• gmp-verlag.de
  • GMP MANUAL Login
  • Shopping cart
Stay informed!

You’d like to be regularly informed on the latest developments in Good Manufacturing Practices?

 

Subscribe to our free GMP Newsletter LOGFILE!

>>> REGISTER NOW

TOP 5 GMP Downloads

1. Questionnaire for preparing GMP-inspections
More than 650 typical questions related to audits and inspections.


2. GDP Audit Checklist
More than 700 questions with reference to regulations.


3. GMP Fundamentals
A quick and comprehensive overview of the complex world of GMP.


4. Industry Guide to handle OOX Test Results
Every single step of the OOX process.


5. The New USP <1231>: Water for Pharmaceutical Purposes
A compact overview of the contents of the new version of USP <1231>.


>>> More Downloads
GMP Compliance Adviser

GMP in Practice: 24 chapters written by internationally renowned industry experts.

 

GMP Regulations: 8 chapters with the most important GMP guidelines and regulations.

 

Image

>>> READ MORE

Award
Image
The New USP <1231>
Water for Pharmaceutical Purposes

a detailed Overview

>>> ORDER NOW

GMP LOGFILE Features

2017-10-25

LOGFILE No. 40/2017 – Calibration of laboratory instruments

Calibration of laboratory instruments

An excerpt of the GMP Compliance Adviser, Chapter 14.D.4

5 minutes reading time

by Josef Künzle, PhD, Wolfgang Nedvidek, PhD

 

Intoduction

The calibration of analytical instruments is stipulated in the GMP Guidelines. During calibration, it is checked whether the qualified status of the instrument has been preserved. Non-calibrated analytical instruments may not be used for testing.

In accordance with the EU GMP Guidelines, Part I, calibration is defined as follows (cf. Figure 1):

Figure 1 Definition of calibration in accordance with the EU GMP Guidelines, Part I, Glossary

Image

It is important to differentiate between calibration, and adjustment and gauging; they are defined as follows:

  • DIN 1319 defines adjustment as follows: "Adjustment is the setting or balancing of a measuring instrument to eliminate systematic measurement deviations to the necessary extent or as far as possible. Adjustment therefore requires an action which permanently alters the instrument."
  • Gauging is the mandatory testing of measurement instruments for compliance with the underlying legal calibration regulations, especially the calibration error limits. A stamp confirms the expected compliance for the period of validity of gauging. Or in other words: gauging is a legally required calibration that can be traced back to national standards (Wikipedia).

Calibration programme

The calibration programme is used to ensure that all instruments are calibrated at regular intervals. The calibration programme can be described in an SOP that is the "higher-level" calibration SOP.

The general requirements that apply to all instruments are listed in Figure 2.

Figure 2 Contents of the calibration programme

Image

The guidelines contain no mandatory requirements with regard to calibration intervals, the question of whether calibration should be carried out on a particular day or month, the scope of calibration or the definition of acceptance criteria. These must be defined internally based on experience. For this reason, the following examples are only suggestions.

Calibration intervals

The calibration intervals can be defined according to the priority of the instruments in the laboratory. Instruments with higher priority are calibrated at shorter intervals than those with lower priority. This approach is illustrated in the example in Figure 3.

Figure 3 Calibration intervals for laboratory instruments based on priority (example)

Image

It is also possible and in many situations imperative to carry out the calibration before use, e.g. in the case of osmometers. This approach also makes sense in the case of instruments that are rarely used.

Because relatively short calibration intervals of 3 months and less are common in laboratories, it is recommended that calibration be scheduled for a particular day. The exact calibration interval is then calculated based on that date (example in Figure 4).

Figure 4 Setting the due date for calibration scheduled for a particular day

Image

Scope of calibration

There are no mandatory requirements with regard to the scope of calibration. Requirements from the pharmacopoeias or widely recognised requirements can be used as a reference point. For example, a balance must be calibrated over the operating range that is used. A photometer used during GMP analyses should meet the requirements of Ph. Eur. 2.2.25. Critical parameters or other lessons learnt during the qualification of the instrument can also be included in the scope of calibration.

Acceptance criteria

The definition of acceptance criteria can be based on general requirements, e.g. from pharmacopoeias, or on the practical application of the instrument. For example, Chapter 2.2.25 of the European Pharmacopoeia contains requirements affecting photometers. On the other hand, a broad acceptance criterion of ±10% can be perfectly acceptable for a 10-µl piston-operated pipette that is used exclusively for pipetting enzymes during enzymatic determination when a fluctuating amount of enzyme does not affect the result.

This text is an excerpt of the GMP Compliance Adviser, Chapter 14.D.4

Authors

Josef Künzle, PhD
Chemist
Basilea Pharmaceutica International Ltd, Basel

Wolfang Nedvidek, PhD

Comments
very useful information.
sandeep vishnani 2017-10-26
 
 
 
Literature recommendation
GMP Compliance Adviser
Single User Licence (monthly subscription)
GMP Fundamentals – A Step-by-Step Guide (download)