Best Practices for Equipment Calibration and Analytical Controls in the Diagnostics Laboratory George Rodrigues, Artel (slides 2-16) Rebecca Butler, CareDx (slides 17-29)
Agenda Agenda Theory / Regulations Applications Discussion
Liquid handling quality assurance Metrology - the science of measuring things Documentary standards - best practices
Analytical Controls
Equipment Calibration
Public Laws Congress Food, Drug & Cosmetics Act http://www.fda.gov/opacom/laws/fdcact/fdctoc.htm Clinical Laboratory Improvement Amendments (CLIA 88) https://www.cms.gov/clia/
Federal Regulations CFR Code of Federal Regulations http://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.
Program Requirements College of American Pathologists CAP http://www.cap.org/apps/cap.portal Clinical Pathology Accreditation - CPA (UK) https://www.ukas.com/services/addreditation-services/medicallaboratory-accredition-iso-15189 Local Quality System Requirements
Consensus Standards & Guides International Organization for Standardization - ISO iso.org ISO 15189; ISO 17025 ASTM International astm.org Many equipment standards Clinical and Laboratory Standards Institute clsi.org/standards Practices, guides, etc.
Key Calibration Requirements for IVD Makers - 21 CFR 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.
Best Practices for Pipette Quality Assurance Calibration Work Flow Record 21 CFR 211.194 Schedule Calibration 21 CFR 211.160 Perform As Found Calibration 21 CFR 211.68 Fail Calibration Alert Remedial Action 21 CFR 211.160 (4) Corrective Maintenance/ Repair Pass Preventive Maintenance Record 21 CFR 211.194 Perform As Left Calibration 21 CFR 211.194 Fail Adjustment/ Corrective Maintenance Pass Return to Service
Best Practices for Pipette Quality Assurance Why Calibrate? Ensure performance is acceptable within the required tolerance limits for intended use Comply with regulations Save time Save money Defend data integrity
Best Practices for Pipette Quality Assurance Interim Verification / Checks Verify Calibration to for Peace of Mind Prior to Critical Work According to a Designated Schedule After Potentially Damaging Activity Maintain Records
Key Calibration Requirements for IVD Makers - 21 CFR 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 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 CMSapproved 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)