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Response to “Cosmetic Microbiological Safety Issues; Public Meeting” [regulations.gov Docket No.: FDA-2011-N-0770, FR Doc No: 2011-28238]
Thank you for the opportunity to provide feedback to “Cosmetic Microbiological Safety Issues; Public Meeting” [regulations.gov Docket No.: FDA-2011-N-0770, FR Doc No.: 2011-28238]. This response document shall briefly address some of the ethical and safety issues associated with utilitising foreskin-derived ingredients in cosmetic products.
Ethical and safety concerns associated with utilitising foreskin-derived ingredients in cosmetic products
Circumcision of male minors, in the absence of a clear and present immediate medical indication, is a controversial practice within the medical profession (KNMG 2010; Smith 2011). Foreskins excised from minors in the absence of a clear and present immediate medical indication, almost invariably present in a normal healthy state, and as such their excision and preservation contributes little to the study of the pathology of disease. Further, the most promising advances in the field of cellular regeneration research, are to be found in cell lines derived from adult sources including dental pulp cells (Authur et al 2008), uterine cells (Bock 2011) and bone marrow cells (Wada et al 2011); diagnostic and therapeutic application of patient-derived cells (HHS 2011; Pasca et al 2011); and fetal cells (Hirt-Burri et al 2008; Ramelet et al 2009), rather than cell lines derived from the excised healthy foreskins of minors.
Products derived from foreskins excised en masse from minors in the absence of clear and present immediate medical indications, are frequently utilised in the commercial medical product, and more especially cosmetics industries (Advanced Healing 2011; Ballantyne 2009; LifeCell 2012; Organogenesis 2011; Pitman 2008; SkinMedica 2011). As observed by the U.S. Department of Health and Human Services Office of Human Research Protections, “Changing technology in the field of genomics has dramatically increased the amount and nature of information about individuals that can be obtained from their DNA” (OHRP 2011). Valid concerns therefore exist for the future privacy of children whose healthy tissues are likely to be acquired by commercial interests in the cosmetic and medical product industries - and may be retained indefinitely - due to presently unforeseeable technological advances in the field of genomics.
Doubts exist about the appropriateness of utilising products derived from foreskin and other healthy tissue excised from minors, in the cosmetic and medical product industries, on the basis of exculpatory consent forms signed by parents and legal guardians of minors, and whether it is appropriate for parents and legal guardians to give explicit consent for these purposes.
The provision of information to parents on circumcision consent forms about the storage, transfer, processing, sale or any other use of excised healthy foreskins is unstudied. However, a survey conducted by Schaefer et al (2011) of consent forms from U.S. in vitro fertilization clinics and the provision of information to egg donors of the potential for embryonic research using donated eggs, concluded that “egg donors in the United States, including some who may have a moral objection to research and stem cell research, are not being informed that embryos created with their donated eggs may in fact be used for these purposes”, suggesting that incomplete information may also be provided to parents about the use of foreskin and other healthy tissue excised from minors. Similarly, information about the original source of human skins cells used in cosmetic and medical products, is ominously absent from the websites of some manufacturers who utilise foreskin-derived ingredients in their products (LifeCell 2012; SkinMedica 2011).
Most foreskin-derived skin-substitute products are regulated by the Food and Drug Administration [FDA] as Human Cells, Tissues, and Cellular and Tissue-based Products [HCT/Ps] or through the Premarket Approval process [PMA] (FDA 2007; FDA 2012). Cellulitis and osteomyelitis are reported as complications in several studies drawn from the clinical literature for FDA regulated skin-substitute products incorporating foreskin-derived ingredients (Edmond 2009; Falanga et al 1998; Marston et al 2003; Naughton et al 1997;Veves et al 2001). Further, as observed by Dr Ron Moy, a dermatologist at the David Geffen School of Medicine at the University of California, Los Angeles, foreskin cells can potentially carry viruses, and although foreskin fibroblasts may be screened for contamination, there is "no test that's perfect" (Ballantyne 2009).
The use of foreskin-derived ingredients in cosmetic products must be brought to a halt as soon as is practical. In the interim, labeling and advertising for all cosmetic products incorporating foreskin-derived ingredients must include clear, generic, black-on-white font product descriptions informing consumers that the product “includes foreskin-derived ingredients”.
Advanced Healing (2011) Dermagraph Active Living Cells Overview Link http://www.dermagraft.com/about/overview/ Accessed: 2012-01-16. Archived by WebCite at http://www.webcitation.org/64jhakjim
Arthur A, Rychkov G, Shi S, Koblar SA, Gronthos S (2008) Adult human dental pulp stem cells differentiate toward functionally active neurons under appropriate environmental cues in Stem Cells. 2008 Jul;26(7):1787-95. Epub 2008 May 22 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18499892
Ballantyne, C (2009) A Cut above the Rest?: Wrinkle Treatment Uses Babies' Foreskins Scientific American 12 February 2009 [Epub] Full-text available at http://www.scientificamerican.com/article.cfm?id=a-cut-above-the-rest-wrin Accessed: 2012-01-18. Archived by WebCite at http://www.webcitation.org/64mLMhvCA
Bock, R (2011) Uterine stem cells used to treat diabetes in mice NIH News Full-text available at http://www.nih.gov/news/health/aug2011/nichd-30.htm Archived by WebCite at http://www.webcitation.org/64jhMI7v9
Edmonds M (2009) Apligraf in the treatment of neuropathic diabetic foot ulcers Int J Low Extrem Wounds. 2009 Mar;8(1):11-8. Epub 2009 Feb 3 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19189997
Falanga V, Margolis D, Alvarez O, Auletta M, Maggiacomo F, Altman M, Jensen J, Sabolinski M, Hardin-Young J (1998) Rapid healing of venous ulcers and lack of clinical rejection with an allogeneic cultured human skin equivalent. Human Skin Equivalent Investigators Group Arch Dermatol. 1998 Mar;134(3):293-300 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/9521027
FDA (2007) Human Cells, Tissues, and Cellular and Tissue-Based Products; Donor Screening and Testing; and Related Labeling 6/19/2007 Final Rule Questions and Answers Food and Drug Administration Full-text available at http://www.fda.gov/BiologicsBloodVaccines/TissueTissueProducts/QuestionsaboutTissues/ucm136397.htm Accessed: 2012-01-18. Archived by WebCite at http://www.webcitation.org/64nYS5LoE
FDA (2012) Premarket Approval (PMA) Process (CBER) Food and Drug Administration Full-text available at http://www.fda.gov/BiologicsBloodVaccines/DevelopmentApprovalProcess/PremarketApprovalPMAProcess/default.htm Accessed: 2012-01-18. Archived by WebCite at http://www.webcitation.org/64nYpCYwg
HHS (2011) Scientists Rejuvenate Cells From Elderly Department of Health and Human Services Health Highlights 1 November 2011 Full-text available at http://www.healthfinder.gov/news/newsstory.aspx?Docid=658486
Hirt-Burri N, Scaletta C, Gerber S, Pioletti DP, Applegate LA (2008) Wound-healing gene family expression differences between fetal and foreskin cells used for bioengineered skin substitutes Artif Organs. 2008 Jul;32(7):509-18 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/18638304
KNMG (2010) Non-theraputic circumcision of male minors Royal Dutch Medical Association Full-text available at http://knmg.artsennet.nl/web/file?uuid=579e836d-ea83-410f-9889-feb7eda87cd5&owner=a8a9ce0e-f42b-47a5-960e-be08025b7b04&contentid=77976
LifeCell (2012) AlloDerm Tissue Matrix defined Full-text available at http://www.lifecell.com/alloderm-regenerative-tissue-matrix/95/ Accessed: 2012-01-18. Archived by WebCite at http://www.webcitation.org/64mqrqxmQ
Marston WA, Hanft J, Norwood P, Pollak R (2003) The efficacy and safety of Dermagraft in improving the healing of chronic diabetic foot ulcers: results of a prospective randomized trial Diabetes Care. 2003 Jun;26(6):1701-5 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/12766097
Naughton G, Mansbridge J, Gentzkow G (1997) A metabolically active human dermal replacement for the treatment of diabetic foot ulcers Artif Organs. 1997 Nov;21(11):1203-10 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/9384327
OHRP (2011) Regulatory Changes in ANPRM Comparison of Existing Rules with Some of the Changes Being Considered Office of Human Research Protections website Full-text available at http://www.hhs.gov/ohrp/humansubjects/anprmchangetable.html Accessed: 2012-01-16. Archived by WebCite at http://www.webcitation.org/64jh4cWek
Organogenesis (2011) Apligraf: How Is It Made? Link http://www.apligraf.com/professional/what_is_apligraf/how_is_it_made/ Accessed: 2012-01-16. Archived by WebCite at http://www.webcitation.org/64jhpT91Q
Pasca SP, Portmann T, Voineagu I, Yazawa M, Shcheglovitov A, Pasca AM, Cord B, Palmer TD, Chikahisa S, Nishino S, Bernstein JA, Hallmayer J, Geschwind DH, Dolmetsch RE (2011) Using iPSC-derived neurons to uncover cellular phenotypes associated with Timothy syndrome Nat Med. 2011 Nov 27;17(12):1657-62. doi: 10.1038/nm.2576 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22120178
Pitman, S (2008) Babies’ foreskin dubbed as new anti-aging treatment Cosmetic Design Full-text available at http://www.cosmeticsdesign.com/Formulation-Science/Babies-foreskin-dubbed-as-new-anti-aging-treatment Accessed: 2012-01-16. Archived by WebCite at http://www.webcitation.org/64ji8mqbP
Ramelet AA, Hirt-Burri N, Raffoul W, Scaletta C, Pioletti DP, Offord E, Mansourian R, Applegate LA (2009) Chronic wound healing by fetal cell therapy may be explained by differential gene profiling observed in fetal versus old skin cells Exp Gerontol. 2009 Mar;44(3):208-18. Epub 2008 Nov 20 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19049860
Schaefer GO, Sinaii N, Grady C (2011) Informing egg donors of the potential for embryonic research: a survey of consent forms from U.S. in vitro fertilization clinics Fertil Steril. 2011 Dec 22. [Epub ahead of print] Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22196714
SkinMedica (2011) Key Ingredients Link http://www.skinmedica.com/skin-care-products/skin-rejuvenation/tns-recovery-complex#tab2 Accessed: 2012-01-16. Archived by WebCite at http://www.webcitation.org/64jiK7Gdx
Smith JF (2011) The professional imperative for obstetrician-gynecologists to discontinue newborn male circumcision Am J Perinatol. 2011 Feb;28(2):125-8. Epub 2010 Aug 10 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed?term=20700861
Veves A, Falanga V, Armstrong DG, Sabolinski ML (2001) Graftskin, a human skin equivalent, is effective in the management of noninfected neuropathic diabetic foot ulcers: a prospective randomized multicenter clinical trial Diabetes Care. 2001 Feb;24(2):290-5 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/11213881
Wada N, Bartold PM, Gronthos S (2011) Human foreskin fibroblasts exert immunomodulatory properties by a different mechanism to bone marrow stromal/stem cells Stem Cells Dev. 2011 Apr;20(4):647-59. Epub 2010 Oct 12 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed?term=20712449