Consumer Antiseptic  
Rub Final Rule 
Questions and Answers 
Guidance for Industry 
 
Small Entity Compliance Guide 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
 
 
 December 2020 
OTC 
   
Consumer Antiseptic  
Rub Final Rule  
Questions and Answers 
Guidance for Industry
 
 
Small Entity Compliance Guide 
 
 
Additional copies are available from: 
Office of Communications, Division of Drug Information  
Center for Drug Evaluation and Research 
Food and Drug Administration 
10001 New Hampshire Ave., Hillandale Bldg., 4th Floor  
Silver Spring, MD 20993-0002  
Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353 
Email: druginfo@fda.hhs.gov  
https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
 
 
 December 2020 
OTC 
 
 
  Contains Nonbinding Recommendations 
 
TABLE OF CONTENTS 
 
 
 
 
I.  INTRODUCTION ...................................................................................................... 1 
II.  BACKGROUND ........................................................................................................ 2 
III.  QUESTIONS AND ANSWERS ................................................................................. 3 
i 
  Contains Nonbinding Recommendations 
 
Consumer  Antiseptic Rub Final  Rule  
Questions and Answers 
Guidance for Industry1 
 
Small Entity Compliance Guide 
 
 
This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on 
this topic.  It does not establish any rights for any person and is not binding on FDA or the public.  You 
can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations.  
To discuss an alternative approach, contact the FDA office responsible for this guidance as listed on the 
title page.   
 
 
 
 
I.  INTRODUCTION  
 
This guidance is intended to help small businesses understand and comply with the Consumer 
Antiseptic Rub Final Rule; Finding  of Ineligibility  for Inclusion  in Final Monograph (Consumer 
Antiseptic Rub FR) (84 FR 14847, April 12, 2019), which applies to active ingredients  used in 
over-the-counter (OTC) consumer antiseptic rub products that are sometimes referred to as rubs, 
leave-on products, or hand sanitizers.  The Consumer Antiseptic Rub FR also applies to active 
ingredients used in OTC consumer antiseptic wipes.   
 
The Consumer Antiseptic Rub FR established that 28 active ingredients used in nonprescription 
consumer antiseptic rub products are not eligible  for evaluation  under FDAs ongoing 
rulemaking  to evaluate the safety and effectiveness of OTC drug products marketed in the United 
States on or before May 1972, which is known as the OTC Drug Review.  Drug products 
containing  these active ingredients  will require approval under a new drug application  (NDA) or 
an abbreviated new drug application  (ANDA) before they can be marketed.   
 
The Consumer Antiseptic Rub FR also established that three active ingredients used in consumer 
antiseptic rub productsbenzalkonium  chloride,  ethyl alcohol, and isopropyl  alcoholare 
eligible  for evaluation under the OTC Drug Review.2  In response to several requests submitted 
to the 2016 Consumer Antiseptic Rub Proposed Rule (Consumer Antiseptic Rub PR) (81 FR 
42912, June 30, 2016), FDA temporarily  deferred further rulemaking  on making a generally 
recognized as safe and effective (GRAS/GRAE) determination  for these three eligible  active 
                                              
1 This guidance has been prepared by the Office of Regulatory Policy and the Division of Nonprescription Drug 
Products in the Center for Drug Evaluation and Research at the Food and Drug Administration.  
2 On March 27, 2020, the Over-the-Counter Monograph Safety, Innovation, and Reform Act (OMSIRA) was signed 
into law as part of the newly enacted Coronavirus Aid, Relief, and Economic Security Act (CARES Act) (Public 
Law No. 116-136, 134 Stat. 281 (March 27, 2020)). OMSIRA is intended to modernize the process by which FDA 
regulates over-the-counter monograph drugs. FDA is in the process of implementing the changes set forth in 
OMSIRA, however, OMSIRA does not revise the findings in the Consumer Antiseptic Rub FR.  
  1  Contains Nonbinding Recommendations 
 
ingredients.  Rulemaking  was temporarily  deferred to allow time for interested parties to 
complete the studies necessary to fill the safety and effectiveness data gaps FDA has identified 
for these three ingredients.3   
 
The Consumer Antiseptic Rub FR was published  on April 12, 2019, with an effective date of 
April 13, 2020. 
 
On March 27, 2020, the President signed into law H.R. 748, the Coronavirus Aid, Relief, and 
Economic Security Act or the CARES Act. The law includes statutory provisions,  which 
FDA refers to as OTC Monograph Reform, that reforms and modernizes the OTC monograph 
drug development and review process. The law replaces the rulemaking  process with an 
administrative  order process to add, remove, or change an OTC monograph. The administrative 
order process is expected to improve efficiency, timeliness and predictability  in the OTC Drug 
Review process. FDA is in the process of implementing  the changes set forth in the CARES Act, 
however, this legislation  does not affect the Agencys findings  in the Consumer Antiseptic Rub 
FR.4  
 
FDA has prepared this guidance in accordance with section 212 of the Small Business 
Regulatory Enforcement Fairness Act (Public Law 104-121,  as amended by Public Law 110-28)5 
to assist small businesses in complying  with the Consumer Antiseptic Rub FR.  
 
In general, FDAs guidance documents do not establish legally  enforceable responsibilities.   
Instead, guidances describe the Agencys current thinking  on a topic and should be viewed only 
as recommendations,  unless specific regulatory or statutory requirements are cited.  The use of 
the word should in Agency guidances means that something  is suggested or recommended, but 
not required. 
  
 
II.  BACKGROUND 
 
The Consumer Antiseptic Rub FR finalizes the 2016 Consumer Antiseptic Rub PR published  in 
the Federal Register of June 30, 2016 (81 FR 42912) and amends the 1994 tentative final 
monograph (TFM) for OTC antiseptic drug products that published  in the Federal Register of 
June 17, 1994 (59 FR 31402) (the 1994 TFM).  The Consumer Antiseptic Rub FR is one of three 
final rules involving  the active ingredient  triclosan required to be published  pursuant to a 
                                              
3 More information on the antiseptic rulemaking deferral letters is available here: 
https://www.fda.gov/drugs/information-drug-class/antiseptic-fda-letters. 
 
4 We note that under 505G(a)(3) of the FD&C Act, which was enacted as part of the CARES Act as described 
above, drugs that were classified as category III in a tentative final monograph (TFM), including the 1994 TFM for 
over-the-counter topical antiseptics (59 FR 31402) as further amended by the 2016 Consumer Antiseptic Rub 
proposed rule (81 FR 42912), are not required to have an approved application under section 505 in order to be 
marketed, as long as they are in conformity with the relevant conditions of use outlined in the applicable TFM and 
comply with all other applicable requirements for nonprescription drugs.   
 
5 5 U.S.C. 601 (note). 
 
  2  Contains Nonbinding Recommendations 
 
Consent Decree entered by the United States District Court for the Southern District of New 
York on November 21, 2013, in Natural Resources Defense Council, Inc. v. United States Food 
and Drug Administration, et al., 10 Civ. 5690 (S.D.N.Y.). 
 
The Consumer Antiseptic Rub FR confirmed the ineligibility  status of 28 active ingredients, 
including  triclosan,  as proposed in the 2016 Consumer Antiseptic Rub PR.  Prior to the 
enactment of the CARES Act, an OTC drug was eligible  for evaluation under the OTC Drug 
Review if its conditions  of use existed in the OTC drug marketplace on or before May 11, 1972 
(37 FR 9464).  Conditions  of use include, among other things,  active ingredient,  dosage form and 
strength, route of administration,  and specific OTC use or indication  of the product ( 330.14(a) 
(21 CFR 330.14(a))).  After the publication  of the 2016 Consumer Antiseptic Rub PR, no 
additional  information  was submitted demonstrating  that any of the 28 active ingredients  was 
marketed as a consumer antiseptic rub on or before May 11, 1972.  OTC consumer antiseptic rub 
products containing  these ineligible  ingredients  are new drugs for which approved NDAs or 
ANDAs are required before marketing.   
 
In response to several requests submitted to the 2016 Consumer Antiseptic Rub PR, FDA 
temporarily  deferred a GRAS/GRAE determination  for three active ingredientsbenzalkonium 
chloride,  ethyl alcohol,  and isopropyl  alcohol--to allow time for interested parties to complete the 
studies necessary to fill the safety and effectiveness data gaps identified  for these ingredients.    
 
As a result of the deferrals, the Consumer Antiseptic Rub FR does not include a determination  on 
the GRAS/GRAE status of benzalkonium  chloride, ethyl alcohol,  or isopropyl  alcohol for use in 
consumer antiseptic rubs.  FDA intends to address the GRAS/GRAE status of these three active 
ingredients either after completion  and analysis of studies to fill  the identified  safety and 
effectiveness data gaps for these ingredients or at another time if these studies are not 
completed.6   
 
The Consumer Antiseptic Rub FR also describes the studies that are necessary, as a scientific 
matter, for FDA to determine whether an active ingredient  is GRAS/GRAE for use in consumer 
antiseptic rubs.       
 
 
III.  QUESTIONS AND ANSWERS     
 
Q1.  What types of antiseptic products are covered by the Consumer Antiseptic Rub FR? 
 
The Consumer Antiseptic Rub FR covers OTC consumer antiseptic rub products that are 
sometimes referred to as rubs, leave-on products, or hand sanitizers.  The Consumer Antiseptic 
                                              
6 The CARES Act added section 505G to the Federal Food, Drug, and Cosmetic (FD&C Act).  Under 505G(a)(3) of 
the FD&C Act, drugs that were classified as category III in a tentative final monograph (TFM), including the 1994 
TFM for over-the-counter topical antiseptics (59 FR 31402) as further amended by the 2016 Consumer Antiseptic 
Rub proposed rule (81 FR 42912) are not required to have an approved application under section 505 in order to be 
marketed, as long as they are in conformity with the relevant conditions of use outlined in the applicable TFM and 
comply with all other applicable requirements for nonprescription drugs.   
  3  Contains Nonbinding Recommendations 
 
Rub FR also covers OTC consumer antiseptic wipes.  These products are intended to be used 
when soap and water are not available and are left on and not rinsed off with water.   
 
The Consumer Antiseptic Rub FR does not address the monograph status of other OTC 
antiseptic products, including:  (1) consumer antiseptic  washes, which are personal care products 
that are intended for use with water and are rinsed off after use, such as antibacterial soaps, 
antibacterial hand washes, and antibacterial body washes; (2) health care antiseptics, which are 
antiseptic products that are intended for use by health care professionals in a hospital setting or 
other health care situations outside of the hospital;  (3) first aid antiseptics, which are skin 
antiseptics, skin-wound cleansers, and skin-wound  protectants used primarily  by consumers for 
first aid use; and (4) antiseptics used by the food industry.  The monograph status of the active 
ingredients intended for use in these other OTC antiseptic products has been and/or will be 
addressed separately.    
 
Q2.  What active ingredients are subject to the Consumer Antiseptic Rub FR? 
 
In the Consumer Antiseptic Rub FR, we found that three active ingredients  were eligible  for 
evaluation under the OTC Drug Review for use in a consumer antiseptic rub.  The three 
ingredients are: 
 
  Benzalkonium  chloride 
  Ethyl alcohol 
  Isopropyl alcohol 
 
As noted above, FDA temporarily deferred a final determination  regarding the GRAS/GRAE 
status of these three active ingredients to allow time for interested parties to complete the studies 
necessary to fill  the safety and effectiveness data gaps identified  for these ingredients. 
 
In the Consumer Antiseptic Rub FR, we also found 28 active ingredients ineligible  for evaluation 
under the OTC Drug Review as a consumer antiseptic rub.  The 28 ingredients are: 
 
  Benzalkonium  cetyl phosphate  
 
  Benzethonium  chloride  
 
  Cetylpyridinium  chloride  
 
  Chloroxylenol   
 
  Chlorhexidine  gluconate 
 
  Cloflucarban  
 
  Combination  of potassium vegetable oil solution,  phosphate sequestering agent, and 
triethanolamine 
 
  4  Contains Nonbinding Recommendations 
 
  Fluorosalan   
 
  Hexachlorophene  
 
  Hexylresorcinol 
 
  Iodine complex (ammonium  ether sulfate and polyoxyethylene  sorbitan monolaurate)   
 
  Iodine complex (phosphate ester of alkylaryloxy  polyethylene  glycol)   
 
  Methylbenzethonium  chloride 
 
  Nonylphenoxypoly  (ethyleneoxy) ethanoliodine 
 
  Phenol (equal to or less than 1.5 percent or greater than 1.5 percent) 
 
  Poloxamer iodine complex  
 
  Polyhexamethylene  biguanide 
 
  Povidone-iodine  (5 to 10 percent)   
 
  Salicylic  acid  
 
  Secondary amyltricresols   
  
  Sodium hypochlorite 
 
  Sodium oxychlorosene   
 
  Tea Tree Oil 
 
  Tribromsalan   
 
  Triclocarban  
 
  Triclosan  
 
  Triple dye  
 
  Undecoylium  chloride iodine  complex  
 
 
  5  Contains Nonbinding Recommendations 
 
 
Q3.  When and how do manufacturers have to comply with this final rule? 
 
In the Consumer Antiseptic Rub FR, FDA found 28 active ingredients ineligible  for evaluation 
under the OTC Drug Review as a consumer antiseptic rub.  On or after the April 13, 2020, 
effective date of the Consumer Antiseptic Rub FR, any OTC consumer antiseptic rub drug 
product containing  one or more of the 28 ingredients that FDA has found ineligible  cannot be 
introduced or delivered for introduction  into interstate commerce unless the drug product is the 
subject of an approved NDA or ANDA.  This means that manufacturers will need to obtain an 
NDA or ANDA to market consumer antiseptic rub drug products containing  any of these 28 
active ingredients.  Alternatively,  manufacturers of consumer antiseptic rubs containing 
ineligible  antiseptic active ingredients  can comply with the Consumer Antiseptic Rub FR by 
removing their products from the market, or reformulating  them to remove the ineligible  active 
ingredients,  and then marketing them appropriately  (e.g., by substituting  one of the three active 
ingredients described above or by marketing the products as antiseptic-free rubs or wipes without 
drug claims).            
 
Q4.  What if my OTC antiseptic product uses an active ingredient not mentioned in the 
Consumer Antiseptic Rub final rule? 
 
OTC consumer antiseptic rub or wipe products containing  active ingredients not mentioned in 
the Consumer Antiseptic Rub FR are considered new drugs, for which an approved NDA or 
ANDA is required before marketing such products.  Manufacturers of such products can also 
pursue one of the alternatives explained in Q3 to comply with this final rule.  
   
 
Q5.  Why did FDA not address final formulation testing or labeling in the Consumer 
Antiseptic Rub FR? 
 
We did not address final product formulation  testing or labeling  requirements in the Consumer 
Antiseptic Rub FR because none of the consumer antiseptic rub active ingredients  that are the 
subject of the Consumer Antiseptic Rub FR were found to be GRAS/GRAE for use in consumer 
antiseptic rub products.  Final formulation  testing and labeling  for the three deferred active 
ingredients may be addressed in the future once their GRAS/GRAE determination  has been 
concluded. 
 
Q6.  Why were three consumer antiseptic rub active ingredients deferred from further 
rulemaking? 
 
FDA temporarily deferred a final determination  on the GRAS/GRAE status of three active 
ingredients used in consumer antiseptic rubsbenzalkonium  chloride,  ethyl alcohol,  and 
isopropyl  alcoholto  allow time for interested parties to complete the studies necessary to fill 
the safety and effectiveness data gaps identified  for these ingredients.  FDA made the decision to 
defer that determination  in response to several requests submitted to the 2016 Consumer 
Antiseptic Rub PR.   
 
  6  Contains Nonbinding Recommendations 
 
Q7.  Where can I get more information, if needed? 
 
Questions regarding compliance with the Consumer Antiseptic Rub FR should be directed to 
CDERCompliance@fda.hhs.gov.   Questions regarding other OTC issues should be directed to 
OTCDrugs@fda.hhs.gov. 
 
 
 
 
  7