FOOD AND DRUG ADMINISTRATION

CENTER FOR DRUG EVALUATION AND RESEARCH

ADVICE

American Cleaning Institute

Attention: Paul C. DeLeo
Associate Vice President, Environmental Safety
1331 L Street, NW, Suite 650
Washington, DC 20005

Dear Mr. DeLeo:

Please refer to your July 20, 2016 submission to docket FDA-2015-N-01 01- 1295 (Safety and
Effectiveness for Health Care Antiseptics; Topical Antimicrobial Drug Products for Over-the-
Counter Human Use). You provided a list of organisms that would be tested as part of a
proposed single time-kill study and a single Minimum Inhibitory Concentration (MIC) and
Minimum Bactericidal Concentration (MBC) study for potential pathogens that may be
encountered in consumer use settings, health care settings, and food handler settings. You
indicated that most of the organisms identified come directly from the Consumer Wash proposed
rule (2013), Health Care Antiseptics proposed rule (1994 & 2015) and Consumer Hand Rub
proposed rule (2016). In addition, you have added other relevant organisms based on the
experience of your scientific experts, such as community-acquired methicillin-resistant
Staphylococcus aureus (A TCC# BAA-1683). You provided the following list of organisms to
include in your proposed time-kill study:

Time-Kill Testing
You propose to test 261 microorgani sms as part of a single time-kill test including 36 strains of
particular organisms based on FDA guidance, and an additional 225 clinical isolates; 25 clinical
isolates for each of the nine organisms identified by FDA in the Consumer Wash proposed rule:
• Enterococcus faecalis
• Staphylococcus aureus
• Streptococcus pyogenes
• Listeria monocytogenes
• Campylobacter jejuni
• Escherichia coli
• Pseudomonas aeruginosa
• Salmonella enterica Serovar Enteritidis
• Shigella sonnei
American Cleaning Institute
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MIC-MBC Testing
Additionally, you propose to test 900 organisms by the MIC and MBC methods, and propose to
test 25 strains and 25 clinical isolates of each of the following 18 microorganisms identified by
FDA in the Health Care Antiseptic proposed rule and the Consumer Hand Rub proposed rule:
• Haemophilus influenza
• Bacteroides fragilis
• Enterobacter species
• Burkholderia cepacia
• Escherichia coli
• Klebsiella pneumoniae
• Pseudomonas aeruginosa
• Serratia marcescens
• Campylobacter j ejuni
• Salmonella enterica
• Shigella sonnei
• Enterococcus faecalis
• Staphylococcus aureus (including methicillin-re sistant strains of Staphylococcus aureus
(MRSA))
• Streptococcus pyogenes
• Listeria monocytogenes
• Streptococcus pneumoniae
• Acinetobacter baumannii
• Candida albicans

We have the following comments:

You may run a single time-kill study for the Health Care Antiseptics, Consumer Antiseptic
Wash, and Consumer Antiseptic Hand Rub monographs and a single MIC/MBC study for the
Health Care Antiseptics and Consumer Antiseptic Hand Rub monographs, so long as it includes
all of the organisms required by the three monographs. We outline the additional organisms
required below. Regarding testing for food handlers antiseptics, note that we continue to classify
the food handler antiseptic washes and rubs as a separate and distinct monograph category, and
we clarify that such products are not part of these rulemakings on the consumer wash and rub
antiseptic monograph (78 FR 76444 at 76446; 81 FR 61106 at 61108; 81 FR 42912 at 429 15)
and health care antiseptic monograph (80 FR 25166 at 25 168). We plan to address OTC
antiseptic products for use by the food handler industry in a separate rulemaking, but have not
yet done so. While it is premature to speculate on what data will be required under the food
handler antiseptic monograph, you may use whatever data you develop for the health care and
consumer antiseptic monographs to the extent that it applies.

In vitro Time-Kill Testing

1. Include the following additional organisms as described in the 1994 and 2015 Health
Care Antiseptic proposed rule and in draft time-kill protocol that was submitted on
January 5, 2016:
• Enterococcus faecalis (ATCC 51575) multidrug resistant and vancomycin
resistant Enteroccoci
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• Enterococcus faecium (ATCC 700221) vancomycin resistant Enteroccoci

• Micrococcus luteus (ATCC 7468)
• Proteus mirabilis (ATCC 7002)
• Staphylococcus epidermidis (ATCC 12228)
• Staphylococcus epidermidis (ATCC 51625) methicillin resistant Staphylococcus
epidermidis (MRSE)
• Staphylococcus haemolyticus (ATCC 29970)
• Staphy lococcus hominis (ATCC 27845)
• Staphylococcus saprophy ticus (ATCC 15305)

We recommend that you test a total of 268 microorganisms as part of a single time-kill.
This includes: a) 43 strains of particular organisms based on the three antiseptic
categories (Consumer Antiseptic Wash, Consumer Antiseptic Hand Rub, and Health Care
Antiseptic), and b) an additional 225 clinical isolates, 25 clinical isolates for each of the
nine organisms identified in the Consumer Antiseptic Wash proposed rule. See previous
guidance given to you in an advice letter dated March 8, 2016, and Table 1 below.
Table 1. Organisms for In Vitro Time-Kill Efficacy Testing for OTC Topical Antiseptic Monographs

Organism ATCC Number Consumer Consumer Health Care

Ant iseptic Hand Antisept ic Antiseptics
Wash PR (December Hand Rub PR PR (May 1.
17, 2013) (J une 30, 2016) 2015)
Enrerococcus (aeculis 19433 X X
E111erococcus (aecolis 29212 X X X
Sroplrdococms aw·cus 6538 X X X
Stophlococcus a11re11S 29213 X X X
methicillin resistanl S. oureus (MRSA) 33591 X X
methicillin resistant S. o11reus (MRSA) 33592 X X
Slreprococcus Pl'O((cuc~ 14289 X X X
SrreprO<·occus pyogcucs 19615 X X X
Listl!ria monoc.·-rtoJ?enes 7644 X X
LiSICI'/11 n!OIIOCJ'IOJ<CIIC.l 19115 X X
Camprlobacrer ieillni 33291 X X
Camp_l·lobocler ;e;rmi 49943 X X
Escherichia coli 11775 X X X
Escherichia coli 25922 X X X
Pseudomonas oem((illosa 15442 X X X
Pseudomonas aeru~inosa 27853 X X X
Salmouclla Clllerico Scromr Enreriridis 13076 X X
Salmouclla enrcrica Scron1r T1phimuritm1 14028 X X
Sltir.!,ella sotmei 9290 X X
.S'hi.r,e/lo somtei 25931 X X
Ha<~nophillls inj/11e11:o TBD or 19418 X X
Bacreroides fm.(!ilis TBD or 25285 X X
Eurerobacrer species TBD or 13048 X X
Burkltoldcria cepocio 25416 X
Burkholdctia Ci!jJOCia 25608 X
Klebsiella pnewnonioe 13883 X X
Klebsiella pneumonioe 27736 X X
Sc11'otia marcesct'JIS 8100 X
Scrrorio morccsccn.l 14756 X X
Srreprococcns pncmno11iae 6303 X X
STreptococcus pueumoniae 49619 X X
.-lcinerobacrer boumamtii TBD or 19606 X
Candida olbicaus TBD or 10231 X
Caudidorropica/is TBD or750 X
Emcrococcus faecalis (.HDR. I'REJ TBD or 51575 X
Emerococcus {oeciwn ri'R£1 TBD or 700221 X
.\licrococcus lmeus TBDor 7468 X
Pmreus mirobilis TBD or 7002 X
Sraphrlococcus cpidennidis TBD or12228 X
SroJ!hrlacoccus epidennidis (MRS£) TBD or5 1625 X
Stophrlococcus ltotmnis TBDor 27845 X
Stopln·lococcus lwemol\'llcus TBD or 29970 X
Stopltrlocaccus sapropltrric11s TBDo r 15305 X
American Cleaning Institute
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MIC/MBC Testing
2. Include the following additional organisms as described in the 1994 and 2015 Health
Care Antiseptic proposed rule:
• Enterococcus faecium (including vancomycin resistant strains of Enterococci)
• Micrococcus luteus
• Proteus mirabilis
• Staphylococcus epidermidis (including methicillin resistant strains of
Staphylococcus epidermidis)
• Staphy lococcus haemolyticus (ATCC 29970)
• Staphylococcus hominis (ATCC 27845)
• Staphylococcus saprophyticus (ATCC 15305)

We recommend that you test 1,250 organisms by the MIC/MBC test method. You would
need to test 25 strains and 25 clinical isolates of each of the following 25 microorgani sms
identified in the Health Care Antiseptic proposed rule and the Consumer Antiseptic Hand
Rub proposed rule. See Table 2 below.

Table 2. Organisms for MIC/MBC Efficacy Testing for OTC Topical Antiseptic Monographs

Organism Consumer Antiseptic Health Care

Hand Rub PR Antiseptics PR
(June 30, 2016) (May 1, 2015)
I Hacmophi/us inflltcllza X X
2 Bacteroides fmgilis X X
3 Enterobactcr species X X
4 Burkholderia cepacia X
5 Escherichia coli X X
6 Klebsiella pneumoniae X X
7 Pseudomonas aeruginosa X X
8 Serratia marcescens X X
9 Campylobacter jejrmi X
10 Salmonella em erica X
II Shigella sonnei X
12 Enterococcusfaecalis X X
13 Staphy lococcus aure us (including methicillin- X X
resistant strains of Stnphrlococcus ourem (lvfRSA))
14 STreptococcus pyogenes X X
15 LisTeria mon ocr!o~en es X
16 Streprococcus pneumoniae X X
17 •.J.cinetobacter baumannii X
18 Candida albicans X
19 Enterococcus.faecium (including vancomycin- X
re~ i sta nt stra i n~ o f Emerococci (VRE))
20 J1icrococcus lureus X
21 Proreus mirabilis X
22 Sraphylococcrts epidermidis (including methicillin- X
resistam strains of Stnphvlococcus cpidermidis (MRSE))
2~ Staphvlococcus hominis X
24 Stapln 1ococcus haemolvticus X
25 Srapln'lococcus saprophyticus X
American Cleaning Institute
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If you have any questions, call Celia Peacock, Regulatory Project Manager at (301) 796-4154.

Sincerely, ~
~UJ) IVJ1 1rrr-vuLV, ~to
Theresa Michele, MD
Director
Division ofNonprescription Drug Products
Office of Drug Evaluation IV
Center for Drug Evaluation and Research