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Quality System Quality System Considerations for Over-Considerations for Over-

The-Counter The-Counter

HIV TestingHIV Testing

Devery Howerton, Ph.D.Devery Howerton, Ph.D.Chief, Laboratory Practice Evaluation and Genomics Chief, Laboratory Practice Evaluation and Genomics

Branch, Division of Public Health Partnerships, Branch, Division of Public Health Partnerships, National Center for Health Marketing, CDCNational Center for Health Marketing, CDC

Atlanta, GAAtlanta, GA

FDA Blood Products Advisory CommitteeNovember 3, 2005

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OutlineOutline

Quality System essentialsQuality System essentials Basic components of testingBasic components of testing CLIA-waived testingCLIA-waived testing Issues to consider in test evaluationIssues to consider in test evaluation

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Quality System Quality System

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

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Path of Workflow for Home Path of Workflow for Home TestingTesting

Pre-analytic AnalyticAnalytic Post-analyticPost-analytic

Obtain testObtain test

Read instructionsRead instructions

Set up test areaSet up test area

Collect specimenCollect specimen

Perform testPerform test

Read resultRead result

Processes:Processes:

Interpret Interpret resultresult

Obtain follow-Obtain follow-up testing, up testing, counseling, counseling, as neededas needed

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Quality System Quality System EssentialsEssentials

1.1. Documents and recordsDocuments and records2.2. OrganizationOrganization3.3. Personnel*Personnel*4.4. EquipmentEquipment5.5. Purchasing and inventory*Purchasing and inventory*6.6. Process control*Process control*7.7. Information management*Information management*8.8. Occurrence management*Occurrence management*9.9. Internal and external assessmentInternal and external assessment10.10. Process improvementProcess improvement11.11. Customer service/satisfactionCustomer service/satisfaction12.12. Facilities and safety*Facilities and safety*

* Apply to * Apply to OTC testingOTC testing

CLSI, Application of a Quality System Model for CLSI, Application of a Quality System Model for Laboratory Services, GP26-A3, 2004Laboratory Services, GP26-A3, 2004

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Basic Components of Basic Components of TestingTesting

Apply no matter where a test is done:Apply no matter where a test is done: Person doing the test (tester)Person doing the test (tester) Testing environmentTesting environment Test materialsTest materials

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Characteristics of the Characteristics of the Self-TesterSelf-Tester

Ability and willingness to Ability and willingness to read instructionsread instructions follow instructionsfollow instructions evaluate results and take appropriate evaluate results and take appropriate

actionaction Awareness of the need to follow Awareness of the need to follow

instructions explicitlyinstructions explicitly

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Characteristics of the Test Characteristics of the Test EnvironmentEnvironment

TemperatureTemperature HumidityHumidity LightingLighting Level, stable work surfaceLevel, stable work surface

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Characteristics of the Characteristics of the Test MaterialsTest Materials

Robustness at temperature and Robustness at temperature and humidity extremeshumidity extremes

Shelf life Shelf life Test instructionsTest instructions Packaging and configurationPackaging and configuration Specimen collection deviceSpecimen collection device

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CLIA*-Waived TestingCLIA*-Waived Testing

Tests that are Tests that are 1.1. Cleared by FDA for home use; Cleared by FDA for home use;

2.2. Employ methodologies that are so Employ methodologies that are so simple and accurate as to render the simple and accurate as to render the likelihood of erroneous results likelihood of erroneous results negligible; or negligible; or

3.3. Pose no reasonable risk of harm to the Pose no reasonable risk of harm to the patient if the test is performed patient if the test is performed incorrectly. incorrectly.

*Clinical Laboratory Improvement Amendments of 1988

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CLIA Waiver CLIA Waiver RequirementsRequirements

1.1.Obtain Certificate of Waiver (CW)Obtain Certificate of Waiver (CW)

2.2.Follow manufacturer instructionsFollow manufacturer instructions

3.3.Permit inspections by HHSPermit inspections by HHS

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Most Frequently Performed Most Frequently Performed Waived TestsWaived Tests

Analyte % of SitesGlucose 44.5Dipstick urinalysis 33.2Fecal occult blood 21.4Urine hCG 15Group A strep antigen 14.7Hemoglobin 7.3Cholesterol 5.7HDL cholesterol 5.2Triglyceride 5.2Prothrombin time 4.8

*HCG indicates human chorionic gonadotropin; and HDL, high density lipoprotein

Tests most frequently performed by Certificate of Waiver sites, from the Centers for Medicare & Medicaid

Services surveyed sites, 2003-2004

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101520253035404550

Gluc

ose

Dipsti

ck u

rinal

ysis

Fecal o

ccul

t blo

od

Urine

hCG

Gro

up A s

trep a

ntig

en

Hemog

lobin

Chole

stero

l

HDL ch

olest

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Triglyc

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Proth

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time

% o

f si

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OTC Tests OTC Tests MonitoringMonitoring

Glucose, glycated hemoglobin, ketoneGlucose, glycated hemoglobin, ketone Cholesterol, HDL, triglyceridesCholesterol, HDL, triglycerides

ScreeningScreening Fecal occult bloodFecal occult blood Urine dipstick chemistries (e.g., Urine dipstick chemistries (e.g.,

microalbumin, pH, nitrites, billirubin)microalbumin, pH, nitrites, billirubin) Fertility/pregnancy Fertility/pregnancy Substance abuseSubstance abuse

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Quality Practices in Quality Practices in CW SitesCW Sites

CMS surveys 2002-2004 (n=4214):CMS surveys 2002-2004 (n=4214): 12% did not have current instructions12% did not have current instructions 21% did not routinely check for changes21% did not routinely check for changes RE: following manufacturers’ instructions, RE: following manufacturers’ instructions,

sites did notsites did not perform quality control perform quality control 21%21% adhere to expiration datesadhere to expiration dates 6% 6% use appropriate specimenuse appropriate specimen 2% 2%

MMWR, in pressMMWR, in press

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Quality Practices in Quality Practices in CW Sites CW Sites (continued)(continued)

From CDC Laboratory Medicine Sentinel From CDC Laboratory Medicine Sentinel Monitoring Network studies (1999-Monitoring Network studies (1999-2002):2002):

57% followed manufacturers’ instructions (WA, 57% followed manufacturers’ instructions (WA, n=306)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 Steindel, et al, Practice patterns of testing waived under the Clinical Laboratory Improvement under the Clinical Laboratory Improvement Amendments, Arch Pathol Lab Med, 126:1471-1479, Amendments, Arch Pathol Lab Med, 126:1471-1479, 20022002

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Recommendations and Recommendations and Guidance for Waived Guidance for Waived

TestingTesting FDA sales restrictions for rapid HIV FDA sales restrictions for rapid HIV

testingtesting CDC QA guidelines for testing with CDC QA guidelines for testing with

OraQuick Rapid HIV testOraQuick Rapid HIV test Good laboratory practices (GLP) for Good laboratory practices (GLP) for

waived testing sites – CLIAC (MMWR waived testing sites – CLIAC (MMWR 11/05)11/05)

CMS GLP guidance documentCMS GLP guidance document Professional organizations, e.g., COLAProfessional organizations, e.g., COLA

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Issues to Consider in Issues to Consider in Test EvaluationTest Evaluation

Instructions and device familiarizationInstructions and device familiarization Evaluation materials, test specimensEvaluation materials, test specimens Specimen collectionSpecimen collection ReproducibilityReproducibility Antibody concentrations near the cutoffAntibody concentrations near the cutoff Comparison with existing method or gold Comparison with existing method or gold

standard standard Clinical diagnosisClinical diagnosis

CLSI, User Protocol for Evaluation of Qualitative Test CLSI, User Protocol for Evaluation of Qualitative Test Performance, EP12-A, 2002.Performance, EP12-A, 2002.

CLSI, Specifications for Immunological Testing for CLSI, Specifications for Immunological Testing for Infectious Diseases, I/LA18-A2, 2001.Infectious Diseases, I/LA18-A2, 2001.

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Issues to Consider in Issues to Consider in Test Evaluation Test Evaluation (continued)(continued)

Test kit stabilityTest kit stability Variability in reagent lots and source Variability in reagent lots and source

materialsmaterials Adequacy of specimenAdequacy of specimen Test performance (timing, reading)Test performance (timing, reading) Analytic sensitivity/specificityAnalytic sensitivity/specificity Methods for assuring quality in the Methods for assuring quality in the

absence of external controlsabsence of external controls

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Issues to Consider in Issues to Consider in Test Evaluation Test Evaluation (continued)(continued)

Follow-up action to be taken by tester Follow-up action to be taken by tester Reactive resultReactive result

Confirmatory testingConfirmatory testing Post-test counselingPost-test counseling Accessing careAccessing care

Non-reactive resultNon-reactive result Considerations for retestingConsiderations for retesting

Manufacturer oversightManufacturer oversight Adverse event reportingAdverse event reporting Production changesProduction changes Lot variabilityLot variability

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SummarySummary

Basic quality systems approach can Basic quality systems approach can be applied to home testingbe applied to home testing

Quality recommendations and Quality recommendations and guidance developed to address gaps guidance developed to address gaps in CLIA-waived testingin CLIA-waived testing

Recommendations for test evaluation Recommendations for test evaluation include evaluation of the total testing include evaluation of the total testing processprocess