Document Z8kLR5Noem5VBrNMbzx7xbKYJ

FILE NAME: Johnson & Johnson (JAJ) DATE: 2015 July 17 DOC#: JAJ045 DOCUMENT DESCRIPTION: Letter to Gene M. Williams, Lawyer, from Innovant Research - Founded by a Former J&J Toxicologist Employee and Current Independent Consultant, Defending the Use of Asbestos as Non-Toxic in Relation to Ovarian Cancer p / \ The Sms Oxford Rd -Chitvtlw Ntwbury RGJ08RT Ui**J Kin|dom Tthphan*: +44 1635 246830 ta e +44 1635 247306 Email: tonova47aoLm Gene M. Williams Shook, Hardy & Bacon, LLP 600 Travis Street, Suite 1600 Houston, Texas 77002 Dear Mr. Williams: 1have prepared die following for the case o f Blaes v. J&J, et al. I hold a Bachelor o f Science degree with Honors in Chemistry & Biochemistry from the University o f S t Andrews, Scotland, U.K. I also hold a Ph.D. degree in Toxicology from the University o f Dundee, Scotland, U.K. l a m a Chartered Biologist holding the Diploma, C. Biol, and my academic background is in foe field of toxicology. I am also a member o ffoe Society of Biology. I have 41 years experience as a Toxicologist in Pharmaceutical, Medical Device and Consumer product areas. During foe period 1976 - 2000,1 was in the employment o f Johnson & Johnson (UJL, 19761994; U.S.A., 1995-1998; and France 1999-2000). Prior to th at I undertook some teaching to medical students followed by employment as a Toxicologist in the Pharmaceutical industry. I was a founding member o f foe British Toxicology society in 1979. From foe time I became employed at Johnson & Johnson as a Toxicologist in 1976,1have been familiar wife the literature and discussion as to talc safety. I am also familiar with the history and background o f foe sourcing, standards and specification o f talc as used by Johnson & Johnson on a worldwide basis. During my employment for Johnson & Johnson in the U.K., I was based in foe medical department and was in regular contact with medical and scientific colleagues in foe United States and kept updated on all matters relating to talc safety. I also sat on a talc issue task force, which dealt with various issues, including talc safety. I was a participant at the FDA sponsored Talc Safety workshop held in 1994 in Washington, D.C. I was also involved in foe collation o f scientific data via foe CTPA (U.K. Trade Association) for foe NTP review o f talc safety in December 2000. I retired from Johnson & Johnson as Worldwide Category Director, Infant & Children's Products, in 2000. Since 2000,1am foe President o f my own company, Innovant Research, which is an independent consultancy in foe field o f toxicology, product safety, and risk assessment Through my company, I have continued to serve as a consultant to Johnson & Johnson both in Europe and in l|Page exhibit i the United States on safety matters, including talc safety, and continue to maintain a strong interest in talc safety today. I am also a Member o f the U.K. Trade Association, the CTPA. I am a Member o f the CTPA Scientific Advisory Committee and the CTPA Talc Committee and the CTPA Toxicology panel. My Curriculum Vitae is attached, which provides further details about my education, training and experience. I have testified as an expert witness one time in the last four years (Berg vs. Johnson and Johnson). JOHNSON & JOHNSON TALC SOURCING Johnson's Baby Powder has been manufactured since 1894. The purity of talc is based on its source. There are only a limited number of talc mines in the world that provide the high grade o f talc that meets the requirements of talc for pharmaceutical applications (Talc USP) and for cosmetic applications (compliance with the CTFA monograph). Mines that include geological structures other than pure talc are not suitable as a source of cosmetic and pharmaceutical grade talc. Beginning in approximately 1946, talc for Johnson & Johnson in the U.S. was sourced from the Italian mine at Val Chisone. In approximately 1967, Johnson & Johnson in the U.S. began to acquire its cosmetic grade talc from the Windsor mine in Vermont, U.S.A. From approximately 2003 until the present, Johnson & Johnson in the U.S. has been acquiring talc through Luzenac (now hnerys) from the Guangxi mine in China. All o f these sources have undergone rigorous testing by Johnson & Johnson in order to become an approved source of talc. TESTING OF JOHNSON & JOHNSON TALC The records indicate that as for back as 1949, there is documented evidence that the specification for Johnson & Johnson cosmetic talc should be free from asbestos and asbestiform minerals. Although asbestos and talc share the same chemical components, their physical structure differs significantly in that asbestos and asbestiform minerals are needle-like in appearance, whereas talc is flat and plate-like. iStSS I t thex abillty l Idto tySsofoiltQntei On the other hand, the flat, plate-like structure o f talc gives it a soft, slippery quality that is desired in personal care products. Although asbestos was not M W ba^thagjrti in I S # ! the presence o f asbestos was, even at that time, considered highly undesirable, as its feel on the skin is regarded as unpleasant and cosmetically unacceptable. As a part o f a program to ensure that the talc used in Johnson & Johnson products was free from asbestos, an independent geological audit o f the talc mine both in Italy and in Vermont was conducted in 1972 by Professor Fred Pooley from the Department of Mineral Exploitation, University o f Wales, U.K. Professor Pooley is considered a world class expert in talc mineralogy and geology. The conclusion o f the audits, for both the Italian and the Vermont mines, was that there was zero evidence o f asbestos in the geology and mineralogy of 2 1P a g e the mines. Additionally, Professor Pooley examined a sample o f Italian talc dating from 1949, as used by Johnson & Johnson in die U.K. Dr. Pooley reported d u t d u quality o f d u talc had not changed. Since 1975, Johnson & Johnson Consumer Companies, Inc. (and its predecessors) has conducted a regular monitoring program o f samples oftalc from mines supplying talc for its products in the U.S. The monitoring program, which is conducted by independent external laboratories, includes assay for asbestos, silica and quartz. These independent laboratories, McCrone & Associates and RJ Lee, have never reported quantifiable asbestos in any o ffre samples tested. In addition, it has been a requirement o f Johnson & Johnson's Raw Material Specification since 1975 for each batch o f talc supplied to Johnson & Johnson to be free from asbestos and in compliance with the CTFA Talc Monograph. This has required the supplier to confirm purity of every batch supplied using state of d u art techniques. There is no evidence of asbestos contamination o f any batch sampled, as certified by the suppliers. In summary, there has never been a documented instance o f asbestos contamination in Johnson St Johnson Consumer Products. QYAMAWCAflERANDTALC S ia m . Johnson & Johnson Consumer Companies, Inc. has closely tracked safety issues related to talc, including studies suggesting that talc may be associated with a higher risk of ovarian cancer. The Company has a safety team dud, among other things, searches for any new literature or published articles that pertain to the safety of talc. There are publications on the safety and non toxic nature of talc going bade to 1944. Since the first Cramer study was published in 1982, J&J CC has thoroughly investigated fee results and has retained independent, outside consultants to analyze each publication and provide a detailed opinion on the methods and results of each o f the studies and/or publications and fee strength o f any association between talc and ovarian cancer. None o f the independent consultants have concluded that there is any causal relationship between talc and ovarian cancer. For one thing, many o f fee studies have shown absolutely no association. Even fee studies that show a statistical association, however, show only a very low relative risk (approximately 1.3), which could easily have resulted from bias or some other confounding fector. This is supported by the lack of a dose-response correlation in virtually all fee studies. Indeed, none of fee authors concluded in their studies that there is a causal relationship between talc and ovarian cancer and most acknowledged fee limitations o f their studies in terms o fpotential biases. There are other concerns regarding the validity o f many o f fee studies. For instance, there is some question whether fee researchers in fee Purdie and Green study used properly matched controls, as there is no evidence feat some o f the known risk factors for ovarian cancer, such as oral contraceptive use, dietary fat intake, body weight, and number o f children, was taken into 3 |P a g e account when matching controls. These factors, alone, could account for the slightly elevated relative risk reported. The results o f die studies involving miners and milters also support a lack o f association between talc and any cancer. While miners exposed to high levels o f talc in talc mines sometimes developed fibrosis (which can occur with any dust), there was no excess o f pulmonary tumors. Rats exposed to similar levels o f talc likewise did not develop an excess o f pulmonary tumors A two-day scientific workshop on "Talc: Consumer Uses and Health Perspectives," co sponsored by the International Society of Regulatory Toxicology and Pharmacology and the United State Food and Drug Association, concluded that talc is not carcinogenic and that there is no causative connection between tale and ovarian cancer. The workshop consisted o f leading exports in epidemiology, safety assessment, toxicology, and clinical medicine, who participated as speakers or as panel members. A number o f epidemiologic studies investigating a possible association between talc and ovarian cancer were reviewed. The workshop concluded that, when taken together, the results o f these studies are insufficient to demonstrate any real association. In addition, participants agreed that there is no basis to conclude that talc is capable o f migrating to the ovaries in the first place (2). Studies conducted by the National Toxicology Program (NTP) have likewise concluded that talc does not migrate to be ovaries. The authors reported that " ...extensive lifetime exposure to talc does not result in the deposition o f talc in fire ovary. Since the animals were exposed for 6hr per day with talc covering the for and cage bars, there was ample opportunity for perineal as well as a oral and respiratory exposure..." (3). This confirms an earlier study in monkeys using radio labeled talc which showed no vaginal translocation flora deposition in the vaginal fornix to the uterine cavity (4). In recent years the safety o f cosmetic talc has been further validated. A Safety Assessment Report by (be independent Cosmetic Ingredient Review (CIR) panel published in 2013 (5) reviewed all relevant published reports at that time and concluded that talc is safe in the present practices o f use and concentration described in this safety assessment It is noteworthy that the reviewers are independent academic experts in (heir fields and in compiling the Report cited some 219 peer reviewed scientific publications. Since the publication o f the CIR Report, other recent publications have further confirmed the conclusions. A recent publication from 2014 has investigated talc use and ovarian cancer. In a prospective cohort study o f 61,576 women (6), the authors concluded there was no influence o f talc on ovarian cancer risk, thus confirming the Conclusions o f foe CIR Report Cramer (7) has suggested that an increased number o f estimated ovulatory cycles correlates directly with risk for both endometrial and ovarian cancer, suggesting that reproductive tissue turnover with an accumulation o f PTEN or pS3 mutations represents a possible common mechanism. However, recently published studies clearly show no relationship between talc usage in the perineal areas and endometrial cancers in women (8,9). In the first o f these studies (8) a population o f 48,526 women was studied and the conclusion was there is no association of 4|P a ge S. Crawford L et al. Perineal Powder use and risk o f endometrial cancer in post-menopausal women. Cancer Causes Control, 23(10): 1673-80,2012. 9. Neill AS et al. Use o f talcum powder and endometrial cancer risk. Cancer Causes Control, 23(3):513-19,2012. 10. Musser, SM. Department of Health and Human Services, Food & Drag Administration, RE Docket numbers: 94P-0420 and FDA-2008-P-0309-0001/CP. March 18,2014. Com parison of Talc Use In other Countries and O varian Cancer Rates Talc powder use was developed in the United States in die 1870s and was adopted more widely in the UK from the early 1900's. However as personal habit, talc use was not widely adopted in other Western countries, it is therefore useful to compare talc use in the UK, with talc use in Sweden where little talc is used. A study was made to compare die amount of talc powder use in these two markets. Using sales data supplied by an Independent company (HU), total talc use (including Johnsons) was measured in UK and Sweden over the 3 years, 2009, 2010,2011. Taking accepted population figures o f 9,380,000 for Sweden and 62,219,000 for UK, it is possible to calculate annual average trie use per person. In Sweden the average annual talc use was 34,920 kg for die whole country; equivalent to use o f only 3.72 grams o f talc per person. In UK the average annual trie use was 2,300,118 kg for the whole country; equivalent to a use o f 36.96 grams o f trie per person. (1) In summary the amount o ftalc use per person in UK is almost lOx more titan in Sweden. For Sweden, the most recent epidemiology sjudy of ovarian cancer incidence was published in November 2008. It reported an age-standardised rate o f 15.3 per 100,000 women (2). Comparable data for the UK repeated a similar figure o f 16.2 per 100,000 women (3). The incidence rates per 100,000 women do vary considerably with rates of 19.2 and 18.7 in Latvia and Lithuania respectively to 10.8 and 7.2 in Spain and Portugal respectively (3). Thus in regards to the above range from 7.7 to 19.2 per 100,000 women, the incidences in UK and Sweden are considered as essentially similar. It is apparent from the above data that the rates o f ovarian cancer in Sweden and United Kingdom bear no relation to the amount of talc usage. Despite the per capita talc use in UK being 10X that used in Sweden, the rates o f ovarian cancer are essentially similar between the two countries. It would be expected that if trie use were a Actor in ovarian cancer, the rates in UK would be much higher than in Sweden. REFERENCES 1. Market Research Data, Personal Communication from Marketing Dept o f Johnson & Johnson Consumer UK and Johnson & Johnson Consumer Sweden. 2. Cane- incidence in Sweden 2007, The National Board o f Health & Welfare ISBN 97891-85999-73-7, pub 25 Nov. 2008. 6 1P a g e 3. Ovarian Cancer. UK incidence statistics, pub by Cancer Research UK. www.cancerresearchuk.org. 4. Granstrom C et al. Population attributable fractions for ovarian cancer in Swedish women by morphological type. Br J Cancer. 88:199-205,2008. Pfr Crymer's Hypotheses Dr. Cramer has published several publications that have attempted to construct a relationship between talc use and ovarian cancer. H ie basis of much of Dr. Cramer's work on this relationship has been to consider meta-analyses o f several studies. However, these analyses have indicated an odds ratio (OR) / Risk Ratio (RR) marginally over 1.0. Typically, several studies quote OR o f0.7,0.84,1.13,1.3,1.27,139,1.33. The topic o f statistical epidemiology is a complex one. It is often stated that several weak links do not make a strong chain. Certainly it is generally accepted by experts in this field that because o f confounding factors, there cannot be a "cause-and-effect" relationship with OR numbers as reported above. Instead, it is generally accepted that an OR o f 2.0 or higher is required to make a cause for a valid association. OR numbers less that this are generally regarded as co-incidental and the result o f bias or confounding factors. Confounding factors are represented by habits data that may not always be accurately recollected in a hindsight questionnaire. For instance, the subject may not recollect body powder habits accurately after many years; there may not be accurate recollection o f dietary and other habits such as dairy intake, alcohol use, etc. Factors that are known to contribute towards ovarian cancer include body mass index, familial history, and dietary intake. Factors known to protect from ovarian cancer include numbers of children, number o f years on an oral contraceptive pill, and breastfeeding. A higher number of children, higher number of years on the oral contraceptive, and breastfeeding offer protection from ovarian cancer, as do tubal ligation and hysterectomy. An important Swedish study (1) used the Swedish database o f 1,030,806 women followed from 1993 through 2004, and identified 3,306 and 822 women with invasive and borderline ovarian cancer, respectively. The Swedish data base follows residents after 1931, along with their biological parents. Factors increasing the Odds Ratio in invasive epithelial ovarian cancer were identified as a family history through a mother proband, which increased the risk of invasive ovarian cancer to 2.54, and through a sister to 2.76 relative to women with no family history. Nulliparity showed a Risk Ratio (RR) o f 2.12 relative to those who had at least 3 children. An earlier Swedish study reported the strong relationship with dairy consumption (2) and risk of serous ovarian cancer. It was reported that after adjustment for potential confounders, women who consumed 4 or more servings o f total dairy products per day had a risk o f serous ovarian cancer twice that o f women who consumed less than 2 servings per day (Risk Ratio: 2.0; 95% CL' 1.1, 3.7; P for trend 0.06). No significant association was found for other subtypes of ovarian cancer. Milk was the dairy product with the strongest positive association with serous ovarian cancer (rate ratio comparing consuming 2 glasses or more o f milk per day with 7|P a ge consuming milk never or seldom (2.0; 95% Cl: 1.1,3.7; P for trend * 0.04). The data indicated that high intakes o f lactose and dairy products, particularly milk, are associated with an increased risk of serous ovarian cancer but not of other subtypes o f ovarian cancer. Dr. Cramer claims to have derived an ovarian cancer OR o f 3.53 in talc users for a sub-group of patients in his recent re-analysis o f dare from the New England Case Control Study. However, there is no indication that other factors that have been associated with an increased risk o f ovarian cancer, such as dairy intake and psychotropic drag use (both o f which Dr. Cramer have published on previously), were controlled for in this analysis. Nor is it clear whether protective factors, such as breastfeeding, were taken into account O f note, use o f less than 360 applications was shown to have a protective effect (OR 034) compared to never users. This evaluation was done for litigation purposes and it is a questionable scientific approach to select a data point relevant to a specific person and to woric backwards rather than to consider overall data. Thus, the usefulness o f this analysis is questionable and certainly cannot be taken to prove that tide use causes ovarian cancer. In summary, the Cramer hypothesis has not shown a truly statistical cause and effect relationship between talc use and ovarian cancer. REFERENCES 1. Granstrom C, Sundquist J, Hemminki K. Population attributable fractions for ovarian cancer in Swedish women by morphological type. Br J Cancer Res, 98:100-205,2008. 2. Larsson SC, Bergkvist L, Wolk A. M ilk and lactose intakes and ovarian cancer risk in the Swedish mammography cohort. Am J Clin Nutr, 80(5): 1353-7,2004. Plaiatifft' experts have suggested that the contamination o f talc with metals such as chromium, arsenic, iron, nickel and lead may lead to immune toxicity. However, the plausibility o f this mechanism in the context o f cosmetic talc products which, at best, may contain trace amounts of some metals, has never been described in foe published literature. Dr. Rosenthal also suggested several other hypotheses as to how cosmetic talc use may cause ovarian cancer. For instance, Dr. Rosenthal's report discusses the possibility that talc particles maybe engulfed by macrophage cells resulting in an immune response and possible macrophage injury. It is hypothesized that macrophages may transport talc particles to distant sites. It is also postulated that talc particles may be taken up by macrophages, and that foe macrophages may be activated, releasing cytokines, oxidants, growth factors and transport talc particles to lymph nodes. It was also postulated by Dr Rosenthal that epithelial cells at the mucosal surface could take up a mineral particle landing on a mucosal surfece. D r Rosenthal reports that talc used in the therapeutic procedure o f pleurodesis may disseminate beyond foe pleura after its use. But none of these hypotheses have been tested with regard to cosmetic talc and there is no scientific literature supporting any o f these hypotheses. Moreover, there has been no evidence presented o f any o f these biological activities in relation to Ms. Bines' tissue samples. For example, Dr Rosenthal hypothesized that talc may cause foe 81P ge N.V deposition o f ferruginous bodies in tissues, which may result in tissue injury. However it is clear from the pathologist report (1) in this case that ferruginous bodies associated with talc particles are not reported by the pathologist Even if ferruginous bodies were present there is no evidence to show a causal relationship to ovarian cancer. Whilst a hypothesis is a valuable means to further investigate a scientific topic, it is important to realize that only by extensive research can a hypothesis be validated. This has simply not occurred in this case. REFERENCES 1. Godleski JJ. Report on pathology slides re Ms S Blaes, April 3rd2015. Evidence of Tale In the Ovarv in This Case Dr. Godleski's report presents his findings of a review o f pathology slides for tissues from Ms. Blaes (1). Specifically, 368 particles were found and analyzed. 226 particles were composed of elements including carbon, sodium, calcium and phosphorus, alone or in combination. These elements can occur endogenously. Further, 140 had elemental composition composed of foreign material; 101 bad a variety o f materials but did not have fee concentrations of both magnesium and silicon; and33 were identified as having magnesium and silicon in the concentrations required for talc, but also had other minerals such as calcium. However, just 6 particles were identified as having only the elements magnesium, silicon and oxygen in fee proportions expected of talc. Finally, Dr. Godleski has stated in his opinion that "talc found in this case is evidence for a causal link between the presence o f talc and the development o f this patients ovarian cancer". But he has given no basis for this conclusion other then fee claim o f fee presence o f talc. The mere presence of a particle does not indicate a cause and effect relationship. This was recognized as far back as 1971 when Henderson and colleagues merely drew attention to fee presence o f talc in tissues and did not suggest it was a cause o f malignancy. Such a claim is certainly not valid from a medical or scientific view. Notably, of fee 368 particles analyzed, only 6 are reported as pure talc. Dr. Godleski failed to answer fee obvious question and feat is what role, if indeed any, is played by fee other 362 particles analyzed. To suggest a causal relationship between talc and ovarian cancer in this case is evidence o f poor scientific judgment. REFERENCES 1. Godleski JJ. Report on pathology slides re Ms. Blaes, April 3rd2015. , 2. Henderson WJ et al. Talc and carcinoma of fee ovary and cervix. J Obstet Gyneacol, Br Commonwealth, 78:266-72,1971. b a b y Po w d e r Johnson & Johnson Baby Products, Inc. began developing a cornstarch-based baby powder in fee early 1970s to 9|P a g e provide a slightly different product that would appeal to a different consumer base, but that would provide similar benefits. Johnson's Baby Powder with Cornstarch was launched in 1980. Cornstarch, which is derived from com, is readily available in the United States. Talc, on the other hand, must be mined from die ground, often from remote and sometimes politically unstable, geographical locations. Also, as described above, die talc used in Johnson's Baby Powder, and other Johnson's personal o ne products, must meet rigorous standards to qualify for use in these products. Research showed cornstarch to be, like talc, non-toxic to humans. However, cornstarch-based baby powder is not the exact equivalent o f talc-based baby powder. For example, talc appears to decrease friction between skin and diapers, which can decrease chafing, better than cornstarch. On the other hand, cornstarch has superior absorptive abilities to talc. Also, blinded consumer comparison tests showed that users tended to prefer talc-based baby powder because of its fragrance and silkier texture. Another complication is that raw cornstarch is more prone to bacterial and fungal contamination and must be stored under more stringent conditions than talc. Cornstarch-based personal care products presently represent approximately one half o f die Johnson & Johnson powder market. Notably, die Shower to Shower Ms. Blaes claimed to have used contains both cornstarch and talc, with cornstarch being the more prominent constituent In summary, Johnson's Baby Powder and Show' to Shower, both o f which contain talc, are non-toxic and safe to use as intended. Johnson & Johnson Consumer Companies, Inc.'s purity standards are stringent and the talc utilized in these products is of the highest quality and is not contaminated with asbestos or any other contaminant Nor has it ever been. Johnson & Johnson Consumer Companies, Inc. has closely tracked talc safety and, based on all the data available to date, there is simply no evidence that talc used perineally causes ovarian cancer. In preparation for this opinion, I was provided with Plaintiffs expert reports as well as Ms. Blaes' medical records. Any opinions set out herein are to a reasonable degree o f scientific certamty. Dated: July 17,2015