Antimicrobial Hand Washing Products: Designed to Protect Patients, but are They Safe for Nurses?

Houston APIC Chapter 006 Presented by GOJO Industries

©2016. GOJO Industries, Inc. All rights reserved. INTRODUCTION

Maria Thompson, RRT, MBA, SSBB

2 Why Is This an Important Topic?

• Current guidance around soap is limited • Regulatory changes affecting soap are happening now and may be confusing for healthcare workers • Product availability may be affected in the future • Soap is an essential part of an effective hand hygiene regimen • IPs are uniquely positioned to help their healthcare facilities interpret the coming changes and make adaptations as needed

3 Objectives 1. Explain the FDA Monograph and forthcoming changes.

2. Describe how the FDA and the healthcare facility will ensure safety from a nurse/healthcare worker and patient safety standpoint.

3. Review available antimicrobial ingredients and their future statuses.

4. Define important attributes of a hand hygiene product, including efficacy, skin health, and aesthetics needed to drive hand hygiene compliance.

4 Efficacy and RECOMMENDATIONS Around Soap

5 Hand Hygiene Overview

Soap and Water: Alcohol-Based Hand Rub (ABHR): – When hand are visibly soiled – In all other clinical situations if or contaminated with blood hands are not visibly soiled or other bodily fluids Hand sanitizing with – In outbreaks of C. difficile alcohol-based hand rub is the gold standard in all – Before eating situations when hands are not visibly soiled – After using the restroom

Visibly soiled = Hands on which dirt or body fluids are readily visible – Hand washing represents approximately 15% of hand hygiene events in acute care facilities 6 History and Science of Soap

• A soap-like material found in clay cylinders during the excavation of ancient Babylon is evidence that soap making was known as early as 2800 B.C. • Records show that ancient Egyptians bathed regularly • The first of the famous Roman baths, supplied with water from their aqueducts, was built about 312 B.C.

Synthetic Surfactants “Modern” Soap Traditional Soap H2O Polar Head, Hydrophilic

+ KOH = H2O Non-Polar Tail, Hydrophobic

Fat / Oil Base Micelles 7 Mechanism of Action of Soap Non-Antimicrobial Antimicrobial Removal

Surfactant Removal Antimicrobial Kill Bacteria

Skin Product Average Log Reductions Average Log Reductions Against Bacteria After Against C. difficile Spores Single Wash After Single Wash Water 1.00 0.75 Plain ~2.00 0.75-1.25 Antimicrobial 2.50-3.00 0.75-1.25 8 *Edmonds et. al. Infection Control and Hospital Epidemiology, March 2013, Vol. 34, No. 3 Non-Antimicrobial vs. Antimicrobial Soap

• CDC and WHO guidelines allow the use of either antimicrobial or non- antimicrobial soap – There is no clinical data demonstrating a clinical benefit of antimicrobial soaps

– Studies are complex, expensive, long- Bacterial Reduction term, difficult to control Centers for Disease Control and Prevention. Guideline for Hand Hygiene in Health-Care Settings: – Selection based on risk profile/tolerance Recommendations of the Healthcare Infection Control Practices Advisory Committee and the – Estimated 60+% of soap sold in healthcare is HICPAC/SHEA/APIC/IDSA Hand Hygiene Task Force. MMWR 2002:51 [pg 27] antimicrobial

Product Average Log Reductions If 10,000 Bacteria on Hands, If 1,000 Bacteria on Hands, How Against Bacteria After How Many CFU Remain on Many CFU Remain on Hands Single Wash Hands After Hand Wash? After Hand Wash? Water 1.00 1,000 100 Plain ~2.00 100 10 Antimicrobial 2.50-3.00 10-30 1-3 9 The Effects of Different Hand Hygiene Regimens on the Reduction of Bacteria from Hands

Baseline = After water = After plain soap = After antimicrobial soap = 10,000 Bacteria 1000 Bacteria 100 Bacteria 10 Bacteria (1 logs= 90%) (2 logs= 99%) (2.5-3 logs = 99.9 %) • Antimicrobial soaps provide the greatest reduction of bacteria • How comfortable are you leaving bacteria on healthcare workers’ hands? • Selection based on risk profile/tolerance

10 FDA Healthcare Antiseptic Monograph

11 Over-the-Counter Drug Monograph System

A drug monograph establishes conditions under which an OTC drug is GRASE (Generally Recognized as Safe and Effective)

• Dosage strength • Category I – GRASE • Dosage forms • Category II – Not safe or not effective • Labeling • Category III – Not enough data to determine safety or effectiveness – Indications Products containing Category I and Category III actives can – Warnings be sold into the market under a Tentative Final Monograph – Directions When monograph is final, categories are replaced by • Efficacy testing terms “monograph” and “non monograph” 12 Monograph vs New Drug Application (NDA) Process

MONOGRAPH NEW DRUG APPLICATION (NDA) • A “rule book” listing ingredients for each • Data demonstrating that a specific therapeutic category formulated drug product is safe and • Lists Generally Recognized As Safe and effective for use as directed for its Effective (GRASE) Active ingredients: approved indication – Dosage strength • FDA reviews sponsor’s submitted safety and efficacy data and approves the • Form product before it can be legally sold • Labeling: • Changes to formulation, manufacturing – Uses (indications) process, or other approved specifications must also be FDA reviewed and approved – Warnings before marketing – Directions • Final formulation testing for some categories

13 Chlorhexidine Gluconate (CHG) and the New Drug Application (NDA) Process

• Chlorhexidine Gluconate introduced into the market after 1972 and therefore not “eligible” for inclusion in the monograph process • Several CHG containing products approved for sale via NDA process for various indications • Products approved through the NDA process are not subject to monograph review • Safety of NDA approved products monitored through active post-marketing surveillance programs

14 Monograph Changes

Federal Register / Vol. 59, No. 116 / Friday, June 17, 1994 / Proposed Rules

DEPARTMENT OF HEALTH AND HUMAN SERVICES Active Ingredient Hand Wash Application Food and Drug Administration Benzalkonium Chloride (BAK) III 21 CFR Parts 333 and 369 [Docket No. 75N-183H] Benzethonium Chloride (BEC) III RIN 0905-AA06 Chloroxylenol (PCMX) III Topical Antimicrobial Drug Products for Over-the-Counter Human Use; Triclosan III Tentative Final Monograph for Health- Care Antiseptic Drug Prouducts Chlorhexidine Gluconate (CHG) New Drug Process AGENCY: Food and Drug Administration, HHS. *Category III: Not enough data to make a final decision on safety and ACTION: Notice of proposed rulemaking effectiveness, but sufficient data for sale of products until monograph is finalized

15 Monograph Schedule per Consent Decree

Consumer Antiseptic Healthcare Antiseptic Consumer Antiseptic Hand Rub Handwash Monograph Products Monograph Products Monograph

Scope Antibacterial Soaps; Antibacterial Soaps and Instant Hand Sanitizers; Residential Residential and Away from Instant Hand Sanitizers in and Away from Home settings, Home settings, excluding Healthcare settings only excluding Healthcare and Healthcare and Food Industry Food Industry

Publication of TFM 12/16/2013 4/30/2015 6/30/2016

TRM Comment Period 6/16/2014 10/31/2015 12/31/2016

FDA Review of final data and 8/31/2016 12/31/2017 3/31/2019 comments

Final Monograph Published 9/15/2016 1/15/2018 4/15/2019

Monograph separated into two separate Consumer Monographs and a Healthcare Monograph (combines handwashes and handrubs) Healthcare facilities are unique: high risk population (patients) and dynamic reservoir of pathogenic organisms

16 Soap Active Ingredients

• Today – Category III (safety and efficacy) active ingredients; Still permitted to use • Final Monograph (1/15/2018) – In order for an active ingredient to make the final monograph any safety / efficacy data gaps would need to be addressed (see below) • Deferrals submitted for BAK, BEC, PCMX – These actives have been given additional time to complete required testing

Table 10. Safety Studies Available for Health Care Antiseptic Active Ingredients1 Active Human Animal Oral Dermal Reproductive Potential Resistance Active Ingredient Hand Wash Ingredient2 Pharmaco Pharmaco Carcino- Carcino- Toxicity Hormonal Potential Application - kinetic - kinetic genicity genicity (DART) Effects (MUsT) (ADME) Benzalkonium Chloride (BAK) III

Benzalkonium Benzethonium Chloride (BEC) III Chloride ○ ○ Chloroxylenol (PCMX) III Benzethonium Chloride ○ ● ○ ○ Triclosan III Chloroxylenol ○ ○ ○ ○

Triclocarban ○ ○ ● ○ ○

Triclosan ○4 ○ ● ● ○ ○

17Empty cell indicates no data available; "○" indicates incomplete data available; "●" indicates available data are sufficient to make a GRAS / GRAE determination. What To Expect When the Healthcare Monograph Finalizes in January 2018 • Most active ingredients may be listed as “Not Generally Recognized as Safe and Effective” including triclosan and triclocarban. – Manufacturers will have 1 year (January 2019) to stop manufacturing and distribution or reformulate healthcare antibacterial soaps containing any of these active ingredients. • Deferred active ingredients will not be subject to the Final Rule and will be given extensions to allow for the submission of new safety and effectiveness data. – FDA will require Industry to provide ongoing progress reports to ensure the process moves forward.

18 Future Monograph Implications for Healthcare Soaps

Current Actives Future Actives Triclosan Triclosan Benzethonium Chloride (BEC) Benzethonium Chloride (BEC) Benzalkonium Chloride (BAK) Benzalkonium Chloride (BAK) Chloroxylenol (PCMX) Chloroxylenol (PCMX) CHG (New Drug Application) CHG (New Drug Application)

Triclosan has not been granted a deferral (40% of the market today)

19 Key Conclusions

• Handwashing is an essential part of an effective hand hygiene regimen • CDC and WHO do not have recommendations for the type of soap used in healthcare facilities • Antimicrobial soaps provide the greatest risk reduction • The FDA is finalizing its monograph; many active ingredients will be no longer available – CHG is a regulatory stable option because products have been proven safe and effective by FDA • Ultimately there are several critical factors that need to be considered when choosing the right soap formulation / formulations for your hospital

20 Soap Formulation and Effective Behaviors for Superior Skin Health

21 Skin Health Overview

• Anatomy of skin • Impact of soap vs. ABHR on skin • Healthcare worker perceptions of skin condition • The cyclical effects of hand hygiene on skin • Formulation + validation methods matter • Solutions to help break the cycle of skin damage

22 Anatomy of the Skin

23 Effects on Stratum Corneum

Normal Stratum Corneum Lipid Structure

Disrupted Stratum Corneum Lipid Structure • Moisture leaves the skin drying • Allergens and pathogens enter skin dermatitis, infection

http://www.reamin.co.uk/en-gb/wp-content/uploads/2013/01/Infection.png 24 QUESTION:

How many of you have talked to healthcare workers who say they do not use sanitizer because it stings and dries their hands?

25 The Cyclical Effects of Hand Hygiene On Skin

Dermatitis 6 progress

Return to use Hand Wash 5 Hand Wash with 1 with Soap Soap several times

Skin burns / 4 stings as a sign of 2 ICD starts early ICD unnoticed

Workplace screening for hand dermatitis: a pilot study., Occup Med. 2016 Jan; Epub 2015 Sep 26., Nichol K, et. al. Use of ABHR Hand hygiene compliance and irritant dermatitis: a 3 occasionally juxtaposition of healthcare issues., Int J Cosmet Sci. 2012 Oct, Epub 2012 Jul 5, Visscher MO1, Randall Wickett R.

26 Repetitive Exposure to Soap and Water

Soap has twofold effect 1. Removes some protective natural oils with each washing 2. Once oils are removed soap reaches living cells and damages them, leading to inflammation and reduced oil production

27 Not all Soaps are Created Equal

• Soap is never meant replace ABHR • But when used, it is important to select the right one • It is possible to formulate a mild soap that is also efficacious

28 The Benefits of a Well-Formulated Product

Antimicrobial Efficacy Skin Health (Skin Microbiology) (Maintain, Protect & Repair)

Skin Feel (Aesthetics) User Acceptance

29 Skin Feel: Aesthetics and Acceptability

User experience - chronic use • Lather • Odor (scent/fragrance) • Rinsability • Skin feel after use – Soft, conditioned, dry, irritated, facilitates easy gloving, etc.

30 Learning from Biology of Skin: pH Effects

– Healthy skin pH is from 4.6 to 5.6 – Saponified (Natural) soap pH is 9.5 to 10.5 – Personal care products are formulated in a wide range of pH; ideal should mimic skin pH

31 Breaking the Cycle of Skin Damage

• Recommended Habits for Soaps – Always wet hands before applying soap to skin – The cooler the water the better – lukewarm at most – Rinse thoroughly – Surfactant residue primary cause of skin irritation – Gloving over surfactant residue exacerbates this issue – Don’t forget all areas on the hands: finger webs / knuckles – Dry hands by patting, not rubbing with towels • Use lotions when needed • Use ABHRs whenever possible • Don’t forget skin care when not at work

32 Factors to Consider When Choosing Soap Antimicrobial vs. Non-Antimicrobial soap Regulatory stability Efficacy (for antimicrobial soaps) Skin health / mildness Skin feel / aesthetics Dispensing solutions Other value added programs

33 Key Conclusions

• Soap choice matters! • Antimicrobial soaps provide the greatest risk reduction and have a history of safe use in healthcare settings • There are regulatory changes coming, and you may be forced to make product changes • Soap can contribute to skin damage, but this can be minimized with proper formulation and using soap when indicated • Choosing a well-formulated soap can make an impact on efforts to improve hand hygiene

34 Objectives 1. Explain the FDA Monograph and forthcoming changes.

2. Describe how the FDA and the healthcare facility will ensure safety from a nurse/healthcare worker and patient safety standpoint.

3. Review available antimicrobial ingredients and their future statuses.

4. Define important attributes of a hand hygiene product, including efficacy, skin health, and aesthetics needed to drive hand hygiene compliance.

35 Questions and Discussion

36