Efficacy of OTC Healthcare Antiseptics: Introduction to the Regulatory Issues

1. Efficacy of OTC Healthcare Antiseptics: Introduction to the Regulatory Issues Susan S. Johnson, Pharm.D., Ph.D. Associate Director Division of Over-The-Counter Drug Products

2. What are the OTC Healthcare Antiseptics? • Healthcare personnel handwashes • Surgical hand scrubs • Patient preoperative skin preparations

3. What is FDA’s current approach to the evaluation of HC antiseptic efficacy? • It is assumed that HC antiseptics play a critical role in infection control, however, the efficacy of individual products must be demonstrated to meet regulatory requirements • FDA’s current regulatory standards are based on actual product performance and have been supported in previous public discussions • FDA currently determines the efficacy of healthcare antiseptics using a surrogate endpoint, the reduction in a log10 count of bacteria from the site of test product application

4. Why has this meeting been convened? • We have received Citizen Petition requests to change (lower) the threshold criteria for the bacterial reduction • We wish to present our review of efficacy data for these products • We are asking the AC to provide input about the standards that FDA needs to have in place to make regulatory decisions

5. What are some of the factors that can influence efficacy of HC antiseptics? • Product Parameters • Active Ingredient • Spectrum of activity (in vitro testing) • Potency / Dose Response • Formulation • Concentration and dose delivered • Vehicle and inactives can influence efficacy • Labeled instructions for use

6. What are some of the factors that can influence efficacy of HC antiseptics? • Use Parameters • Adherence to labeled instructions • Practice standards & actual use • Frequency of use • Patient Parameters • Health status influences on risk for infection • Type of procedure • Resident and Transient Bacteria • Amount • Pre and post use of product • Virulence

7. How does FDA assess efficacy? • Randomized, Controlled Trials (RCT) • Provide analytical strength • Can control for multiple confounders • Selection of active & vehicle control / comparators is critical

8. Which endpoints are used in RCT? • Clinical Endpoints • Clinical relevance is evident • Degree of difficulty and expense are important to industry • Surrogate Endpoints • Scientific basis • Regulatory precedent • Current standards for OTC healthcare antiseptics

9. What should be considered when using surrogate endpoints to assess HC antiseptic efficacy? • Validity • Information about links to clinical outcomes is limited • Existing trials were not designed to validate standard • Primary basis for surrogate is use of antiseptics in practice • Test Methodology • Evaluate conditions of use • Provide information for intended labeling • Needs to characterize tolerability of products • Need standardization of all procedures

10. What should be considered when using surrogate endpoints to assess HC antiseptic efficacy? • Decision Thresholds • Current criteria are based on NDA performance • Any changes should be data-driven • Analysis • Predicated on validity, methods and thresholds • Need to evaluate response of the test product in the context of variability in the test methods and amongst subjects

11. What information do epidemiologic studies provide for HC antiseptics? • Actual use information on large populations • Often used to suggest practice standards • Can be used to generate hypotheses to be later tested in RCT • Relatively insensitive to treatment differences & changes • Extrapolation for regulatory decision-making is limited

12. What is FDA asking the AC to address? • Can we continue to rely on surrogate markers to assess HC antiseptic efficacy? • Is there compelling evidence to change our surrogate efficacy criteria? • What is the best way to analyze efficacy data? • What labeling information would be helpful for clinicians to fully understand product efficacy?