Discussion of positive examples and points of improvement in the implementation of Annex 1, with focus on CCS, Pupsit and new technologies. Discussion of inspection findings in Austria and third country inspections.

Major changes of Annex 1 compared to previous version. Is the updated Annex 1 fit for future now? What are the most discussed changes, where are hurdles for industry or for GMP inspectorates? A personal view from an inspector.

Parametric Release is not even an alternative for product sterility tests. It secures a better statistical coverage for the entire batch while it allows to speed up the release process at the same time.  By setting it up right it offers a win win situation improving manufacturers productivity and strengthening patient safety at the same time.  The presentation will invite you into Bipso´s journey towards parametric release, gives an overview about the regulatory background and  elucidates practical aspects and challenges for implementation.

Seal Tightness Drones to Support Container Closure Integrity Assurance|A novel method for monitoring vial sealing and container handling using 'drones' (sensor-enabled replica containers) that measure seal force, pressure, and shock will be explained. This new technology gives insights into the process variability inherent in the capping and crimping process and throughout the filling and packaging process. Data will be shared that focuses on the interrelationships of components and crimping performance. Anticipated applications will be presented including data generated that gives insights into material properties and how they impact seal tightness.

The management of the capping and crimping process for vials has always faced challenges due to the lack of a suitable method to monitor the process with the absence of an in-process analytical monitoring tool. Residual Seal Force (RSF) is sometimes used but adoption of RSF is not uniform in industry due to limitations with reproducibility. Industry practice still often relies on rudimentary checks carried out by operators that are not quantitative. The method under development with project partner SmartSkin to monitor this assembly process will be explained as well as the progress made toward integrating this method as a GMP application. Integrating these new seal tightness measurements into a control plan which supports the holistic approach and assurance of container closure integrity (CCI).

With the recent implementation of the new version of European Union EudraLex Volume 4 Annex 1 (or simply Annex 1), pharmaceutical manufacturers must evaluate maintenance of product contact equipment through cleaning and sterilization as part of the Contamination Control Strategy (CCS). According to Annex 1, the CCS includes a set of controls for microorganisms, endotoxin/pyrogens, and particles to ensure process performance and product quality. It is especially critical to define the contamination risks and identify appropriate controls for critical surfaces, namely product contact equipment that is cleaned, sterilized, and used in parenteral drug manufacture.

This presentation walks through an example “life cycle” for product contact equipment, identifying potential contamination risks and mitigation solutions, to demonstrate best practices for achieving CCS implementation and regulatory compliance. 

Details on protection of clean product contact parts and sterilization in the autoclave are included. Post sterilization maintenance, including material transfer and aseptic presentation into the filling environment (isolator or RABS), rounds out the life cycle evaluation. 

Pharma 4.0 has brought innovative technologies to the pharmaceutical industry, with digital and data tools becoming essential for value creation and process automation. However, the integration of these technologies faces challenges due to strict regulations such as authority guidelines, GxP compliance, and validation approaches. Virtual Reality has emerged as a powerful tool, providing solutions for different use cases, especially in training. This technology promises multiple benefits to an organization, including value creation for people, planet, and business. Although the validation of platforms and LMS integration are regulated by guidelines, such as CFR21, validating VR training content remains a significant obstacle. To unlock the full potential of VR in cleanroom operator training, we introduce an effective and robust approach for VR content validation. This approach will integrate all critical elements and helps us to unleash VR's full potential, resulting in enhanced training experiences and improved performance. Adopting a fully validated end-to-end VR system paves the way for a harmonized global training approach which allows the industry to harness the full potential of Virtual Reality and unlock new opportunities for growth and development on a global scale.

“Steam sterilization of stoppers. The biological validation of a worst-case load: how to assess the risk of an incorrect biological validation and mitigate it with the right approach.”
A theoretical perspective and the practical example of a load. How to sterilize and validate a heat stable load: the cycle, how the cycle may have an impact on the biological result of a validation procedure. The choice of the right biological indicator and the rationale behind the validation approach chosen.
An overview of Rules, Standards about sterilizing a not heat sensitive load and the impact of the load on the choice of the biological validation procedure.

ATMP production is often highly manual and varied aseptic operations can occur over multiple shifts and days.  Assuring operators are adequately qualified poses a unique challenge since processes can involve multiple different types of interventions which require different aseptic skills.  In addition, the new Annex 1 requires for stringent qualification of operators in these processes.  This presentation will cover one approach for a robust operator aseptic qualification approach that balances the changing requlatory expectations, sterility assurance requirements, and business needs.  From assessing the process interventions to leveraging production data, a holistic approach is needed in the current aseptic processing environment.