SOP-312
Equipment Calibration and Maintenance; Local Laboratory Requirements
- Number
- SOP-312
- Category
- Study Conduct
- Edition
- Reference Edition 1.3
- Approx. pages
- 7
[YELLOW] the site fills in. [DEFAULT: green] a value the site may keep or change.
On this page
1. Purpose
This SOP describes how [SITE NAME] keeps equipment used for trial activities fit for purpose through inventory, calibration, preventive maintenance and handling of out-of-tolerance results, and how the site meets laboratory requirements for testing done on site (CLIA) and for local laboratories used in trials. ICH E6(R3) lists records showing maintenance and calibration of equipment used for important trial activities, and documentation that laboratory tests used in the trial are suitable, among the essential records.
2. Scope
This SOP applies to all equipment at any [SITE NAME] location, or carried by site staff to home or remote visits, that generates trial data, affects participant safety, or stores investigational product (IP) or specimens. Examples:
- vital signs monitors, sphygmomanometers, scales, stadiometers, thermometers, pulse oximeters
- electrocardiograph (ECG) machines, spirometers, ultrasound or other imaging equipment owned by the site
- centrifuges, pipettes used for aliquoting, timers
- refrigerators, freezers, ambient storage areas, temperature data loggers and monitoring probes
- point-of-care testing devices (glucose meters, urine dipstick readers, pregnancy tests, INR meters, HbA1c analyzers)
- emergency equipment (automated external defibrillator, crash cart items, suction, oxygen)
- sponsor-provided equipment (ECG carts, spirometers, tablets, wearables, IP storage units)
It also covers CLIA certification for on-site testing and documentation for local laboratories. Out of scope: computerized systems and software validation (SOP-401), facility maintenance not related to trials, and temperature excursion handling for IP (SOP-304). Where the protocol, sponsor or manufacturer requirement is stricter than this SOP, the site follows the stricter requirement.
3. Responsibilities
| Role | Responsibilities |
|---|---|
| Principal Investigator (PI) | Assesses the clinical impact of out-of-tolerance equipment on participant safety and data. Signs the laboratory director role on the CLIA certificate where the PI holds it. Reviews local laboratory results under SOP-500. |
| Site Director | Owns the equipment program and budget. Engages calibration and biomedical service vendors. Holds or assigns the CLIA certificate and laboratory director role. |
| Quality Lead | Maintains F-312-01. Tracks calibration and maintenance due dates. Reviews out-of-tolerance impact assessments. Opens CAPA where warranted. |
| Clinical Research Coordinator (CRC) or Lead CRC | Uses only equipment that is in date and labeled. Performs and records daily checks and quality control assigned to them. Removes failed equipment from use and reports it. Manages sponsor-provided equipment for assigned studies. |
| Regulatory Coordinator | Files calibration certificates, CLIA certificates, laboratory accreditations and normal ranges in the Investigator Site File (ISF) or the site's central equipment and laboratory file, and sends copies to sponsors on request. |
| All Research Staff | Check the calibration label before use. Do not use equipment that is overdue, damaged or tagged out of service. |
4. Definitions
| Term | Definition |
|---|---|
| Calibration | Comparison of an instrument's measurements against a reference standard of known accuracy, traceable to national standards (for example NIST), with adjustment where needed and a certificate recording results. |
| Verification (performance check) | A check that equipment reads within tolerance against a reference (for example a check weight on a scale), without adjustment. |
| Preventive maintenance (PM) | Scheduled inspection, cleaning, part replacement and safety testing per the manufacturer's recommendations. |
| Tolerance | The acceptable difference between the instrument reading and the reference value, as set by the manufacturer, the sponsor or this SOP. |
| Out of tolerance (OOT) | A calibration or verification result outside the accepted tolerance. |
| Impact assessment | The documented review of trial data and participant safety affected by equipment found out of tolerance, back to the last acceptable calibration or check. |
| CLIA | Clinical Laboratory Improvement Amendments of 1988, implemented at 42 CFR 493, regulating laboratory testing on human specimens for health assessment, diagnosis, prevention or treatment. |
| Waived test | A test categorized by FDA as simple with low risk of erroneous results, which may be performed under a CLIA Certificate of Waiver if the manufacturer's instructions are followed. |
| Local laboratory | A clinical laboratory near the site or participant (hospital or commercial laboratory) used for protocol tests instead of, or in addition to, the sponsor's central laboratory. |
| Central laboratory | A laboratory contracted by the sponsor to test specimens from all sites in a trial. |
| Normal ranges (reference ranges) | The range of test values a laboratory reports as normal for its method and population, used to interpret results. |
5. Procedure
5.1 Equipment inventory
5.1.1
The Quality Lead keeps an equipment inventory on F-312-01 listing, for each item: unique site asset number, description, manufacturer, model, serial number, location, owner (site or sponsor and study), whether it is used for trial data, safety or storage, calibration and PM frequency, last and next due dates, vendor, and status (in service, out of service, retired).
5.1.2
New equipment is added to F-312-01 before first use. Before it is used for trial activities, it has a documented acceptance check: installation per manufacturer, initial calibration or verification certificate, and a calibration label.
5.1.3
Each item carries a label showing the asset number and the next calibration or PM due date. Items with no label are treated as out of service.
5.1.4
Retired equipment is marked "retired" on F-312-01 with the date and reason. Its records are retained under SOP-402 because they support trial data generated while it was in use.
5.2 Calibration and preventive maintenance schedule
5.2.1
The calibration and PM frequency for each item follows, in order of precedence:
- the protocol, laboratory manual or sponsor requirement
- the manufacturer's instructions
- the site defaults below where the manufacturer is silent
5.2.2
Site defaults where no other requirement exists:
- clinical measurement devices (blood pressure monitors, scales, thermometers, pulse oximeters, ECG machines, spirometers): calibration or verification [DEFAULT: every 12 months]
- centrifuges (speed and timer) and pipettes: [DEFAULT: every 12 months]
- temperature monitoring probes and data loggers: calibration certificate traceable to NIST, renewed [DEFAULT: every 12 months, or at the interval on the certificate if shorter]
- refrigerators and freezers: PM [DEFAULT: every 12 months], plus temperature monitoring under 5.4
- emergency equipment: checks as the manufacturer specifies and at least [DEFAULT: monthly], with AED self-test status checked [DEFAULT: weekly]
5.2.3
Calibration is performed by a qualified vendor whose reference standards are traceable to national standards, or by trained staff using a documented method and traceable reference (for example certified check weights). Vendors are qualified under SOP-105.
5.2.4
The Quality Lead reviews upcoming due dates [DEFAULT: monthly] and schedules service so that no equipment used in trials goes past its due date. Equipment that will be overdue is replaced with a calibrated unit or removed from trial use.
5.2.5
Daily or per-use checks required by the manufacturer or the protocol (for example spirometer volume calibration with a 3-liter syringe, glucose meter control solutions, ECG lead check) are done by the user and recorded on the device's check log or in source.
5.3 Certificates and records
5.3.1
For each calibration or PM, the site keeps the certificate or service report showing: equipment identification, date, as-found and as-left results, tolerance, pass or fail, reference standard used and its traceability, and the technician's name.
5.3.2
The Quality Lead reviews each certificate on receipt, checks the as-found results, and updates F-312-01. An as-found result outside tolerance triggers 5.5 even if the as-left result passes.
5.3.3
Certificates are filed centrally in the equipment file. When a sponsor asks for them, the Regulatory Coordinator files copies, or a reference to the central location, in the ISF (ICH E6(R3) Appendix C, C.2.12, allows non-trial-specific essential records to be kept outside trial files if their location is recorded).
5.4 Temperature-controlled storage and monitoring devices
5.4.1
Every refrigerator, freezer and room used to store IP, specimens or temperature-sensitive kits is monitored under the single temperature rule in SOP-304, section 5.4: continuous monitoring (a logger or system that records at set intervals and alarms), or a calibrated min/max thermometer read each business day with a documented closed-day plan. A min/max thermometer is not continuous monitoring.
5.4.2
Thermometers, probes and data loggers have a current calibration certificate traceable to NIST, with the stated accuracy appropriate for the storage range. Expired loggers are taken out of service and replaced before the expiry date.
5.4.3
Daily review, closed-day coverage and data gaps follow SOP-304, section 5.4. Excursions are handled under SOP-304 (IP) or SOP-311 (specimens).
5.4.4
Electronic temperature monitoring systems are listed on the computerized system inventory (SOP-401, F-401-01).
5.5 Out-of-tolerance results and equipment failure
5.5.1
Any staff member who finds equipment damaged, malfunctioning or failing a check stops using it, attaches an "OUT OF SERVICE: DO NOT USE" tag, and notifies the Quality Lead and the Lead CRCs of affected studies the same day.
5.5.2
The Quality Lead records the event on F-312-01 and starts an impact assessment covering the period from the last acceptable calibration or check to the failure. The assessment identifies:
- which studies, participants and visits used the equipment in that period
- the size and direction of the error compared with protocol thresholds (for example eligibility cut-offs for blood pressure or weight, dose calculations based on weight, safety stopping rules)
- whether any eligibility decision, dose, safety assessment or endpoint could have been affected
5.5.3
The PI reviews the impact assessment and decides on actions, for example repeat measurements, re-review of eligibility, notification of participants or their physicians, or data corrections.
5.5.4
The Lead CRC notifies the sponsor of any potential impact on trial data or participant safety and records it as a deviation under SOP-308 where data or safety were affected. The sponsor decides on data handling.
5.5.5
The Quality Lead files the completed impact assessment with the equipment record, and opens a CAPA under SOP-703 if the cause is systemic (for example a missed calibration schedule).
5.6 Sponsor-provided equipment
5.6.1
On receipt, the CRC records sponsor-provided equipment on F-312-01 with study, serial number and the sponsor's calibration or maintenance requirements, and files the shipping and calibration records in the ISF.
5.6.2
The sponsor is responsible for calibration and maintenance of its equipment unless the agreement says otherwise. The CRC follows the sponsor's instructions for daily checks, software updates and returns, and tracks any calibration due date set by the sponsor.
5.6.3
Sponsor equipment is used only for its study unless the sponsor permits other use in writing.
5.6.4
Faults with sponsor equipment are reported to the sponsor's help desk or vendor. The CRC records the ticket number and, if trial data were affected, follows 5.5.
5.6.5
Equipment issued to participants (for example wearables, ePRO devices, home spirometers) is tracked by serial number against participant ID on F-312-01 or the sponsor's device log, so the site can show which device generated which data. The CRC trains the participant and records the training (ICH E6(R3) Annex 1, 2.12.10(d)). At closeout, the CRC returns sponsor equipment as instructed and records the return.
5.7 On-site testing and CLIA
5.7.1
Any test on a human specimen performed at the site whose result is used to assess a participant's health (eligibility, safety, dosing, or reported back to the participant or their physician) is subject to CLIA. The research laboratory exception in 42 CFR 493.3(b)(2) applies only when no patient-specific results are reported for diagnosis, prevention, treatment or health assessment. Protocol-required point-of-care tests used for eligibility or safety do not meet that exception.
5.7.2
Before any on-site testing begins, the Site Director confirms that the site holds a CLIA certificate that covers each test performed, at each location where it is performed. The certificate types are:
- Certificate of Waiver: waived tests only (for example urine pregnancy tests, dipstick urinalysis, many glucose and INR meters). The site must follow the manufacturer's instructions exactly.
- Certificate for Provider-Performed Microscopy Procedures (PPM): specified microscopy procedures performed by a physician, midlevel practitioner or dentist during the patient's visit, plus waived tests.
- Certificate of Compliance: moderate and high complexity testing, with inspection by the state agency on behalf of CMS.
- Certificate of Accreditation: moderate and high complexity testing, with inspection by a CMS-approved accreditation organization (for example CAP, COLA, The Joint Commission).
- Registration Certificate: issued temporarily while a laboratory applying for compliance or accreditation awaits inspection.
5.7.3
The Site Director confirms the test complexity of each device and kit from the FDA CLIA database or the package insert before use. A test is not run if its complexity exceeds the site's certificate.
5.7.4
Waived testing is done only by staff trained on the specific device, using in-date reagents, controls at the frequency the manufacturer specifies, and the manufacturer's procedure without modification. Training and control results are recorded.
5.7.5
State law may add requirements for laboratory licensure or testing personnel.
5.7.6
The Regulatory Coordinator keeps the current CLIA certificate(s) and the list of tests performed on site in the central equipment and laboratory file, sends copies to sponsors, and tracks renewal (CLIA certificates are issued for two years). Renewal fees are paid before the certificate expires.
5.7.6.1
The Site Director notifies CMS through the CLIA state agency within 30 days of any change in ownership, name, location or director. The rule depends on the certificate type: 42 CFR 493.39(b) (waiver), 493.53(b) (PPM), 493.51(a) (compliance, which also covers a change in technical supervisor for high complexity testing) and 493.63(a) (accreditation, where the accreditation organization is also notified). The Site Director checks the rule for the site's certificate type on eCFR.
5.7.6.2
A test outside the site's certificate type is not run until the certificate covers it (section 5.7.3). For waiver and PPM certificates, HHS is notified before such a test is performed and reported (42 CFR 493.39(a), 493.53(a)); for compliance and accreditation certificates, a new specialty or subspecialty is notified within 6 months (42 CFR 493.51(b), 493.63(b)).
5.7.7
Sponsor-provided point-of-care devices are subject to the same CLIA requirements as site devices.
5.8 Local and central laboratories
5.8.1
The protocol states which tests go to the central laboratory and which, if any, may be done at a local laboratory. The site uses a local laboratory for protocol tests only where the protocol or sponsor permits it.
5.8.2
For each laboratory used in a study (central, local, specialty), the Regulatory Coordinator files in the ISF before first use:
- the current CLIA certificate, and accreditation certificate (for example CAP) where held
- the normal ranges for each protocol test, with units and effective date
- the laboratory director's name, and CV if the sponsor requires it
5.8.3
For IND studies, clinical laboratories used for the study are listed on Form FDA 1572, Section 4 (SOP-101 and SOP-204). When a new local laboratory is added during the study, the Regulatory Coordinator updates the 1572 or records the laboratory as the sponsor instructs, and files its certifications and normal ranges. For device studies, the site follows the sponsor's investigational plan for laboratory identification.
5.8.4
The Regulatory Coordinator tracks expiry dates of laboratory certificates and requests updated certificates and normal ranges [DEFAULT: on expiry and at least annually]. When a laboratory changes its normal ranges, the new ranges and effective date are filed so that each result can be interpreted against the ranges in effect on the date of testing.
5.8.5
Local laboratory results used in the trial are reviewed, signed and dated by the PI or a delegated Sub-I, with clinical significance of abnormal values assessed under SOP-500.
5.8.6
Where the site uses its own on-site laboratory results in a trial, it provides the sponsor with its CLIA certificate, normal ranges and any accreditation, exactly as for a local laboratory.
5.9 Annual review
5.9.1
The Quality Lead reconciles F-312-01 against equipment physically present at each location at least [DEFAULT: annually], and records the reconciliation. Missing or unlisted equipment is resolved.
6. Related Forms and SOPs
- F-312-01 Equipment Inventory and Calibration Log
- F-304-02 Temperature Monitoring Log
- F-304-03 Temperature Excursion Report
- F-308-01 Protocol Deviation Log
- F-105-01 Service Provider Qualification and Oversight Record
- F-401-01 Computerized System Inventory and Access Log
- SOP-101 Roles and Responsibilities of the Principal Investigator
- SOP-105 Oversight of Service Providers and Vendors
- SOP-204 Essential Documents and the Investigator Site File
- SOP-304 Investigational Product Management
- SOP-308 Protocol Deviations and Noncompliance
- SOP-311 Biological Specimen Collection, Processing and Shipping
- SOP-401 Computerized Systems and Electronic Records
- SOP-402 Record Retention, Archiving and Destruction
- SOP-500 Adverse Event Identification, Assessment and Recording
- SOP-703 Corrective and Preventive Action (CAPA)
- Appendix A State Law Worksheet
- Appendix B Central and Site Responsibility Matrix (Model N only)
7. References
| Reference | Title |
|---|---|
| ICH E6(R3) Annex 1, 2.2 | Resources (adequate facilities) |
| ICH E6(R3) Annex 1, 2.12.10(d) | Equipment for data acquisition provided to participants |
| ICH E6(R3) Appendix C | Essential Records (maintenance and calibration records; laboratory certification and normal ranges) |
| 42 CFR 493 Subpart A | CLIA general provisions, including 493.3(b) exceptions and 493.15 waived tests |
| 42 CFR 493 Subparts B, C and D | Certificate of Waiver; Registration Certificate, PPM Certificate and Certificate of Compliance; Certificate of Accreditation |
| 21 CFR 312.53(c)(1) | Form FDA 1572 information, including clinical laboratory facilities |
| FDA guidance (Sept 2024) | Conducting Clinical Trials With Decentralized Elements (local clinical laboratory facilities) |
| FDA Guidance (May 2010; Revision 1 draft, May 2021) | Information Sheet Guidance for Sponsors, Clinical Investigators, and IRBs: Frequently Asked Questions, Statement of Investigator (Form FDA 1572) |
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