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Revision of the EU GMP Guide – Annex 17 (Part I)

  • 14 October 2015
  • Annex 17, GMP, parametric release, PAT, pharmaceutical development, QbD, QRM, RTRT,

ASE Pharma Solutions

On 15 September 2015, the European Commission released for public consultation (until 11 December 2015) a draft revised version of Annex 17: Real Time Release Testing of the EU GMP Guide.

Comparing to current version of this annex, an application of the concept, which under specific circumstances, and where authorised, allows batch release based on information collected during the manufacturing process, product knowledge, process understanding and control, is extended. So far this concept has been mainly applied to sterility testing of terminally sterilised products and has become associated with parametric release applications. Recent guidelines adopted in the ICH context (ICH Q8, Q9 and Q10 as well as Q11) have made it possible to apply a similar release decision process to tests other than sterility, this approach has been called Real Time Release Testing (RTRT). The main aim of the changes to the guideline is to incorporate the application of RTRT to any stage in the manufacturing process and to any type of finished products, including active substances and intermediates.


Sterility test

Additionally, advances in the application of process analytical technology (PAT), quality by design (QbD) and quality risk management (QRM) principles to pharmaceutical development and manufacturing have shown that appropriate combination of process controls together with timely monitoring and verification of pre-established material attributes provides greater assurance of product quality than finished product testing (conventionally regarded as the end-product testing) alone.

ex of PAT

Where a RTRT procedure has been established and authorised in the Marketing Authorisation, the Qualified Person can certify the batches based on the compliance of the process data to the approved release criteria together with appropriate GMP compliance. It should be noted here, that it is not acceptable to perform an actual test on a product (active substance or finished product) motivated by an undesired or unacceptable result as determined by the approved RTRT approach. End testing for release purpose can be acceptable if RTRT information elements are not available, for example due to analytical equipment failure.

Moreover, the process for this form of batch release should be integrated into and controlled through the pharmaceutical quality system. It is required to prepare a RTRT master plan. This should include, as a minimum, but not limited to:

  1. a quality risk assessment, including a full process related risk assessment,
  2. a change control program,
  3. a control strategy,
  4. a personnel training program,
  5. an equipment and facility design and qualification program,
  6. a deviation/CAPAs system,
  7. a process development and validation program,
  8. a contingency procedure in case of a process sensor/equipment failure,
  9. a periodic review/assessment program to measure effectiveness of the RTRT plan for continued assurance of product quality, that includes a monitoring program over the product’s lifecycle for critical material attributes and process parameters.

The draft revised Annex 17 is defining now Parametric Release as one form of RTRT.

All details you will find in the draft revised Annex 17: Real Time Release Testing.