1. Regulatory History and Attributes of Consumer Antiseptics Nonprescription Drugs Advisory Committee Meeting Silver Spring, Maryland October 20, 2005 Colleen Kane Rogers, PhD Division of Nonprescription Regulation Development Nonprescription Drugs Advisory Committee Meeting Silver Spring, Maryland October 20, 2005 Colleen Kane Rogers, PhD Division of Nonprescription Regulation Development Center for Drug Evaluation and Research

2. Nonprescription Drugs Advisory Committee October 20, 2005 2 Overview The Monograph Process Defining Consumer Antiseptics Attributes of Consumer Antiseptics Concerns Regarding Consumer Antiseptics The Monograph Process Defining Consumer Antiseptics Attributes of Consumer Antiseptics Concerns Regarding Consumer Antiseptics

3. Nonprescription Drugs Advisory Committee October 20, 2005 3 OTC Monograph Process Category I: GRASE (Generally Recognized As Safe and Effective) Category II: not GRASE Category III: cannot determine if safe and effective Category I: GRASE (Generally Recognized As Safe and Effective) Category II: not GRASE Category III: cannot determine if safe and effective Advisory Review Panel

4. Nonprescription Drugs Advisory Committee October 20, 2005 4 OTC Monograph Process Category I: GRASE Category II: not GRASE Category III: cannot determine if safe and effective Category I: GRASE Category II: not GRASE Category III: cannot determine if safe and effective ANPR

5. Nonprescription Drugs Advisory Committee October 20, 2005 5 OTC Monograph Process ANPR TFM Comments

6. Nonprescription Drugs Advisory Committee October 20, 2005 6 OTC Monograph Process TFM Comments Data FM

7. Nonprescription Drugs Advisory Committee October 20, 2005 7 Antiseptic Monograph 1972 – Advisory Review Panel 1974 – Advance Notice of Proposed Rulemaking (ANPR) 1978 – Proposed Rule (TFM) 1994 – Proposed Rule (Amended TFM) Final Rule (FM) 1972 – Advisory Review Panel 1974 – Advance Notice of Proposed Rulemaking (ANPR) 1978 – Proposed Rule (TFM) 1994 – Proposed Rule (Amended TFM) Final Rule (FM)

8. Nonprescription Drugs Advisory Committee October 20, 2005 8 Antiseptic vs. Disinfectant Antiseptic –Antimicrobial used on the skin –Regulated by FDA Disinfectant –Antimicrobial used on inanimate objects or surfaces –Regulated by EPA Antiseptic –Antimicrobial used on the skin –Regulated by FDA Disinfectant –Antimicrobial used on inanimate objects or surfaces –Regulated by EPA

9. Nonprescription Drugs Advisory Committee October 20, 2005 9 Consumer Antiseptics Consumer products are currently marketed as: –Antibacterial soaps –Antibacterial wipes –Antibacterial bodywashes –Hand sanitizers Consumer products are currently marketed as: –Antibacterial soaps –Antibacterial wipes –Antibacterial bodywashes –Hand sanitizers

10. Nonprescription Drugs Advisory Committee October 20, 2005 10 Defining Consumer Antiseptics – FDA Panel defined ‘antimicrobial soap’: –Reduces the microbial flora of the skin –May reduce residents and transients 1978 TFM: intended for the general public in non-hospital settings 1994 TFM: called ‘antiseptic handwash’ Panel defined ‘antimicrobial soap’: –Reduces the microbial flora of the skin –May reduce residents and transients 1978 TFM: intended for the general public in non-hospital settings 1994 TFM: called ‘antiseptic handwash’

11. Nonprescription Drugs Advisory Committee October 20, 2005 11 Labeling Claims 1974 ANPR and 1978 TFM: –Antimicrobial/ antibacterial soap –Deodorant soap/ reduces odor 1978 TFM: –Different uses require different labeling for consumers and healthcare personnel –Insufficient data to accept claims for ‘prevention of infection’ 1974 ANPR and 1978 TFM: –Antimicrobial/ antibacterial soap –Deodorant soap/ reduces odor 1978 TFM: –Different uses require different labeling for consumers and healthcare personnel –Insufficient data to accept claims for ‘prevention of infection’

12. Nonprescription Drugs Advisory Committee October 20, 2005 12 Labeling Claims 1994 TFM: –Antiseptic/ antiseptic handwash –For handwashing to decrease bacteria on the skin After changing diapers After assisting ill persons –Recommended for repeated use 2003 Citizen Petition (SDA/CTFA): –Request anti-viral claims 1994 TFM: –Antiseptic/ antiseptic handwash –For handwashing to decrease bacteria on the skin After changing diapers After assisting ill persons –Recommended for repeated use 2003 Citizen Petition (SDA/CTFA): –Request anti-viral claims

13. Nonprescription Drugs Advisory Committee October 20, 2005 13 Defining Consumer Antiseptics – Industry 1994 TFM –3 healthcare categories –1 consumer category 1995 Healthcare Continuum Model –3 healthcare categories –2 consumer categories –1 food handler category 1994 TFM –3 healthcare categories –1 consumer category 1995 Healthcare Continuum Model –3 healthcare categories –2 consumer categories –1 food handler category

14. Nonprescription Drugs Advisory Committee October 20, 2005 14 Active Ingredients Used in Consumer Antiseptics Ethanol Triclosan Triclocarban Quaternary ammonium compounds –Benzalkonium chloride –Benzethonium chloride Ethanol Triclosan Triclocarban Quaternary ammonium compounds –Benzalkonium chloride –Benzethonium chloride

15. Nonprescription Drugs Advisory Committee October 20, 2005 15 Proposed Consumer Antiseptic “Handwash” Attributes – FDA Attributes: –Broad spectrum –Fast-acting –Persistent (if possible) Recommended efficacy testing: –Same as healthcare personnel handwashes –Specific bacterial reductions after 1 st and 10 th washes Attributes: –Broad spectrum –Fast-acting –Persistent (if possible) Recommended efficacy testing: –Same as healthcare personnel handwashes –Specific bacterial reductions after 1 st and 10 th washes

16. Nonprescription Drugs Advisory Committee October 20, 2005 16 Proposed Consumer Antiseptic “Handwash” Attributes – Industry Attributes: –Broad spectrum –Fast-acting not essential –Persistent Recommended efficacy testing: –Single wash to demonstrate efficacy –No cumulative effect Attributes: –Broad spectrum –Fast-acting not essential –Persistent Recommended efficacy testing: –Single wash to demonstrate efficacy –No cumulative effect

17. Nonprescription Drugs Advisory Committee October 20, 2005 17 Proposed Consumer Antiseptic Bodywash Attributes – Industry Attributes: –Limited or broad spectrum –Fast-acting not essential –Persistent Recommended efficacy testing: –Significant reduction in resident flora compared to baseline – OR – –Significant reduction in transient flora compared to use of placebo/ bland soap Attributes: –Limited or broad spectrum –Fast-acting not essential –Persistent Recommended efficacy testing: –Significant reduction in resident flora compared to baseline – OR – –Significant reduction in transient flora compared to use of placebo/ bland soap

18. Nonprescription Drugs Advisory Committee October 20, 2005 18 Potential Hazards from Using Consumer Antiseptics Individual –Irritation –Contact dermatitis –Antibiotic resistance –Incomplete immune system ‘education’ Societal –Antibiotic resistance –Impact on ecosystems –Secondary exposure Individual –Irritation –Contact dermatitis –Antibiotic resistance –Incomplete immune system ‘education’ Societal –Antibiotic resistance –Impact on ecosystems –Secondary exposure

19. Nonprescription Drugs Advisory Committee October 20, 2005 19 Concerns Raised by the 1972 Panel Routine use of antimicrobials may have a long-term harmful effect by reducing normal flora (hypothetical) Widespread use of antibiotics, antiseptics, and hard surface disinfectants may produce an increase in gram-negative infections Exposure of the entire body to antimicrobial chemicals when alternate methods of odor control are available Routine use of antimicrobials may have a long-term harmful effect by reducing normal flora (hypothetical) Widespread use of antibiotics, antiseptics, and hard surface disinfectants may produce an increase in gram-negative infections Exposure of the entire body to antimicrobial chemicals when alternate methods of odor control are available

20. Nonprescription Drugs Advisory Committee October 20, 2005 20 Concerns Raised by FDA Proliferation of triclosan-containing products –In 1994 TFM, based on new information, concluded that proliferation was not a concern Antibiotic and antiseptic resistance related to healthcare antiseptics (1997 NDAC) –Decreased susceptibility to antiseptics was not a concern at that time –Recommended surveillance Proliferation of triclosan-containing products –In 1994 TFM, based on new information, concluded that proliferation was not a concern Antibiotic and antiseptic resistance related to healthcare antiseptics (1997 NDAC) –Decreased susceptibility to antiseptics was not a concern at that time –Recommended surveillance

21. Nonprescription Drugs Advisory Committee October 20, 2005 21 Current FDA Concerns Antibiotic and antiseptic cross- resistance Environmental concerns –Secondary exposure –Impact on ecosystems Antibiotic and antiseptic cross- resistance Environmental concerns –Secondary exposure –Impact on ecosystems

22. Nonprescription Drugs Advisory Committee October 20, 2005 22 What Do We Need to Know? Finalizing the Monograph Need NDAC input to develop some policies –What population would benefit from consumer antiseptics? –How do we measure the benefit of these products? –Which potential hazards, if any, pose a concern? Finalizing the Monograph Need NDAC input to develop some policies –What population would benefit from consumer antiseptics? –How do we measure the benefit of these products? –Which potential hazards, if any, pose a concern?