983, she prepared for MEC her recapitulation of the FDA's panel meeting and comments of Dr. Mishra on the lack of valid scientific data to justify the safety and efficacy of the silicone gel breast implant. Id. at 1760. However, MEC did no animal testing in preparation for the premarket approval and only tested for physical properties of the silicone gel breast implant. Although the FDA had requested all animal toxicity studies, Lock failed to reveal that low concentrations of silicon had been found in distant organs of the beagles. Id. At 1322 & 1884.

FN131. Id. at 1322 & 1429.

*14 The adverse findings from the shortened beagle study were never disclosed in MEC's sales literature. [FN132]

FN132. Deposition of Lynch at 1916-17. Much testimony on the beagle study was presented at trial. In addition to Lynch's deposition, Dr. Williams testified that the MEC dog studies were intended to extend in time over seven to eight years the observation of tissue reaction in another, larger species, the beagle, with a longer lifetime than a rabbit. The same dog had several implant sites used and was implanted over a period of time using a number of different implant materials. While some of the dogs became sick, Dr. Williams testified this was determined to be from a well-known condition in the dogs, not from the implant, and on examination of the organs, the tissue reaction to the gel and shell was good. Dr. Williams stated that MEC used a General Electric material in most of the dogs, only later using a Dow Corning 515 and 517 gel and shell material in two dogs, Dogs 450R and 395R. He stated that the director of the world's premier testing organization today, Dr. Wallen of the North American Science Associates Incorporated ("NAMSA") which was conducting the tests for MEC, advised MEC to go back to use of rabbits to study long-term tissue response to biomaterials. Further, he stated that when the veterinarian, Dr. Patricia Teer, examined the dogs, she found local tissue reaction was good with little evidence of significant response. The only finding of significance was confined to the kidney which she attributed to naturally occurring disease and not to silicon. Dr. Williams stated that "this was consistent with my observations in similar cases." When questioned about Lynch's letter, Defendant's Exhibit 1277 and Plaintiff's Exhibit 3.151 dated October 23, 1978, describing the pathologist's histological report noting silicon present in the liver, kidney, thyroid, and lymph nodes using energy dispersive x-ray analysis, Dr. Williams testified that silicon is present in most animals in low levels, and EDAX cannot distinguish between silica and silicon. It can only tell if an element is present, not if it is a compound. He noted that when the last dog in the study, 395R, was sacrificed July 11, 1979, its tissue and organs were put into a fixative in containers and mailed to MEC. Lynch wrote to the president of MEC on July 17, 1979 that he wanted to see if dog 450R had silicon through the use of a Molecular Optical Laser Examiner ("MOLE"), but according to Dr. Williams, a MOLE could not be used because it was determined there was an insufficient level of silicon present. Dr. Williams opined that the research on dogs 450R and 395R was appropriate, and that there was no evidence of silicone migration to the organs or that the silicone gel breast implant was inappropriate for implant into humans. However, Dr. Williams admitted that MEC's representations that for up to seven years long-term implants in dogs were evaluated were not true as to dogs 450R and 395R, which were implanted in 1976-1977 and sacrificed in 1979. See Plaintiff's Exhibit 7.92. Dr. Williams further admitted that he had read Lynch's statement on deposition that the dog studies were worthless, but Dr. Williams maintained steadfastly that they were valuable to show biocompatibility. Dr. Harris Busch, who was qualified as an expert in pharmacology as it relates to the immunology of drugs, including the testing and warnings as to drug usage, reflected that despite MEC's claim in its literature dispensed to physicians and others that 15 to 18 organs of dogs were tested for 7 years, not a single dog was studied for 7 years and not one dog had 15 to 18 organs reviewed. From his review of the documents, the dogs in the beagle study had similar toxicity and inflammatory reaction, fibrous tissue formation, and tissue destruction which Dr. Busch opined occurred in women who had received MEC's silicone gel breast implants. Lynch also stated that both laboratories working on this beagle study, Wedge Creek Research and Cape Laboratories (owned in part by Lynch), had found these changes in the beagles. However, since up to eight different materials had been injected into the same dog, it was not a valid experiment, and the results could not be interpreted. Reviewing Plaintiff's Exhibits 3.145, 3.146, and 3.151, Dr. Busch opined that silicone was found distributed widely in the tissues, liver, and kidneys of dog 450R, and that what had been found was silicone, not silicon, a free element of silicone, as had been identified by the pathologist, Dr. Mora. According to Dr. Busch, it is not possible from the test results to determine whether what was found was silicon, silica (which is silicon combined with oxygen molecule groups), or silicone. Dr. Busch stated that the test results indicated that whatever was found was part of a complex compound which would require that further tests be done, not necessarily the state of the art test advocated by Lynch in his report of July 17, 1979. Plaintiff's Exhibit 3.157. However, no further tests were done by MEC.

The testimony of William Stith, a manager of MEC's Life Sciences Department from December of 1977 until July of 1978 and the director of this department thereafter, [FN133] reveals the attitude of MEC on testing its breast implant product. Stith was in charge of product reliability, setting up the "Good Manufacturing Practice" ("GMP") required by the FDA effective December of 1978, and investigating and resolving problems in biocompatibility testing of implant device components. [FN134] He testified that his goal was not to be sure that implants did not cause abnormalities in the organs of women who were implanted. Further, he felt there was no indication that it would be necessary for MEC to institute biocompatibility testing for this, and he did not feel that this was important. [FN135] He testified that he felt the ninety-day rabbit studies were long-term implant studies and that his goal was to look at the biocompatibility of the product in conjunction with the tissue at the implant site. [FN136] If there was migration of silicone gel from the implant to other body parts, he did not necessarily want to determine this. [FN137] He did not implement any long-term study of the effect of implants on women and does not know if MEC ever implemented one. [FN138] He expected doctors using the product to keep track of the results. [FN139] Referring to a document which he stated lists the MEC tests done by July 20, 1977 on the Dow Corning 515, 517, and 518 components of the silicone gel breast implant manufactured by MEC, Stith testified that except for the beagle study, the document reflects that the longest implant study done on the Dow Corning 515 silicone gel was a seven-day implant test and that, further, no ninety-day implant with histopathology was done on the implant gel or shell. [FN140] No other implant studies were implemented after this date except for two implant studies he directed on new materials, the seven-day test and the ninety-day test. [FN141] Stith stated that instead of conducting tests on the long-term effect of such product, including gel bleed, he felt MEC could rely on the U.S. Pharmacopeia testing requirements for an implantable medical device made of polydimethylsiloxane designed for lifetime use, as well as a few other tests designed for drugs being placed in plastic containers. [FN142]

FN133. Deposition of Stith at 87-91.

FN134. Id. at 87-88 & 90-104.

FN135. Id. at 119-22.

FN136. Id. at 130-48.

FN137. Id. at 148.

FN138. Id. at 157-58.

FN139. Id.

FN140. Id. at 189-94; Plaintiff's Exhibit 3.389.

FN141. Deposition of Stith, at 808-16; Plaintiff's Exhibit 4.18.

FN142. Deposition of Stith at 827-28 & 855.

Stith's testimony was reinforced by Gary A. Golwitzer, a manufacturing engineer with Surgitek and BMS beginning in 1982 until he became a full engineer in 1986. Golwitzer testified that part of his job duties included dealing with the FDA's concerns incident to the premarket approval and that, although he knew of gel bleed from the beginning of his employment, he believed a reasonably prudent manufacturer would find out about the constituents of gel bleed before selling the product. He was responsible, along with others, for designing and implementing tests on the implant product. No investigation or testing of gel bleed was done by his employer to his knowledge except for a ten-minute massage test, a dry bleed test which he described as worthless, a filter paper test, a test for permeability in one direction, and an aqueous test. [FN143]

FN143. Deposition of Golwitzer at 30-36, 70-73, 178, 182, & 192-199.

Golwitzer testified that Plaintiff's Exhibit 2.247 is a summary of the analysis done on gel bleed studies. Id. at 216.

*15 Thus, not only were the standard clinical trials not done on the silicone gel breast implants, other than short-term animal studies and the abandoned, yet inconclusive and alarming beagle study, but also MEC undertook no effort to gather clinical data or to study users of its breast implants over a period of years on a regular basis by keeping a patient registry. In the chapter on testing in his 1976 book published eight years before Plaintiff received her implants, Lynch advocated clinical trials on humans to complete the series of tests necessary for implantable products in humans. [FN144] This was not done by MEC at any time with regard to its breast implants. Under standards for testing materials to be used in the human body, Lynch described in his book three safety tests of such materials which should be done:

FN144. A clinical trial is a formal procedure in which the medical device to be tested is used in a controlled population of patients with the physicians attending the patients filling out forms describing the human experience and sending the forms to the manufacturer. Deposition of Lynch at 1902-04. Lynch stated that if several years after implant a woman had a tissue reaction showing inflammation, or a foreign body reaction with foamy histocytes and

giant cell reaction, it would indicate the implant was not biocompatible with the host. Id. at 1709-11. This reaction occurred in Plaintiff.

(1) Short-term acute animal testing (less than seven days);

(2) Long-term animal testing; and

(3) Limited clinical trials in human beings. [FN145]

FN145. Id. at 1905-1906. Lynch wrote "It is not uncommon that design changes are found necessary during this stage of testing." Lynch later testified he described this testing for "prospective" material, meaning new material, which silicone was not. Id. at 2443-2445. However, he admitted that silicone gel breast implants were the first long-term medical device which combined the use of silicone elastomer with silicone gel. Further, not only was the

use of this combination of materials new, but also MEC knew the combination resulted in the silicone shell being permeated by the silicone gel. Id. at 2571. After MEC stopped using General Electric XD copolymer in its breast implant shells, Lynch stated that all silicone breast implant shells MEC produced and used with silicone gel were permeable and bled uncross-linked molecules. Id. at 2571-2572.

Lynch admitted that MEC did not follow these steps which he described for safety testing of implants sold by the company for humans. [FN146]

FN146. Id. at 1906 & 2517-23. Lynch testified that MEC did not do long- term animal tests and clinical tests in humans because MEC did a variety of tests with excellent results and silicone was not a new material. Id. at 2443-45.

Lynch stated that it was his opinion that silicone gel breast implants would eventually wear out. [FN147] Toward the late 1970s, MEC began receiving reports that its implants were wearing out, which in some cases involved trauma. [FN148] In 1975, Lynch established a protocol at MEC to investigate the issue of shell fatigue and learned that such fatigue was basically connected to the fold in the breast implant shell and the motion of the fold. [FN149] Lynch stated: