Definition:

Calibration is The set of operations which establish, under specified conditions, the relationship between values indicated by a measuring instrument or measuring system, or values represented by a material measure, and the corresponding known values of a reference standard. ISPE-GAMP Calibration Management- 2.2

Program:

The calibration of instruments, apparatus, gauges, and recording devices at suitable intervals in accordance with an established written program containing specific directions, schedules, limits for accuracy and precision, and provisions for remedial action in the event accuracy and/or precision limits are not met. Instruments, apparatus, gauges, and recording devices not meeting established specifications shall not be used. FDA- 21 CFR – 211- 160(b)(4)

Standards, Tolerances, and Intervals:

When deciding on calibration ranges and limits, the instrument ranges, the manufacturer’s accuracy, and the process requirements should be taken into account. Process ranges, tolerances, alert, and action limits are interrelated.

The full range of an instrument may prove most appropriate for the calibration range. Conversely, for instruments that have a full calibrating range much greater than the actual operating values, it may be appropriate to reduce the maximum and minimum calibration range closer to that of the standard operating values. ISPE- GAMP Calibration Management- 5.1.5

Calibration Frequency:

calibration should be planned and executed to suitable calibration frequencies. In order to define suitable calibration frequencies, the risk and consequences of an incorrect indication should be risk assessed.

Where the probability of error detection is low and the consequences high, a high calibration frequency should be adopted. Where error detection and consequences are considered to be moderate, a lower calibration frequency may be adopted. ISPE- GAMP Calibration Management- 5.1.6

In general, product critical instruments should initially be calibrated on at least a biannual basis until there is enough historical data to determine reliability. 

Responsibilities:

The main responsibilities of the independent quality units should not be delegated. These responsibilities should be described in writing and should include, but not necessarily be limited to: Making sure that effective systems are used for maintaining and calibrating critical equipment. EU- GMP- ICH- Q7A- 2.22.12

Out of Tolerance Conditions:

Defective equipment should be removed from production and quality control areas. If this is not possible, it should be clearly labeled as defective to prevent use. WHO- TRS- 986- Annex 2- 13.1

Conclusion:

In the pharmaceutical and food industries, calibration management is a cornerstone of quality assurance. Adhering to GMP and ISO/IEC 17025 standards ensures that measuring instruments and systems are reliable, accurate, and traceable. By implementing a robust calibration program, organizations can enhance product quality, compliance, and overall operational efficiency. Stay tuned for more in-depth insights into calibration management in future articles.

Note: The content provided here is based on the regulatory information available up to January 2024, and it is advisable to check for any updates or amendments to standards and regulations that may have occurred after this date.

References

1. ICH Topic Q 7a  Good Manufacturing Practice for Active Pharmaceutical Ingredients

2. FDA- 21 CFR – Part 211 CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS

3. ISPE-GAMP Calibration Management

4.WHO, TRS 986, Annex 2, WHO good manufacturing practices for pharmaceutical products: main principles