[Federal Register Volume 83, Number 235 (Friday, December 7, 2018)]
[Notices]
[Pages 63168-63176]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2018-26561]



[[Page 63168]]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2018-N-3458]


Food Handler Antiseptic Drug Products for Over-the-Counter Human 
Use; Request for Data and Information

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice; request for data and information.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
the establishment of a docket to obtain data, information, and comments 
that will assist the Agency in assessing the safety and effectiveness 
of food handler antiseptic drug products (i.e., antiseptic hand washes 
or rubs intended for use in food handling settings) for over-the-
counter (OTC) human use. We are asking manufacturers of food handler 
antiseptics and other interested parties to submit safety and 
effectiveness data on OTC food handler antiseptics marketed for use by 
food handlers in commercial or regulated environments where growth, 
harvest, production, manufacturing, processing, packaging, 
transportation, storage, preparation, service, or consumption of food 
occurs. We also are inviting comments and requesting data on 
definitions, eligibility, current conditions of use of food handler 
antiseptics; safety and effectiveness criteria; as well as test methods 
to demonstrate the effectiveness of food handler antiseptics. In 
general, we are seeking input on current use conditions of antiseptics 
used in the food handler setting and recommended testing to establish 
the effectiveness of OTC food handler antiseptics. This information and 
data will inform FDA's ongoing review of OTC antiseptic drug products 
and will specifically inform our review of food handler antiseptic 
products.

DATES: Submit either electronic or written comments, data, or 
information by February 5, 2019.

ADDRESSES: You may submit data and comments as follows. For each 
comment, indicate the specific question to which you are responding. 
Please note that late, untimely filed comments will not be considered. 
Electronic comments must be submitted on or before February 5, 2019. 
The https://www.regulations.gov electronic filing system will accept 
comments until 11:59 p.m. Eastern Time at the end of February 5, 2019. 
Comments received by mail/hand delivery/courier (for written/paper 
submissions) will be considered timely if they are postmarked or the 
delivery service acceptance receipt is on or before that date.

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments. Comments submitted 
electronically, including attachments, to https://www.regulations.gov 
will be posted to the docket unchanged. Because your comment will be 
made public, you are solely responsible for ensuring that your comment 
does not include any confidential information that you or a third party 
may not wish to be posted, such as medical information, your or anyone 
else's Social Security number, or confidential business information, 
such as a manufacturing process. Please note that if you include your 
name, contact information, or other information that identifies you in 
the body of your comments, that information will be posted on https://www.regulations.gov.
     If you want to submit a comment with confidential 
information that you do not wish to be made available to the public, 
submit the comment as a written/paper submission and in the manner 
detailed (see ``Written/Paper Submissions'' and ``Instructions''). We 
note however, that the OTC drug monograph process is a public process; 
and, the Agency intends to consider only non-confidential material that 
is submitted to the docket in response to this request for information, 
or that is otherwise publicly available in evaluating if a relevant 
ingredient is generally recognized as safe and effective (GRAS/GRAE).

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand Delivery/Courier (for written/paper 
submissions): Dockets Management Staff (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Dockets 
Management Staff, FDA will post your comment, as well as any 
attachments, except for information submitted, marked and identified, 
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No. 
FDA-2018-N-3458 for ``Food Handler Antiseptic Drug Products for Over-
the-Counter Human Use; Request for Data and Information.'' Received 
comments, those filed in a timely manner (see ADDRESSES), will be 
placed in the docket and, except for those submitted as ``Confidential 
Submissions,'' publicly viewable at https://www.regulations.gov or at 
the Dockets Management Staff between 9 a.m. and 4 p.m., Monday through 
Friday.
     Confidential Submissions--To submit a comment with 
confidential information that you do not wish to be made publicly 
available, submit your comments only as a written/paper submission. You 
should submit two copies total. One copy will include the information 
you claim to be confidential with a heading or cover note that states 
``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.'' The Agency will 
review this copy, including the claimed confidential information, in 
its consideration of comments. The second copy, which will have the 
claimed confidential information redacted/blacked out, will be 
available for public viewing and posted on https://www.regulations.gov. 
Submit both copies to the Dockets Management Staff. If you do not wish 
your name and contact information to be made publicly available, you 
can provide this information on the cover sheet and not in the body of 
your comments and you must identify this information as 
``confidential.'' Any information marked as ``confidential'' will not 
be disclosed except in accordance with 21 CFR 10.20 and other 
applicable disclosure law. For more information about FDA's posting of 
comments to public dockets, see 80 FR 56469, September 18, 2015, or 
access the information at: https://www.gpo.gov/fdsys/pkg/FR-2015-09-18/pdf/2015-23389.pdf.
    Docket: For access to the docket to read background documents or 
the electronic and written/paper comments received, go to https://www.regulations.gov and insert the docket number, found in brackets in 
the heading of this document, into the ``Search'' box and follow the 
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Pranvera Ikonomi, Center for Drug 
Evaluation and Research, Food and Drug Administration, 10903 New 
Hampshire Ave., Bldg. 22, Rm. 5418, Silver Spring, MD 20993-0002, 240-
402-0272.

SUPPLEMENTARY INFORMATION: 

Table of Contents

I. Introduction
II. Table of Abbreviations/Commonly Used

[[Page 63169]]

Acronyms in This Document
III. Background
    A. Background on Topical Antiseptics
    B. Regulatory History of Food Handler Antiseptics
IV. Proposed Effectiveness Models and Indications for Food Handler 
Antiseptics
    A. Health Care Continuum Model
    B. FDA Comments on the Proposed Health Care Continuum Model
    C. Inclusion of Antiviral Indications in Food Handler 
Antiseptics
    D. FDA Response on the Proposed Model for Antiviral Indications 
of the Antiseptic Products
V. Data
VI. Questions for Public Input
    A. Definition of Food Handler Antiseptics
    B. Active Ingredients for Food Handler Antiseptic Products
    C. Safety
    D. Effectiveness
VII. References

I. Introduction

    We are seeking public input regarding the safety and effectiveness 
of food handler antiseptics to inform FDA's ongoing review of OTC 
antiseptic drug products and the Agency's review of the active 
ingredients used in these products in the food handler setting. The 
Agency seeks data and information about these topical antiseptics and 
how the active ingredients should be tested and evaluated for safety 
and effectiveness.
    This Request for Information (RFI) covers only OTC food handler 
antiseptics that are intended for use by food handlers in commercial or 
regulated environments where growth, harvest, production, 
manufacturing, processing, packaging, transportation, storage, 
preparation, service, or consumption of food occurs. This RFI does not 
cover consumer antiseptic washes (78 FR 76444, December 17, 2013; 81 FR 
61106, September 6, 2016); health care antiseptics (80 FR 25166, May 1, 
2015; 82 FR 60474, December 20, 2017); consumer antiseptic rubs (81 FR 
42912, June 30, 2016); or antiseptics identified as ``first aid 
antiseptics'' in the 1991 First Aid tentative final monograph (TFM) (56 
FR 33644, July 22, 1991).
    FDA has tentatively concluded that, based on FDA's current 
categorization of other antiseptic products and considering factors 
that may include specific microorganisms of concern in food handling 
environments as well as the safety of repeated-exposure use patterns, 
food handler antiseptics may differ from antiseptic products addressed 
in other rulemakings. There has been support from industry and 
interested parties for an OTC food handler antiseptic category, and 
some information and data have been submitted in support of 
establishing such a category. However, we believe more data and 
information are needed to assist the Agency in evaluating the safety 
and effectiveness criteria appropriate for food handler antiseptics.

II. Table of Abbreviations/Commonly Used Acronyms in This Document

------------------------------------------------------------------------
       Abbreviation/ acronym                    What it means
------------------------------------------------------------------------
ANPR...............................  Advance Notice of Proposed Rule.
AOAC...............................  Association of Official Analytical
                                      Chemists (now ``AOAC
                                      International'').
ASTM...............................  American Society for Testing and
                                      Materials (now ``ASTM
                                      International'').
ATCC...............................  American Type Culture Collection.
CDC................................  Centers for Disease Control and
                                      Prevention.
FDA................................  Food and Drug Administration.
FD&C Act...........................  Food Drug and Cosmetic Act.
FR.................................  Federal Register.
GRAS/GRAE..........................  Generally recognized as safe and
                                      effective.
HACCP..............................  Hazard analysis and critical
                                      control point.
HCCM...............................  Health Care Continuum Model.
MIC................................  Minimum Inhibitory Concentration
                                      Testing.
OTC................................  Over-the-counter.
PCPC...............................  Personal Care Products Council.
RFI................................  Request for information.
SDA................................  Soap and Detergent Association.
TFM................................  Tentative final monograph.
U.S.C..............................  United States Code.
------------------------------------------------------------------------

III. Background

A. Background on Topical Antiseptics

    This RFI is part of FDA's ongoing evaluation of the safety and 
effectiveness of OTC drug products marketed in the United States on or 
before May 11, 1972 (OTC Drug Review). The OTC topical antimicrobial 
rulemaking has had a broad scope, encompassing drug products that may 
contain the same active ingredients, but that are labeled and marketed 
for different intended uses. In 1974, the Agency published an advance 
notice of proposed rulemaking (ANPR) for topical antimicrobial products 
that encompassed products for both health care and consumer use. The 
1974 ANPR covered seven different intended uses for these products: (1) 
Antimicrobial soap; (2) health care personnel hand wash; (3) patient 
preoperative skin preparation; (4) skin antiseptic; (5) skin wound 
cleanser; (6) skin wound protectant; and (7) surgical hand scrub (39 FR 
33103 at 33140, September 13, 1974). FDA subsequently identified skin 
antiseptics, skin wound cleansers, and skin wound protectants as 
antiseptics used primarily by consumers for first aid use and referred 
to them collectively as ``first aid antiseptics.'' FDA published a 
separate TFM covering the first aid antiseptics in the 1991 First Aid 
TFM (56 FR 33644). The remaining categories of topical antimicrobials 
were addressed in the 1994 TFM for healthcare antiseptic drug products 
(59 FR 31402, June 17, 1994). The 1994 TFM covered: (1) Antiseptic hand 
wash (i.e., consumer hand wash); (2) health care personnel hand wash; 
(3) patient preoperative skin preparation; and (4) surgical hand scrub 
(59 FR 31402 at 31442).
    The 1994 TFM did not distinguish between consumer antiseptic washes 
and rubs and health care antiseptic washes and rubs. In the 2013 
Consumer Wash Proposed Rule, we proposed that our evaluation of OTC 
antiseptic drug products be further subdivided into health care 
antiseptics and consumer antiseptics (78 FR 76444 at 76446). These 
categories are distinct based on the proposed use setting, target 
population, and the fact that each setting presents a different level 
of risk for infection. In the 2013 Consumer Wash Proposed Rule (78 FR 
76444 at 76446-76447) and the 2016 Consumer Rub Proposed Rule (81 FR 
42912 at 42915-42916), we proposed that our evaluation of OTC consumer 
antiseptic drug products be further subdivided into consumer washes 
(products that are rinsed off with water, including hand washes and 
body washes) and consumer rubs (products that are not rinsed off after 
use, including hand rubs and antibacterial wipes).

B. Regulatory History on Food Handler Antiseptics

    In the 1994 TFM, FDA also identified a new category of antiseptics 
for use by the food industry, which historically had been marketed for 
use by food handlers in federally inspected meat and poultry processing 
plants, and other food handling establishments (59 FR 31402 at 31440). 
As stated in the 2016 Consumer Wash Final Rule (81 FR 61106 at 61109; 
September 6, 2016) and the 2017 Health Care Antiseptic Final Rule (82 
FR 60474 at 60483, December 20, 2017), we classify the food handler 
antiseptics as separate and distinct from the other OTC topical 
antiseptics. Based on FDA's current categorization of other OTC 
antiseptic products and given the additional issues raised by the 
public health consequences of foodborne illness, differences in 
frequency and type of use, and contamination of the hands by dirt, 
grease and other oils, we believe that a separate evaluation of food 
handler antiseptics is warranted. Food handler antiseptics include 
antiseptic products labeled for use in commercial or other regulated 
settings where food is grown, harvested, manufactured, packed, held, 
transported, prepared, served, or

[[Page 63170]]

consumed. The intended use of these products (the reduction of 
microorganisms on the skin for the purpose of preventing disease caused 
by transfer of microorganism from hands to foods) makes them drugs 
under the provisions of the Federal, Food, Drug, and Cosmetic Act (FD&C 
Act), which defines a drug to include an article intended for use in 
the diagnosis, cure, mitigation, treatment, or prevention of disease in 
man (section 201(g)(1) of the FD&C Act; 21 U.S.C. 321(g)(1)).
    FDA has determined that the safety and effectiveness of active 
ingredients intended for use in food handler antiseptic products needed 
to be demonstrated, and we proposed to include an evaluation of the 
safety and effectiveness of these active ingredients in the rulemaking 
for OTC topical antimicrobial drug products (59 FR 31402 at 31440). In 
the 1994 TFM, we requested relevant data and information to assist in 
characterizing this category of food handler antiseptics (59 FR 31402 
at 31440), but we did not discuss what data would be necessary to 
support a GRAS/GRAE determination. In response to the 1994 TFM, we 
received public comments pertaining to food handler antiseptic hand 
washes (see section IV), including an industry proposal, the Health 
Care Continuum Model (HCCM), which refers to the effectiveness, 
effectiveness testing requirements, and labeling of antiseptic products 
discussed in the 1994 TFM, including the antiseptic hand wash products 
used by food handlers (Refs. 1 and 2). We also received comments in 
response to the 1994 TFM regarding antiviral testing for antiseptic 
products used by food handlers (59 FR 31402).
    FDA also received comments pertaining to food handler antiseptics 
in response to the 2013 Consumer Antiseptic Wash proposed rule. One of 
these comments was submitted from the Personal Care Products Council 
(PCPC) and American Cleaning Institute in the form of a citizen 
petition (FDA-1975-N-0012-0493) (Ref. 3) requesting that FDA, among 
other things, define food handler antiseptic hand washes or rubs as 
antiseptic products for use in commercial establishments and other 
regulated settings, establish food handler antiseptic hand washes as a 
separate category, and consider food handler antiseptic products as 
professional use products similar to health care antiseptics.

IV. Proposed Effectiveness Models and Indications for Food Handler 
Antiseptics

    In response to the 1994 TFM, FDA received comments pertaining to 
food handler antiseptic hand washes. The comments that addressed food 
handler antiseptic hand washes generally agreed that they should be 
evaluated in the review of antiseptic products. FDA also received 
comments and a citizen petition proposing an effectiveness model for 
antiseptic products in general, including food handler antiseptics, as 
well as a proposal on specific indications for food handler antiseptics 
(Refs. 1, 2, 33, and 14). We describe and respond to the proposed model 
and indications in sections IV.A. through IV.D.

A. Health Care Continuum Model

    A comment from two trade associations proposed regulating food 
handler antiseptics as part of the HCCM (Ref. 1). This regulatory model 
included proposed labeling, final formulation testing requirements, and 
effectiveness testing criteria. The proposed testing included in vitro 
and in vivo testing that is modeled after FDA's previously proposed 
testing for OTC health care antiseptic drug products (Ref. 1). Table 1 
summarizes the HCCM's proposed in vitro and in vivo testing and other 
effectiveness criteria for food handler antiseptics.

                    Table 1--Summary of Industry Proposed Testing of Food Handler Antiseptics
                                          [Health Care Continuum Model]
----------------------------------------------------------------------------------------------------------------
                                            Test organisms  (American type culture
          Proposed test method                 collection strain number (ATCC))            Efficacy criteria
----------------------------------------------------------------------------------------------------------------
Establish in vitro spectrum of            Candida albicans. (ATCC 10231). *.........  None Stated.
 antimicrobial activity of active         Enterobacter cloacae. (ATCC 13047)........
 ingredient (Minimum inhibitory           Entercoccus faecalis. (ATCC 19433)........
 concentration testing (MIC)).            Escherichia coli. (ATCC 25922). *.........
                                          Klebsiella pneumoniae (ATCC 10031)........
                                          Listeria monocytogenes (ATCC 7644).*
                                          Proteus mirabilis (ATCC 7002).............
                                          Pseudomonas aeruginosa (ATCC 9027)........
                                          Pseudomonas stutzeri (ATCC 17588).........
                                          Salmonella choleraesuis (ATCC 10708).*
                                          Salmonella enteritidis (ATCC 13076).*
                                          Salmonella typhi (ATCC 6539).*
                                          Salmonella typhimurium (ATCC 11311).*
                                          Shigella dysenteraiae (ATCC 13313)........
                                          Shigella sonnei (ATCC 11060).*
                                          Staphylococcus aureus (ATCC 6538).*
                                          Streptococcus pyogenes (ATCC 19615).*
Establish in vitro spectrum of            Escherichia coli (ATCC 25922). *..........  None Stated.
 antimicrobial activity of end-use        Klebsiella pneumoniae. (ATCC 10031).......
 formulation (MIC).                       Listeria monocytogenes. (ATCC 7644). *....
                                          Pseudomonas stutzeri. (ATCC 17588)........
                                          Salmonella choleraesuis (ATCC 10708).*
                                          Salmonella enteritidis (ATCC 13076).*
                                          Salmonella typhi (ATCC 6539).*
                                          Salmonella typhimurium (ATCC 11311).*
                                          Shigella sonnei (ATCC 11060).*
                                          Staphylococcus aureus (ATCC 6538).*

[[Page 63171]]

 
Establish broad spectrum and fast acting  Escherichia coli (ATCC 11229).............  1 minute: 1 log10
 claims for formulations (In vitro Time   Klebsiella pneumoniae (ATCC 10031)........   reduction
 Kill Test).                              Listeria monocytogenes (ATCC 7644).*......  5 minutes: 2 log10
                                          Salmonella typhi (ATCC 6539).*............   reduction
                                                                                      Must meet criteria for 4
                                                                                       of 5 strains.
                                          Staphylococcus aureus (ATCC 6538)
General Use Hand Wash Method              Serratia marcescens (ATCC 14756) or.......  1st wash 1.5 log10
 (Formulation).                           Escherichia coli (ATCC 11229).............   reduction.
                                                                                      5th wash: 2 log10
                                                                                       reduction.
American Society for Testing and          Serratia marcescens (ATCC 14756) or.......  Rubs: 2 log10 reduction.
 Materials International (ASTM) Hand Rub  Escherichia coli (ATCC 11229).............
 Method (Formulation).
----------------------------------------------------------------------------------------------------------------
* Organisms included in the Hazard Analysis and Critical Control Point Principles and Application Guidelines
  (Ref. 4).

    The HCCM proposal explained that the ATCC strains recommended for 
in vitro testing were chosen to represent a broad spectrum of bacteria 
that ``present a challenge to antisepsis'' and are the principal 
foodborne pathogens and contaminants. The model also proposed the use 
of clinical simulation studies to demonstrate the effectiveness of 
final formulations that rely on the reduction of the same surrogate 
organisms that historically have been used to demonstrate the 
effectiveness of health care personnel and antiseptic hand washes. More 
specifically, two protocols were proposed for clinical simulation 
studies: (1) A General Hand Wash Method for the demonstration of fast-
acting and persistent activity of products used with water; and (2) an 
ASTM method for the evaluation of alcohol-based hand rub formulations 
to demonstrate the fast-acting antimicrobial activity of leave-on 
products. The proposal also provides log-reduction effectiveness 
criteria that are similar to the effectiveness criteria for health care 
personnel hand antiseptics proposed in the 1994 TFM (59 FR 31402 at 
31444) (see table 1). The Soap and Detergent Association (SDA) stated 
that the proposed HCCM ``log reduction and acceptance criteria will 
demonstrate the appropriate effectiveness of products used in a food 
handling environment'' (Ref. 5). However, the HCCM did not define the 
appropriate level of effectiveness or include data to support 
corresponding effectiveness testing criteria.
    The SDA also recommended the continued use of the Association of 
Official Analytical Chemists (AOAC International) chlorine equivalency 
test for in vitro effectiveness testing of food handler antiseptics 
(Ref. 6). The SDA suggested that an antiseptic activity equivalent to 
50 parts per million of available chlorine be a strict requirement for 
food handler antiseptic products (Ref. 5).

B. FDA Comments on the Proposed Health Care Continuum Model

    FDA identified several issues in the proposed HCCM. The use 
conditions of food handler antiseptics vary widely. Heavily soiled 
items are common in food preparation and food handling settings, and in 
general, antiseptic products are considered to be less effective in 
soiled hands (Ref. 7). Studies simulating moderate and heavily soiled 
hand conditions showed decreased efficacy of antiseptic products, 
suggesting that the organic load, i.e., the amount of fat, grease, 
blood, and debris associated with food handling, affects the efficacy 
of antiseptic products (Ref. 8). The transfer of bacteria from 
contaminated food items and surfaces to hands may also be affected by 
the organic load contained in such items (Ref. 9). Use conditions vary 
in both organic and bacterial load, resulting in moderate to high 
levels of bacterial contamination. These differences are, in some 
cases, related to the setting in which a product is used. The 
differences may be related to other factors as well. The proposed HCCM 
does not take into consideration the wide-ranging use conditions of 
food handler antiseptics, and it raises the question of how to best 
address the broad spectrum of situational challenges stemming from 
these varied uses.
    Contact time is another factor that is expected to impact an 
antiseptic's effectiveness. The Food Code, a model that represents 
FDA's advice for a uniform system of provisions that address the safety 
and protection of food offered at retail and in food service 
establishments, specifies that a food handler's hand cleaning regimen 
should last ``at least 20 seconds'' using a cleaning compound in a hand 
washing sink (Ref. 10). In the method for in vivo efficacy testing 
proposed in the HCCM, contact times vary from 30 seconds to 5 minutes. 
These timeframes do not reflect the hand cleaning procedures 
recommended in the Food Code. The contact times used in effectiveness 
testing should be appropriately related to reasonable real-life 
conditions of use, as reflected in product labeling. We are interested 
in comments on appropriate contact times for in vivo effectiveness 
testing.
    The HCCM proposal also requires the demonstration of an 
antiseptic's effectiveness after multiple hand washes or rubs and 
proposes effectiveness criteria that range from 1.5 to 2 
log10 reduction of the test organism. Given the manner in 
which food handler antiseptics are currently used (i.e., short contact 
times with use of antiseptics, high bacterial loads, and expectations 
that these products be effective after a single use), the proposed in 
vivo effectiveness testing does not appear to reflect food handler 
antiseptic use situations and raises the question of what criteria best 
demonstrate the effectiveness of food handler antiseptics.
    When evaluating food handler antiseptics, it is important to focus 
on the foodborne pathogens most often known to cause foodborne illness 
through contamination of food by food employee's hands (Ref. 11). The 
list of ``Pathogens Transmitted by Food Contaminated by Infected Person 
Who Handle Food, and Modes of Transmission of Such Pathogens'' is 
available on the Centers for Disease Control and Prevention (CDC) 
website (https://www.cdc.gov/foodsafety/pdfs/pathogens-by-food-handlers-508c.pdf). The in vitro testing proposed in the HCCM includes 
only bacterial species.

[[Page 63172]]

However, in 2014, the CDC reported that bacterial foodborne illness 
accounted for only 51 percent of food-borne disease outbreaks. Viruses 
were cited as the second most common cause of disease outbreaks (43 
percent). Thus, over one-third of food-borne disease outbreaks included 
in the CDC report were not caused by bacteria (Ref. 12). Further, 
norovirus was reported as the most common cause of confirmed, single-
etiology outbreaks, accounting for 284 outbreaks (43 percent); its 
transmission from contaminated hands to food items plays a major role 
in this foodborne illness. Parasites, including the protozoan species 
Giardia lamblia, Cryptosporidium species, and Cyclospora cayentanensis, 
accounted for a much smaller number of outbreaks, but should also be 
taken into consideration. These considerations raise questions 
concerning the antimicrobial spectrum of activity that food handler 
antiseptic active ingredients should demonstrate to be considered 
effective and the appropriate in vitro studies to assess such activity 
(see section IV.C and IV.D.).
    In addition, in a 2005 meeting of FDA's Nonprescription Drugs 
Advisory Committee (Ref. 13) the committee observed that the existing 
test methods for topical antiseptics used in consumer and professional 
settings are based on the premise that bacterial reductions translate 
to a reduced potential for infection. Although bacterial reduction can 
be demonstrated using tests that simulate conditions of actual use, no 
corresponding clinical data demonstrate that bacterial reductions of 
the required magnitude produce a corresponding reduction in infection. 
For consumer antiseptic wash products, FDA has since recommended 
clinical outcome studies to demonstrate the products' clinical benefit 
and their superiority compared to plain soap and water (78 FR 76444, 81 
FR 61106). This concern--whether the product's efficacy can be 
evaluated solely by in vitro tests--remains valid also for food handler 
antiseptics.
    In light of the questions raised by FDA's review of the proposed 
HCCM, we have concluded that additional public input is needed before a 
proposed monograph for OTC food handler antiseptics can be developed. 
Therefore, FDA is seeking comments and requesting submission of data 
and information relevant to a number of questions related to OTC food 
handler antiseptics (see section V.)

C. Inclusion of Antiviral Indications in Food Handler Antiseptics

    In response to the 1994 TFM, the Agency also received a citizen 
petition in 2003 from the SDA and Cosmetic Toiletry and Fragrance 
Association \1\ (SDA/PCPC Petition) requesting that the proposed rule 
be amended to include antiviral indications for OTC consumer, food 
handler, and health care personnel antiseptics (Ref. 14). The SDA/PCPC 
Petition proposed labeling, final formulation testing requirements, and 
effectiveness criteria to demonstrate the antiviral activity of 
antiseptics (Ref. 15). Table 2 summarizes the SDA/PCPC Petition's 
proposed testing and other effectiveness criteria for food handler 
antiseptics.
---------------------------------------------------------------------------

    \1\ In 2007, the CTFA changed its name to the Personal Care 
Products Council (PCPC).

 Table 2--Summary of Petitioner's Proposed Testing for Demonstration of Antiviral Effectiveness of Food Handler
                                                   Antiseptics
----------------------------------------------------------------------------------------------------------------
                                                                                        Effectiveness criteria
          Proposed test method                 Test organisms (ATCC strain No.)        (reduction of viral load)
----------------------------------------------------------------------------------------------------------------
Establish antiviral activity of active    Rotavirus Wa (ATCC VR-2018)...............  None stated.
 ingredient (None).                       Rhinovirus Type 37 (ATCC VR-1147) or......
                                          Rhinovirus Type 13 (ATCC VR-284)..........
Establish antiviral activity of           Rotavirus Wa (ATCC VR-2018)...............  2 log10.
 formulation.                             Rhinovirus Type 37 (ATCC VR-1147) or......  Contact time: Unspecified,
(ASTM E1838 \1\--fingerpad method)......  Rhinovirus Type 13 (ATCC VR-284)..........   should reflect use
(ASTM E2011 \2\--entire-hand method)....                                               conditions
----------------------------------------------------------------------------------------------------------------
\1\ ASTM E1838; ``Standard Test Method for Determining the Virus-Eliminating Effectiveness of Hygienic Handwash
  and Handrub Agents using Fingerpads of Adults.''
\2\ ASTM E2011; ``Standard Test Method for Evaluation of Hygienic Handwash and Handrub Formulations for Virus-
  Eliminating Activity Using the Entire Hand.''

    The SDA/PCPC Petition included studies and publications in which 
the antiviral activity of several active ingredients included in the 
1994 TFM and their final formulations were assessed by both in vitro 
test methods and clinical simulation studies (i.e., studies that 
simulate conditions of use to evaluate a product's efficacy in human 
subjects).
    The SDA/PCPC Petition recommends testing against respiratory and 
enteric viral pathogens to determine the antiviral activity of the 
antiseptics: Rhinovirus Type 37 (ATCC VR-1147) or Rhinovirus Type 13 
(ATCC VR-284) and Rotavirus Wa (ATCC VR-2018). The rationale for this 
recommendation is based on the premise that both viruses are important 
hand-transmitted pathogens, less susceptible to inactivation than 
enveloped viruses, and are known to survive for a significant period on 
skin and surfaces commonly contacted by hands. As such, they present an 
adequate challenge for testing the antiviral activity of antiseptic 
products.
    Regarding the test methods for demonstration of virucidal 
effectiveness, the SDA/PCPC Petition proposed two specific methods: 
ASTM E1838 and ASTM E201. Both these methods present simulation models 
of viral contamination, and both measure the reduction of viral load on 
fingerpads (ASTM E1838) or on the entire hand (ASTM E201) after the 
application of the antiseptic test product. The SDA/PCPC Petition also 
proposed a 2 log10 reduction of the test virus or viruses as 
the criterion for antiviral effectiveness. Although several in vitro 
tests such as the carrier method (Ref. 16) and suspension tests (Ref. 
17) are presented in the submission, there is no recommendation with 
regard to in vitro test methods for demonstration of

[[Page 63173]]

virucidal activity of antiseptic products and/or their active 
ingredients.
    Lastly, the SDA/PCPC Petition suggested a two-step approach for 
antibacterial and antiviral labeling: Providing that the antibacterial 
criteria as laid out in the rulemaking have been met, the antiviral 
labeling would be optional for products that in addition to 
antibacterial criteria, meet the antiviral criteria.

D. FDA Response to the Proposed Model for Antiviral Indications of the 
Antiseptic Products

    FDA responded to the SDA/PCPC Petition on March 26, 2010, and 
denied the petition's request that FDA amend the 1994 TFM (Ref. 18). 
The submitted data were reviewed by FDA, and the following points were 
addressed:
    In vitro data included in the SDA/PCPC Petition do not clearly 
demonstrate the effectiveness of the antiseptic active ingredients or 
product formulations against viruses. Primarily, the in vitro results 
obtained may not predict the antiseptic's effectiveness against viruses 
on human skin. An evaluation of effectiveness against viruses on human 
skin would need to be supported by adequate in vivo studies. In most of 
the studies, the test conditions and results vary considerably. Also, 
most studies lacked vehicle and neutralization controls; this 
undermines the validity of the data and makes it difficult to evaluate 
the contribution of the antiseptic product in the reduction of the 
viral concentration.
    Clinical simulation studies included in the SDA/PCPC Petition were 
not adequately controlled to distinguish the antiviral effectiveness of 
the antiseptic and eliminate bias. These studies lacked proper controls 
and adequate statistical analyses. Most studies lacked either vehicle 
or placebo controls such as washing with plain soap and water. In the 
few studies in which a vehicle control was included, the advantage of 
the antiseptic product use was not demonstrated. Moreover, the use of 
plain soap and water was often found to be as or more effective than 
using the test antiseptic. Most studies also lacked proper 
documentation of neutralization and they were not randomized or 
blinded. Overall, the lack of adequate comparison controls rendered the 
submitted studies insufficient to demonstrate antiviral effectiveness.
    The SDA/PCPC Petition proposed using an enteric pathogen, Rotavirus 
Wa Type 30, and a respiratory pathogen, Rhinovirus Type 37, for testing 
antiseptic viral activity. After reviewing submitted data and current 
publications, FDA determined that viruses vary significantly in their 
susceptibility to antiseptics and that this variability makes it 
difficult to extrapolate the effectiveness results obtained from the 
proposed viruses to a broader range of viruses (Ref. 19).
    The SDA/PCPC Petition's proposed 2 log10 reduction of 
viral contamination as the criterion for determination of effectiveness 
is inadequate; viruses vary in their infectivity titers, and 2 
log10 titer reduction achieved in the proposed viruses may 
be irrelevant to other viral pathogens. We currently have no data to 
evaluate the significance of 2 log10 reduction of test 
viruses and how such reduction would relate to a reduced risk of viral 
infections. In addition, the 2 log10 reduction of viral 
titers was achieved in alcohol-based products, but in studies where 
soap and water were used, the virus reduction was in the range of 1 
log10. In conclusion, FDA determined that given these large 
variations, the clinical relevance of the proposed criterion for 
antiviral effectiveness was not supported by the data and may not be 
applicable to many viral pathogens. The surrogate measure of antiviral 
effectiveness would need to be validated and its significance should be 
supported by clinical data.
    FDA found the test methods proposed in the SDA/PCPC Petition 
inadequate to support a general antiviral indication; the proposed ASTM 
methods do not account for data variability, nor do they provide 
guidance on adequate study size and data analysis. Moreover, the 
studies submitted in support of the proposed methods are insufficient 
to demonstrate comparable results between the two ASTM methods proposed 
due to the small study size.
    In short, data reviewed by FDA are insufficient to support general 
antiviral labeling for antiseptic products including food handler 
antiseptics. Additional data that adequately demonstrate the antiviral 
effectiveness of antiseptic active ingredients and their product 
formulations are needed to properly address the antiviral activity of 
food handler antiseptics.

V. Data

    Data to support the effectiveness of several antiseptic active 
ingredients were also submitted to the FDA-1975-N-0012-0494 docket by 
the PCPC in response to the Consumer Wash Proposed Rule (Ref. 20). 
Comments received from the PCPC asserted that the data provided 
demonstrated effectiveness based on the industry's proposed standard of 
effectiveness for food handler antiseptic products. However, because 
FDA currently has insufficient information to determine what 
constitutes an adequate demonstration of effectiveness of antiseptic 
active ingredients intended for use in the food handler setting, an 
evaluation of the submitted data would be premature.

VI. Questions for Public Input

    Based on the history of food handler antiseptics and a review of 
our records and data received, we have determined that additional new 
data and information are needed to inform FDA on the safety and 
effectiveness of the active ingredients used in food handler 
antiseptics and drug products containing them. Thus, we are soliciting 
data and information that will help address the questions that follow.

A. Definition of Food Handler Antiseptics

    As discussed in section III, we view food handler antiseptics as a 
category that includes antiseptic products used in regulated settings 
where food is grown, harvested, produced, manufactured, processed, 
packed, transported, prepared, served, or consumed.
    In response to the questions that follow, FDA is seeking data and 
other information on defining food handler antiseptic products and any 
other information relevant to their definition.
     What are the categories of workers who might use the food 
handler antiseptic products?
     In what settings are food handler antiseptics used? What 
should be the boundaries (e.g., growth, harvest, production, 
manufacturing, processing, packaging, transportation, storage, 
preparation, service, and consumption) of regulated use of food handler 
antiseptics? Are there any additional details and information to be 
considered related to scope-of-use settings of food handler 
antiseptics?
     What types of antiseptic products are used by food 
handlers and what terms are used in the food industry to describe such 
products (e.g., wash, or leave-on products)?
     How frequently are food handler antiseptics used?

B. Active Ingredients for Food Handler Antiseptic Products

    An OTC drug is eligible for the OTC Drug Review if its conditions 
of use existed in the OTC drug marketplace on or before May 11, 1972 
(37 FR 9464), or if drug products with the same conditions of use have 
been marketed for a material time and extent such that they meet the 
requirements for eligibility under FDA's time and extent application 
regulation (Sec.  330.14 (21 CFR

[[Page 63174]]

330.14)). Conditions of use include, among others, active ingredient, 
dosage form and strength, route of administration, and specific OTC use 
or indication of the product (Sec.  330.14(a)).
    To determine eligibility for the OTC Drug Review, FDA typically 
must have actual product labeling or a facsimile of labeling that 
documents the conditions of marketing of a product prior to May 1972 
(21 CFR 330.10(a)(2)). FDA considers a drug that is ineligible for 
inclusion in the OTC monograph system to be a new drug that will 
require FDA approval under a new drug application (NDA) or an 
abbreviated new drug application (ANDA). Also, an active ingredient's 
ineligibility for evaluation under the OTC Drug Review for a specific 
indication does not affect its eligibility for evaluation for other 
indications under the OTC Drug Review.
    FDA's recognition of the potential eligibility of food handler 
antiseptic products for evaluation under the OTC Drug Review is 
relatively new. We expect that many of the antiseptic active 
ingredients found in products currently used by food handlers may not 
have been on the U.S. market when the OTC Drug Review was first 
established, or that it may be difficult to establish eligibility based 
on use at that time. It may be possible, however, that some of the 
active ingredients currently used in these products have been in use in 
or outside of the United States for a material time and extent such 
that they meet the requirements for eligibility under FDA's time and 
extent application regulation (Sec.  330.14). We are, therefore, 
seeking information about food handler antiseptic active ingredients 
and the products in which they are found.
    For the active ingredients used in food handler antiseptics, we ask 
for submission of the following information:
     What are the active ingredients currently used in food 
handler antiseptic products?
     How long and to what extent (e.g., number of units or 
volume sold) have currently marketed active ingredients been in the 
marketplace inside and/or outside of the U.S. market?
     What active ingredients were in products on the market for 
food handler use prior to 1972, and what evidence of eligibility for 
evaluation for use in food handler antiseptic products under the OTC 
Drug Review is available for these active ingredients?
     What other information relevant to the eligibility of 
active ingredients for use in food handler antiseptic products is 
available?

C. Safety

    In the consumer antiseptic wash and rubs, and in the health care 
antiseptics rulemakings for OTC topical antiseptic active ingredients, 
the following data are required to determine the safety of these active 
ingredients as part of the risk-to-benefit evaluation of the product's 
use (81 FR 61106 at 61117, 81 FR 42912, 80 FR 25166):

 Animal toxicology data
 Carcinogenicity
    [cir] Dermal and Oral Exposure
 Absorption, Distribution, Metabolism & Excretion
    [cir] Dermal and Oral Exposure
 Developmental & Reproductive Toxicology
 Hormonal Effects
 Human absorption data from a Maximal Usage Trial
 Development of Antimicrobial Resistance

    To better assess the criteria for a determination of the safety of 
active ingredients used in food handler antiseptics, we welcome 
information to answer the following questions and any other issues 
related to evaluating the safety of these products:
     Should the data required to demonstrate the safety of 
active ingredients intended for use in food handler antiseptic products 
be the same as the safety criteria for active ingredients intended for 
use in consumer antiseptic and health care antiseptic products?
     If antiseptic hand rubs or leave-on products are used, the 
presence of residual antiseptic products on the hands of food handler 
professionals may result in indirect consumer exposure (i.e., ingestion 
of residual antiseptic due to transfer of such residues from food 
handlers to food contact surfaces and/or food). Are additional studies 
required to address this concern?
     If additional studies are required to address indirect 
consumer exposure to antiseptic ingredients, what should they be?
     On a daily basis, how frequently do food handlers use food 
handler antiseptic products in the workplace? Are there any 
requirements related to the frequency of using food handler antiseptics 
in the workplaces where food is handled (e.g., produce safety 
standards)?
     What data are available to support the long-term safety of 
the active ingredients of these products (e.g., oral and dermal 
carcinogenicity studies)?
     How should the potential for antimicrobial resistance to 
these active ingredients be assessed?
     What data are available regarding antimicrobial resistance 
for these products, and how should the potential of food handler 
antiseptics' use with potential emergence of antimicrobial resistance 
be assessed?
     What other issues should be taken into consideration to 
support evaluation of the safety of food handler antiseptic products?

D. Effectiveness

    New information on potential risks posed by the long-term use of 
certain antiseptic active ingredients prompted us to reconsider the 
data necessary to determine that active ingredients used in consumer or 
health care antiseptic products are generally recognized as safe and 
effective for their intended use. Based on new data as well as on input 
provided during the Nonprescription Drugs Advisory Committee meeting of 
March 2005, we have reevaluated the effectiveness data needed for 
consumer and health care antiseptic active ingredients (78 FR 76444, 81 
FR 42912, 80 FR 25166).
    For topical antiseptics used both in consumer and health care 
settings, the following studies in table 3 are required or proposed to 
be required to demonstrate effectiveness.

  Table 3--Effectiveness Data Requirements for OTC Consumer and Health
                            Care Antiseptics
------------------------------------------------------------------------
         Required tests                In vitro             In vivo
------------------------------------------------------------------------
Consumer Antiseptic Washes......   Time-kill   Clinical
                                   Assay *             Outcome Studies
                                                      [cir] Evaluates
                                                       the effect of
                                                       antiseptic use in
                                                       decreasing the
                                                       incidence of
                                                       infections.
Consumer Antiseptic Rubs........   Minimal     Clinical
                                   Bactericidal        Simulation
                                   Concentration *.    Studies
                                   Time-kill  [cir] Measures the
                                   Assay *..           reduction of
                                                       bacteria on skin
                                                       due to antiseptic
                                                       use.

[[Page 63175]]

 
Health Care Antiseptics.........   Minimal     Clinical
                                   Bactericidal        Simulation
                                   Concentration **.   Studies
                                   Time-kill  [cir] Measures
                                   Assay **..          reduction of
                                                       bacteria on skin
                                                       due to antiseptic
                                                       use
                                                      [cir] Evaluates
                                                       the persistence
                                                       of bactericidal
                                                       activity by
                                                       measuring
                                                       bacteria on skin
                                                       6 hours post
                                                       product
                                                       application for
                                                       surgical hand
                                                       scrub and patient
                                                       preoperative skin
                                                       preparation
                                                       antiseptic
                                                       products.
------------------------------------------------------------------------
* Test organisms are representative of infections occurring in consumer
  settings.
** Test organisms are representative of infections occurring in health
  care settings.

    To assess the effectiveness criteria for food handler antiseptic 
active ingredients, as well as the testing methods necessary to 
demonstrate effectiveness, we are interested in gathering information 
on the following questions related to in vivo testing:
     What studies should be used for a demonstration of 
efficacy in vivo?
     Should effectiveness be established through clinical 
outcome study (e.g., show a statistically significant reduction in 
food-borne illness associated with the use of a food handler antiseptic 
in comparison to vehicle or washing with plain soap and water)?
     Do the data support use of a simulation model as a 
surrogate for effectiveness, such as bacterial log reduction on the 
hands of a food handler or on food following use of the product? What 
data can be used to link a simulation model to clinical outcomes 
related to food-borne illness (i.e., model validation)?
     If the bacterial log reduction method for assessing 
effectiveness is used, what should be the required log reduction 
criteria for food handler antiseptics and what are the data that 
support such log reduction criteria?
     Are there any other criteria, such as reduction of 
transmission of microorganisms after use of food handler antiseptics 
that should be considered to determine the effectiveness of food-
handler antiseptics?
     The Health Care Antiseptics Final Rule requires that for 
surgical hand scrub and patient preoperative skin preparation 
indications, the antiseptic activity of the product must be both 
immediate and persistent (82 FR 60474 at 60488). The effectiveness 
criteria for such products require that, in addition to the immediate 
antibacterial activity demonstrated by log reduction, bacterial growth 
is also suppressed for 6 hours after product use. Should food handler 
antiseptics' action be persistent?
     How are food handler antiseptics used in food handler 
settings? Are they used according to the manufacturer's directions of 
use or according to establishment-based standard operating procedures?
     Given the importance of a consistently effective product, 
should the dose of a food handler antiseptic vary with the product or 
should a standard dose be required?
     For the same reasons noted earlier, should the recommended 
length of time and/or frequency of use of the antiseptic product be 
consistent and standardized for all food handler antiseptics?
    We would also like information as it relates to the following 
questions on in vitro testing:
     How should the products demonstrate effectiveness in 
vitro?
     What in vitro test methods should be used, e.g., minimal 
bactericidal concentration and Time-kill Assay?
     What organisms should food handler antiseptics be required 
to demonstrate effectiveness against? Should viruses and other 
organisms (e.g., protozoa) be tested as well as bacteria?
     Should the test methods address the effects of organic 
load (i.e., high fat content, blood, or other materials) and dirt or 
soil on the effectiveness of food handler antiseptics?
     What other variables could impact the effectiveness of 
food handler antiseptics besides organic load, and how should the 
effect of such variables be taken into consideration during testing?
     How quickly must these products demonstrate effectiveness?
     At what specific time point(s) should effectiveness be 
measured?

VII. References

    The following references marked with an asterisk (*) are on display 
at the Dockets Management Staff (see ADDRESSES) and are available for 
viewing by interested persons between 9 a.m. and 4 p.m., Monday through 
Friday; they also are available electronically at https://www.regulations.gov. References without asterisks are not on public 
display at https://www.regulations.gov because they have copyright 
restriction. Some may be available at the website address, if listed. 
References without asterisks are available for viewing only at the 
Dockets Management Staff. FDA has verified the website addresses as of 
the date this document publishes in the Federal Register, but websites 
are subject to change over time.

*1. Comment submitted in Docket No. FDA-1975-N-0012-0111, Volume 1 
of 4, Part A. Available at https://www.regulations.gov/document?D=FDA-1975-N-0012-0111.
*2. Comment submitted in Docket No. FDA-1975-N-0012-0085. Available 
at https://www.regulations.gov/document?D=FDA-1975-N-0012-0085.
*3. Comment submitted in Docket No: FDA-1975-N-0012-0493. Available 
at https://www.regulations.gov/document?D=FDA-1975-N-0012-0493.
*4. FDA, ``HACCP Principles & Application Guidelines.'' Available at 
https://www.fda.gov/Food/GuidanceRegulation/HACCP/ucm2006801.htm. 
Accessed on May 15, 2018.
*5. Comment submitted in Docket No. FDA-1975-N-0012-0081. Available 
at https://www.regulations.gov/document?D=FDA-1975-N-0012-0081.
6. AOAC International ``AOAC 955.16-1955, Chlorine (available) in 
Disinfectants. Germicidal Equivalent Concentration.'' Available at 
http://www.aoacofficialmethod.org/index.php?main_page=product_info&cPath=1&products_id=1578. Accessed 
on May 15, 2018.
7. Boyce, J.M. and D. Pittet, ``Guideline for Hand Hygiene in 
Health-Care Settings; Recommendations of the Healthcare Infection 
Control Practices Advisory Committee and the HICPAC/SHEA/APIC/IDSA 
Hand Hygiene Task Force,'' Morbidity and Mortality Weekly Report, 
51:1-45, 2002.
8. Edmonds, S.L., R.R. McCormack, S.S Zhou, et al., ``Hand Hygiene 
Regimens for the Reduction of Risk in Food Service Environments,'' 
Journal of Food Protection, 75(7):1303-1309, 2012.
9. Chen Y., K.M. Jackson, F.P. Chea, et al., ``Quantification and 
Variability Analysis of Bacterial Cross-Contamination Rates in 
Common Food Service Tasks,'' Journal of Food Protection 64(1): p. 
72-80, 2001.

[[Page 63176]]

*10. FDA, Food Code 2017 2-301.12. Available at https://www.fda.gov/downloads/Food/GuidanceRegulation/RetailFoodProtection/FoodCode/UCM595140.pdf. Accessed on May 15, 2018.
*11. ``Diseases Transmitted through the Food Supply: Pathogens 
Transmitted by Food Contaminated by Infected Person Who Handle Food, 
and Modes of Transmission of Such Pathogens.'' Available at https://www.cdc.gov/foodsafety/pdfs/pathogens-by-food-handlers-508c.pdf.
*12. Gould, H., et al. ``Surveillance for Foodborne Disease 
Outbreaks-United States 1998-2008,'' Morbidity and Mortality Weekly 
Report, Surveillance Summaries 62 (2).
*13. Transcript of the October 20, 2005, Nonprescription Drugs 
Advisory Committee Meeting. Available at http://wayback.archive-it.org/7993/20170404055923/https:/www.fda.gov/ohrms/dockets/ac/05/transcripts/2005-4184T1.pdf. Accessed May 15, 2018
*14. Comment submitted in Docket No. FDA-1975-N-0012-0037. Available 
at https://www.regulations.gov/searchResults?rpp=25&po=0&s=FDA-1975-N-0012-0037&fp=true&ns=true. Accessed May 15, 2018.
*15. Comment submitted in Docket No. FDA-1975-N-0012-0038. Available 
at https://www.regulations.gov/searchResults?rpp=25&po=0&s=FDA-1975-N-0012-0038&fp=true&ns=true.
16. ASTM International, ``ASTM E2720, Standard Practice for 
Evaluation of Effectiveness of Decontamination Procedures for Air-
Permeable Materials when Challenged with Biological Aerosols 
Containing Human Pathogenic Viruses.'' Available at https://www.astm.org/search/fullsite-search.html?query=E2720&toplevel=products-and-services&sublevel=standards-and-publications. Accessed on May 15, 
2018.
17. ASTM International, ``ASTM E1052, Standard Test Method to Assess 
the Activity of Microbicides against Viruses in Suspension.'' 
Available at https://www.astm.org/search/fullsite-search.html?query=e1052&resStart=0&resLength=10&toplevel=products-and-services&sublevel=standards-and-publications&. Accessed on May 
15, 2018.
*18. Petition Denial Response Letter from FDA to PCPC and SDA. No. 
FDA-1975-0012-0042. Available at https://www.regulations.gov/document?D=FDA-1975-N-0012-0042. Accessed on May 15, 2018.
19. Steinman, J., ``Some Principles of Virucidal Testing,'' Journal 
of Hospital Infection, 48:S15-S17, 2001.
*20. Comment submitted in Docket No. FDA-1975-N-0012-0494. Available 
at https://www.regulations.gov/document?D=FDA-1975-N-0012-0494.

    Dated: December 3, 2018.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2018-26561 Filed 12-6-18; 8:45 am]
BILLING CODE 4164-01-P


