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:
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

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 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

14. Quality Practices in CW Sites
CMS surveys (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 ( ):
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: , 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