Appendix 17 of the EU GMP: Updates and revisions

The content of this GMP guideline has evolved from defining parametric release to defining Real-Time Release Testing (RTRT).


Revision of Appendix 17

Both concepts may be allowed if certain criteria are met as an alternative to routine end-of-production testing of active substances and/or finished products with the nuance that RTRT can be integrated at any stage of the manufacturing process and to any type of finished product or active substance, including intermediates, whereas parametric release is the release of a batch of sterilised product into its final container.

Focus on parametric release: defined as the release of a batch of sterilised product (wet heat, dry heat or ionising radiation) into the final container based on the review of critical process control parameters. It is an aspect of RTRT.

Parametric release of the sterilised product into the final container is based on a review of the process monitoring documentation (e.g. temperature, pressure, sterilisation time) rather than verification of a sample for a specific attribute in conjunction with compliance with specific GMP requirements, in relation to parametric release, and providing assurance of the product quality (Appendix 17 of the EU GMP: Updates and revisions: EMA: Guideline on Real-Time Release Testing and ICH Q8-Q9-Q10 Q&A).

Publication contents

STERIGENE proposes to meet the requirement for parametric release (Appendix 17 of the EU GMP: Updates and revisions) using the options available on the THEMA 4 control system (on ovens and autoclaves):

By a parametric graphical release called “Golden Cycle”

It is a set of functions that the user can activate and use separately.

  • Golden Cycle: comparison of the executed program graph (using TE and TP internal and/or external sensors) with the configured “ideal temperature and pressure graph” (based on validated cycles), with the results of the comparison calculated and recorded in graphical and analytical format in the batch report.
  • Temperature uniformity: calculation and reporting of the time and space uniformity of the temperature during processing (sterilisation phase) on the selected internal or external TEs, with management of the defined alarms.
  • Verification of saturated steam conditions: calculation of the pressure range in the sterilisation phase and verification of its adequacy with respect to the defined conditions.
  • Balancing time calculation: with alarm management if outside the user-defined acceptance range.


Via an analytical parametric release

This is an automatic analysis of the “critical parameters” occurring during cycle execution.

It is configured by the user (for each phase of the program) and verifies if the values are either within a predefined range or equal to a fixed value.

This option generates an electronic report with all requested values that can be fed back by the external systems (SCADA and historian) for parametric batch release.

The Parametric Release Table is based on analysis of the parameters defined for each phase and enables the results to be exported to a central system (SCADA). This is an offline analysis of the data collected and stored in the process report.