The deadline for submitting comments on the draft revision of Chapter 1 of the Good Manufacturing Practices (GMP) is approaching. On 3 September 2025, the European Commission opened the consultation on the draft text of Chapter 1, which detail requirements on the Pharmaceutical Quality System (PQS). The consultation will remain open until 3 December 2025.
The initiative initiative is a significant step in the ongoing overall revision of the pharmaceutical legislation. The PQS is indeed the key element of the design and operation of all pharmaceutical processes run according to the Good Manufacturing Practices. It also plays a fundamental role in regard to the adoption and utilisation of the risk-based approach to assessment of the GMP compliance. Once the revised text will reach finalisation and approval, the resulting GMP framework will be deeply updated, which is expected to have a positive impact on the quality and safety of the manufactured medicines.
The revision of Chapter 1 aims to update the regulatory framework on the basis of scientific, industrial and risk management advancements occurred since the 2013 version of the guidance. The new GMPs will also align with international best practice. To this instance, the draft text of the new GMP’s Chapter 1 has been revised by the EMA GMDP Inspectors Working Group in cooperation with the Pharmaceutical Inspection Co-operation Scheme (PIC/S).
Comments on the draft text of the revised Chapter 1 can be submitted via the online platform EUSurvey or through the pertinent industrial association. The European Industrial Pharmacists Group (EIPG) will play an active role in collecting comments and observations from its member associations of industrial pharmacists. A common position will then be prepared for submission to the European authorities on the basis of these comments and observations.
Harmonisation with the ICH Q9(R1) guideline
The revised Chapter 1 of the GMPs aims at aligning the text to the latest update of the ICH Q9(R1) guideline on Quality Risk Management (QRM), which was adopted on 18 January 2023.
The expected result of the chosen strategic and proactive approach to quality risk management is a reduced variability in quality outcomes. This is considered essential for achieving an effective pharmaceutical quality system and facilitating continual improvement, as well as in enabling informed and timely decisions throughout the product lifecycle.
Furthermore, manufacturing risks should always be proactively identified in order to prevent shortages and mitigate supply chain vulnerabilities.
The Pharmaceutical Quality System
Point 1.4 (viii) of the PQS paragraph includes a new phrase stating that “Quality risk management should be used in the design and validation/qualification of such systems”, thus clearly extending the application of the QRM principles to the entire manufacturing pharmaceutical cycle.
The new paragraph 1.4 (xviii) has also clarifies the importance of using quality risk management, alongside knowledge management, to provide an early warning system. This may prove relevant in many different situations, for example to effectively oversee and respond to evolving quality and/or manufacturing risks that might arise both from the pharmaceutical company or its external partners. Not less important is the impact this approach could have on managing potential product shortage issues.
Another addition to the draft text of GMP’s Chapter 1 is paragraph 1.8 (v). This addresses the management of external product availability risks that could affect quality or manufacturing. Such risks could arise from issues experienced by suppliers of raw materials, contracted organisations or service providers, and so on.
Quality control and Product Quality Review
The draft text of the revised GMP’s Chapter 1 presents no change with respect to the paragraphs dealing with the requirements for Quality Control.
As for the Product Quality Review (par. 1.10), a significantly long new text has been added at the term of section (xii). This refers to cases where only a few batches of a product are manufactured within a 12-months review period. In such instances, trending data from the previous product quality review should be included to ensure the consistency of the process is evaluated based on a more extensive set of data. Trending data from the previous reviews could also be useful when a larger number of batches are manufactured within a 12-month review period. Importantly, the product quality review should be also performed in the absence of any batches manufactured during the review period. In such cases, the draft text specifies the parameters that should at least be included in the analysis, together with a review of the previous product quality review. Among the parameters to be considered are stability results, returns, complaints, recalls, relevant deviations (including those arising from qualification and validation activities) and regulatory background (e.g. marketing authorisation variations submitted, granted or refused, including those for third-country export-only dossiers, and any relevant post-marketing commitments).
The additional text also addresses the review timeframes, stating that these can be appropriately adjusted and must be always justified based on manufacturing and campaign duration. In this instance, a specific procedure would be required to clarify the chosen timeframe criteria. The draft also suggests that the robustness of the product quality review could be be enhanced by including results from the previous period in the trending analysis.
Many more possibilities for grouping
The revised par. 1.11 introduces many new possibilities for grouping products for quality reviews. This approach would now also include products containing the same (or similar) active substances, products manufactured using the same equipment or on the same production line, and so on.
Justification for grouping must always be provided, together with evidence that grouping products enhances the overall review of the related manufacturing processes and facilitates review of all associated data for all individual products in the group. The added text also emphasises that the chosen strategy should not hinder the detection of any adverse trends for individual products, and that reviewing only the data associated with a representative product or a worst-case product in a group is unacceptable. Grouping strategies, together with responsibilities, should be included in specific technical agreements signed between the marketing authorisation holders and manufacturers.
Quality Risk Management
Paragraph 1.12 now clearly states that QRM is a systematic process that informs risk-based decision-making. According to the revised text of par. 1.13, this approach should be used throughout the entire product lifecycle to assess product quality. The revision also emphasises the importance of knowledge for making informed decisions, triggering re-evaluations and stimulating continual improvement.
A note added to the first principle of QRM (par. 1.14) specifies that quality-related risks also include situations that affect product availability. Each site along the manufacturing and distribution supply chains should manage this type of occurrence under the responsibility of the relevant parties.
Compared to the 2013 version of the GMPs, the QRM principles have also been further expanded with the addition of the new paragraphs 1.15, 1.16 and 1.17. The former establishes that QRM activities should be conducted at an appropriate level of formality reflecting the complexity of the assessed process. Subjectivity should also be managed and minimised to avoid impacting the effectiveness of QRM activities and decision-making processes (1.16). The review of QRM process results should be based on a specific mechanism that takes into account all new knowledge and experience (1.17).
