PQR – Investigations of a Dog

The draft revision of Eudralex Volume 4 Chapter 1 marks a substantial evolution from the current version, reflecting regulatory alignment with ICH Q9(R1), enhanced risk-based approaches, and a new emphasis on knowledge management, proactive risk detection, and supply chain resilience.

Core Differences at a Glance

The draft update integrates advances in global quality science—especially from ICH Q9(R1)—anchoring the Pharmaceutical Quality System (PQS) more firmly in knowledge management and risk management practice.
Proactive risk identification and mitigation are highlighted, reflecting the need to anticipate supply disruptions and quality failures, beyond routine compliance.
The requirements for Product Quality Review (PQR) are clarified, notably in how to handle grouped products and limited-batch scenarios, enhancing operational clarity for diverse manufacturing models.

Philosophical Shift: From Compliance to Dynamic Risk Management

Where the current Chapter 1 (in force since 2013) framed the PQS largely as a static structure of roles, documentation, and reviews, the draft version pivots toward a learning organization approach: knowledge acquisition, use, and feedback become core system elements.

Emphasis is now placed on systematic knowledge management as both a regulatory and operational priority. This serves as an overt marker of quality system maturity, intended to reduce “invisible failures” and foster analytical vigilance—aligning closely with falsifiable quality frameworks.

Risk-Based Decision-Making: Explicit and Actionable

The revision operationalizes risk-based thinking by mandating scientific rationale for risk decisions and clarifying expectations for proportionality in risk assessment. The regulator’s intent is clear: risk management can no longer be a box-checking exercise, but must be demonstrably linked to daily site operations and lifecycle decisions.

This brings the PQS into closer alignment with both the adaptive toolbox and the take-the-best heuristics: decisive focus on the most causally relevant risk vectors rather than exhaustive factor listing, echoing playbooks for effective investigation and CAPA prioritization.

Product Quality Review (PQR) and Batch Grouping

Clarification is provided in the revised text on how to perform quality reviews for products manufactured in small numbers or as grouped products, a challenge long met with uncertainty. The draft provides operational guidance, aiming to resolve ambiguities around the statistical and process review requirements for product families and low-volume production.

Supply Chain Resilience, Shortage Prevention, and Knowledge Networks

The draft gives unprecedented attention to shortage prevention and supply chain risk. Manufacturers will be expected to anticipate, document, and mitigate vulnerabilities not only in routine operations but also in emergency or shortage-prone contexts. This aligns the PQS with broader public health objectives, situating quality management as a bulwark against systemic healthcare risk.

International Harmonization and the ICH Q9(R1) Impact

Most significantly, the update explicitly references alignment with ICH Q9(R1) on Quality Risk Management, making harmonization with international best practice an explicit goal. This pushes organizations toward the global baseline for science- and risk-driven GMP.

The effect will be increased regulatory predictability for multinational manufacturers and heightened expectations for knowledge-handling and continuous improvement.

Summary Table: Draft vs. Current Chapter 1

Feature	Current Chapter 1 (2013)	Draft Chapter 1 (2025)
PQS Philosophy	Compliance/document control	Knowledge management & risk management
Risk Management	Implied, periodic	Embedded, real-time, evidence-based
ICH Q9 Alignment	Partial	Explicit, full alignment to Q9(R1)
Product Quality Review (PQR)	General guidance	Detailed, incl. grouped/low-batch
Supply Chain & Shortages	Minimal focus	Proactive risk, shortage prevention
Corrective/Preventive Action (CAPA)	System-oriented	Rooted in risk, causal prioritization
Lifecycle Integration	Weak	Strong, with embedded feedback

Operational Implications for Quality Leaders

The new Chapter 1 will demand a more dynamic, evidence-driven PQS, with robust mechanisms for knowledge transfer, risk-based priority setting, and system learning cycles. Technical writing, investigation reports, and CAPA logic will need to reference causal mechanisms and risk rationale explicitly—a marked shift from checklists to analytical narratives, aligning with the take-the-best causal reasoning discussed in your recent writings.

To prepare, organizations should:

Review and strengthen knowledge management assets
Embed risk assessment into the daily decision matrix—not just annual reviews
Foster investigative cultures that value causal specificity over exhaustive documentation
Reframe supply chain oversight as a continuous risk monitoring exercise

This systemic move, when enacted, will shift GMP thinking from historical compliance to forward-looking, adaptive quality management—an ambitious but necessary corrective for the challenges facing pharmaceutical manufacturing in 2025 and beyond.

In a regulated industry, such as pharmaceuticals or medical devices, knowing your changes impact your regulatory partners is a critical aspect of change management. For example, the MHRA in their yearly summarizations of GMP inspection deficiencies consistently cites failure to perform adequate review of need of regulatory notification (for example, see 2016 trends). And to be frank, we in the industry are often looking for more guidance, which drives responses like ICHQ12 and the FDA’s March 2018 draft guidance CMC Changes to an Approved Application: Certain Biological Products and all the other similar guidances out there.

These all follow a similar risk-based approach, and this approach should be built into your change management system (and applicable change control process).

regulatory structure2

The major difference between Supportive Information and Do-and-Record is usually what goes in your product quality report (APR/PQR). Fro example, I often see qualification of facility fit into the Do-and-Record area. These changes may not be fillable, but you certainly want to review and account for.

Many companies manage this through their regulatory affairs organization, but that can be time consuming. It is better to take the time to identify the supportive and do-and-record categories out front, thus removing the need for an extra assessment. The PQR review process is a great tool for ensuring consistent execution.

This risk based approach should look at the dossiers, taking into account any special market considerations, as well as current best practices in the regulations. For those companies lucky enough to be more towards the QbD model, established conditions will greatly help here.

Then build a matrix to help guide your changes. An example could include items like these:

Facility, Equipment, Manufacturing Systems, Utilities & Automation	Equipment/instrument maintenance
	Decommissioning of equipment not classified as critical equipment
	Computer programming that affects non-production equipment
	Alarms (i.e., notification system for out of tolerances)
	Cleaning and Sanitization of Manufacturing facilities and non-product Contact equipment
	Upgrade of Application Software or operating system
	Alarm setpoint changes
	Creating user groups and modifying user group privileges
	Tuning parameter, adjustment to the gain, reset and rate of a PID controller
Manufacturing Processes	In-process labeling
	Changes to Process Control and Operating Parameters (tightening/shifting) within current non-established conditions
	Change in equipment sterilization times
	The addition of in-process or final product samples
	Changes to sample volume for in-process or finished product samples
	Addition of new ancillary equipment (e.g. no product contact, does not control process steps) to the process

You can then further delineate between Supportive Information and Do-and-Record on a few other criteria, such as qualification/validation impact.

Like many areas of good system management, this is an area where a forethought and design can reap dividends in making your changes more nimble while preventing a compliance mishap. Tapping into the PQR makes all this part of your knowledge management system, and allows you to grow as your needs grow. This is definitely not a once-and-done process.

Tag: PQR

Draft revision of Eudralex Volume 4 Chapter 1