Response to FDA Request for Information on Talc Johnson & Johnson Consumer Inc. P-710 March 17, 2016 U.S. Food and Drug Administration Center for Drug Evaluation and Research Central Document Room 5901-B Ammendale Rd. Beltsville, MD 20705-1266 ATTN: Theresa Michele, MD, Director, Division of Nonprescription Drug Products, ODE IV Re: Response to FDA Request for Information on Talc Dear Dr. Michele: This submission is our written response to the following email request from CAPT Janice Adams-King, MSN, CRNP, CPHN (USPHS), Safety Regulatory Project Manager, Office of Drug Evaluation IV, Division of Nonprescription Drug Products (DNDP), Center for Drug Evaluation and Research (CDER), dated 25 February 2016: “Please provide all safety literature and data regarding talc, including data in support of the safety of this active ingredient and data that shows potential harmful effects for this active ingredient, by March 17, 2016.” At Ms. Adams-King’s suggestion, JJCI immediately contacted Dr. Nakissa Sadrieh, Director, Cosmetics Staff, Office of Cosmetics and Colors (OCAC), Center for Food Safety and Applied Nutrition via a phone call, followed by an email memo. Later on the same day (25 February 2016), DNDP requested a teleconference with JJCI, following which the referenced email request for additional information on talc was sent to JJCI. The data and information contained in this submission constitute trade secrets and confidential commercial information (see 21 C.F.R. 20.61). Johnson & Johnson Consumer Inc. hereby claims the legal protections afforded such trade secret and confidential information under 5.U.S.C. 552(b), 21 U.S.C. 331(j) and 18 U.S.C. 1905. Further dissemination may only be made with the express written permission of Johnson & Johnson Consumer Inc. Page 1 of 2 Johnson & Johnson Consumer Inc. 199 Grandview Road, Skillman, NJ 08558 (908) 874-1702 COMPANY CONFIDENTIAL Page 1 of 446 Protected Document – Subject to Protective Order Page 1 of 17 P-710_1 of 17 Provided by Johnson & Johnson through www.factsabouttalc.com Response to FDA Request for Information on Talc Johnson & Johnson Consumer Inc. Response to FDA Request for Information on Talc This submission is our response to the referenced email request and includes a summary of key published reviews of talc safety and ovarian cancer, relevant post-marketing talc safety data, and information on chemistry, manufacturing, and controls. This submission is being provided on compact disk. As the size of this submission is over 20 MB, we are unable to transmit the submission via email, given our company’s email message size restriction of 10 MB for inbound and outbound messages. If you have any questions, please contact me at 908-874-1702 or by email at [email protected]. Sincerely, Digitally signed by Jethro Ekuta DN: c=US, o=JNJ, ou=Employees, Jethro ou=1018932, cn=Jethro Ekuta, [email protected] Reason: I am the author of this document. Ekuta Date: 2016.03.15 17:19:15 -04'00' Adobe Acrobat version: 11.0.10 Jethro Ekuta, D.V.M., Ph.D., RAC, FRAPS Vice President, Regulatory Affairs North America Johnson & Johnson Consumer Inc. cc: CAPT Janice Adams-King, MSN, CRNP, CPHN (USPHS) – 15 CD Copies Safety Regulatory Project Manager Office of Drug Evaluation IV, CDER/FDA Division of Nonprescription Drug Products 10903 New Hampshire Avenue, Building #22, Room 5416 Silver Spring, MD 20993 The data and information contained in this submission constitute trade secrets and confidential commercial information (see 21 C.F.R. 20.61). Johnson & Johnson Consumer Inc. hereby claims the legal protections afforded such trade secret and confidential information under 5.U.S.C. 552(b), 21 U.S.C. 331(j) and 18 U.S.C. 1905. Further dissemination may only be made with the express written permission of Johnson & Johnson Consumer Inc. Page 2 of 2 COMPANY CONFIDENTIAL Protected Document – Subject to Protective Order Page 2 of 446 Page 2 of 17 P-710_2 of 17 Provided by Johnson & Johnson through www.factsabouttalc.com Response to FDA Request for Information on Talc Johnson & Johnson Consumer Inc. Response to FDA Request for Information on Talc Johnson & Johnson Consumer Inc. 17 March 2016 Confidentiality Statement The data and information contained in this submission constitute trade secrets and confidential commercial information (see 21 C.F.R. 20.61). Johnson & Johnson Consumer Inc. hereby claims the legal protections afforded such trade secret and confidential information under 5.U.S.C. 552(b), 21 U.S.C. 331(j) and 18 U.S.C. 1905. Further dissemination may only be made with the express written permission of Johnson & Johnson Consumer Inc. COMPANY CONFIDENTIAL Protected Document – Subject to Protective Order Page 3 of 446 Page 3 of 17 P-710_3 of 17 Provided by Johnson & Johnson through www.factsabouttalc.com Response to FDA Request for Information on Talc Johnson & Johnson Consumer Inc. Table of Contents Title Page Response to FDA Request for Information on Talc 5 1 INTRODUCTION 5 2 SAFETY LITERATURE REVIEWS 6 2.1 Governmental and Nongovernmental Agency Reviews 6 2.1.1 US Food and Drug Administration (FDA) 6 2.1.2 US National Toxicology Program (NTP) 6 2.1.3 National Cancer Institute (NCI) 6 2.1.4 World Health Organization (WHO) 6 2.2 Expert Panel Reviews 7 2.2.1 Cosmetic Ingredient Review (CIR) 7 2.3 Epidemiology Study Reviews 7 2.4 Toxicology Study Reviews 10 3 COMPANY SAFETY DATA REVIEWS 11 3.1 Chemistry, Manufacturing, and Controls 11 3.2 Post-marketing Safety Database Review 12 3.2.1 Current Review of Company Post-marketing Data 12 3.2.2 Routine Safety Surveillance 15 4 SUMMARY 15 5 REFERENCE LIST 16 References 18 FDA 2014 Petition Denial Letter 18 Cashen 1994 Citizen Petition 25 Epstein 2008 Citizen Petiton 30 National Toxicology Program (NTP) 2014 13th Report on Carcinogens (contd) 36 National Cancer Institute 2016 Ovarian, Fallopian Tube, and Primary (contd) 41 World Health Organization International Agency for Research on Cancer 2010 49 Fiume 2015 Safety Assessment of Talc as Used in Cosmetics 193 Houghton 2014 Perineal powder use and risk of ovarian cancer 257 Gates 2010 Risk factors for epithelial ovarian cancer (contd) 263 Gertig 2000 Prospective study of talc use and ovarian cancer 272 Wu 2015 African Americans and Hispanics remain (contd) 276 Wu 2009 Markers of inflammation and risk (contd) 284 Terry 2013 Genital powder use and risk of ovarian cancer (contd) 291 Cramer 1999 Genital talc exposure and risk of ovarian cancer 303 Merritt 2008 Talcum powder, chronic pelvic inflammation (contd) 309 Rosenblatt 2011 Genital powder exposure and the risk of (contd) 316 Chang 1997 Perineal Talc Exposure and Risk of Ovarian Carcinoma 322 Moorman 2009 Ovarian cancer risk factors (contd) 328 Cramer 2016 The association between talc use and ovarian cancer (contd) 337 Gates 2008 Talc use, variants of the GSTM1, GSTT1 (contd) 369 Vitonis 2011 Assessing ovarian cancer risk (contd) 379 Shim 2015 Inhalation of talc induces infiltration (contd) 392 Office of Consumer Medical Safety 2016 Analysis of post-marketing safety (contd) 401 COMPANY CONFIDENTIAL Protected Document – Subject to Protective Order Page 4 of 446 Page 4 of 17 P-710_4 of 17 Provided by Johnson & Johnson through www.factsabouttalc.com Response to FDA Request for Information on Talc Johnson & Johnson Consumer Inc. 1 INTRODUCTION Johnson & Johnson Consumer Inc. (JJCI) contacted FDA (Janice Adams-King, Division of Nonproprietary Drug Products, DNDP, Center for Drug Evaluation and Research and Nakissa Sadrieh, Office of Cosmetics and Colors, OCAC, Center for Food Safety and Applied Nutrition) on 25 February 2016 DNDP scheduled a teleconference with the Company for 25 February 2016, and following the teleconference that same day, DNDP sent an email to JJCI requesting the following: “Please provide all safety literature and data regarding talc, including data in support of the safety of this active ingredient and data that shows potential harmful effects for this active ingredient, by March 17, 2016.” This response is based on JJCI’s understanding of FDA’s request and includes a summary of key published reviews of talc safety and ovarian cancer (Section 2), recent post-marketing talc safety data, and information on chemistry, manufacturing, and controls (Section 3). Please note that talc is inactive, ie, not a pharmacologically active ingredient, and is a major component in many body powders such as Johnson's® Baby Powder and Shower to Shower® Powder, which are classified as cosmetics per regulation. Various governmental and non-governmental agencies as well as other expert panels have examined whether talc is a carcinogen, and none have concluded that it is a carcinogen. Many countries have allowed the use of talc, among them the United States, those in the European Union (EU), Canada, Argentina, Brazil, China, India, Israel, South Africa, Turkey, and Indonesia. There are a number of local monographs which define standards for talc used in both drug formulas and cosmetic body powders. Examples of countries that regulate talc in cosmetics include the US, EU, China, Canada, UK, and Brazil. The US FDA lists talc as Generally Recognized as Safe (GRAS) for use in foods and Generally Recognized as Safe and Effective (GRASE) for drugs. It is also listed as a color additive that may be used in coloring drug products and as a component of colors for use in drugs and cosmetics. Talc used in JJCI body powders meets pharmaceutical specifications as established by the European and US Pharmacopoeia. COMPANY CONFIDENTIAL Protected Document – Subject to Protective Order Page 5 of 446 Page 5 of 17 P-710_5 of 17 Provided by Johnson & Johnson through www.factsabouttalc.com Response to FDA Request for Information on Talc Johnson & Johnson Consumer Inc.