Calibration and Qualification of QC Laboratory Equipment

In short: Every instrument used for testing in a QC laboratory must be uniquely identified, qualified for its purpose, calibrated against traceable standards and checked at planned intervals. Equipment that fails or is doubtful must be taken out of service until it is repaired and requalified. This guide is for QC analysts, supervisors and students.

Why this matters

A test result is only as reliable as the instrument that produced it. Regulators therefore expect a laboratory to show that each balance, pH meter, HPLC or piece of volumetric glassware was suitable on the day it was used. The expectation appears in the WHO good practices for pharmaceutical quality control laboratories (WHO TRS 1052, Annex 4, 2024, section 5.3), in 21 CFR 211.160(b)(4) and in EU GMP Part I Chapter 6 (para 6.7).

Four related terms

Identification and status labelling

• Give each item of equipment, instrument or device a unique identification, including its modules and accessories. WHO TRS 1052 Annex 4 (para 5.26) lists manufacturer, model, serial number, laboratory ID, location and the manufacturer’s instructions.
• Label, code or otherwise mark all equipment that needs qualification, calibration or maintenance so that its status and the next due date are visible (para 5.36). This also applies to devices such as volumetric glassware and automatic dispensers that need calibration.
• Keep a schedule of due dates so that nothing is used after it has lapsed.

Equipment qualification (DQ, IQ, OQ, PQ)

WHO TRS 1052 Annex 4 (paras 5.27 to 5.29) states that analytical equipment must be shown to be fit for its intended purpose through design qualification (DQ), installation qualification (IQ), operational qualification (OQ) and performance qualification (PQ).

• All four stages apply when new equipment is bought. Parts of DQ and IQ may need repeating after major changes, and the performance aspects are carried out throughout the equipment life cycle.
• Qualification should follow pharmacopoeial requirements first, address the intended use and follow the manufacturer’s recommendations.
• When equipment is bought, write a user requirement specification and ask the supplier for documents and support for qualification (para 5.32).
• For a standard commercial instrument, DQ is often covered by the supplier’s design and the user requirement specification, so the laboratory concentrates on IQ, OQ and PQ. Record the reasoning if DQ is not performed separately.

For examples of the protocols, see installation qualification protocol and report and performance qualification protocol and report.

Calibration and performance verification plan

The laboratory should write a policy that says, for each type of analytical equipment, how often it is serviced and which events trigger service (para 5.33). A qualification and maintenance matrix gives a clear overview of what is due, when, and whether staff or an external provider will do it (para 5.34).

21 CFR 211.160(b)(4) requires calibration of instruments, apparatus, gauges and recording devices at suitable intervals, following a written programme with directions, schedules, accuracy and precision limits and remedial action when limits are not met. Equipment that does not meet its limits must not be used.

Write a specific procedure for each equipment type, considering the type of equipment, how much it is used and the supplier’s advice. The following are example in-house criteria, not regulatory limits:

• pH meter: check with certified buffer solutions before use.
• Analytical balance: check daily with the internal calibration or a check weight, verify periodically with certified test weights, and requalify at a defined interval (for example annually) using certified reference weights.
• HPLC: calibrate pressure, flow, oven temperature, detector and gradient performance at a defined interval. See HPLC calibration, part 1.

Who may use the equipment, and which documents must be available

• Only authorised, trained personnel should operate equipment.
• Current SOPs on use, maintenance, verification, qualification and calibration, together with the manufacturer’s manuals, must be readily available to analysts.
• A schedule of the dates on which verification or calibration is due must be available. See also SOP for calibration.

Equipment records and logbooks

Keep a record for each item used for testing, verification or calibration. It should include at least:

1. identity of the equipment;
2. manufacturer’s name, model and serial number or other unique identification;
3. qualification, verification and calibration required;
4. current location, where appropriate;
5. the manufacturer’s instructions, or where they are kept;
6. dates, results and copies of reports and certificates of all calibrations, adjustments, acceptance criteria and the due date of the next action;
7. maintenance carried out and the maintenance plan;
8. a history of damage, malfunction, modification or repair.

WHO TRS 1052 Annex 4 (para 5.44) also asks for equipment logbooks showing the modules that make up the equipment, its history from initial qualification, and dates of subsequent maintenance, calibration and qualification. Recording the time for which equipment was used is a useful addition.

Qualification documents should name who performed each test, the specification and acceptance criteria, the date and result, the reason for qualification, what to do on failure, and the signatures of the performer and the authorising person (para 5.43).

Record retention: equipment and calibration records that support a batch result should be kept for at least 1 year after the expiry date of the respective product batch (EU GMP Part I Chapter 4, para 4.11, or 5 years after QP certification if longer; 21 CFR 211.180(a)), and longer if local law or the marketing authorisation requires.

Handling, maintenance and out-of-service equipment

• Write procedures for safe handling, transport and storage of measuring equipment.
• Service should be carried out by competent maintenance staff, internal or external, and followed by performance checks (para 5.35).
• Equipment shown to be defective or out of its specified limits must be taken out of service and clearly labelled. It should not be used until it has been repaired and requalified (para 5.40).
• Requalify after events such as relocation or reinstallation, service interruptions, repair or maintenance, modification, a change of use, or suspect results that point to an instrument problem (para 5.39). Equipment that has been outside the laboratory’s direct control or has had major repair should be requalified before use.
• Assess changes through change control to decide whether requalification is needed (para 5.38).

Traceability

Calibration and qualification should, where relevant and possible, be traceable to certified reference materials and to national or international standards such as the International System of Units, SI (WHO TRS 1052 Annex 4, para 5.37). Each test result should also be traceable to a suitable primary reference substance (pharmacopoeial or the manufacturer’s) or, where appropriate, to a certified reference material (para 6.53).

Further guidance

WHO TRS 1052 Annex 4 (para 5.46) points to further guidance on equipment qualification, including:

• the USP general chapter on analytical instrument qualification (<1058>);
• the OMCL network core document Qualification of equipment (PA/PH/OMCL (08) 73), published by EDQM, with its instrument-specific annexes;
• The International Pharmacopoeia (11th edition, 2023).

Frequently asked questions

Is calibration the same as qualification? No. Qualification shows the equipment is fit for its intended purpose over its life cycle. Calibration compares readings against a traceable standard at set intervals.

Can design qualification be skipped? For a commercially available standard instrument, the supplier’s design and your user requirement specification may cover it, so IQ, OQ and PQ are the main work. Justify and record the decision.

What if an instrument is found out of calibration? Take it out of service, label it, and assess the impact on results obtained since the last good check under your deviation procedure. Repair and requalify before reuse.

Do volumetric glassware and dispensers need calibration? Yes where their accuracy affects results; they need status identification like other devices.

References

1. WHO. WHO good practices for pharmaceutical quality control laboratories. WHO Technical Report Series No. 1052, 2024, Annex 4, section 5.3 (paras 5.24 to 5.45).
2. US FDA. 21 CFR 211.160(b)(4), Calibration of instruments, apparatus, gauges and recording devices (eCFR, current).
3. European Commission. EudraLex Volume 4, EU GMP Part I, Chapter 6: Quality Control (revised 2014), para 6.7.
4. European Commission. EU GMP Part I, Chapter 4: Documentation, para 4.11; 21 CFR 211.180(a).
5. United States Pharmacopeia. General chapter <1058> Analytical instrument qualification (USP–NF, current official version).
6. EDQM, General European OMCL Network. Qualification of equipment: core document, PA/PH/OMCL (08) 73 R5.