Clinical trial NCT03155178
Conditions: Bacterial Recovery of Skin Flora Post-product Application
Sponsor: Solventum US LLC
Start date: 2016-12-05; Completion date: 2017-04-25
Enrollment: 69 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Evaluate persistent antimicrobial effectiveness of chlorhexidine gluconate containing products on abdominal and inguinal sites following a saline and wipe challenge.

Detailed description:
Persistent antimicrobial effectiveness was evaluated by measuring the regrowth of normal skin flora at 48 hours, 72 hours and 96 hours, and the suppression of regrowth relative to post-prep (10-min) at 48 hours, 72 hours and 96 hours.

Arms: arm 1: Apply topically for 30 seconds (abdominal site) or 2 minutes (inguinal site), and allow to dry for 3 minutes. arm 2: Apply topically for 30 seconds (abdominal site) or 2 minutes (inguinal site), and allow to dry for 3 minutes.
Interventions: intervention 1: 3M CHG/IPA Prep intervention 2: ChloraPrep
Intervention descriptions: intervention 1: Apply topically to intact dry skin (abdominal site) for 30 seconds or moist skin (inguinal site) for 2 minutes. intervention 2: Apply topically to intact dry skin (abdominal site) for 30 seconds or moist skin (inguinal site) for 2 minutes.

Protocol documents:
Prot_SAP_000.pdf: 
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Clinical Study Protocol
Study Number and Protocol Title
EM-05-013953
96-hour Antimicrobial persistence
assessment
 
 
Following Exposure to Saline 
and Blotting
Principal Investigator
 
 
 
Sub-Investigators:
 
 
 
Research Facility
Eurofins Evic Romania/ S.C. BIO HIGH 
TECH S.R.L.
Bucharest 040256 Romania
IRB/EC
Name: Chesapeake Institutional Review 
Board 
Address: 6940 Columbia Gateway Drive, 
Suite 110, Columbia, Maryland, 21046, USA


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Sponsor
3M Health Care
3M Center
St. Paul, MN  55144-1000
3M Study Monitor
3M Medical Monitor
 
  


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Table of Contents
1.
BACKGROUND INFORMATION.................................................................................7
1.1 Name, Description and Intended Use of the Investigational Product ....................................7
1.2 Summary of Relevant Studies..............................................................................................7
1.3 Risk/Benefit Summary ........................................................................................................8
1.4 Investigational Material Application....................................................................................8
1.5 Good Clinical Practices and Regulatory Requirements ........................................................8
1.6 Study Population .................................................................................................................8
2.
STUDY OBJECTIVES ....................................................................................................9
3.
STUDY DESIGN..............................................................................................................9
3.1 Study Type and Methodology..............................................................................................9
3.2 Primary and Secondary Endpoints .....................................................................................12
3.3 Randomization and Blinding .............................................................................................12
3.4 Study Products and Labeling .............................................................................................12
3.4.1
Study Products.......................................................................................................12
3.4.2
Investigational Products Labeling and Accountability............................................13
3.4.3
Other Product Labeling..........................................................................................13
3.4.4
Additional Study Supplies......................................................................................14
3.5 Study Duration ..................................................................................................................15
3.6 Study Termination/Subject Discontinuation or Withdrawal ...............................................15
3.6.1
Study Termination .................................................................................................15
3.6.2
Subject Discontinuation or Withdrawal..................................................................16
3.7 Source Data.......................................................................................................................16
3.8 Computerized Systems ......................................................................................................16
3.9 Protocol Modifications ......................................................................................................16
3.9.1
Protocol Amendments............................................................................................16
3.9.2
Protocol Deviations................................................................................................17
4.
SUBJECT SELECTION ................................................................................................17
4.1 Subject Inclusion Criteria ..................................................................................................17
4.2 Subject Exclusion Criteria .................................................................................................18
4.3 Subject Informed Consent .................................................................................................19
5.
TREATMENT OF SUBJECTS .....................................................................................19
5.1 Medication(s)/Treatment(s) Not Permitted.........................................................................19
5.2 Subject Compliance...........................................................................................................19
5.3 Study Procedures...............................................................................................................19
5.3.1
Pretreatment Phase (Washout) ...............................................................................19
5.3.2
Screening Phase.....................................................................................................20
5.3.3
Treatment Phase ....................................................................................................20
6.
ASSESSMENT OF EFFICACY ....................................................................................22


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6.1 Efficacy Parameters...........................................................................................................22
6.2 Assessment Methods .........................................................................................................23
6.2.1
Microbiological Methods.......................................................................................23
6.3 Subject Discontinuation.....................................................................................................23
7.
ASSESSMENT OF SAFETY.........................................................................................24
7.1 Safety Parameters..............................................................................................................24
7.2 Assessment Methods .........................................................................................................24
7.3 Adverse Events..................................................................................................................24
8.
STATISTICS ..................................................................................................................25
8.1 Data Sets Analyzed............................................................................................................25
8.2 Statistical Methods ............................................................................................................25
8.2.1
Efficacy Analyses ..................................................................................................25
8.2.2
Safety Analyses .....................................................................................................25
8.3 Sample Size Justification...................................................................................................26
8.4 Criteria for Termination of the Study.................................................................................26
8.5 Procedures for Accounting for Missing, Unused, and Spurious Data..................................26
8.6 Deviations to Statistical Plan .............................................................................................26
9.
MONITORING ..............................................................................................................26
10.
QUALITY CONTROL AND QUALITY ASSURANCE..............................................26
11.
ETHICS ..........................................................................................................................26
12.
DATA HANDLING AND RECORD KEEPING ..........................................................27
12.1 Study Personnel.................................................................................................................27
12.2 Pre-Study Documentation Requirements ...........................................................................27
12.3 Completion and Return of Case Report Forms...................................................................27
12.4 Final Report.......................................................................................................................27
12.5 Records, Reports and Retention Requirements...................................................................27
13.
REFERENCES...............................................................................................................28
14.
APPENDICES ................................................................................................................29
14.1 Study Flow Diagrams ........................................................................................................29
14.2 Study Product Application Instructions..............................................................................31
14.3 Confirmation of Release & Receipt of Clinical Supplies....................................................32
14.4 Study Product Disposition Form........................................................................................33
14.5 Subject Instructions ...........................................................................................................34
14.6 Elements of Informed Consent...........................................................................................35
14.7 Test Site Diagrams ............................................................................................................37
14.8 Skin Irritation Rating Scale................................................................................................38
14.9 Protocol for Neutralization Validation ...............................................................................39
14.9.1 Background ...........................................................................................................39
14.9.2 Objective ...............................................................................................................39


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14.9.3 Subject Entry Criteria ............................................................................................39
14.9.4 Test Organism .......................................................................................................40
14.9.5 Study Products.......................................................................................................40
14.9.6 Materials, Supplies and Equipment ........................................................................41
14.9.7 Study Procedures ...................................................................................................42
14.9.8 Control of Bias.......................................................................................................43
14.9.9 Data Evaluation .....................................................................................................43


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1.
BACKGROUND INFORMATION
 
 
 
 
 
 
 
 
 
 
 
 
The purpose of this study is to evaluate
 3M CHG/IPA 
Prep compared with a commercially available skin prep
 
in suppressing the growth of 
residual skin flora by measuring the regrowth of normal skin flora following exposure to fluids 
and mechanical removal by wiping on the abdomen at 48 hours, 72 hours and 96 hours.
1.1
Name, Description and Intended Use of the Investigational Product
(3M CHG/IPA Prep) is an 
investigational new drug containing 2% w/v chlorhexidine gluconate (CHG) and 70% v/v 
isopropyl alcohol (IPA)
 contains 2% w/v CHG and 
70% v/v IPA and will be used as the marketed comparator prep.  
.  
1.2
Summary of Relevant Studies
 
 
 Refer to the Investigator Brochure 
 
for a summary of these studies. 


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1.3
Risk/Benefit Summary
There are minimal anticipated adverse health risks for the participants of this study.  
Considerable safety and efficacy data are available for the active ingredients in the 
investigational product and preclinical safety studies,
, have been completed.  
 
 
 
There are no direct health benefits to subjects who participate in this study.
1.4
Investigational Material Application 
This study will be conducted using
 
 3M CHG/IPA Prep and 
.  Both products will 
be applied topically to intact skin of the subject’s abdominal and inguinal regions.    
The products will be applied as intended per instructions for use 
  
 
 
    
1.5
Good Clinical Practices and Regulatory Requirements
 
 
  
 
This study will be conducted in compliance with the protocol, Good Clinical Practice (GCP), 
Declaration of Helsinki and applicable state, federal and regional regulations including 21 CFR 
312 (Investigational New Drug Application), 50 (Protection of Human Subjects), 56 
(Institutional Review Boards), 54 (Financial Disclosure by Clinical Investigators).  And in 
accordance with the European Directive 95/46/EC on the protection of individuals with regard to 
the processing of personal data and on the free movement of such data and with the Romanian 
Order No 677/2001 for the protection of persons concerning the processing of personal data and 
free circulation of such data.  And in spirit with Directive of the European Parliament and 
Council 2001/20/EC, and Romanian Order No. 904/25.07.2006.
1.6
Study Population
Healthy subjects, ages 18 or older, of either gender who meet the study inclusion/exclusion 
criteria are eligible for enrollment into this study.
A sufficient number of subjects will be enrolled in the screening phase to provide a minimum of 
50 treatment sites per anatomical region, per treatment, per collection time that meet the baseline 
requirements on treatment day and have an intact dressing at the collection time.  Subjects must 
satisfy all Screening Day and Treatment Day Inclusion/Exclusion Criteria prior to collection of 
screening baselines and Treatment Day procedures.  If the required numbers of subjects do not 


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qualify from the initial screening group, additional subjects will be recruited, as needed.
Treatment day baseline requirement is greater than or equal to 3.0 log10 CFU/cm2 on the 
abdomen and greater than or equal to 5.0 CFU/cm2 on the groin.
Each subject will be identified by a screening identification number, and a treatment number.  
Subject treatment numbers will not be assigned until a subject has passed the screening criteria, 
including screening baseline bacterial counts.
Both the right and left sides of the abdomen and/or groin must meet the screening baseline 
requirements stated in the Inclusion Criteria to qualify for treatment of that anatomical region in 
the study.
2.
STUDY OBJECTIVES
The primary objective of this study is to evaluate the persistent antimicrobial effectiveness of the 
3M CHG/IPA Prep
) and 
) on the abdomen and 
groin following a saline and wipe challenge by measuring the regrowth of normal skin flora at 48 
hours, 72 hours and 96 hours.  The secondary objective is to evaluate the suppression of 
regrowth relative to post-prep (10-minute) of 3M CHG/IPA Prep and 
 at 48 hours, 72 
hours and at 96 hours post-prep.
Safety will also be evaluated based on the incidence of adverse events reported during the study 
and assessment of skin irritation ratings.
3.
STUDY DESIGN
3.1
Study Type and Methodology
This is a randomized, controlled, third-party blind, single-center study in healthy subjects using a 
paired comparison design where each subject receives both study products on the abdomen 
and/or groin.  The study staff performing the bacterial enumeration and the statistician 
performing the analysis will be blinded to the study products.
This study will be conducted using a modification of ASTM E1874-14 Standard Test Method for 
Recovery of Microorganisms from Skin using the Cup Scrub Technique.1  
Time points for sample collection are baseline, 10 minutes, 48 hours, 72 hours and 96 hours.  
After collection of the 10 minute time point sample, a repetitive saline soak and wiping 
procedure is performed to simulate the fluid and mechanical removal challenges occurring in 
surgery.      
Table 3.1A provides a summary of the study procedures.  A schematic diagram of the study is 
included in Appendix 14.1.


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Table 3.1A Study Summary
14-day 
Pretreatment 
Phase
Screening 
Phase
Treatment Phase
T=0
T=48 hours
T=72 hours
T=96 hours
Perform the 
Informed 
Consent 
process.
The 
Inclusion/Exc
lusion
Criteria will 
be reviewed 
to ensure 
eligibility for 
the study.  If 
these criteria 
are satisfied, 
subjects will 
sign the 
consent form.  
Complete 
Inclusion/ 
Exclusion 
Criteria form; 
Assign sequential 
subject number;
Complete
Inclusion/ 
Exclusion 
Criteria form
Complete 
48-hour  
Compliance 
Form
Complete 
72-hour 
Compliance 
Form
Complete 
96-hour 
Compliance
Form
Assign 
subject 
screening 
number
Perform visual 
skin assessment
Perform visual 
skin assessment
Perform 
skin 
irritation 
rating
Perform 
skin 
irritation 
rating
Perform 
skin 
irritation 
rating
Complete 
Inclusion/
Exclusion 
Criteria form
Collect 
screening 
baseline 
samples from 
abdominal and 
inguinal regions
Perform skin 
irritation rating
Collect 48-
hour 
 
post-prep 
regrowth 
samples
Collect 72-
hour 
 
post-prep 
regrowth 
samples
Collect 96-
hour 
 
post-prep 
regrowth 
samples
Review 
subject 
instructions 
for wash out 
and dispense 
subject 
personal 
hygiene kit
Count screening 
plates, 
determine 
which subjects 
qualify for
study
Per 
randomization, 
mark test areas, 
collect baseline 
samples from 
abdominal and 
inguinal regions
Check the
dressings 
covering the 
72-hour and 
96-hour 
sampling
sites and 
reinforce as 
necessary.
Check the 
dressings 
covering the 
96-hour 
sampling
sites and 
reinforce as 
necessary.  


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Schedule for 
clipping 72 
hours prior to 
screening, if 
needed.
Contact eligible 
subjects, 
schedule 
Treatment Day 
(schedule for 
clipping 72 
hours prior to 
treatment, if 
needed) 
Per 
randomization, 
apply study 
products
Perform skin 
irritation rating, 
collect 10-
minutes
 
 post-
prep samples
Challenge test 
sites with 
repetitive saline 
soak and wiping:  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
48-, 72- and 96-
hour regrowth 
sites with semi-
occlusive 
dressings


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3.2
Primary and Secondary Endpoints
Primary Endpoint:
The primary measure of persistence is the suppression of regrowth relative to baseline of 3M 
CHG/IPA Prep and
 at 48 hours, 72 hours and at 96 hours post-prep.  
Secondary Endpoint:
The secondary measure of persistence is the suppression of regrowth relative to post-prep (10-
minute) of 3M CHG/IPA Prep and
 at 48 hours, 72 hours and at 96 hours post-prep.
The principal measure of safety will be the incidence of adverse events reported during the study 
and a summary of the skin irritation rating scores.  
 
3.3
Randomization and Blinding
The left and right test areas on each subject’s abdominal and inguinal regions will be randomized 
to receive either the investigational product, 3M CHG/IPA Prep, or the marketed comparator 
product, 
  The inguinal region baseline and all post-prep samplings will be 
randomized to sites within each test area.  The Investigator is responsible to assure that the study 
randomization is followed.  The randomization schedule will be provided to the study site in a 
separate document.
The study products cannot be blinded from the Investigator or study staff performing the product
application, sample collection and skin assessment due to the obvious differences in applicator 
design and other physical characteristics.  However, the study staff performing the bacterial 
enumeration will not be involved in the study product application or the collection of samples 
and, therefore, will be blinded to the study products.  The statistician performing the analysis will 
also be blinded until after data lock.
3.4
Study Products and Labeling
3.4.1
Study Products

Investigational prep:  3M™CHG/IPA Film-forming Patient Preoperative Skin Preparation, 
2% w/v CHG/70% v/v IPA,
 
 
 

Comparator prep:  
 
2% w/v CHG/70% v/v IPA
 
 
  
3M CHG/IPA Prep and the marketed comparator prep will be applied topically to intact skin of 
the abdominal and inguinal (groin) regions of the subject.  The prep will be applied with repeated 
back-and-forth strokes for 30 seconds on the abdomen or 2 minutes on the groin and allowed to 
dry for 3 minutes.


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Detailed instructions for application and removal of the study products are provided in the 
Investigational Product Application Instructions (Appendix 14.2).
3.4.2
Investigational Products Labeling and Accountability
3M will label, package and ship the study products to the research facility.  The 3M CHG/IPA 
Prep will be provided in individual 
 packages, and labeled as below.
Sample Investigational Product Label 
CAUTION: New Drug-Limited by Federal Law to Investigational Use
For use in study EM 05-013953
3M Health Care, St. Paul, MN 55144-1000
3M CHG/IPA Prep
   Subject Number:
Product ID: 
Lot: TBD
Directions: Use as directed in protocol
Warning:  Contents are flammable until dry.
3M requires Investigators to maintain accountability and adequate inventory security of the study
products at all times. The Investigator or designee will: 
●
Document receipt of study products on the Confirmation of Release & Receipt of Clinical 
Supplies form (Appendix 14.3) and return the completed form to 3M, 
●
Store study products in a secure facility accessible only to authorized individuals,
●
Dispense study products only to subjects properly enrolled into the study,
●
Account for inventory and disposition using the Study Product Disposition Form (Appendix 
14.4), and
●
Dispose of used and unused study products as agreed upon.  Once accounted for the study 
products may be disposed.  Documentation shall be maintained concerning the disposal and 
will contain:  the quantity of the study product(s) disposed of, the date and manner of 
disposal, the staff member who conducted the disposal.  NOTE: Record the subject number 
on the package label and retain the label for inventory purposes.  The used applicator can be 
discarded.
In addition, copies of all completed Study Product Disposition Forms and disposal records must 
be retained in the Investigator Study Documentation File.  The originals of all Study Product
Disposition Forms and disposal records must be sent to the Sponsor’s Clinical Monitor.
3.4.3
Other Product Labeling
The comparator prep, 
is available for commercial use.  The 
 products 
will be provided in original marketed packaging with an over label, as below, placed on each 
applicator pouch.


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Sample Marketed Comparator Prep Label 
Commercialized Product
For use in study EM-05-013953
3M Health Care, St. Paul, MN 55144-1000
Subject Number: 
Directions: Use as directed in protocol
Warning:  Contents are flammable until dry.
3.4.4
Additional Study Supplies
Sponsor will provide the following:
●
Study Material Disposition forms
●
Randomization schedule
●
Data Collection Sheets (DCSs)
●
Investigational products
Study site will provide the following:
●
Subject Informed Consent forms, IRB/EC-approved
●
 
 
 
 


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 counter 
3.5
Study Duration
The expected duration of this study for each subject is up to 4 weeks.  Each subject’s 
participation will involve at least a 14-day Pretreatment Phase (washout), a 1-day Screening 
Phase, and a 4-day Treatment Phase.  Following the Pretreatment Phase, each subject will be 
required to visit the test facility on an arranged date for collection of screening baseline samples 
from the abdominal and inguinal regions.  Subjects will remain on washout until notified that 
they do or do not qualify for the study.  Subjects whose screening baseline samples meet the 
requirements described in the Inclusion Criteria (Section 4.1) will be notified and invited to 
participate in the Treatment Phase of the study.  The Treatment Phase will be scheduled no 
sooner than 72 hours from the screening baseline collection.  Each subject who chooses to 
participate in this study will be required to return to the test facility for Treatment Day and again 
at 48 hours, 72 hours and 96 hours after treatment for sample collection.  Table 3.1A indicates 
the sequence of events throughout the study and a schematic diagram of the study is included in 
Appendix 14.1.
3.6
Study Termination/Subject Discontinuation or Withdrawal
3.6.1
Study Termination
Conditions that may warrant termination of the study by 3M include, but are not limited to the 
following:


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●
The discovery of an unexpected, serious, or unreasonable risk to study subjects,
●
Insufficient adherence to protocol requirements,
●
Failure of the Investigator to enroll subjects into the study at an acceptable rate,
●
Failure of the Investigator to comply with pertinent state, federal or regional regulations or 
applicable privacy regulations,
●
Submission of knowingly false information from the Investigator to 3M,
●
Termination of IND or IRB/EC approval, or withdrawal of the IRB/EC approval, 
●
A decision on the part of 3M to suspend or discontinue evaluation of the investigational 
product.
3.6.2
Subject Discontinuation or Withdrawal
The Investigator may discontinue individual subjects from the study at any time.  Subjects 
entering the study may withdraw at any time without penalty.  The right of each test subject to 
withdraw from the study and the right of each test subject to privacy, confidential treatment of 
personal data, and protection from view by others not conducting the study will be respected at 
all times.  The Investigator will provide a written report on the appropriate case report form
including the date and reason for discontinuance.
3.7
Source Data
Electronic data capture (eDC) will be used for this study.  If not entered directly into eDC, data 
will first be recorded onto a DCS, followed by entry into the appropriate electronic case report 
form (eCRF).  Wherever the data are entered first is considered the source document.
3.8
Computerized Systems
All study data will be loaded into the 
data management system.
The current 3M Health Care document storage system,
, will be used to store the study 
documents.  
, may be used 
for study documentation and data analysis.
3.9
Protocol Modifications
3.9.1
Protocol Amendments
A protocol amendment is defined as a change in procedure that is identified and documented 
before initiation.  A significant amendment means one that affects the safety, rights or welfare of 
subjects, the scope of the investigation or the scientific quality of the study.
All protocol amendments must be documented and approved by the Investigator and study
monitor prior to implementation. All protocol amendments must also be pre-approved by the 
reviewing IRB/EC prior to implementation.
3M will submit significant protocol amendments to the Investigator for submission to the 
IRB/EC.  3M will also notify the Investigator when a protocol amendment may be implemented.


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3.9.2
Protocol Deviations
A protocol deviation is defined as a change in procedure that has not been documented before 
initiation and therefore has not been reviewed and approved with the study sponsor and/or 
reviewing IRB/EC prior to initiation.  All deviations from the study protocol are to be 
documented and reported to the investigator/study sponsor and reviewing IRB/EC.
A deviation is a departure from the protocol that will likely affect the safety, rights or welfare of 
subjects, the scope of the investigation or the scientific quality of the study.
A protocol deviation is only for an individual subject.  Deviations that potentially affect 1) 
subject safety, rights or welfare, 2) data integrity or 3) compromise the statistical analysis of the 
study require immediate communication to 3M.  The Investigator must contact the 3M study 
monitor
.  A Protocol Deviation Form must be completed by the 
Investigator and include the type of deviation and a description of the circumstances surrounding 
the deviation.  A copy is sent to the 3M study monitor
 
 identifying the 
occurrence.
Deviations, which are made to protect the life or physical well-being of a subject in an 
emergency, must be reported by the Investigator to the IRB/EC within 5 working days of 
occurrence.
4.
SUBJECT SELECTION
Healthy subjects will be recruited.  A suitable number of subjects will be enrolled in the 
pretreatment, screening and treatment phase, such that a total of 50 subjects are evaluable for 
efficacy at completion of the study.  
Subjects must follow all Subject Instructions (Appendix 14.5) and satisfy inclusion/exclusion 
criteria prior to enrollment into the treatment phase of the study.  
All subjects will be provided verbal and written information about the study procedures, and 
subject instructions (Appendix 14.5).  The following inclusion/exclusion criteria will be 
reviewed on pretreatment, screening and treatment day to establish eligibility for participation:
4.1
Subject Inclusion Criteria
Subjects to whom all of these conditions apply will be eligible for enrollment in this study:
1. Subjects of either gender and any race who are at least 18 years of age,
2. Subjects must be in good general health,
3. Subjects who agree to be and appear to be compliant with the requirements of the study,
4. Subjects who have good skin condition on the test sites,
5. Subjects who are willing to report to the study facility approximately 72 hours prior to 
Screening or Treatment Day for clipping, if needed,
6. Subjects who are willing to avoid showering and tub-bathing within 72 hours prior to 
Screening and Treatment Days (sponge-baths may be taken; however, the lower abdomen 
and upper thigh regions must be avoided),


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7. Subjects who are willing to avoid showering, tub-bathing, swimming, and vigorous physical 
activity that may cause sweating once study products have been applied,
8. Subjects who are willing to return to the study facility at 48 hours, 72 hours and 96 hours 
after treatment for sample collection, and
9. Subjects who have Screening Day baseline counts of > 3.00 log10 per cm2 bilaterally on the
abdominal region and/or > 5.00 log10 per cm2 bilaterally on the inguinal region.
4.2
Subject Exclusion Criteria
Subjects to whom any of these conditions apply will be excluded from this study:
1. Participation in another clinical study in the past 30 days, current participation in another 
clinical study, or previous participation in this study,
2. Has taken antihistamines in the 48 hours prior to Treatment Day, 
3. Any tattoos, scars, breaks in the skin, or any form of dermatitis, or other skin disorders 
(including acne) on the applicable test areas,
4. A history of skin allergies,
5. A history of skin cancer within 6 inches of the test areas,
6. Known sensitivity to acrylate-, chlorhexidine gluconate-, or alcohol-containing products, or 
to medical tape, metals, natural rubber latex, vinyl, or skin-marking inks, 
7. A medical diagnosis with physical condition that may put the subject at risk, such as a 
current or recent severe illness, hepatitis, organ transplant, congestive heart disease, or any 
immunocompromised conditions, such as AIDS (or HIV positive),
8. Any medical condition or use of any medications that, in the opinion of the Investigator, 
should preclude participation,
9. Pregnancy, possible pregnancy, attempting pregnancy, or nursing,
10. Topical antimicrobial exposure within 14 days prior to Screening Day and throughout the 
study.  Restrictions include, but are not limited to antimicrobial soaps, medicated shampoos, 
medicated lotions, antiperspirants/deodorants, perfumes, after shaves, and colognes,
11. Use of systemic or topical antibiotic medications, steroid medications (other than for 
hormonal contraception or postmenopausal reasons), or any other product known to affect 
the normal microbial flora of the skin within 14 days prior to Screening Day and throughout 
the study,
12. Exposure of the test areas to solvents, acids, bases, strong detergents, fabric softener-treated 
clothing, or other household chemicals within 14 days prior to Screening Day and throughout 
the study,
13. Swimming in chemically treated pools or bathing in hot tubs, spas, or whirlpools within 14 
days prior to Screening Day and throughout the study,
14. Use of tanning beds, hot waxes, or depilatories (in the applicable test areas) within 14 days 
prior to Screening Day and throughout the study
15. Bathing and showering within 72 hours prior to Screening Day and throughout the study, or


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16. Subject has used moisturizers or any topical treatment (eg lotion, sunscreen or shaving 
cream) on the test sites in the 24-hour period prior to participation in the study.
4.3
Subject Informed Consent
The Investigator or designee must ensure that written informed consent to participate in the 
investigation is obtained before including any individual as a subject in the investigation.  The 
Investigator or designee must provide the prospective subject or the representative sufficient 
opportunity to consider whether or not to participate, and minimize the possibility of coercion or 
undue influence.  The process is designed to 1) give the subject all the information that they need, 
2) ensure that the subject understands the information and 3) give the subject a chance to consider 
study participation.  The process should permit the subject to ask questions and exchange 
information freely.
Specifically, the Investigator or designee is to explain to each subject all elements of informed 
consent as specified in 21 CFR 50.25 (Appendix 14.6).  After the explanation, the subject or 
representative will voluntarily sign and date the consent form if they wish to participate in the 
study.  A copy of the consent form must be provided to the subject.  A signed and dated copy of 
the consent form must be maintained in the Investigator study documentation file at all times.  
Consent and study participation, with date, must be documented in the subject’s record.
5.
TREATMENT OF SUBJECTS
5.1
Medication(s)/Treatment(s) Not Permitted
Exposure of the test areas to antimicrobial agents is not permitted within 14 days prior to 
Screening Day and for the duration of the study.  Restrictions include, but are not limited to 
antimicrobial soaps, antiperspirants/deodorants, shampoos, lotions, perfumes, after shaves, 
colognes, steroid medications (other than for hormonal contraception or postmenopausal 
reasons), and topical or systemic antibiotics.
5.2
Subject Compliance
Answers to the Inclusion/Exclusion Criteria questions asked at the beginning of the Screening 
and Treatment Phases, and Compliance questions prior to the 48 hour, 72 hour and 96 hour
sample collection will determine compliance to the requirements of the study.
5.3
Study Procedures
These study procedures are based on ASTM E1173-15, Standard Test Method for Evaluation of 
Preoperative, Precatheterization, or Preinjection Skin Preparations.2
5.3.1
Pretreatment Phase (Washout)
The Inclusion/Exclusion Criteria will be reviewed with each subject to ensure eligibility for the 
study.  If these criteria are satisfied, subjects will sign the consent form.  Prior to the scheduled 
Screening Day, subjects will undergo a minimum 14-day pretreatment phase to allow for the 
removal of any antimicrobial agents from the subjects’ skin.  Subjects are to refrain from the use 
of products containing antibacterial agents as written in the Subject Instructions (Appendix 14.5).  
Subjects will be given personal hygiene kits containing non-antimicrobial products for use 


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during this period.  Subjects will be instructed to use these products through completion of the 
Treatment Phase or until notified by the Investigator or designee.
In addition, subjects must avoid systemic or topical antibiotics or medications and contact with 
chemically treated swimming pools or hot tubs, hot waxes, and depilatories on the test areas for 
14-days before the scheduled Screening Day.  If it becomes necessary to take systemic 
antibiotics or to apply topical medications to the test areas within this pretreatment period, the 
subject must contact the Investigator as soon as reasonably possible so that another subject may 
be recruited.
If subjects require hair removal to facilitate sample collection, the subject will be asked to return 
to the test facility approximately 72 hours before the Screening Day.  Subjects will not be 
allowed to shower or bathe for 72 hours prior to their scheduled screening appointment.  Sponge-
baths may be taken; however, the lower abdomen and upper thigh regions must be avoided.
5.3.2
Screening Phase
Prior to collection of the screening baseline samples, the Investigator or a designee will complete 
the screening Inclusion/Exclusion form.  A visual skin assessment of the test areas will be 
performed and the screening baseline samples will be collected using the cup scrub technique 
described in Section 6.2.1.1. 
 
Samples from both the left and right sides of the abdominal and/or inguinal regions must meet 
the values indicated in the Inclusion Criteria to be enrolled into the Treatment Phase of the study.  
Those subjects who qualify will be notified and will continue to follow the instructions in 
Appendix 14.5 until completion of the scheduled Treatment Day.  If subjects require hair 
removal to facilitate sample collection, the subject will be asked to return to the test facility 
approximately 72 hours before Treatment Day.  Subjects will not be allowed to shower or bathe 
for 72 hours prior to Treatment Day.  Sponge-baths may be taken; however, the lower abdomen
and upper thigh regions must be avoided.
5.3.3
Treatment Phase
A sufficient number of subjects who meet the Inclusion Criteria will be enrolled into the 
Treatment Phase of the study, such that at least 50 abdominal and 50 inguinal regions 
(randomized between left and right sides) are evaluable at completion of the study.
The Investigator or a designee will complete the treatment Inclusion/Exclusion form.  If these 
criteria are satisfied, a visual skin assessment will be performed to evaluate the condition of each 
test area.
5.3.3.1
Preparation of Test Areas
A Test Site Diagram for the abdominal test areas is shown in Appendix 14.7.
Abdominal Region:
The test area within the abdominal region is defined as the area below and to the right or left of 
the umbilicus, approximately midway between the umbilicus and the pubis. Using a 6” x 6” 
sterile template, the corners of each abdominal test area will be marked directly onto the skin 


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using a non-toxic skin marker.  Five sampling sites will be numbered within each abdominal test 
area.  The positioning and numbering of the abdominal sampling sites are standard for all 
subjects
  The 5 sampling sites within each abdominal test area represent the baseline 
(pre-prep) site, 4 post-prep sample sites (10-min, 48-hr, 72-hr, 96-hr).  Sampling sites
 
ill be randomized as the 4 post-prep sample sites.  Sampling site  is designated as the 
baseline sample site.      
After abdominal test areas are marked and sampling sites are numbered, baseline samples will be 
collected from the right and left test areas
 using the cup scrub technique 
described in Section 6.2.1.1.
Inguinal Region
The test area within the inguinal region is defined as the uppermost inner aspect of the thigh (the 
inguen), centering the long axis of the template along the inguinal crease immediately below the 
groin.  If, due to a subject’s anatomy, the test area cannot be centered along the inguinal crease, 
the area should be positioned on the upper, inner thigh as close to the crease as possible.  In no 
instance should sampling be performed on areas not having skin-to-skin contact.  Using a 2” x 6” 
sterile template, the corners of each inguinal test area will be marked directly on the skin using a 
non-toxic skin marker.  Five sampling sites will be numbered within each inguinal test area.  The 
positioning and numbering of the inguinal sampling sites are standard for all subjects. 
 
  The 5 
sampling sites within each inguinal test area represent one baseline (pre-prep) site and the 4 post-
prep sample sites (10-min, 48-hr, 72-hr and 96-hr).  Sites
 will be randomized as the 
baseline and 10-min sampling sites.  Sites 
 will be randomized as the 48-hr, 72-hr and 
96-hr sampling sites.  
After inguinal test areas are marked and sample sites are numbered, baseline samples will be 
collected from the right and left test areas per the randomization schedule using the cup scrub 
technique described in Section 6.2.1.1.
5.3.3.2
Study Product Application
Following baseline sample collection, contralateral abdominal and/or inguinal test areas will 
each be prepped with 1 of the 2 study products according to the randomization provided.  
Treatments will be randomized between left and right test areas.
The study product will be applied per the randomization schedule and the Investigational Product
Application Instructions (Appendix 14.2).  The duration of each prep procedure will be recorded 
on the appropriate form.
5.3.3.3
Evaluation of Skin Irritation
Prior to collection of the baseline and post-prep samples (10-min, 48-hour, 72-hour and 96-hour), 
the skin in each test area will be evaluated for indications of skin irritation, based on the Skin 
Irritation Rating Scale (Appendix 14.8).  Skin irritation ratings for each area will be recorded on 
the Skin Irritation Rating form.  


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  Any area with a rating of 3 should not be sampled.
5.3.3.4
Timing of Post-Prep Sample Collection
Microbial samples will be collected at 10 minutes 
), 48 hours
 72 hours 
(
 and 96 hours
 post-prep from the abdomen and/or groin.  Post-prep timing 
begins upon completing the application of the study products, including the 3-minute drying 
time.  Microbial samples will be collected using the cup scrub technique described in Section
6.2.1.1.
5.3.3.4.1 Saline and Wiping Challenge
After the 10-minute post-prep samples have been collected, the remaining sample sites (48 hour, 
72 hour and 96 hour) will be challenged with repetitive saline soaks and blotting
 
 
 
 
After the repetitive saline soak and wiping challenge is complete, a sterile semi-occlusive 
dressing will be secured over the challenged sample sites (48 hour, 72 hour and 96 hour) to allow 
subjects restricted mobility and to protect the sites from contamination between sampling times.  
 
  The subjects will be allowed to leave the clinical test facility as long as they return 48
hours, 72 hours and 96 hours later for collection of the 48-hour, 72-hour and 96-hour samples.  
Subjects should be reminded that they are to avoid showering, tub-bathing, swimming, vigorous 
physical activity that may cause sweating, and any other activities that may compromise the 
integrity of the test sites until their final sample collection has been completed.  
In the event that the dressings on the 48-hour, 72-hour and/or 96-hour sampling sites have been 
compromised, the site will not be sampled and the loss of dressing integrity will be recorded on 
the appropriate data collection sheet (DCS).
The dressings covering the 72-hour and 96-hour sampling sites will be observed and reinforced 
as necessary during the 48-hour post-prep time point.  The dressings covering the 96-hour 
sampling sites will be observed and reinforced as necessary during the 72-hour post-prep time 
point.
Following the final sample collection, residual study products will be removed from the subject’s 
skin
.
6.
ASSESSMENT OF EFFICACY
6.1
Efficacy Parameters
The primary measure of persistence is the suppression of regrowth relative to baseline of 3M 
CHG/IPA Prep and
 at 48 hours 72 hours and at 96 hours post-prep.  


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The secondary measure of persistence is the suppression of regrowth relative to post-prep (10-
minute) of 3M CHG/IPA Prep and 
 at 48 hours 72 hours and at 96 hours post-prep.
6.2
Assessment Methods
6.2.1
Microbiological Methods
6.2.1.1
Sample Collection and Processing
Quantitative cultures will be obtained from sampling sites using a modification of the cup scrub 
method of Williamson and Kligman.3
 
A sterile scrub cup will be placed and held firmly on each site.  Scrub 1:  
 
SSS will be aseptically pipetted into the scrub cup.  The skin will be scrubbed in a 
circular motion with moderate pressure for 1 minute using a sterile policeman.  Using a sterile 
transfer pipette, the scrub solution will be transferred to a sterile collection tube.  Scrub 2:  
 
fresh SSS will be pipetted into the scrub cup and the scrub procedure will be 
repeated.  This solution will be pooled with the solution from Scrub 1 for a total sample volume 
of approximately 6 mL per site.
Following collection, each sample tube will be capped tightly 
 
followed by a
 
 30-second vortex.  A 1.0 mL aliquot of each 
sample will be diluted into sterile tubes containing 9.0 mL PBW.  Serial 10-fold dilutions will be 
performed in PBW.  One-milliliter (1.0-mL) aliquots of selected dilutions will be pour-plated in 
duplicate using TSA+N.  Samples must be plated within 30 minutes of collection.  
 
  After 72 
 hours of aerobic incubation at 30 ± 2°C, colonies 
will be counted and viable cells in the original sample will be calculated using standard methods.  
.
6.2.1.2
Collection of Raw Data
Raw colony counts from each of the dilutions will be recorded on the appropriate data collection 
sheet (DCS) for each subject.  
6.2.1.3
Neutralization of Investigational Products
Prior to Treatment Day the effectiveness of the neutralizers contained in the microbial sampling 
solution will be tested based on ASTM E1054-08 (2013), Standard Test Methods for Evaluation 
of Inactivators of Antimicrobial Agents.4 The protocol for neutralization validation is provided in 
Appendix 14.9.
6.3
Subject Discontinuation
The Investigator or designee may discontinue individual subjects from the study at any time.  
Subjects may voluntarily withdraw from the study at any time.  The Investigator or designee will 


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provide a written report on the appropriate form including the date and reason for 
discontinuation.  Subjects who have been previously screened may not be re-entered into the 
study.
7.
ASSESSMENT OF SAFETY
7.1
Safety Parameters
The principal measure of safety will be the incidence of adverse events reported during the study 
and a summary of the skin irritation rating scores.  
 
7.2
Assessment Methods
The Investigator or designee will assess the subject’s skin condition prior to collection of the 
baseline, 10-min, 48-hour, 72-hour, and 96-hour post-prep samples using the Skin Irritation 
Rating Scale (Appendix 14.8).
7.3
Adverse Events 
The Investigator is responsible for identifying adverse events that occur to each subject.  An 
adverse event can be identified by the Investigator or reported by the subject.
Definitions:
●
Adverse event (AE) means any undesirable clinical occurrence in a subject whether or not it 
is considered to be drug related.
●
Drug-related adverse event (ie, adverse drug experience) is an adverse event that is 
considered by the Investigator to have a reasonable likelihood of being associated with the 
investigational drug.
●
Life-threatening adverse drug experience is any adverse drug experience that places the 
subject, in the view of the Investigator, at immediate risk of death from the reaction as it 
occurred (does not include a reaction that, had it occurred in a more severe form, might have 
caused death).
●
Serious adverse drug experience is an adverse drug experience that is fatal or life-threatening, 
is permanently or significantly disabling/incapacitating, requires inpatient hospitalization or 
prolongation of existing hospitalization, or results in a congenital anomaly/birth defect.
●
Unexpected adverse drug experience is one not previously identified in nature, severity or 
frequency of incidence in the current Investigator brochure, in the clinical plan, or elsewhere 
in the current IND application and amendments.
Recording and Reporting:
The Investigator records each AE occurring in the study, including those not thought to be 
associated with the drug, on the Adverse Event Record.  Documentation includes the AE 
description, severity at onset, seriousness, date of onset and resolution, relationship to the 
investigational drug, action taken, and outcome.


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The Investigator must promptly report all adverse drug experiences to the 3M study monitor.  If 
the adverse drug experience is also considered by the Investigator to be serious and/or 
unexpected the Investigator must report it to the IRB/EC as soon as possible.
3M reports (by telephone or fax) a death or life-threatening adverse drug experience to the FDA 
within 7 days of notification, and submits a follow-up report within 15 days.
A serious and unexpected adverse drug experience involving a non-3M commercialized product 
is reported to the 3M study monitor and IRB/EC.
If a subject does not experience an AE during the study, the absence of such must be recorded on 
the form.
8.
STATISTICS
8.1
Data Sets Analyzed
Subjects with an average treatment day baseline of >3.0 log10 CFU/cm2 for the abdominal region 
and/or >5.0 log10 CFU/cm2 for the inguinal region will be included in the analysis.  The analyses 
will use paired t-tests.  Thus, at any sample time, a subject must not only meet treatment day 
baseline requirements but also have log10 recovery values from both products.  At each sample 
time, analysis will be conducted using all subjects meeting treatment day baseline requirements 
and also having log10 recovery values from both products at that sampling time.  For the 
secondary outcomes, the subjects must also have log10 recovery values from both products at 10 
minutes.
8.2
Statistical Methods
Paired t-tests will be used to analyze the primary and secondary outcomes by sampling time.  A 
Hochberg step-up procedure will be used to adjust for multiple comparisons.  This will be done 
separately for the primary outcomes and for the secondary outcomes. A family error rate of 0.05 
will be used.
8.2.1
Efficacy Analyses
Summary tables will be produced for baseline log10 recovery, log10 reduction from baseline at 10 
minutes, log10 recovery at the 4 sampling times and log10 regrowth from the 10 min log10
recovery for 48 hours, 72 hours and 96 hours.
The mean paired difference between products, the 95% confidence interval and the p-value will 
be produced for log10 recovery at 48 hours, 72 hours and 96 hours and for the log10 regrowth 
from the 10 min log10 recovery for 48 hours, 72 hours and 96 hours.
8.2.2
Safety Analyses
Adverse events and skin irritation scores will be summarized.  McNemar’s test will be used to 
test for a difference between products in adverse event.


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8.3
Sample Size Justification
The standard deviation of the paired differences in log10 reduction observed in study
was, approximately, 1.0.  A sample size of 45 provides 80% power to detect a difference of 0.5 
log10 at alpha=0.017 (to allow for adjustment for multiple comparisons).  Fifty subjects will be 
enrolled to allow for loss of subjects and uncertainty in variability.
8.4
Criteria for Termination of the Study
3M reserves the right to terminate the study at any time for business reasons.
8.5
Procedures for Accounting for Missing, Unused, and Spurious Data
Any non use of data will be discussed and justified in the blinded review of data at the data lock 
meeting and documented in the meeting minutes.
8.6
Deviations to Statistical Plan
Any deviation from the statistical plan discussed above will be documented in the study report.
9.
MONITORING
3M, as sponsor of this study, is responsible for ensuring the proper conduct of the study with 
regard to protocol adherence and validity of the data recorded.  3M has therefore assigned a 
study monitor to this study.  The progress of the study will be monitored by:
●
Periodic on-site review
●
Ongoing review of electronic documentation 
●
Telephone and e-mail communications 
●
Review of source documents
The Investigator or designee will give the 3M study monitor direct access to source documents 
that support data on the eCRFs and make available such records to authorized 3M, quality 
assurance, IRB/EC, and regulatory personnel for inspection and/or copying.
10. QUALITY CONTROL AND QUALITY ASSURANCE
3M is responsible for implementing and maintaining quality assurance and quality control 
systems through written standard operating procedures (SOPs) to ensure that this study is 
conducted and data are generated, documented and reported in compliance with the protocol, 
GCP and regulations cited in Section 1.5 of this protocol.  Study monitoring is carried out to 
accomplish this.
11. ETHICS
This study will be conducted in accordance with the principles that have their origin in the 
Declaration of Helsinki, 21 CFR 50 (Informed Consent) and 56 (IRBs).  The study will start only 
after approval of the protocol and consent form by the IRB/EC.  The approval letter or notice 
must contain the IRB/EC name, meeting date, and sufficient information to identify the protocol 


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and informed consent by name and number that were reviewed.  3M, prior to study initiation, 
must receive a copy of the IRB/EC approval letter.
12. DATA HANDLING AND RECORD KEEPING
12.1 Study Personnel
Prior to study initiation, the Investigator must provide 3M with a signed Form FDA 1572.  
This form identifies all sub-investigators who will be assisting the Investigator in the 
conduct of the study.  The Investigator will provide a log of signatures/initials prior to 
study initiation.
12.2 Pre-Study Documentation Requirements
Prior to study initiation, the Investigator must provide 3M with the following documents:

Signed protocol including any amendments in place prior to study initiation

Curriculum vitae for the Investigator and any co-investigators

IRB/EC approved consent form

IRB/EC study approval letter

IRB/EC name, location and membership list

IRB/EC certification

Signed Form FDA 1572

Financial Disclosure  

Signed research agreement
12.3 Completion and Return of Case Report Forms
Electronic data capture (eDC) software will be used for this study.  Data may be recorded onto 
data collections sheets prior to data entry or may be entered directly into the eDC system.  
Microbiological count data will be recorded onto DCSs prior to entry into the eDC system.  If a 
correction is required, a single line must be drawn through the error.  The person making the 
correction will initial, date, and provide a reason for the error (if not self-evident).  Once the 
forms are completed, the monitor will review the case report form (CRF) to assure accuracy and 
completeness.  
12.4 Final Report
 
 
 
The Investigator will submit the Investigator Final Report to 3M and the IRB/EC. 
12.5 Records, Reports and Retention Requirements
Study records must be kept until 3M provides notification that the documents can be destroyed.  
This may extend beyond the 2 years required by law.  In order to comply with regulatory 
requirements, the Investigator must arrange for the retention of all study records for 2 years 


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following the date a marketing application is approved for the drug and indication investigated, 
or if no application is filed, until 2 years after completion/termination of the study [see 21 CFR 
312.62 (c) and 21 CFR 812.140(d)].  
Records to be retained in the Investigator study file include, but are not restricted to:

Signed study protocol, amendments, deviations

Applications to the IRB/EC

IRB/EC approval of protocol, consent form, authorization form and amendments to any of 
these documents

Signed consent forms 

Case report forms and/or data collection forms

Adverse event reports

Records of receipt, use, or disposition of the investigational drug

Correspondence relating to the study

Investigator Brochure 

Statement of Investigator

Financial disclosure documents

Final Report
13. REFERENCES
1
Butterfield, CT.  The selection of a dilution water for bacteriological examinations.  J 
Bacteriol 1932; 23: 355-68.
2
ASTM International. ASTM E1173, standard test method for evaluation of preoperative,
precatheterization, or preinjection skin preparations. West Conshohocken [PA]: ASTM Int’l; 
2015.
3
Williamson P, Kligman PM.  A new method for the quantitative investigation of cutaneous 
bacteria.  J Invest Dermatol 1965; 45:498-503.
4
ASTM International. ASTM E1054, standard test methods for evaluation of inactivators of 
antimicrobial agents.  West Conshohocken [PA]: ASTM Int’l; 2013.


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14. APPENDICES
14.1 Study Flow Diagrams
Screening Day


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Treatment Day


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14.2 Study Product Application Instructions
 
 
 
 
  
 
 
 
 
 
 
 
 


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14.3 Confirmation of Release & Receipt of Clinical Supplies
   
 


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14.4 Study Product Disposition Form
 
 
 
 


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14.5 Subject Instructions
 
 
 
 
 
 
 
 
 
 
 
 
 


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14.6 Elements of Informed Consent
These elements of consent should be included as applicable to the study being conducted.
1. Statement that the study involves research.
2. Purpose(s) of the research.
3. Expected duration of subject’s participation.
4. Procedures to be followed and identification of any procedures that are experimental.
5. A description of any reasonable foreseeable risks or discomforts to the subject.
a) Risks/discomforts from study procedures.
b) Foreseeable risks associated with the investigational product, which include adverse 
experiences listed in the Investigator’s Brochure or package insert.
6. A description of any benefits to the subject or to others which may reasonably be expected 
from the research.
7. A disclosure of appropriate alternative procedures or courses of treatment, if any, that might 
be advantageous to the subject.
8. Extent to which confidentiality of records identifying subject will be maintained.
a) Possibility that representatives of 3M and the FDA may inspect and make copies of the 
records.
b) Suggested text: “I understand that, at any time, an agent of 3M may also review any 
hospital, physician, or insurance billing or any other costs which relate to therapy 
incurred as a direct result of my participating in this study.
9. An explanation as to whether any compensation or medical treatments are available if injury 
occurs for research involving more than minimal risk.  The explanation should involve a 
description of the compensation or treatment available or a statement describing where 
further information may be obtained.
10. Whom to contact for answers to pertinent questions about research and research subject’s 
rights.
11. Whom to contact in the event of research-related injury to the subject.
12. Participation is voluntary:
a) Refusal to participate will involve no penalty or loss of benefits to which subject is 
otherwise entitled.
b) Subject may discontinue participation at any time without penalty or loss of benefit to 
which subject is otherwise entitled.


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ADDITIONAL ELEMENTS OF CONSENT
When appropriate, one or more of the following elements of information shall also be provided 
to each subject.
1. A statement that the particular treatment or procedure may involve risks to the subject (or 
embryo or fetus, if subject became pregnant) which are currently unforeseeable.
2. Anticipated circumstances under which subject’s participation may be terminated by the 
Investigator without regard to subject’s consent.
3. Any additional costs to the subject that may result from participation in the research.
4. A statement explaining the consequences of subject’s decision to withdraw during the course 
of the research which may relate to subject’s willingness to continue participation will be 
provided to the subject.
5. A statement that significant new findings developed during the course of the research which 
may relate to subject’s willingness to continue participation will be provided to the subject.
6. Approximate number of subjects involved in the study.
Nothing in these regulations is intended to limit the authority of a physician to provide 
emergency medical care to the extent the physician is permitted to do so under applicable 
federal, state, or local laws.
Informed consent allows the subject to fully understand his/her participation and serves to 
protect the Investigator and Sponsor from potential negligence claims. A fully informed subject 
is the best protection against such claims.
The informed consent requirements in these regulations are not intended to preempt any 
applicable federal, state, or local laws that require additional information be disclosed for 
informed consent to be legally effective.  Some states, such as California and Oregon, require 
further action on the Investigator’s part concerning subject consent.


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14.8 Skin Irritation Rating Scale
 


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14.9 Protocol for Neutralization Validation
14.9.1 Background
In order to accurately assess the efficacy of an antimicrobial product, it is necessary to 
completely inactivate the antimicrobial agent at the time point being evaluated.  Inadequate 
neutralization will allow killing or inhibition of the microorganisms to continue beyond the 
specified contact time, resulting in an overestimation of antimicrobial activity.
Standard sampling solution (SSS) is a buffered detergent solution that is commonly used in 
studies where microbial sampling of skin is conducted.  Neutralizers have been added to 
inactivate the antimicrobial, CHG, present in the active study products. 
 
 
  The effectiveness and 
nontoxicity of these neutralizer systems must be assessed to demonstrate that there is no effect 
on the growth of microorganisms and that the antimicrobial ingredient is inactivated.
The density of normal human skin flora generally ranges from 102 to 105 CFU/cm2 depending on 
the body site.  However, since significant neutralizer or toxic effects are more easily detected at a 
lower cell density, the efficacy and toxicity of these neutralizers will be assessed against a lower 
bacterial concentration. 
This is an in vivo test where the active study products are applied to the skin using the same 
application instructions used for the study (Appendix 14.2). Scrub cup samples are collected and 
inoculated with low levels of
 
.  Two contact times after inoculation 
will be evaluated: immediately (<1 minute) and
 (to test for residual antimicrobial 
activity between sample collection and the time of plating).
14.9.2 Objective
The objective of this assay is to determine the ability of the sampling solutions to completely 
neutralize the active ingredients contained in 3M CHG/IPA Prep and 
 when applied 
to the abdomen of test subjects without exhibiting toxicity to the test organisms.
14.9.3 Subject Entry Criteria
Six subjects will participate in this study.  Subjects must meet the inclusion and exclusion criteria 
in Sections 4.1 and 4.2 of the protocol to which this neutralizer validation is attached, except for 
the baseline bacterial count, the 72-hour exclusion from showering/bathing, and the length of the 
washout period.  The neutralization subjects do not require a minimum baseline count and they 
only need to avoid topical and systemic antimicrobials for 7 days (not 14 days) prior to 
Treatment Day.  Subjects will be asked to provide information on demographics and 
inclusion/exclusion criteria and sign the Informed Consent Form before beginning the 7-day 
washout period.  When subjects return to begin their participation in the study they will again be 
asked to provide information relative to inclusion/exclusion criteria.  If they meet all 


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inclusion/exclusion criteria, they may be enrolled. 
 
Each subject will receive both active study products (3M CHG/IPA Prep and
), which 
will be applied to 2 separate test areas on the abdomen.  See diagram below.
14.9.4 Test Organism
The test organisms for this study ar
 
14.9.5 Study Products

3M CHG/IPA Prep, 



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14.9.6 Materials, Supplies and Equipment


Subject Informed Consent forms, IRB/EC-approved

 
 
 
 


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
 
14.9.7 Study Procedures
14.9.7.1 Preparation of Inoculum
One day prior to beginning the neutralization assay, the test organisms from a stock culture slant 
or from a lyophilized vial will be inoculated on TSA. The plates will be incubated for 24 ± 4 
hours at 35° ± 2°C.
Immediately prior to initiating the neutralization assay, an inoculum suspension for each test 
organism will be prepared in PBW solution from the overnight culture on the TSA plate, and the 
concentration adjusted to approximately 108 – 109 CFU/mL.
Dilute the inoculum suspension with PBW to achieve an appropriate concentration 
(approximately 104 CFU/mL) for inoculation of the test samples.  The density of the test inocula 
must be verified by direct plating at the beginning and end of the study.
14.9.7.2 Preparation of Test Area and Post-Prep Sampling
Neutralization samples will be evaluated on the abdomen.  The test areas on each subject’s 
abdomen will be assigned according to a computer-generated randomization schedule to receive 
1 of the 2 study products.  The subject number, location of the product application, location of 
the sites sampled within the test area, and the time of sample collection will be documented.  
Each subject will be treated with both study products, one in each test area.
Abdominal test areas will be marked using a sterile 1.5” x 5” template
 
  One 1.5” x 5” area will be 
delineated on one side of the body containing two 1” x 1” sampling sites and the other 1.5” x 5” 
area will be delineated on the opposite side of the abdomen, containing two 1” x 1” sampling 
sites, to yield 4 sampling sites for each subject.  One tube from each test area will be inoculated 
with 
 and the other will be inoculated with 
.
After the test areas are marked, each area will be prepped with three 70% isopropyl alcohol 
swabs for a total of 1 minute and allowed to dry for 3 minutes.
Each test area will be treated with 1 of the 2 study products, according to the instructions for the 
inguinal region provided in Appendix 14.2 of the protocol to which this neutralizer validation is 
attached.
Samples will be collected, using the scrub cup technique, at 10 minutes
 post-prep.  
Post-prep timing begins upon completion of study product application, including the 3-minute 
drying time.  The sampling technique is described in Section 6.2.1.1 of the protocol to which this 
neutralizer validation is attached.


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Residual product should be removed from test areas after sample collection is complete 
 
Each pooled sample (~6 mL) will be capped tightly
.  
 followed by vortex mixing for 30 seconds.  Five mL 
will be transferred to a clean tube and immediately inoculated with 100 μL of the appropriate 
diluted inoculum (Section 14.9.7.1 of the neutralization validation).  This will yield an organism 
concentration of ~20 – 200 CFU/mL.
Immediately (<1 minute) and at
 minutes 
 post-inoculation,
aliquots of 
the inoculated samples will be pour-plated in triplicate using TSA+N.  Plates will be incubated 
inverted at 35 + 2oC for 48 
 hours.
14.9.7.3 Numbers Control and Toxicity Control
This testing will be performed in triplicate.
Numbers Control (NC):
Add 100 µL of the appropriate diluted inoculum to a tube containing 5 mL PBW to yield final 
inoculum concentrations of ~20-200 CFU/mL.  
 
  Pour-plate triplicate
aliquots immediately (<1 minute) and 
minutes 
 post-inoculation in the same manner as 14.9.7.2, except using TSA without 
neutralizers.
Toxicity Control (TC-MSS):
Add
 5.0 mL SS
 
to a clean tube.  Add 100 µL of the appropriate 
diluted inoculum to the 5-mL tube to yield final inoculum concentrations of ~20-200 CFU/mL.  
Pour-plate triplicate 
L aliquots immediately (<1 minute) and 
) 
post-inoculation in the same manner as 14.9.7.2.
These controls will provide assurance that the test organisms are not adversely affected by the 
treatments or the sampling procedures.
14.9.7.4 Enumeration
.  Enumerate plates and calculate 
CFU/mL for each sample.  Convert data to log10 CFU/mL.
14.9.8 Control of Bias
Bias is controlled by internal controls and triplicate plating.
14.9.9 Data Evaluation
Recovery for each of the samples will be expressed as log10 CFU/mL.


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Neutralizer Effectiveness: 
If the mean log10 CFU/mL of the sample is not more than 0.3 log10 less than the mean log10
CFU/mL of the NC, the neutralization will be considered effective.

Mean log10 CFU/mL from NC − Mean log10 CFU/mL from sample (use corresponding time 
points)
Neutralizer Toxicity:
If the mean log10 CFU/mL of the TC is not more than 0.3 log10 less than the mean log10 CFU/mL 
of the NC, the sampling solutions will be considered non-toxic.

Mean log10 CFU/mL from NC − Mean log10 CFU/mL from TC (use corresponding time 
points).