[ HOW-TO GUIDE ]
How to Implement Real-Time Release Testing
Build an RTRT strategy that a regulator can approve and a site can run.
What a how-to is not
A how-to is SPEQ’s practitioner method, not a procedure. It does not replace your own SOP, it is not a validated approach, and the judgement calls in it belong to your quality unit.
Real-time release testing replaces some or all end-product tests with in-process measurements and controls, where authorised. EU GMP Annex 17 sets the minimum criteria and the quality-system elements, and ICH Q13 and FDA’s PAT guidance describe the measurement and control that make it possible. This is the order to build it in.
- 1
Choose the attribute and prove the prediction
Pick the finished-product attribute to replace and show, with scientific evidence from material, product and process knowledge, that the real-time measurements and controls are accurate predictors of it. Annex 17 makes this the first minimum criterion.
- 2
Design the control strategy
Define the in-process controls, material attributes and process parameters to be monitored, the sampling plan and the acceptance and rejection criteria. In a continuous process, include the criteria for diverting non-conforming material and for restarting collection.
- 3
Qualify the measurements
Qualify and validate the in-line and on-line methods and their models, with particular attention to probes placed inside the manufacturing equipment, and write a contingency procedure for sensor or equipment failure.
- 4
Build it into the quality system
Cover risk assessment, change control, specific training for a cross-functional team, deviation and CAPA, and a periodic review of the RTRT plan’s effectiveness. Engage the regulatory authorities before and during assessment, as Annex 17 requires.
- 5
Run it as approved
Once approved, use RTRT routinely for release. If results fail or trend toward failure, investigate — do not switch to end-product testing instead. Report RTRT-controlled attributes on the certificate of analysis as “Complies if tested” with the Annex 17 footnote.
- !Adding sensors without demonstrating that they predict the attribute being replaced.
- !No contingency procedure for a failed probe or analyser during production.
- !Falling back to end-product testing when RTRT results fail, which Annex 17 does not allow.
- !Changing equipment or methods without assessing the effect on the RTRT model under change control.
How to Implement Real-Time Release Testing: frequently asked questions
Common questions on implement real-time release testing.
Does RTRT need regulatory approval?
Yes. Annex 17 says a combination of in-process monitoring and controls may substitute for end-product testing when authorised, and that interaction with the relevant regulatory authorities is required before and during assessment.
What must an RTRT strategy include in the quality system?
Annex 17 section 3.3 lists quality risk management with a full process-related risk assessment, change control, the control strategy, specific personnel training, qualification and validation policy, deviation/CAPA, a contingency procedure for sensor or equipment failure, and a periodic review of the plan’s effectiveness.
Is RTRT limited to continuous manufacturing?
No. Annex 17 applies RTRT to any stage in manufacturing and to any type of finished product or active substance, including intermediates. Continuous manufacturing makes it more natural, because ICH Q13 control strategies already rely on real-time measurement.
WHERE NEXT
- DO ITOpen the Real-Time Release Testing Strategy Plan template →The structure these steps fill in.
- UNDERSTAND ITReal-Time Release Testing →The principles behind the procedure.
- ALL GUIDESBrowse all 127 how-to guides →
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