1 Nonprescription Drugs AC Meeting Nonprescription Drugs AC Meeting March 23, 2005 March 23, 2005 Testing of Healthcare Testing of Healthcare Antiseptic Drug Products Antiseptic Drug Products Michelle M. Jackson, Ph.D. Microbiologist Division of Over-The-Counter Drug Products
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1 Nonprescription Drugs AC Meeting March 23, 2005 Testing of Healthcare Antiseptic Drug Products Michelle M. Jackson, Ph.D. Microbiologist Division of.
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1Nonprescription Drugs AC MeetingNonprescription Drugs AC MeetingMarch 23, 2005March 23, 2005
Testing of Healthcare Testing of Healthcare Antiseptic Drug ProductsAntiseptic Drug Products
Michelle M. Jackson, Ph.D.Microbiologist
Division of Over-The-Counter Drug Products
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Surgical Hand ScrubSurgical Hand Scrub
Courtesy of Hill Top Research Inc.
• Add sampling fluid*
• Fasten glove securely above the wrist
• Massage for 1 minute
* Neutralizers are incorporated
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Surgical Hand Scrub
Courtesy of Hill Top Research Inc.
• Aliquot of sampling fluid is withdrawn & transferred to dilution tubes* • Surface plating* within 30 minutes of sampling (Microbial Enumeration)
* Neutralizers are incorporated
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Surgical Hand Scrub
Surgical ScrubIndustry Coalition’s
Proposal Reduction (log10)
FDA TFM Proposal
Reduction (log10)
Wash 1 1(No persistence criteria)
1(persistence*)
Wash 2 No Criteria 2
Wash 11 No Criteria 3
* 6-Hour Persistence: prolonged or extended antimicrobial activity that prevents or inhibits the proliferation or survival of microorganisms after product application.
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Patient Preoperative Skin Preparation
Label Indication:• Helps reduce bacteria that
potentially cause skin infection.
• For the preparation of the skin prior to surgery.
• For the preparation of the skin prior to injection.
Testing Process:• Measures immediate and
persistent reduction after single treatment.
Bacterial Reduction (log10)
1-log CFU / pre-injection
2-log CFU / abdomen (dry site)
3-log CFU / groin (moist site)
TFM Endpoints:
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Patient Preoperative Skin PreparationMethodology
• Inclusion / Exclusion • Washout period for 14 days
• No bathing 24 hrs prior to baselines
• Baseline screening counts– Pre-injections > 1.0 x 103
– Large enough to show> 2 log for Abdomen (dry site)
> 3 log for Groin (moist site)
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• Treatment samples are taken from the site area using the cylinder sampling technique
Courtesy of Hill Top Research Inc.
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Patient Preoperative Skin Preparation
Surgical ScrubIndustry Coalition’s
Proposal Reduction (log10)
FDA TFM Proposal
Reduction (log10)
Pre-injection 1 1
Abdomen1
(No persistence criteria)2
(persistence*)
Groin2
(No persistence criteria)3
(persistence*)
* Persistence: prolonged or extended antimicrobial activity that prevents or inhibits the proliferation or survival of microorganisms after product application.
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Industry Coalition’s Comments
TFM Criteria● “overly stringent”
● inappropriate in antiseptic products with proven clinical benefit because they cannot meet
the current criteria. - Monograph: alcohol & iodine - NDA: chlorhexidine gluconate
● all antiseptic products only need to be effective after a single use.
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Performance Criteria
Industry’s ProposalBacterial Reduction
(log10)
FDA TFM Proposal Bacterial Reduction
(log10)
Healthcare Personnel Handwash
Wash 1 1.5 2
Wash 10 ---- 3
Surgical Hand Scrub*
Wash 1 1 1
Wash 2 --- 2
Wash 11 --- 3
Patient Preoperative Skin Preparation*
Preinjection 1 1
Abdomen 1 2
Groin 2 3
* Industry has recommended removal of the 6-hour persistence criteria for these products.
1.5
----
2
1
1
1
---
---
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Other Considerations for Effectiveness Criteria
• Surrogate endpoints– lack of clinical validation– level of residual bacteria on the skin not measured– virulence of the residual bacteria not considered
• Criteria based on earlier NDA data
• Consistently applied to monograph products • Industry deviates from TFM
– variability in testing procedure– not compared to vehicle or active control– statistical analysis
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Industry Coalition’s ProposalPoints to Consider
• Majority designed as product comparisons
• Few studies used TFM methodology
• Significant variation in test conduct
• Neutralizer validation data not generally provided
• Generally sample sizes were small
• Alcohol alone (rubs/leave-on) did not meet the 10th wash 3-log reduction
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Product compared to reference• Hand wash
– significantly more effective than plain soap– average of 2.8 log*
• Hand rub (leave-on)– not be significantly less effective than 60% IPA– average of 4.6 log*
Product compared to reference• Hand wash
– significantly more effective than plain soap– average of 2.8 log*
• Hand rub (leave-on)– not be significantly less effective than 60% IPA– average of 4.6 log*
* Kampf and Ostermeyer, J Hosp Infect (2002) 52: 219-224.
European Performance Criteria
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Summary of Testing Methodology
• We measure bacterial log reduction on the testing methodology for healthcare personnel handwash, surgical hand scrub, and patient preop. These log reductions are used as surrogate endpoints to evaluate effectiveness. How should we analyze this data?
• The relationship of these outcomes and a corresponding reduction in the incidence of nosocomial infections in the healthcare setting where the products are used remains undefined.
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Concluding Remarks
• Aware of limitations of test methods
• Assume incidence of infection:– related to current use of existing products– lowering these standards may increase
infection rates
• Need research to validate these surrogates
• Need to have products on the market and the use of actionable criteria in the meantime