Quality System Considerations for Over-The-Counter HIV Testing

1. Quality System Considerations for Over-The-Counter HIV Testing FDA Blood Products Advisory Committee November 3, 2005 Devery Howerton, Ph.D. Chief, Laboratory Practice Evaluation and Genomics Branch, Division of Public Health Partnerships, National Center for Health Marketing, CDC Atlanta, GA

2. Outline • Quality System essentials • Basic components of testing • CLIA-waived testing • Issues to consider in test evaluation

3. Quality System …provides a basic framework for laboratories and other healthcare units to direct and control activities and functions along the path of workflow with a focus on managing quality…

4. Path of Workflow for Home Testing Processes: Analytic Post-analytic Pre-analytic Obtain test Read instructions Set up test area Collect specimen Perform test Read result Interpret result Obtain follow-up testing, counseling, as needed

5. Quality System Essentials • Documents and records • Organization • Personnel* • Equipment • Purchasing and inventory* • Process control* • Information management* • Occurrence management* • Internal and external assessment • Process improvement • Customer service/satisfaction • Facilities and safety* * Apply to OTC testing CLSI, Application of a Quality System Model for Laboratory Services, GP26-A3, 2004

6. Basic Components of Testing Apply no matter where a test is done: • Person doing the test (tester) • Testing environment • Test materials

7. Characteristics of the Self-Tester • Ability and willingness to • read instructions • follow instructions • evaluate results and take appropriate action • Awareness of the need to follow instructions explicitly

8. Characteristics of the Test Environment • Temperature • Humidity • Lighting • Level, stable work surface

9. Characteristics of the Test Materials • Robustness at temperature and humidity extremes • Shelf life • Test instructions • Packaging and configuration • Specimen collection device

10. CLIA*-Waived Testing Tests that are • Cleared by FDA for home use; • Employ methodologies that are so simple and accurate as to render the likelihood of erroneous results negligible; or • Pose no reasonable risk of harm to the patient if the test is performed incorrectly. *Clinical Laboratory Improvement Amendments of 1988

11. CLIA Waiver Requirements • Obtain Certificate of Waiver (CW) • Follow manufacturer instructions • Permit inspections by HHS

12. Most Frequently Performed Waived Tests

13. OTC Tests • Monitoring • Glucose, glycated hemoglobin, ketone • Cholesterol, HDL, triglycerides • Screening • Fecal occult blood • Urine dipstick chemistries (e.g., microalbumin, pH, nitrites, billirubin) • Fertility/pregnancy • Substance abuse

14. Quality Practices in CW Sites CMS surveys 2002-2004 (n=4214): • 12% did not have current instructions • 21% did not routinely check for changes • RE: following manufacturers’ instructions, sites did not • perform quality control 21% • adhere to expiration dates 6% • use appropriate specimen 2% MMWR, in press

15. Quality Practices in CW Sites (continued) From CDC Laboratory Medicine Sentinel Monitoring Network studies (1999-2002): • 57% followed manufacturers’ instructions (WA, n=306) • 58% used liquid controls (AK, n=211) • 68% followed recommended QC (NY, n=607) Steindel, et al, Practice patterns of testing waived under the Clinical Laboratory Improvement Amendments, Arch Pathol Lab Med, 126:1471-1479, 2002

16. Recommendations and Guidance for Waived Testing • FDA sales restrictions for rapid HIV testing • CDC QA guidelines for testing with OraQuick Rapid HIV test • Good laboratory practices (GLP) for waived testing sites – CLIAC (MMWR 11/05) • CMS GLP guidance document • Professional organizations, e.g., COLA

17. Issues to Consider in Test Evaluation • Instructions and device familiarization • Evaluation materials, test specimens • Specimen collection • Reproducibility • Antibody concentrations near the cutoff • Comparison with existing method or gold standard • Clinical diagnosis CLSI, User Protocol for Evaluation of Qualitative Test Performance, EP12-A, 2002. CLSI, Specifications for Immunological Testing for Infectious Diseases, I/LA18-A2, 2001.

18. Issues to Consider in Test Evaluation (continued) • Test kit stability • Variability in reagent lots and source materials • Adequacy of specimen • Test performance (timing, reading) • Analytic sensitivity/specificity • Methods for assuring quality in the absence of external controls

19. Issues to Consider in Test Evaluation (continued) • Follow-up action to be taken by tester • Reactive result • Confirmatory testing • Post-test counseling • Accessing care • Non-reactive result • Considerations for retesting • Manufacturer oversight • Adverse event reporting • Production changes • Lot variability

20. Summary • Basic quality systems approach can be applied to home testing • Quality recommendations and guidance developed to address gaps in CLIA-waived testing • Recommendations for test evaluation include evaluation of the total testing process