M4Q Revision 2: Shaping the Future of Quality Submissions

The pharmaceutical industry is on the cusp of a significant evolution in regulatory submissions with the upcoming ICH M4Q Revision 2 (R2). As highlighted in a recent webinar led by Maurice Bancsi and industry experts, the goal of R2 is to enhance the efficiency of both submission and regulatory assessment processes, ultimately accelerating access to medicinal products while integrating data required for manufacturing and marketing licenses.

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Timeline and Implementation

R2 is expected to reach Step 4 by June 2027, signalling the adoption of the final guideline. In anticipation of the finalization, companies will likely begin implementing the updated framework, from early 2027, to be ready once the global roll-out mid-2027 starts. Importantly, while R2 will initially apply to new marketing authorization applications (MAAs), and updates to and renewal of legacy products and may require careful planning for post-implementation updates, especially for products with frequent quality variations.

Objectives and Benefits

The primary objective of Revision 2 is to improve submission and assessment efficiency. By moving to a structured, modular format, R2 provides a clear framework for capturing essential quality information, allowing regulators to assess applications more efficiently. The update is expected to benefit patients, industry, and regulatory agencies alike, ensuring faster access to high-quality medicinal products while streamlining internal processes for pharmaceutical companies.

Key Features of Revision 2

1. Structured Data and Modular Approach:
   R2 introduces a more structured way of capturing data across Modules 2 and 3. Core quality information, such as development summaries, control strategies, and product lifecycle management, will have a designated place in the dossier. This structured approach contrasts with Revision 1, where information was often dispersed and repetitive, making assessment more cumbersome.

2. Integration with ECTD 4.0 and IDMP:
   M4Q R2 is closely linked with eCTD 4.0 and SPQS, ensuring alignment with modern regulatory frameworks. Flexible content organization in R2 allows for easier integration of both manufacturing and marketing license data.

3. DMCS Framework:
   The Description, Manufacture, Control, and Storage (DMCS) framework underpins the new structure, providing a consistent method for documenting drug substance and drug product information. This ensures traceability, facilitates efficient review, and supports post-approval changes seamlessly.

4. Core Quality Information Centralization:
   Module 2 now centralizes regulatory narratives and critical quality data, reducing redundancy and improving clarity. Module 3 serves as a repository for detailed supporting data, complementing Module 2 summaries while maintaining flexibility for future updates.

Practical Considerations for Implementation

Implementing R2 requires thoughtful planning, particularly for legacy products. Webinar speakers emphasized the importance of building cross-reference tables and bridging documents during the transition, ensuring content alignment between Revision 1 and Revision 2. Companies with products prone to frequent variations, such as biologics, may benefit from a proactive reformatting strategy, whereas those with more stable products could adopt a gradual approach.

Proactive implementation also supports smoother interactions with regulators. By centralizing quality data in a database-driven format, companies can generate updated reports efficiently, reduce transcription errors, and maintain consistency between GMP and regulatory datasets. This approach not only facilitates regulatory submissions but also positions companies to guide authorities in adopting the new framework.

Harmonization and Global Considerations

Harmonizing specifications across different regions remains a challenge, as regulatory requirements vary between countries. While complete alignment may not be immediately feasible, providing consistent, database-driven data allows regulators to draw comparable conclusions. Over time, this approach will support greater global standardization and reduce inefficiencies associated with managing multiple legacy formats.

Looking Ahead

M4Q Revision 2 represents a major step forward for pharmaceutical regulatory submissions, particularly for lifecycle management of dossiers, and biotech and advanced therapy products with frequent updates. By centralizing core quality information and embracing modular, structured documentation, R2 promises to streamline regulatory processes while ensuring robust oversight of medicinal product quality.

Companies that plan ahead and adopt structured, database-driven approaches will not only ease the transition from legacy systems but also contribute to shaping the future of regulatory compliance, benefiting patients, industry, and regulators alike.