GMP Compliance Adviser Update No. 1/2020

With this GMP Compliance Adviser UPDATE you have direct access to all prime regulatory changes and to our GMP expert interpretations. Here are the new features at a glance:


GMP in Practice

Chapter 4

4.F Calibration (+++NEW version+++)

GMP Regulations

Chapter E 

ICH Guidelines

E.12 ICH Q12: Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management


GMP in Practice

Chapter 4.F Calibration

Calibration is understood as the comparison of a measured value with the correct value of a standard under given conditions. During adjustment, the measuring instrument is set to the smallest possible deviation from the correct value. This requires an intervention on the measuring instrument.
Official calibration is an official inspection, evaluation and marking of a measurement device. It is a prerequisite for the permit to use the instrument for the intended purpose and under the corresponding conditions of use for a further calibration period.
The requirement to perform calibration can be found in the EU GMP Guidelines as well as in the 21 CFR, the GMP regulations of the USA. In addition, calibration is required by ISO standards 9001 and 13485. A cornerstone of calibration is metrological traceability, which is established
in hierarchical form. This ranges from the factory standard over several stages to the SI standard units. Due to the uninterrupted chain of comparison measurements with specified measurement uncertainties, worldwide comparability of measurement results is ensured.
In addition to the purely technical implementation of calibration activities, the organisation and management of calibration have an important function as
support processes for production, quality control and related areas. This requires a holistic organisation of the calibration process. In practice, all the activities in
this area are summarised under the term calibration management. One part of this is test equipment management.
Calibrations can be carried out by means of direct exposure or by comparison measurements. Selection of the method is usually founded on the effort involved and the technical feasibility in relation to the required accuracy.
Even the most accurate calibration remains only an approximation to the true value of the measured quantity, since random error influences can never be completely avoided in practice. Therefore, measurement results without the associated measurement uncertainty are incomplete. Only by specifying the uncertainty can the actually measured values be evaluated and compared.
GMP-compliant documentation of a factory calibration is provided in the form of a calibration certificate. Its contents should be based on the DIN EN ISO 10012 standard. The documentation of a calibration, which is carried out by a body accredited according to DIN EN ISO/IEC 17025, is provided in the calibration certificate. The binding contents of such a calibration certificate are inter alia defined by the German accreditation body DAkkS.
(Hansjörg Gutmann, Markus Kopf, Markus Salemink, Christian Sander, PhD)

GMP Regulations

Chapter E: ICH Guidelines

E.12 ICH Q12 Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management

The new ICH guideline provides guidance on a framework to facilitate the management of post-approval chemistry, manufacturing and controls (CMC) changes in a more predictable and efficient manner across the product lifecycle.

  • Objectives and potential benefits of ICH Q12 i.e. include:
  • Harmonisaiton of change management
  • Facilitation of risk-based regulatory oversight
  • Control strategy as a key component of the dossier
  • Reduction of unnecessary costs and time for industry and regulators
  • Support for continuous improvement
  • Promotion of innovation in manufacturing.

Two of the main tools that are presented for this purpose are

  • Established conditions (ECs), necessary elements that are critical for quality
  • Post-approval change management protocol (PACMP), a tool for predictability of information required to support a CMC change to structure the ECs

ICH Q12 should be seen in line with ICH Q8 to Q11 and complements this series of ICH quality guidelines. It is an optional document and the introduced tools and concepts can be adopted, if appropriate. In step 5 ICH Q12 is to be implemented in the ICH regions. Please note: The document is fully in line with the US regulatory framework. In the EU legal adjustments will be necessary to achieve full compatibility with ICH Q12.

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