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

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

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…

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

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

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

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

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

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

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

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

Most Frequently Performed Waived Tests

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

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

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

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

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.

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

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

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