United States Government Publishing Office publisher pbl distributor dst United States National Archives and Records Administration Office of the Federal Register author aut Government Organization text government publication eng FR Regulatory Information 2016_register executive 2018-02-08 article Part IV Proposed Rules D09002ee1c7f5fb47 D09002ee1c7f5fdca United States Department of Health and Human Services originator org United States Government Agency or Subagency United States Food and Drug Administration originator org United States Government Agency or Subagency The Food and Drug Administration (FDA or Agency) is issuing this proposed rule to amend the 1994 tentative final monograph or proposed rule (the 1994 TFM) for over-the-counter (OTC) antiseptic drug products. In this proposed rule, we are proposing to establish conditions under which OTC consumer antiseptic products intended for use without water (referred to throughout as consumer antiseptic rubs or consumer rubs) are generally recognized as safe and generally recognized as effective (GRAS/GRAE). In the 1994 TFM, certain antiseptic active ingredients were proposed as being GRAS for antiseptic rub use by consumers based on safety data evaluated by FDA as part of its ongoing review of OTC antiseptic drug products. However, in light of more recent scientific developments and changes in the use patterns of these products, we are now proposing that additional safety data are necessary to support the safety of antiseptic active ingredients for this use. We also are proposing that all consumer antiseptic rub active ingredients have in vitro data characterizing the ingredient's antimicrobial properties and in vivo clinical simulation studies showing that specified log reductions in the amount of certain bacteria are achieved using the ingredient. 81 FR 42912 https://www.govinfo.gov/app/details/FR-2016-06-30/2016-15410 2016-15410 fr30jn16-53 RIN 0910-AF69 4164-01-P Docket No. FDA-2016-N-0124 (Formerly Part of Docket No. FDA-1975-N-0012) https://www.govinfo.gov/app/details/FR-2016-06-30/2016-15410 https://www.govinfo.gov/content/pkg/FR-2016-06-30/html/2016-15410.htm https://www.govinfo.gov/content/pkg/FR-2016-06-30/pdf/2016-15410.pdf Administrative Practice and Procedure Drugs Labeling Medical Devices Reporting and Recordkeeping Requirements 26 p. 42912 42937 81 FR 42912 Title 21 Part 310 21 CFR Part 310 RIN 0910-AF69 Safety and Effectiveness of Consumer Antiseptics; Topical Antimicrobial Drug Products for Over-the-Counter Human Use; Proposed Amendment of the Tentative Final Monograph; Reopening of Administrative Record; Federal Register Vol. 81, Issue PRORULE 2016-15410 IV DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 2016-12-27 Docket No. FDA-2016-N-0124 (Formerly Part of Docket No. FDA-1975-N-0012) 4164-01-P 2016-15410 Proposed rule.

The Food and Drug Administration (FDA or Agency) is issuing this proposed rule to amend the 1994 tentative final monograph or proposed rule (the 1994 TFM) for over-the-counter (OTC) antiseptic drug products. In this proposed rule, we are proposing to establish conditions under which OTC consumer antiseptic products intended for use without water (referred to throughout as consumer antiseptic rubs or consumer rubs) are generally recognized as safe and generally recognized as effective (GRAS/GRAE). In the 1994 TFM, certain antiseptic active ingredients were proposed as being GRAS for antiseptic rub use by consumers based on safety data evaluated by FDA as part of its ongoing review of OTC antiseptic drug products. However, in light of more recent scientific developments and changes in the use patterns of these products, we are now proposing that additional safety data are necessary to support the safety of antiseptic active ingredients for this use. We also are proposing that all consumer antiseptic rub active ingredients have in vitro data characterizing the ingredient's antimicrobial properties and in vivo clinical simulation studies showing that specified log reductions in the amount of certain bacteria are achieved using the ingredient.

Submit electronic or written comments by December 27, 2016. See section IX of this document for the proposed effective date of a final rule based on this proposed rule. Anita Kumar, Center for Drug Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 22, Rm. 5445, Silver Spring, MD 20993, 301-796- 1032. Administrative Practice and Procedure Drugs Labeling Medical Devices Reporting and Recordkeeping Requirements Safety and Effectiveness of Consumer Antiseptics: Topical Antimicrobial Drug Products for Over-the-Counter Human Use; Tentative Final Monograph; Reopening of Administrative Record , http://aac.asm.org/content/49/2/781.full.pdf+html http://ac.els-cdn.com/S0141022904001085/1-s2.0-S0141022904001085-main.pdf?_tid=b24dcd2a-2b59-11e6-9e77-00000aab0f02&acdnat=1465157672_20da9f1e4b98722e189e8520c5050c00 http://ac.els-cdn.com/S096483050500137X/1-s2.0-S096483050500137X-main.pdf?_tid=67672f92-2b57-11e6-8f11-00000aacb35e&acdnat=1465156688_42b5bfa1b42253d87614efd8e6e6f809 http://ajph.aphapublications.org/doi/pdf/10.2105/AJPH.79.1.92 http://bmcinfectdis.biomedcentral.com/articles/10.1186/1471-2334-10-78 http://dij.sagepub.com/content/49/1/108.full.pdf+html http://dmd.aspetjournals.org/content/26/3/197.full.pdf+html http://ehp.niehs.nih.gov/wp-content/uploads/116/9/ehp.11200.pdf http://emergency.cdc.gov/disasters/handhygienefacts.asp http://europepmc.org/abstract/MED/10803793 http://europepmc.org/abstract/med/3727356 http://jac.oxfordjournals.org/content/60/5/947.full.pdf http://jcn.sagepub.com/content/27/2/258.full.pdf+html http://journals.plos.org/plosone/article/asset?id=10.1371%2Fjournal.pone.0096288.PDF http://jpet.aspetjournals.org/content/260/2/463.long http://jpet.aspetjournals.org/content/263/3/1056.long http://jpet.aspetjournals.org/content/85/1/61.full.pdf+html http://monographs.iarc.fr/ENG/Monographs/vol71/mono71.pdf http://monographs.iarc.fr/ENG/Monographs/vol96/mono96.pdf http://nepis.epa.gov/EPA/html/DLwait.htm?url=/Exe/ZyPDF.cgi/P1005J4P.PDF?Dockey=P1005J4P.PDF http://online.liebertpub.com/doi/pdf/10.1089/mdr.2006.12.83 http://onlinelibrary.wiley.com/doi/10.1002/bdra.23232/full http://onlinelibrary.wiley.com/doi/10.1002/bdrb.20167/full http://onlinelibrary.wiley.com/doi/10.1002/jat.1316/pdf http://onlinelibrary.wiley.com/doi/10.1002/jat.2550150210/epdf http://onlinelibrary.wiley.com/doi/10.1002/jat.2550150612/epdf http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2265.1999.00639.x/abstract http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2672.2001.01460.x/epdf http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2672.2002.01667.x/epdf http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2672.2003.02140.x/epdf http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2672.92.5s1.4.x/epdf http://onlinelibrary.wiley.com/doi/10.1111/apm.1969.77.issue-2/issuetoc http://onlinelibrary.wiley.com/doi/10.1111/j.1530-0277.1983.tb05426.x/epdf http://onlinelibrary.wiley.com/doi/10.1111/j.1530-0277.1993.tb00847.x/epdf http://onlinelibrary.wiley.com/doi/10.1111/j.1574-6968.1998.tb13905.x/pdf http://onlinelibrary.wiley.com/doi/10.1111/j.1574-6968.2006.00547.x/epdf http://onlinelibrary.wiley.com/doi/10.1111/j.1651-2227.2008.01057.x/epdf http://onlinelibrary.wiley.com/doi/10.1111/j.1749-6632.2002.tb04924.x/epdf http://onlinelibrary.wiley.com/doi/10.1211/0022357001773742/epdf http://press.endocrine.org/doi/pdf/10.1210/en.2005-1058 http://press.endocrine.org/doi/pdf/10.1210/en.2007-1057 http://pubs.acs.org/doi/pdf/10.1021/es011055j http://pubs.niaaa.nih.gov/publications/FASDFactsheet/FASDfact.htm http://rspb.royalsocietypublishing.org/content/276/1667/2521 http://toxsci.oxfordjournals.org/content/107/1/56.full.pdf+html?sid=f797a245-5b8c-413a-a124-1274d1a0b704 http://toxsci.oxfordjournals.org/content/113/2/367.full.pdf+html?sid=459e5732-786d-46ea-ab58-af2b9f517835 http://toxsci.oxfordjournals.org/content/117/1/45.full.pdf+html?sid=44df51a6-52c0-43cc-a629-e609dd1f2b64 http://toxsci.oxfordjournals.org/content/22/1/139.full.pdf+html http://toxsci.oxfordjournals.org/content/23/3/407.full.pdf http://www.ajemjournal.com/article/S0735-6757 http://www.ajicjournal.org/article/S0196-6553 http://www.cdc.gov/exposurereport/ http://www.cdc.gov/hicpac/pdf/guidelines/disinfection_nov_2008.pdf http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5116a1.htm http://www.cdc.gov/ncbddd/fasd/alcohol-use.html http://www.eje-online.org/content/151/Suppl_3/U45.long http://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/EconomicAnalyses/default.htm http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/NonprescriptionDrugsAdvisoryCommittee/UCM421121.pdf http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM071292.pdf http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm074959.pdf http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm369043.pdf http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM473464.pdf http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/Over-the-CounterOTCDrugs/StatusofOTCRulemakings/ucm070821.htm http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm http://www.fda.gov/ohrms/dockets/ac/05/briefing/2005-4098B1_02_01-FDA-TOC.htm http://www.fda.gov/ohrms/dockets/ac/05/transcripts/2005-4184T1.pdf http://www.fda.gov/regulatoryinformation/dockets/default.htm http://www.fda.gov/ucm/groups/fdagov-public/@fdagov-drugs-gen/documents/document/ucm072112.pdf http://www.fda.gov/ucm/groups/fdagov-public/@fdagov-drugs-gen/documents/document/ucm368107.pdf http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Safety/S1A/Step4/S1A_Guideline.pdf http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Safety/S1B/Step4/S1B_Guideline.pdf http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Safety/S5_R2/Step4/S5_R2_Guideline.pdf http://www.inchem.org/documents/ehc/ehc/ehc103.htm#SectionNumber%3A8.3 http://www.inchem.org/documents/ehc/ehc/ehc103.htm#SectionNumber:8.3 http://www.jstor.org/stable/10.1086/669514?seq=1#page_scan_tab_contents http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1803104/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2265044/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2945443/pdf/nihms-208619.pdf http://www.ncbi.nlm.nih.gov/pmc/articles/PMC321691/pdf/0976.pdf http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3312300/pdf/mge0103_0187.pdf http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3851816/pdf/1471-2334-13-472.pdf http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4180309/pdf/12879_2014_Article_3830.pdf http://www.ncbi.nlm.nih.gov/pmc/articles/PMC523567/pdf/0085-03.pdf http://www.ncbi.nlm.nih.gov/pmc/articles/PMC90308/ http://www.ncbi.nlm.nih.gov/pubmed/12571685 http://www.ncbi.nlm.nih.gov/pubmed/12595925 http://www.ncbi.nlm.nih.gov/pubmed/15706763?dopt=Abstract http://www.ncbi.nlm.nih.gov/pubmed/16835633 http://www.nejm.org/doi/pdf/10.1056/NEJMoa040079 http://www.niaid.nih.gov/topics/commoncold/Pages/default.aspx http://www.oecd-ilibrary.org/environment/oecd-guidelines-for-the-testing-of-chemicals-section-4-health-effects_20745788 http://www.pubfacts.com/detail/17927841/Quantity-of-ethanol-absorption-after-excessive-hand-disinfection-using-three-commercially-available- http://www.regulations.gov http://www.sciencedirect.com/science/article/pii/0278691588901263 http://www.sciencedirect.com/science/article/pii/S0022202X15459317 http://www.sciencedirect.com/science/article/pii/S0022354915432745 http://www.sciencedirect.com/science/article/pii/S0022354915435336 http://www.sciencedirect.com/science/article/pii/S0022354915440456 http://www.sciencedirect.com/science/article/pii/S0043135409001456 http://www.sciencedirect.com/science/article/pii/S0195670104000131 http://www.sciencedirect.com/science/article/pii/S0195670199906540 http://www.sciencedirect.com/science/article/pii/S019665539970088X http://www.sciencedirect.com/science/article/pii/S0272059084710189 http://www.sciencedirect.com/science/article/pii/S0272059096922848 http://www.sciencedirect.com/science/article/pii/S0273230096900422 http://www.sciencedirect.com/science/article/pii/S0300483X08002850 http://www.sciencedirect.com/science/article/pii/S089062380800364X http://www.sciencedirect.com/science/article/pii/S1382668907000683 http://www.sciencedirect.com/science/journal/0041008X/209/2 http://www.springer.com/medicine/surgery/journal/423 http://www.tandfonline.com/doi/abs/10.3109/15569529709048888 http://www.tandfonline.com/doi/full/10.1080/10826068.2014.923452 http://www.tandfonline.com/doi/pdf/10.1080/10937400902894160 https://books.google.com/books?id=3f-kPJ17_TYC&printsec=frontcover&source=gbs_ViewAPI#v=onepage&q&f=false https://jac.oxfordjournals.org/content/49/4/631.full.pdf https://www.astm.org/ https://www.federalregister.gov https://www.jstage.jst.go.jp/article/jvms/70/6/70_6_595/_pdf https://www.researchgate.net/publication/11173057_Biodegradation_of_high-concentration_isopropanol_by_a_solvent-tolerant_thermophile_Bacillus_pallidus_Extremophiles https://www.researchgate.net/publication/6427071_Bore_E_et_al_Adapted_tolerance_to_benzalkonium_chloride_in_Escherichia_coli_K-12_studied_by_transcriptome_and_proteome_analyses_Microbiology_153_935-946 Vol. 81, no. 126 Office of the Federal Register, National Archives and Records Administration 2016-06-30 continuing daily deposited born digital 542 p. 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