SOP for Calibration of Instruments and Measuring Devices (Example)

In short: This is an illustrative SOP template for a general calibration control system covering all equipment, instruments and measuring devices at a pharmaceutical site. It shows how to classify instruments, set intervals, label status, keep traceability and handle out-of-calibration results. Adapt it to your own quality system; the intervals and limits are examples, not regulatory requirements.

Note: This is an example SOP. Document numbers, intervals, tolerances and responsibilities must be set and approved under your own quality system.

See also: HPLC Calibration - A Complete Guide Part 1 for instrument-specific calibration of HPLC.

Regulatory background

Both US and EU GMP expect a written calibration programme with records:

• 21 CFR 211.68(a) requires automatic, mechanical or electronic equipment to be routinely calibrated, inspected or checked according to a written program, with records kept.
• 21 CFR 211.160(b)(4) requires laboratory instruments and apparatus to be calibrated at suitable intervals under a written program that includes directions, schedules, accuracy and precision limits and remedial action. Instruments not meeting specifications must not be used.
• EU GMP Chapter 3, paragraph 3.41 says measuring, weighing, recording and control equipment should be calibrated and checked at defined intervals by appropriate methods, with adequate records.
• EU GMP Chapter 6 (paragraphs 6.5 and 6.7) requires control laboratory equipment to meet Chapter 3 and laboratory documentation to include procedures and records for calibration or qualification of instruments.

1. Objective

To define the general requirements for an effective calibration control system, so that measuring and test equipment is calibrated and kept within accuracy limits suitable for its intended use.

2. Scope

This procedure applies to the calibration of all equipment, instruments and measuring devices.

3. Responsibility

• Follow-up: Concerned department officer or executive.
• Overall responsibility: Head of the concerned department.
• Head QA: Approves this SOP and the calibration planner.

4. Procedure

4.1 Classification of instruments

1. Each calibrated instrument is tagged with an identification number for tracking, as per Annexure II (calibration status label). The label also shows the date of last calibration and the next due date.
2. Instruments that do not need calibration because of their nature or application are tagged “NO CALIBRATION REQUIRED”.
3. An instrument found outside calibration limits is labelled “OUT OF CALIBRATION” at once. Head Engineering is informed, and the instrument is recalibrated, repaired or replaced before further use.
4. Head QA is also informed, to assess the impact on product quality if the instrument was used during the period it was out of calibration.

4.2 Calibration intervals

1. Intervals are assigned to each type of instrument so that it is likely to be within calibration limits whenever it is used.
2. Instruments are assigned a frequency from the table below.

Example only: the frequencies and windows above are a site choice, not a regulatory requirement. Set yours from the instrument’s criticality, manufacturer’s advice and calibration history.

3. The initial interval for new equipment is based on the manufacturer’s recommendation and the judgement of the Engineering department.
4. Intervals may be changed when calibration data or other information supports it, through the change control procedure.
5. The calibration date is entered on the label and documents. The next due date is the day before the same date in the next period. For example, if calibration is done on 10 Jan 2022, the due date for a 12-month interval is 09 Jan 2023.
6. The Master List of Calibration Status of Measuring Devices, Equipment, Instruments and Utilities is maintained as per Annexure I, in soft and hard copy.
7. When repair or adjustment is needed, the instrument is tagged “OUT OF CALIBRATION”. Whether repaired in-house or by an outside contractor, it is recalibrated before returning to service.
8. The tag is not removed until repair is complete and the instrument has been recalibrated.

4.3 Traceability

1. The calibration system provides a way to trace measurement values to recognised national standards. In India this usually means calibration by a laboratory accredited by NABL (National Accreditation Board for Testing and Calibration Laboratories) to ISO/IEC 17025:2017, with traceability to national measurement standards. Documentation includes the calibration agency and certificate data.
2. Calibration standards that are not traceable to national standards (for example, reference materials or internal standards) need documented evidence of their validity.

4.4 Outside contractor control

1. Engineering, in coordination with QA, ensures that the contractor’s calibration system meets all requirements.
2. Head QA and Head Engineering review and approve the contractor’s procedure.
3. All documents supplied by the contractor are reviewed and duly signed.

4.5 General requirements

1. Instruments, equipment and measuring devices are calibrated as per the SOP of the respective instrument.
2. Calibration limits are defined for each instrument or device.
3. Calibration status must be easy to see. Each item carries a calibration status label as described in its own calibration SOP. If an outside agency calibrates the item, the agency supplies the label. The label format is in Annexure II.
4. A calibration certificate contains:
   1. Name of the instrument, equipment or device
   2. Identification number
   3. Range under calibration
   4. Name and range of the standard instrument used
   5. Calibration certificate of that standard, with its validity period
   6. Date and time of calibration
   7. Calibration status
   8. Calibration due date
   9. Acceptance criteria
5. Engineering prepares and updates, separately, the master list of calibration status. It shows the name, identification number, location, calibration date and due date of each item.

Note: Spare measuring devices are calibrated at the normal frequency. They can then replace a device that malfunctions or whose calibration is about to lapse.

4.6 QC instruments and out-of-calibration results

1. All QC instruments are calibrated as per the standard calibration procedure of the respective instrument.
2. An out-of-calibration instrument or device is labelled “OUT OF CALIBRATION” and reported to the HOD of the concerned department, Head Engineering and Head QA. It is not used until it is satisfactorily recalibrated.
3. For critical instruments with a direct effect on product quality or analytical results, products and samples tested between the last good calibration and the date the instrument was found out of calibration are reassessed.

5. Training

• Trainer: Head - Quality Assurance
• Trainees: All departmental and sectional heads

6. Distribution

7. Annexures

• Annexure I: Calibration calendar
• Annexure II: Calibration label

8. Abbreviations

QA: Quality Assurance; QC: Quality Control; HOD: Head of Department; SOP: Standard Operating Procedure; NABL: National Accreditation Board for Testing and Calibration Laboratories.

Frequently asked questions

How often should instruments be calibrated?

GMP does not fix one interval. 21 CFR 211.160(b)(4) says “suitable intervals”, and EU GMP 3.41 says “defined intervals”. Set them from risk, criticality, manufacturer’s advice and history, and review them with data.

What should I do when an instrument is found out of calibration?

Label it, stop its use, inform Engineering and QA, and assess the impact on results and batches tested since the last good calibration. Investigate under your deviation procedure.

Can I rely on a balance’s built-in auto-calibration?

FDA’s equipment Q&A says auto-calibration should not replace an external performance check. Verify it periodically with traceable standards.

References

1. US FDA, 21 CFR 211.68, Automatic, mechanical, and electronic equipment (current eCFR text, Part 211).
2. US FDA, 21 CFR 211.160(b)(4), General requirements (laboratory controls) (current eCFR text, Part 211).
3. European Commission, EudraLex Volume 4, EU GMP Part I, Chapter 3: Premises and Equipment (revision effective 1 March 2015), paragraph 3.41.
4. European Commission, EudraLex Volume 4, EU GMP Part I, Chapter 6: Quality Control (revision effective 1 October 2014), paragraphs 6.5 and 6.7.
5. ISO/IEC 17025:2017, General requirements for the competence of testing and calibration laboratories.

Revision history