Industry news

Revised EU GMP Chapter 1

The EU issued the final version of the revision of Chapter 1 of Part 1 of the EU GMP Guide in September 2012 and this revision is effective from 31 January 2013.

The title of Chapter 1 has been changed to “Pharmaceutical Quality System” in order to integrate with the principles described in ICH Q10 (which is published in Part III of the EU GMP Guide).

The draft changes issued in 2009 included numerous direct quotes from ICHQ 10 but these are not included in the final version. However, it should be noted that by adding new requirements to Chapter 1 it will make them apply to veterinary medicinal products, as well as human products, in the EU, even though ICH Q10 has not been adopted by VICH.

The main changes in the revised Chapter 1 are in the areas of:

• the Pharmaceutical Quality System itself,
• continuous improvement and change management,
• supply chain management,
• senior management responsibilities,
• deviations and CAPA.

With respect to Pharmaceutical Quality Systems, the new text states:

“…the Pharmaceutical Quality System can extend to the pharmaceutical development lifecycle stage as described in ICH Q10, which while optional, should facilitate innovation and continual improvement and strengthen the link between pharmaceutical development and manufacturing activities.” and

“The size and complexity of the company’s activities should be taken into consideration when developing a new Pharmaceutical Quality System or modifying an existing one. The design of the system should incorporate appropriate risk management principles including the use of appropriate tools. While some aspects of the system can be company-wide and others site-specific, the effectiveness of the system is normally demonstrated at the site level.”

The revised Chapter contains an extensive list of items that the Pharmaceutical Quality System (PQS) should ensure. Whilst some of these items were listed in the previous version under the Quality Assurance section there are several new items that the PQS should ensure:

• product realisation is achieved by designing, planning, implementing, maintaining and continuously improving a system that allows the consistent delivery of products with appropriate quality attributes
• product and process knowledge is managed throughout all lifecycle stages
• verifying that each delivery is from the approved supply chain
• processes are in place to assure the management of outsourced activities
• a state of control is established and maintained by developing and using effective monitoring and control systems for process performance and product quality
• the results of product and processes monitoring are taken into account in batch release, in the investigation of deviations, and, with a view to taking preventive action to avoid potential deviations occurring in the future.
• continual improvement is facilitated through the implementation of quality improvements appropriate to the current level of process and product knowledge
• arrangements are in place for the prospective evaluation of planned changes and their approval prior to implementation taking into account regulatory notification and approval where required;
• after implementation of any change, an evaluation is undertaken to confirm the quality objectives were achieved and that there was no unintended deleterious impact on product quality;
• an appropriate level of root cause analysis should be applied during the investigation of deviations, suspected product defects and other problems
• this can be determined using Quality Risk Management principles. In cases where the true root cause(s) of the issue cannot be determined, consideration should be given to identifying the most likely root cause(s) and to addressing those. Where human error is suspected or identified as the cause, this should be justified having taken care to ensure that process, procedural or system-based errors or problems have not been overlooked, if present. Appropriate corrective actions and/or preventative actions (CAPAs) should be identified and taken in response to investigations. The effectiveness of such actions should be monitored and assessed, in line with Quality Risk Management principles.

The new Chapter 1 states that “senior management has the ultimate responsibility to ensure an effective PQS is in place … senior management’s leadership and active participation in the PQS is essential.”

The need for periodic management review, with the involvement of senior management, is specified.

The final PQS expectation is that “The Pharmaceutical Quality System should be defined and documented. A Quality Manual or equivalent documentation should be established and should contain a description of the quality management system including management responsibilities.”

The list of basic GMP requirements also has some additions:

• significant deviations are fully recorded, investigated with the objective of determining the root cause and appropriate corrective and preventive action implemented;
• the distribution of products should take account of Good Distribution Practices.

Together these changes are significant but if a company has already made changes to their quality management systems to meet ICH Q10 then they should already comply with most of the new Chapter 1.