The European Commission has issued a draft update to Chapter 1 of the EudraLex GMP Guide, the section that defines expectations for the Pharmaceutical Quality System. The revision is limited in scope but introduces changes with broad implications, aligning the chapter with ICH Q9(R1) on Quality Risk Management.
The additions bring new emphasis on proactive risk management, early detection of manufacturing risks, and the role of quality systems in preventing product shortages. They also reinforce the expectation that monitoring and control systems must be risk-based, that Product Quality Reviews provide meaningful insight even when production is limited, and that supply chain risks are managed as part of GMP obligations.
Key Changes in the Draft
The draft revision to Chapter 1 introduces a series of targeted updates that carry significant weight for how companies design, operate, and monitor their Pharmaceutical Quality Systems.
Each change strengthens the link between quality risk management and the daily functioning of GMP activities. While the structure of the chapter remains essentially unchanged, the additions reflect a shift toward risk-based oversight, shortage prevention, and more rigorous evaluation of process performance and product reviews.
Proactive Approach to Quality Risk Management
The opening change defines a proactive approach to risk management as a strategic requirement for an effective Pharmaceutical Quality System. This is not a supporting element but a foundation for continual improvement and informed decision-making across the product lifecycle.
- The draft text specifies that QRM must enable timely and science-based decisions, rather than serving only as retrospective justification.
- Continual improvement is directly tied to proactive risk-based practices.
- Risk management is presented as a driver of PQS effectiveness, not just a compliance tool.
For companies, this means that risk management activities must be visible in routine operations and not limited to validation files or inspection preparation. The expectation is that risk assessments will influence both short-term operational controls and long-term lifecycle strategies, with management actively relying on them in decision-making.
SEE ALSO: Quality Risk Management in the Pharmaceutical Industry
Risk-Based Shortage Prevention
The draft introduces shortage prevention as part of the Pharmaceutical Quality System. This represents a shift in regulatory expectations: product availability is now treated as an integral part of quality oversight, rather than just a matter of the supply chain.
- The text requires risk-based prevention and mitigation activities linked to product quality and manufacturing risks.
- The reference to Chapter 5 underscores that this obligation is tied to operational procedures, not just policy statements.
- Shortages are recognised as a patient safety concern, since interruptions in supply can harm patients as much as defects in quality.
Section 1.8 (v) adds a new requirement to manage external product availability risks. This broadens GMP responsibilities to include risks from outside the manufacturing site.
- Risks related to raw material suppliers, contract manufacturers, and service providers must be included in the PQS.
- The focus is not only on quality defects but also on continuity of supply.
- Oversight must extend across the supply chain to ensure risks are adequately identified and controlled.
This means that supplier qualification and monitoring procedures will need to evolve. Beyond audits and certificates, companies will need structured risk assessments that capture availability threats such as dependency on a single source, geopolitical risks, or vulnerabilities in logistics.
Early Warning Systems
A new clause (1.4 xviii) introduces the expectation that companies combine risk management and knowledge management to provide an early warning system. This reflects a more forward-looking view of how PQS should operate.
- Early warning mechanisms should support oversight and timely response to evolving risks.
- The scope encompasses risks associated with suppliers, contractors, and other external partners.
- Product shortage issues are explicitly identified as risks that must be anticipated, not only addressed once they occur.
This change makes it clear that risk management cannot be static. Companies must establish mechanisms, such as trend analysis, data integration, or supplier oversight, that detect problems before they escalate, providing management with the opportunity to act proactively.
Product Quality Reviews
The section on Product Quality Reviews has been expanded with detailed expectations to strengthen their role as a monitoring tool.
- Trending data from previous reviews must be included when few batches are produced.
- Reviews must still be performed even if no batches were manufactured, covering stability data, complaints, deviations, recalls, and regulatory commitments.
- Timeframes can be adjusted for campaign manufacturing, but justification and documented criteria are required.
- Grouping of products is permitted, but it must be scientifically justified and cover all products individually.
- Reviewing only a “worst-case” or representative product is explicitly deemed unacceptable.
- Where the marketing authorisation holder is not the manufacturer, technical agreements must clearly define the responsibilities for conducting the review.
These changes significantly raise the standard for PQRs. They will require more analytical work, more data integration, and stronger agreements between manufacturers and MAHs.
SEE ALSO: Product Quality Review – PQR in GMP
Strengthened Quality Risk Management Section
The last group of changes reinforces and clarifies the principles of QRM, drawing directly on ICH Q9(R1).
- Risk management is described as a systematic process for assessment, control, communication, and review.
- It applies proactively and retrospectively across the lifecycle.
- Risk to quality explicitly includes risks that impact product availability.
- Each site in the supply chain must manage risks within its responsibility.
- Formality must be proportionate to risk: simplified approaches for minor issues, rigorous methods for complex or high-impact risks.
- Subjectivity must be minimised to avoid biased or inconsistent outcomes.
- Results of QRM must be reviewed in light of new knowledge and experience, supported by mechanisms for monitoring and reassessment.
This section confirms that regulators expect QRM to be dynamic. Outputs cannot remain static; they must evolve as new risks emerge and process knowledge grows.
Outlook
The draft revision of Chapter 1 reinforces the expectation that a Pharmaceutical Quality System must be more than a compliance framework. It must function as a proactive, risk-based system that protects both the quality and the availability of medicines.
The changes introduced place stronger accountability on companies to:
- Integrate risk-based shortage prevention into their PQS.
- Maintain a state of control through monitoring systems that are designed and qualified using risk management principles.
- Establish early warning mechanisms that combine QRM and knowledge management to anticipate risks before they affect patients.
- Expand supply chain oversight to include availability risks from suppliers, contractors, and service providers.
- Perform more robust Product Quality Reviews, ensuring that data, even in low-volume or no-batch situations, provides meaningful oversight.
- Apply QRM with proportional formality, reduced subjectivity, and ongoing review.
Taken together, these updates represent a shift toward resilience in pharmaceutical operations. Regulators are making it clear that patient protection extends beyond safety and efficacy to include uninterrupted access.
Companies will need to adjust both culture and processes to demonstrate that their PQS is not only effective but forward-looking, capable of anticipating risks and maintaining continuity of supply.
