The European Directorate for the Quality of Medicines & HealthCare (EDQM) has announced the release of Pharmeuropa, Issue 38.2, opening 46 draft texts for public consultation until 30 June 2026.
Among the drafts published in this issue, three updates stand out for their relevance to laboratories, manufacturers, and regulators: Guidelines for using the test for bacterial endotoxins (5.1.10), Particle-size distribution analysis by analytical sieving (2.9.38), and Sieves (2.1.4). The revised bacterial endotoxins chapter has also been highlighted separately by EDQM in a dedicated consultation notice.
In this article, we will provide a summary and explanation of the key changes.
| Draft | What changed | Why it matters |
|---|---|---|
| 5.1.10. Guidelines for using the test for bacterial endotoxins PA/PH/Exp. BET/T (25) 12 ANP |
• Better integration of rFC • Clearer distinction for amoebocyte lysate-specific provisions • Section 11 reinstated for replacement of a prescribed method • rCRs referenced as alternative methods • Changing between methods A–G requires renewed interference testing |
• Supports movement toward non-animal-derived BET methods • Clarifies expectations for method replacement and justification • Important for QC implementation, validation and monograph compliance |
| 2.9.38. Particle-size distribution analysis by analytical sieving PA/PH/Exp. POW/T (22) 6 ANP |
• Title changed from estimation to analysis • General test sieves content moved to 2.1.4 • Adhesion and cohesion added as biasing factors • Terminology updated: material → powder or granules • Mesh / sieve opening → aperture |
• Makes the chapter more clearly analytical in scope • Improves consistency with ISO terminology • Helps labs address method limitations and sources of bias more clearly |
| 2.1.4. Sieves PA/PH/Exp. POW/T (25) 26 ANP |
• Receives the Test sieves section from 2.9.38 • Aperture tolerance formulas/table removed from the chapter • More direct reliance on ISO 3310-1:2016 • Centralizes core sieve description and requirements |
• Creates one main Ph. Eur. chapter for sieve specifications • Reduces duplication between related chapters • Supports clearer qualification, selection, and interpretation of test sieves |
Guidelines for Using the Test for Bacterial Endotoxins (General Chapter 5.1.10)
Reference: PA/PH/Exp. BET/T (25) 12 ANP
The revised chapter 5.1.10 is the most prominent technical update in this issue. EDQM states that the chapter has been revised to add the method using recombinant factor C (rFC) and to clarify which specific provisions apply only when using amoebocyte lysate. EDQM also notes that the methods using rFC and recombinant cascade reagents (rCRs) avoid animal-derived reagents.
Key changes include:
- Better integration of rFC into the chapter structure.
- Clearer distinction between provisions that apply generally and those that apply only to lysate-based methods.
- Reinstatement of Section 11 on the replacement of a method prescribed in a monograph.
- Addition of a reference to rCRs as an alternative method under the General Notices.
- Clarification that, because methods A-G contain different reagents, changing from one method to another requires the test for interfering factors to be repeated.
Implications:
This revision gives clearer pharmacopoeial support to recombinant BET approaches, but it does not present them as automatic replacements for existing methods. For QC laboratories and manufacturers, the message is that moving to rFC or considering rCR still requires a controlled, product-specific implementation strategy, especially where monograph compliance and interference testing are involved.
Particle-Size Distribution Analysis by Analytical Sieving (General Chapter 2.9.38)
Reference: PA/PH/Exp. POW/T (22) 6 ANP
The revised chapter 2.9.38 is part of a pharmacopoeial harmonization update. According to the briefing note, the title has been changed from “particle-size distribution estimation” to “particle-size distribution analysis” to better reflect the analytical nature of the test.
The note also explains that the general Test sieves section has been transferred to chapter 2.1.4, leaving 2.9.38 focused on the analytical sieving method itself.
Key changes include:
- Change in title from “estimation” to “analysis”.
- Transfer of the general test sieves description to chapter 2.1.4.
- Explicit inclusion of adhesion and cohesion alongside electrostatic charging as potential sources of analytical bias.
- Replacement of “material” with “powder or granules” for greater clarity.
- Replacement of “mesh” and “sieve opening” with “aperture” to align with ISO terminology.
- Editorial changes throughout the text to improve clarity.
Implications:
The revision makes the chapter more analytical in tone and more precise in terminology. For laboratories using sieving in particle-size control, the updated wording should support more consistent method development, transfer, and interpretation, while also making the limitations of dry sieving more explicit.
Sieves (General Chapter 2.1.4)
Reference: PA/PH/Exp. POW/T (25) 26 ANP
The revision of 2.1.4. Sieves complements the changes in 2.9.38. Its briefing note explains that the Test sieves section has been transferred into this chapter so that the Ph. Eur. has one central chapter describing sieve specifications and related requirements. The same note states that the tolerance formulas and related table have been deleted because this information is already covered in ISO 3310-1:2016.
Key changes include:
- Transfer of the Test sieves section from 2.9.38 into 2.1.4.
- Removal of aperture tolerance formulas and the related table from this chapter because those details are already covered in ISO 3310-1:2016.
- Clearer positioning of 2.1.4 as the central Ph. Eur. reference point for sieve description.
- Continued alignment of suitable pharmacopoeial test sieves with the current edition of ISO 3310-1.
Implications:
This update is mainly structural, but it still matters in practice. It reduces duplication, more clearly separates sieve specifications from the analytical sieving procedure, and should make it easier for laboratories to interpret expectations regarding sieve selection, qualification, and use.
Implications for Industry and Stakeholder Comments
The publication of these drafts highlights EDQM’s continued effort to keep the European Pharmacopoeia both scientifically robust and operationally practical. Although these are still draft texts, they already indicate the direction of travel for future implementation and interpretation.
For industry professionals, several points stand out:
- For Quality Control Laboratories: The revised BET chapter provides greater clarity on method selection, alternative-method use, and interference testing, especially when recombinant approaches are being considered. The revisions to chapters 2.9.38 and 2.1.4 also clarify sieving terminology and analytical expectations, reducing ambiguity during method transfer, routine testing, and audit review.
- For Manufacturers and Product Developers: The update to 5.1.10 is relevant for companies evaluating rFC or other non-animal-derived endotoxin test strategies. At the same time, the revisions to the sieving chapters help ensure that particle-size evaluation and sieve-related controls remain aligned with current analytical practice and harmonized terminology.
- For Regulators and Inspectors: These drafts support a more consistent interpretation of analytical requirements by clarifying the chapter’s scope, terminology, and expectations regarding method replacement. In particular, the revised BET guidance may help reduce uncertainty when assessing alternative endotoxin test approaches in a pharmacopoeial context.
EDQM invites stakeholders, including industry professionals, national authorities, and other interested parties, to submit comments through the Pharmeuropa consultation process. Feedback received during this stage may influence the final text before adoption into the official Ph. Eur.
Conclusion
The drafts published in Pharmeuropa 38.2 show EDQM’s continued focus on refining analytical chapters and improving the usability of the Ph. Eur. The revised BET guidance is the most strategically relevant update in this group, while the two sieving chapters reflect ongoing harmonization and cleanup of analytical terminology and chapter structure.
Stakeholders involved in endotoxin testing, particle-size analysis and pharmacopoeial compliance should review these drafts carefully and submit comments before 30 June 2026.
