The traceability of pharmaceutical manufacturing processes and procedures is critical to successfully navigating the complex maze of government regulations that impact the design, development, production and distribution of medications.

The recent introduction of the EudraLex Volume 4 Annex 1 guidance regarding the manufacturing of sterile medicinal products (which will take effect in late August of 2023) is an example of good manufacturing practices (GMPs) that help ensure quality and safety is built inside the process (quality by design). It illustrates how new regulations are introduced to grow trust in the life sciences business.

Sterilisers play a key role in producing injectable medicines like vaccines. Life science firms and the machine builders that support them are asked to find the most efficient way to meet the data integrity principles applied to the records of each heat sterilisation cycle.

Point 8.50 of the EudraLex Volume 4 Annex 1 stipulates that “each heat sterilisation cycle should be recorded electronically or by hardcopy, using equipment with suitable accuracy and precision. The system should have safeguards and/or redundancy in its control and monitoring instrumentation to detect a cycle not conforming to the validated cycle parameter requirements and abort or fail this cycle (e.g., by the use of duplex/double probes connected to independent control and monitoring systems).”

New sterilisation control challenges for both OEMs and firms

When handling the challenges of heat and steam sterilisation with a focus on monitoring and controlling activities, life sciences stakeholders and the OEMs supplying them with machines and equipment are faced with multiple options for meeting the regulatory compliance mandate; still, they must always properly balance the trade-off between efficiency, cost and time-to-market.

The new Annex 1 changes the status quo for OEMs and potentially introduces more machine building cost, time and risk. OEMs must qualify any new device added to their equipment and minimise downtime risks. They must train their staff, expand their maintenance capabilities and manage delays in time-to-market due to extended testing procedures.

Changes have an impact on Quality Control managers too. They are confronted with tens of thousands of pages of regulatory statutes that they need to recognise and manage, and new regulations are published continuously. It is critical for quality managers to have access to trustable solutions to stay up-to-date and ahead of validation inspectors.

Separate qualification and validation are now required

As said, in the case of the new EudraLex Volume 4 Annex 1 regulation, the crux of the issue is the ability to document the positive completion of the sterilisation process. This could be achieved through a separate monitoring system that provides the simplicity, robustness and accuracy expected by regulators. Organisations like Watlow that understand the new mandates and their impact on the sterilisation process are in a solid position to meet this challenge.

Via the recent acquisition of Eurotherm, Watlow has developed a paperless sterilisation quality management solution that combines industry regulatory knowledge with hardware and software components, making it easy for OEMs to integrate the new EudraLex Volume 4 Annex 1 requirement into their production machines. Using the solution designed by Watlow, a best-in-class sensor connected to a redundant solution delivers the mandatory monitoring and recording. The solution digitally feeds the control system simultaneously achieving simplicity, robustness and an extremely high level of accuracy.

Monitoring sensors are the most critical device in the sterilisation process. If the sensor fails, the sterilisation batch has to be put on hold. It is well worth the money to invest in a high-quality sensor and enable the high-availability redundant monitoring solution to provide the environmental measurements to the control system, like what is done by Environmental Monitoring Systems toward Building Management Systems.

OEMs can maintain the current sensor positions, along with the same schematic drawings, thermal couplers and cabinet entrances, without making many changes. This is helpful from a training and maintenance perspective. In addition, high-quality sensors and better precision help to optimise energy efficiency, and the enhanced accuracy generate far fewer alarms, thereby helping to reduce quality control costs.

Regulatory inspectors recognise the system as EudraLex Volume 4 Annex 1, Point 8.50-compliant because of the built-in safeguards and/or redundancy that cross-check both the control system and the separate monitoring system, ensuring that each is operating within the low margin-of-error-prescribed safety performance parameters. The quality control functions within the system generate one single version of the truth via electronic format reports that can be attached to the operator batch reports submitted to the regulatory bodies.

For more information

With its consultative approach, Watlow helps machine builders and end users address new regulatory mandates with a solution that appropriately integrates the sensors, power supplies, heating control and sterilisation monitoring required for compliance. To learn more, visit our Life Sciences compliance website.