New EMA Guideline on Real Time Release Testing

Medicinal products must comply with the requirements stated in the authorised specifications before they can be released for sale. Under certain circumstances an alternative strategy may be allowed for the systematic end-product testing. So far, this concept has been primarily used for the sterility testing of products terminally sterilised. As defined in the ICH Guidelines Q8, Q9 and Q10, it is now possible to extend such release decisions to other applications. This approach is called "Real Time Release Testing (RTRT)".

The EMA has published a new Guideline on Real Time Release Testing (formerly Guideline on Parametric Release) which should enter into force in October 2012.

The Guideline is valid for active substances, intermediates and finished products. Yet, the introduction of RTRT always requires pre-authorization by the competent authority. Even if an authorisation is available for RTRT, a specification has to be established and each batch of a product should comply with it if tested. Basically, a specification is also necessary for stability studies.

The condition for the application of RTRT is adequate validation of the RTR test method. Substantial comparative data through parallel testing of production batches are expected.

If the test results of RTRT fail or are trending toward failure, RTRT may not be simply substituted by "normal" end-product testing. The results of RTRT should be given in the Certificate of Analysis as "complies if tested" with a footnote: "Controlled by approved Real Time Release Testing".

Usually, RTRT comprises a combination of process controls which may utilise process analytical technology (PAT) instruments and tools, e.g. NIR or Raman.

RTRT can also apply to continuous manufacturing processes for the manufacture of APIs.

RTRT will be one of the key topics addressed at the QbD/PAT Conference organised by the University of Heidelberg on 26/27 September 2012 in the Marriott Hotel in Heidelberg, Germany. This year, the conference will welcome many top-class speakers who will come for the first time to Heidelberg.

Please also see the complete EMA "Guideline on Real Time Release Testing (formerly Guideline on Parametric Release)".

Author:
Dr Günter Brendelberger
CONCEPT HEIDELBERG (a service provider entrusted by the ECA Foundation)