© 2017 Artel

Best Practices for Equipment Calibration and Analytical Controls in the

Diagnostics Laboratory

George Rodrigues, Artel (slides 2-16)Rebecca Butler, CareDx (slides 17-29)

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Agenda

AgendaTheory / RegulationsApplications Discussion

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Liquid handling quality assurance

Metrology - the science of measuring things

Documentary standards - best practices

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Analytical Controls

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Equipment Calibration

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Congress

Food, Drug & Cosmetics Acthttp://www.fda.gov/opacom/laws/fdcact/fdctoc.htm

Clinical Laboratory Improvement Amendments (CLIA ’88)https://www.cms.gov/clia/

Public Laws

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Federal Regulations

CFR – Code of Federal Regulationshttp://www.gpoaccess.gov/cfr/index.html

42 CFR Part 493 – Clinical- CLIA

21 CFR Part 820 – GMP- In vitro

Also know as the QSR, Quality System Requirements.

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Program Requirements

College of American Pathologists – CAPhttp://www.cap.org/apps/cap.portal

Clinical Pathology Accreditation - CPA (UK)https://www.ukas.com/services/addreditation-services/medical-laboratory-accredition-iso-15189

Local Quality System Requirements

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Consensus Standards & Guides

International Organization for Standardization - ISOiso.org

ISO 15189; ISO 17025

ASTM Internationalastm.org

Many equipment standards

Clinical and Laboratory Standards Instituteclsi.org/standards

Practices, guides, etc.

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820.72 Inspection, measuring, and test equipment(b) Calibration. Calibration procedures shall include specific directions and limits

for accuracy and precision. When accuracy and precision limits are not met, there shall be provisions for remedial action to reestablish the limits and to evaluate whether there was any adverse effect on the device’s quality. These activities shall be documented.

(1) Calibration standards. Calibration standards used for inspection, measuring, and test equipment shall be traceable to national or international standards. If national or international standards are not practical or available, the manufacturer shall use an independent reproducible standard. If no applicable standard exists, the manufacturer shall establish and maintain an in-house standard.

(2) Calibration records. The equipment identification, calibration dates, the individual performing each calibration, and the next calibration date shall be documented. These records shall be displayed on or near each piece of equipment or shall be readily available to the personnel using such equipment and to the individuals responsible for calibrating the equipment.

Key Calibration Requirements for IVD Makers - 21 CFR

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Schedule Calibration

21 CFR 211.160

Perform As Found Calibration

21 CFR 211.68Corrective

Maintenance/Repair

Perform As Left Calibration

21 CFR 211.194

Return to Service

RemedialAction

21 CFR 211.160 (4)

Adjustment/Corrective

Maintenance

CalibrationAlert

Preventive Maintenance

Record21 CFR 211.194

Record21 CFR 211.194

Pass

Fail

Fail

Pass

Calibration Work FlowBest Practices for Pipette Quality Assurance

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Best Practices for Pipette Quality Assurance

• Ensure performance is acceptable within the required tolerance limits for intended use

• Comply with regulations

• Save time

• Save money

• Defend data integrity

Why Calibrate?

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Best Practices for Pipette Quality Assurance

• Verify Calibration to for Peace of Mind

• Prior to Critical Work

• According to a Designated Schedule

• After Potentially Damaging Activity

• Maintain Records

Interim Verification / Checks

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42 CFR 493.801 Enrollment and testing of samples Each laboratory must enroll in a proficiency testing (PT) program that meets the

criteria of this part and is approved by HHS. …

For each specialty, subspecialty and analyte or test, participate for one year before changing program.

The laboratory must test the samples in the same manner as patients' specimens. …

The samples must be tested with the regular patient workload by personnel who routinely perform the testing.

The laboratory must test samples the same number of times that it routinely tests patient samples.

Laboratories must not engage in Inter-laboratory communications pertainent to the results of proficiency testing samples, prior to reporting results.

What if no approved PT program is available?

Key Calibration Requirements for IVD Makers - 21 CFR

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42 CFR 493.1236 Evaluation of PT performance The laboratory must verify the accuracy of …

Any analyte or subspecialty … that is not evaluated or scored by a CMS-approved proficiency testing program.

At least twice annually, the laboratory must verify the accuracy of the following:

Any test or procedure it performs that is not included in (PT program)

Key Calibration Requirements for IVD Makers - 21 CFR