Jarvis PICnet Presentation Final...3/3/2014 1 HEALTH CANADA STANDARDS AND FACTORS INFLUENCING THE CLINICAL EFFECTIVENESS OF ALCOHOL-BASED HAND RUBS (ABHRS) William R. Jarvis, M.D.

3/3/2014

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HEALTH CANADA STANDARDSAND FACTORS INFLUENCINGTHE CLINICAL EFFECTIVENESSOF ALCOHOL-BASED HAND RUBS

(ABHRS)(ABHRS)

William R. Jarvis, M.D.Jason and Jarvis Associates, Jason and Jarvis Associates, LLCLLC

©2014 Jason and Jarvis Associates, LLC. All rights reserved.

Learning ObjectivesLearning Objectives

• Understand registration options for ABHR

• Become familiar with Health Canada standards and test requirements

• Understand key differences between ABHR product efficacy

• Learn how to make informed decisions on selecting ABHR products

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AgendaAgenda

•• Overview of the Health Canada Overview of the Health Canada Standards Standards

•• Methods to Evaluate ABHRMethods to Evaluate ABHRMethods to Evaluate ABHR Methods to Evaluate ABHR EfficacyEfficacy

•• Factors Influencing ABHR Factors Influencing ABHR Antimicrobial EfficacyAntimicrobial Efficacy

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Overview of the Health Canada Standards

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Health Canada Standards for ABHR Human‐Use Antiseptic Drugs

Guidance Document: Guidance Document: HumanHuman‐‐Use Use Antiseptic DrugsAntiseptic Drugs

Antiseptic Skin Cleanser Antiseptic Skin Cleanser MonographMonograph

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lth Risk

lth Risk

Health Canada Risk Management for Hand Antiseptic Products

•• Health Care SettingsHealth Care Settings: Higher presence of pathogens : Higher presence of pathogens that may cause HAIs than in other settings: that may cause HAIs than in other settings: Antimicrobial efficacy of highest priority: higher Antimicrobial efficacy of highest priority: higher safety risk to health if the product is not effectivesafety risk to health if the product is not effective

•• Professional Food SettingsProfessional Food Settings: (food processing plants, : (food processing plants, restaurants, retail supermarkets, fast food outlets)restaurants, retail supermarkets, fast food outlets) ––

Increase

d H

ea

Increase

d H

ea

restaurants, retail supermarkets, fast food outlets) restaurants, retail supermarkets, fast food outlets) product protects food handlers and prevents product protects food handlers and prevents transmitting disease through foodtransmitting disease through food

•• Commercial:* Commercial:* general public, commercial or general public, commercial or institutional settings institutional settings

•• Personal Domestic:* Personal Domestic:* self selected, domestic useself selected, domestic use

6*Mongraph registration is available for Personal Domestic and Commerical Use if not securing any non‐monograph claims.

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Test Differences –Monograph & Guidance Document

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Use/Purpose Differences –Monograph & Guidance Document

Monograph uses and purposes (claims) •• No No data submitted or reviewed data submitted or reviewed

by by Health CanadaHealth Canada

–– Antiseptic Antiseptic cleansercleanser

Non‐monograph uses and purposes (claims)•• Data Data submission required and submission required and

reviewed by Health Canada reviewed by Health Canada ––varied post guidancevaried post guidance

•• For use on package labelsFor use on package labels–– Medicated cleanserMedicated cleanser

–– Kills Kills harmful bacteria or germs harmful bacteria or germs

–– Effective in destroying certain Effective in destroying certain bacteria and removing impurities to bacteria and removing impurities to provide antiseptic cleansing provide antiseptic cleansing

–– For personal hand hygiene to For personal hand hygiene to help help prevent the spread of prevent the spread of certain certain bacteria bacteria

•• For use on package labelsFor use on package labels–– General Indication Areas: General Indication Areas:

•• Log Reduction Claims, Persistence Log Reduction Claims, Persistence Claims, Time Kill Claims, Organism Claims, Time Kill Claims, Organism Specific, etc.Specific, etc.

–– Label claims specific to categories:Label claims specific to categories:

•• For Hospital and Healthcare For Hospital and Healthcare Professional Use / For Use in Professional Use / For Use in Food Food PremisesPremises

•• To reduce bacteria, mycobacteria, To reduce bacteria, mycobacteria, fungi, and viruses on skinfungi, and viruses on skin

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Frequently Asked Questions

•• Are any ABHR products registered for Hospital and Are any ABHR products registered for Hospital and Healthcare Professional Use? Healthcare Professional Use? –– NoNo

•• Why are no ABHR Why are no ABHR products registered for Healthcare products registered for Healthcare Professional Use? Professional Use? –– Extensive testing requirementsExtensive testing requirements

–– Significant investment Significant investment –– time and costtime and cost

–– Human safety risksHuman safety risks

•• Are my products effective if they don’t have approved Are my products effective if they don’t have approved Healthcare claims? Healthcare claims? –– Maybe. Lack of Maybe. Lack of approval approval does not mean lack of does not mean lack of evidenceevidence

–– Verify related efficacy dataVerify related efficacy data

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•• How can I verify the efficacy of products? How can I verify the efficacy of products? –– Request third party, independent lab data using unmodified standard Request third party, independent lab data using unmodified standard

test methods. test methods. MManufacturers should have data on file to share anufacturers should have data on file to share

•• Can I use products registered before the Guidance?Can I use products registered before the Guidance?–– Yes. Health Canada does not require these products to be Yes. Health Canada does not require these products to be

resubmitted under theresubmitted under the GuidanceGuidanceresubmitted under the resubmitted under the GuidanceGuidance–– If adding If adding nonnon‐‐monograph monograph claims, would use the claims, would use the GuidanceGuidance

•• Does it make a difference if use/purpose claims Does it make a difference if use/purpose claims were granted by Health Canada before or after were granted by Health Canada before or after the Guidance?the Guidance?–– Requirements in current Guidance do not apply to Requirements in current Guidance do not apply to prepre‐‐Guidance Guidance

monograph monograph registrationsregistrations–– There were less standardized requirements preThere were less standardized requirements pre‐‐GuidanceGuidance

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•• Are claims obtained through the Monograph before Are claims obtained through the Monograph before the Guidance still valid?the Guidance still valid?–– Yes. Yes. EEarlier arlier nonnon‐‐monograph claims (e.g., healthcare, commercial, monograph claims (e.g., healthcare, commercial,

kill claims, kill claims, organism organism specific, specific, etc.) are based on previous etc.) are based on previous requirements, not more extensive 2009 Guidance test requirements, not more extensive 2009 Guidance test requirementsrequirements

•• Is a Healthcare claim under the Monograph the same Is a Healthcare claim under the Monograph the same as Healthcare Professional use under the Guidance?as Healthcare Professional use under the Guidance?–– No. Different support documentation was needed for a preNo. Different support documentation was needed for a pre‐‐

Guidance claim as compared to the Guidance Guidance claim as compared to the Guidance

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Summary

•• New more extensive Health Canada regulatory New more extensive Health Canada regulatory guidance released in 2009 for different environmentsguidance released in 2009 for different environments

•• All ABHR products with a product license can be sold All ABHR products with a product license can be sold in in CanadaCanada

•• No ABHR products are approved or Healthcare No ABHR products are approved or Healthcare Professional Use yetProfessional Use yet

•• Review of Review of claims and third claims and third party efficacy data is party efficacy data is important criteria for product selection to maximize important criteria for product selection to maximize patient safetypatient safety

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Methods to Evaluate ABHR Efficacy

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Log Reduction Tutorial

Log Reduction Percent Reduction of Bacteria

1 90%

2 99%

3 99.9%

4 99.99%

5 99.999%

Example: Start with 1 million bacteriaExample: Start with 1 million bacteria

•• 1 log reduction: 900,000 are killed and 100,000 remain1 log reduction: 900,000 are killed and 100,000 remain



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++

Health Canada Efficacy Testing Requirements

in vitro(Time‐Kill) broad

range of pathogens

in vitro(Time‐Kill) broad

range of pathogens

++in vivo‐

representative organisms only

in vivo‐representative organisms only

In vitro data (test tube) is not always predictive of in vivo (on hands) results and should be interpreted cautiously

In vitro data (test tube) is not always predictive of in vivo (on hands) results and should be interpreted cautiously

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Health Canada Standard forin vitro Efficacy Tests

DData ata request request on on key subset of key subset of BBacteriaacteria (20), (20), FFungiungi (2) and Viruses (2) and Viruses ((14)14)

Minimum Acceptable Level of Efficacy (Canada):Bacterial (log10)= 5 (99.999%)

Fungi & Viruses (log10) = 4 (99.99%)

Minimum Acceptable Level of Efficacy (Canada):Bacterial (log10)= 5 (99.999%)

Fungi & Viruses (log10) = 4 (99.99%)

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Bacteria/ Suspension

Test Product 15/30‐S Contact Time

Bacteria Log Reduction

In vitro results do not predict antimicrobial performance on handsIn vitro results do not predict antimicrobial performance on hands

Comparison of in vivo Bactericidal Test Methods

EN1500EN1500: Hygienic Hand Rub : Hygienic Hand Rub •• Single product crossSingle product cross--over designover design•• Typically 3 Typically 3 mL mL for 30 for 30 secondsseconds•• Must show nonMust show non--inferiority to inferiority to

internal reference.internal reference.

ASTM E1174/ Healthcare Personnel Handwash (HCPHW)

• Product evaluated at single and multiple uses

• No specified application volume

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ASTM E1174/HCPHW

•• Predicts the reduction Predicts the reduction of organisms by washing of organisms by washing or sanitizing hands after or sanitizing hands after handling contaminated handling contaminated objectsobjects

•• Measures reduction Measures reduction of transient organisms of transient organisms after single and/or multiple after single and/or multiple product usesproduct uses

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1st Application: 3 log

10th Application: 3 log

Health Canada Endpoints:

Bacterial Reduction (log10)Bacterial Reduction (log10)

ASTM International. E‐1174‐06: Standard test method for evaluation of the effectiveness of healthcare personnel or consumer handwash formulations. 2006. West Conshohocken, PA, ASTM International.

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In vivo Fingerpad Method (Fungal)

1. Wash hands, dry, mark fingerpads

2. Add test organism suspension to fingerpad

3. Allow test organism to dry on fingerpads

Test Organism suspension

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4. Expose fingerpad to hand sanitizer

5. Hand sanitizer removes and/or inactivates test organism

6. Expose finger to buffer to remove any remaining test organism

7. Calculate test organism reduction

Summary and Conclusions

•• It is important to understand ABHR test methods It is important to understand ABHR test methods when evaluating and interpreting product claimswhen evaluating and interpreting product claims

–– Data from Data from in vivo in vivo methods is essential to differentiate methods is essential to differentiate ABHR efficacyABHR efficacy

–– Be cautious of “99.99999% game”Be cautious of “99.99999% game”gg

•• Health Canada requires testing using various test Health Canada requires testing using various test methodsmethods

•• It is important to ask It is important to ask manufacturers manufacturers for the test data for the test data to ensure products were evaluated to ensure products were evaluated in vivo in vivo using using methods that are accepted by Health Canada methods that are accepted by Health Canada

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Factors Influencing ABHR Antimicrobial Efficacy

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Multiple Factors of Antimicrobial Efficacy:

Alcohol Type

Application Technique

Alcohol Concentration

Product Formulation

Product Format

Application Volume

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Concentration Dependence of the Activity of Short‐Chain Alcohols

•• Test substances: Test substances: –– AlcoholAlcohol‐‐inin‐‐waterwatermixturesmixtures

T M h dT M h d•• Test Method = Test Method = EN1500EN1500–– 1 minute contact time1 minute contact time

Adapted from: Rotter et al. 1977. Mitt. D. Österr. San. Verw. 78:170‐172.

Efficacy of alcohol‐in water solutions influenced by alcohol concentrations

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Influence of ABHR Formulation

•• ABHR formulations often contain:ABHR formulations often contain:–– AlcoholAlcohol

–– WaterWater

–– ThickenersThickeners

–– MoisturizersMoisturizers

–– Buffering SystemsBuffering Systems

–– Secondary ActivesSecondary Actives

–– SurfactantsSurfactants

•• Ingredients create specific attributes:Ingredients create specific attributes:–– Skin tolerance, skin moisturization, aesthetic properties Skin tolerance, skin moisturization, aesthetic properties

(e.g., skin feel, fragrance)(e.g., skin feel, fragrance)

–– Enable specific delivery formats (rinse, gel, foam)Enable specific delivery formats (rinse, gel, foam)

•• Specific ingredients may improve or inhibit Specific ingredients may improve or inhibit antimicrobial efficacy of ABHR formulationsantimicrobial efficacy of ABHR formulations

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In vivo ABHR Efficacy: Formulation has a Greater Influence than Alcohol Concentration

•• Method = HCPHWMethod = HCPHW

•• 2 mL application volume2 mL application volume

•• Test products = Commercial Test products = Commercial healthcare ABHRs healthcare ABHRs

l i hi bl i hi b

P=0.77

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•• No relationship between No relationship between efficacy and ethanol efficacy and ethanol concentrationconcentration

In formulated ABHR products, alcohol concentration is not the critical determinant of efficacy:

FORMULATION MATTERS

Edmonds, S.E., Macinga, D.R., Mays‐Suko, P., Duley, C., Rutter, J., Jarvis, W.R., Arbogast, J.W. 2012. Amer. J. Infect. Control. 40:521‐5.

Does Product Form Influence Efficacy?

BMC Infect Dis. 2010;10:78

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CJIC. 2011;26:21

Product Form Does Not Influence Efficacy

HCPHW (2 mL application) Error bars 95% C.I.

aseline

•• Both gel and foam formulations met Both gel and foam formulations met in vivo in vivo HCPHW requirementsHCPHW requirements

•• Formulation more important than product formFormulation more important than product form

Edmonds, S.E., Macinga, D.R., Mays‐Suko, P., Duley, C., Rutter, J., Jarvis, W.R., Arbogast, J.W. 2012. Amer. J. Infect. Control. 40:521‐5. 27

Log 1

0Red

uction from Ba

Application 10Requirement

70% EtO

H Gel

70% EtO

H Foam

90%

EtOH Gel

WHO 80%

EtOH

70%

EtO

H G

el

70%

EtO

H F

oam

90%

EtO

H G

el

WH

O 8

0% E

tOH

Application 1 Application 10

Application 1Requirement

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Guidance Regarding ABHR Application Volume

“Apply a palmful of alcohol‐based handrub and cover all surfaces of the hands [and] rub hands until dry.”

“Entire process should take 20‐30 seconds.”

“Apply a palmful of alcohol‐based handrub and cover all surfaces of the hands [and] rub hands until dry.”

“Entire process should take 20‐30 seconds.”

WHO Guidelines on Hand Hygiene in Health Care (2009)WHO Guidelines on Hand Hygiene in Health Care (2009)

“Apply sufficient product such that it will remain in contact with th h d f i i f 15 d b f th d t“Apply sufficient product such that it will remain in contact with th h d f i i f 15 d b f th d t

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CDC Guideline for Hand Hygiene in HealthCDC Guideline for Hand Hygiene in Health‐‐Care Settings (2002)Care Settings (2002)

“Ideal volume of product to apply to the hands is not known and may vary for different formulations. However, if hands feel dry after rubbing hands together for 10–15 seconds, an insufficient volume of product likely was applied.”

“Ideal volume of product to apply to the hands is not known and may vary for different formulations. However, if hands feel dry after rubbing hands together for 10–15 seconds, an insufficient volume of product likely was applied.”

PIDAC Best Practices in Hand Hygiene in HealthPIDAC Best Practices in Hand Hygiene in Health‐‐Care Settings (2010)Care Settings (2010)

the hands for a minimum of 15 seconds before the product becomes dry (usually one to two pumps).”the hands for a minimum of 15 seconds before the product becomes dry (usually one to two pumps).”

Audience Poll

Is Is ABHR efficacy ABHR efficacy dependent dependent uponupon

hhow ow much much I I apply to my hands?apply to my hands?

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Healthcare Workers’ Perceptions of ABHR Application Volume

N = 174

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3/4 of Healthcare Workers do not believe application volume influences efficacy

Macingaet al. Abstract. APIC's 39th Annual Educational Conference & International Meeting, San Antonio, TX. June 2012

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Influence of Application Volume on in vivo ABHR Efficacy (ASTM E2755)

•• Test product: Test product: 62% ethanol ABHR gel62% ethanol ABHR gel

3

4

5

g10

Red

uct

ion

3

4

5

g10

Red

uct

ion

g 10

Red

uctio

n

ABHR efficacy increases

0 1 2 3 40

1

2

Application Volume (ml)

Mea

n L

og

0 1 2 3 40

1

2

Application Volume (ml)

Mea

n L

og

Application Volume (mL)

Mea

n Lo

g

Macinga et al. 2011. App. Environ. Microbiol. 77:8588. 31

linearly with application volume

…But how long are healthcare workers willing to spend sanitizing their hands?

N = 174

Healthcare workers expect Hand Hygiene to be relatively quick

Most common Most common answeranswer = 5 seconds!= 5 seconds!

Macingaet al. Abstract. APIC's 39th Annual Educational Conference & International Meeting, San Antonio, TX. June 2012

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Typical ABHR Dispenser Outputs and ABHR Dry Times

Code ABHR Active: Output (mL)a Dry Time(s)b

A 70% ethanol 1.2 mL 22

B 70% ethanol 1.1 mL 21

C 62% ethanol 1.3 mL 25

D 61% ethanol (w/w) 1.3 mL 26

TouchTouch‐‐Free Free Gel Gel DispensersDispensersaa1010‐‐stroke average output stroke average output

bbA single actuation of product A single actuation of product was applied to was applied to subjects hands subjects hands and the time to rub in dry and the time to rub in dry was was measured. measured. NN= 10= 10‐‐12 12

E 63% isopropanol 0.9 mL 21

F 85% EtOH (w/w) 1.0 mL 17

Code Active: Output (mL)a Dry Time(s)b

H 70% ethanol v/v 0.9 mL 16

I 70% ethanol v/v 1.1 mL 21

J 70% ethanol (v/v) 0.6 mL 12

K 70% ethanol (v/v) 0.6 mL 15

TouchTouch‐‐Free Free FoamFoam DispensersDispensersCurrent dispenser outputs for gels consistent with Canada, WHO and CDC guidelines.

Output for some foam dispensers may be too low.

Macingaet al. Infect Control Hosp Epidemiol. 2013, 34:299. 33

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g1

0 R

edu

ctio

n3

4

5p=0.69

In vivo ABHR Efficacy at More Realistic Volumes

•• HCPHW Method: HCPHW Method: Application 10 log Application 10 log reductions for various reductions for various marketed ABHRs marketed ABHRs

•• Alcohol concentration Alcohol concentration does not drive efficacydoes not drive efficacy

Health Canada Standard

Application 10 log reductionsApplication 10 log reductions2 2 mL mL application volume application volume

Percent Ethanol (v/v)

Mea

n L

og

50 60 70 80 90 1000

1

2does not drive efficacy does not drive efficacy

•• Only 2 products met Only 2 products met Health Canada efficacy Health Canada efficacy requirements at 2 mL requirements at 2 mL application volumeapplication volume

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Standard

Majority of products do not meet Health Canada efficacy requirements at realistic doses

Edmonds, S.E., Macinga, D.R., Mays‐Suko, P., Duley, C., Rutter, J., Jarvis, W.R., Arbogast, J.W. 2012. Amer. J. Infect. Control. 40:521‐5.

What’s next?

• Science advances the guidelines

• Guidance set standards

• Need to demand more efficacious products through substantiated efficacy

• User acceptance still critical to compliance – extreme efficacy standards could have adverse impact on user acceptance if not formulated properly

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Summary and Conclusions

•• Formulation mattersFormulation matters–– Efficacy should be judged on Efficacy should be judged on in vivo in vivo Health Canada performance Health Canada performance

criteria and not on just alcohol content or wet/dry time criteria and not on just alcohol content or wet/dry time

–– Know the Know the in vivo in vivo efficacy of the products, scrutinize the methods, efficacy of the products, scrutinize the methods, data, dispensed vs. tested volumesdata, dispensed vs. tested volumes

C l itC l it i ABHR i t ti i C di ABHR i t ti i C d

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•• Complexity Complexity in ABHR registration in Canadain ABHR registration in Canada–– Multiple paths for different environmentsMultiple paths for different environments

–– Significant updates to submission process in the last 6 Significant updates to submission process in the last 6 yearsyears

•• Data Data is needed to make informed product choices is needed to make informed product choices –– Get manufacturer dataGet manufacturer data

–– Ensure studies conducted by independent, third partyEnsure studies conducted by independent, third party

–– Ensure tests use standard, unEnsure tests use standard, un‐‐modified test methods as modified test methods as recommended by Health recommended by Health CanadaCanada

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THANK THANK YOUYOU

William R. Jarvis, [email protected]

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Jarvis PICnet Presentation Final...3/3/2014 1 HEALTH CANADA STANDARDS AND FACTORS INFLUENCING THE CLINICAL EFFECTIVENESS OF ALCOHOL-BASED HAND RUBS (ABHRS) William R. Jarvis, M.D.

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