- Annex 17 of EudraLex Volume 4, titled Real Time Release Testing and Parametric Release, provides guidance on the use of modern release strategies as alternatives to traditional end-product testing. Specifically, it addresses the principles and requirements for implementing Real Time Release Testing (RTRT) and Parametric Release in the manufacture of medicinal products. This annex reflects the European Union’s effort to integrate scientific and technological advancements, such as Quality by Design (QbD) and Process Analytical Technology (PAT), into Good Manufacturing Practice (GMP).
- Real Time Release Testing is defined in the annex as the ability to evaluate and ensure the quality of a product based on process data and controls rather than end-product testing alone. This includes the use of in-process monitoring, predictive models, and other analytical tools to demonstrate that the product consistently meets predefined quality criteria. By relying on real-time measurements of critical quality attributes (CQAs) and process parameters, manufacturers can ensure product quality throughout the manufacturing lifecycle, thus enabling faster and more efficient batch release.
- Parametric release, a subset of RTRT, is most commonly applied to sterile products, particularly where sterility assurance can be validated through rigorous process control and environmental monitoring, rather than through traditional sterility tests. This is especially relevant for terminally sterilized products, where the sterility of each batch can be assured through validated sterilization cycles and robust supporting data, rather than relying solely on biological indicators or finished product testing.
- The annex underscores the importance of a thorough understanding of the manufacturing process, including robust risk assessments, process validation, and continuous monitoring systems. Manufacturers must establish a control strategy that ensures all quality attributes are consistently met and that the process is capable of delivering quality product without relying exclusively on end-point testing. A well-defined pharmaceutical quality system (PQS) is essential to support RTRT or parametric release, with clearly documented responsibilities, deviation management, and continual improvement mechanisms.
- A critical responsibility outlined in Annex 17 is that of the Qualified Person (QP). The QP must be satisfied that the data generated from RTRT or parametric release meets all regulatory requirements and that the batch conforms to the terms of the marketing authorisation (MA). This includes verifying that all systems used for real-time data acquisition are validated, secure, and compliant with data integrity principles.
- Annex 17 also addresses data management, emphasizing that systems used in RTRT must ensure traceability, auditability, and data security. All measurements, including those from PAT tools, must be captured, evaluated, and stored in a manner that supports compliance with GMP and regulatory expectations. Any failure of the RTRT or parametric release system must be thoroughly investigated, and conventional release methods should be in place as a contingency.
- To implement RTRT or parametric release, companies must include the approach in the regulatory submission (e.g., the MA dossier), supported by detailed justification, process validation data, and a clearly defined control strategy. Regulatory authorities may review the appropriateness of the proposed strategy before granting approval, ensuring that patient safety and product quality are not compromised.
- In conclusion, Annex 17 of EudraLex Volume 4 facilitates the use of innovative, science-based approaches to batch release by enabling Real Time Release Testing and Parametric Release. It promotes efficiency, product quality, and regulatory flexibility, provided that manufacturers demonstrate a robust understanding and control of their processes. By shifting focus from end-product testing to in-process assurance, Annex 17 supports the pharmaceutical industry’s transition toward more modern, agile, and data-driven manufacturing models—while maintaining the core objective of safeguarding patient health.
Further reading:
- EudraLex – Volume 4 – Good Manufacturing Practice (GMP) guidelines
- EudraLex – The Rules Governing Medicinal Products in the European Union, Volume 4 EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use Annex 17: Real Time Release Testing and Parametric Release
