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

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

3. 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. 4 Path of Workflow for Home Testing Pre-analytic AnalyticPost-analytic Obtain test Read instructions Set up test area Collect specimen Perform test Read result Processes: Interpret result Obtain follow-up testing, counseling, as needed

5. 5 Quality System Essentials 1. Documents and records 2. Organization 3. Personnel* 4. Equipment 5. Purchasing and inventory* 6. Process control* 7. Information management* 8. Occurrence management* 9. Internal and external assessment 10. Process improvement 11. Customer service/satisfaction 12. Facilities and safety* * Apply to OTC testing CLSI, Application of a Quality System Model for Laboratory Services, GP26-A3, 2004

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

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

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

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

10. 10 CLIA*-Waived Testing Tests that are 1. Cleared by FDA for home use; 2. Employ methodologies that are so simple and accurate as to render the likelihood of erroneous results negligible; or 3. Pose no reasonable risk of harm to the patient if the test is performed incorrectly. *Clinical Laboratory Improvement Amendments of 1988

11. 11 CLIA Waiver Requirements 1. Obtain Certificate of Waiver (CW) 2. Follow manufacturer instructions 3. Permit inspections by HHS

12. 12 Most Frequently Performed Waived Tests

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

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

15. 15 Quality Practices in CW Sites (continued) From CDC Laboratory Medicine Sentinel Monitoring Network studies (1999-2002): 57% followed manufacturers’ instructions (WA, n=306) 57% followed manufacturers’ instructions (WA, n=306) 58% used liquid controls (AK, n=211) 58% used liquid controls (AK, n=211) 68% followed recommended QC (NY, n=607) 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. 16 Recommendations and Guidance for Waived Testing FDA sales restrictions for rapid HIV testing FDA sales restrictions for rapid HIV testing CDC QA guidelines for testing with OraQuick Rapid HIV test CDC QA guidelines for testing with OraQuick Rapid HIV test Good laboratory practices (GLP) for waived testing sites – CLIAC (MMWR 11/05) Good laboratory practices (GLP) for waived testing sites – CLIAC (MMWR 11/05) CMS GLP guidance document CMS GLP guidance document Professional organizations, e.g., COLA Professional organizations, e.g., COLA

17. 17 Issues to Consider in Test Evaluation Instructions and device familiarization Instructions and device familiarization Evaluation materials, test specimens Evaluation materials, test specimens Specimen collection Specimen collection Reproducibility Reproducibility Antibody concentrations near the cutoff Antibody concentrations near the cutoff Comparison with existing method or gold standard Comparison with existing method or gold standard Clinical diagnosis 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. 18 Issues to Consider in Test Evaluation (continued) Test kit stability Test kit stability Variability in reagent lots and source materials Variability in reagent lots and source materials Adequacy of specimen Adequacy of specimen Test performance (timing, reading) Test performance (timing, reading) Analytic sensitivity/specificity Analytic sensitivity/specificity Methods for assuring quality in the absence of external controls Methods for assuring quality in the absence of external controls

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

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