Draft Annex 17: Real Time Release Testing, Revision 1

On 15 September 2015, a consultation was launched on a draft revised Annex 17: Real Time release Testing. The document is for consultation until 11 December 2015.

The reasons for the changes in the document are that the previous Annex 17 "only focused on the application of Parametric Release for the routine release of terminally sterilised products waiving the performance of a test for sterility on the basis of successful demonstration that predetermined and validated sterilising conditions have been achieved."

In the section "Scope" of the draft document it is pointed out that the Annex „is intended to outline the requirements for application of a Real Time Release Testing (RTRT) approach in manufacturing, where the control of critical parameters and relevant material attributes may be used as an alternative to routine finished product testing of medicinal products. The main aim of the changes to this 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.”

Furthermore, the draft defines RTRT as “a combination of in-process monitoring and controls” that "may provide sufficient evidence to justify batch release without the tests being repeated on a sample of the finished product“.

In addition the draft document emphasizes that "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."

The draft annex is based on elements of ICH Q8, Q9, Q10 and Q11 "and will detail regulatory expectations for a batch release system based on the information collected during manufacturing process, through product knowledge and process understanding and control."

Since the control strategy is dynamic and may change this should be handled as a life cycle approach requiring the use of quality risk management and knowledge management.  This is recently also highly discussed in relation with the new planned ICH Q12 Guideline on "Life Cycle Management".

Further information on the consultation can be found on the EudraLex Website.