The European Directorate for the Quality of Medicines & HealthCare (EDQM) has announced the release of Pharmeuropa, Issue 37.4, inviting comments on several revised draft texts that reflect ongoing efforts to enhance clarity, scientific accuracy, and regulatory alignment across the European Pharmacopoeia (Ph. Eur.).
Among the new drafts, three updates stand out for their relevance to laboratories, manufacturers, and regulators: Cannabis flower (3028), Residual solvents (2.4.24), and Rubber closures for containers for aqueous parenteral preparations (3.2.9).
In this article, we will provide a summary and explanation of the key changes.
Pharmeuropa 37.4 Draft Summary
| Pharmeuropa 37.4 Draft | Main Changes Introduced | Implications for Industry |
|---|---|---|
|
Cannabis Flower (Monograph 3028) PA/PH/Exp. 13B/T (25) 40 ANP |
• Acceptance criterion for the Δ⁹-THC zone in Identification Test C widened: it may now be faint or absent in freshly dried THC-dominant types. • Additional acceptance criteria added for immature seeds and longer leaves in herbal drug preparations prescribed as medicinal products. |
• Aligns monograph expectations with natural plant variability observed in member states. • Prevents false non-compliance in early-harvested material while maintaining pharmacological consistency. • Reflects realistic quality evaluation for medicinal cannabis. |
|
Identification and Control of Residual Solvents (General Chapter 2.4.24) PA/PH/Exp. MG/T (25) 2 ANP |
• Complete editorial revision for improved clarity. • Explicit distinction between non-targeted (screening) and targeted (quantitative) analysis. • Addition of a new system suitability solution prepared from Class 2 residual solvents. • Updated chromatograms to include cyclopentyl methyl ether and tert-butyl alcohol. |
• Enhances transparency and consistency in method validation and transfer. • Prevents misuse of non-targeted methods for quantitative control. • Strengthens harmonization with ICH Q3C requirements for residual solvent control. |
|
Rubber Closures for Containers for Aqueous Parenteral Preparations, for Powders and for Freeze-Dried Powders (General Chapter 3.2.9) PA/PH/Exp. 16/T (24) 18 ANP |
• Reducing substances test now explicitly includes 0.01 M sodium thiosulfate for titration difference calculation. • Extractable zinc test clarified — acidification of the sample solution now mandatory for accurate AAS determination. • Terminology updated — “rubber” replaced by “closure” to cover coated and bi-layer systems. |
• Increases precision and repeatability of analytical tests for container closures. • Clarifies expectations for extractables and leachables assessment under GMP. • Aligns terminology with modern pharmaceutical packaging technology. |
Cannabis Flower (Monograph 3028)
Reference: PA/PH/Exp. 13B/T (25) 40 ANP
The monograph for Cannabis flos (Cannabis flower) has undergone targeted revisions focusing on identification testing and foreign matter limits.
Identification Test C (HPTLC): The acceptance criterion for the Δ⁹-tetrahydrocannabinol (THC) zone in the THC-dominant type has been widened. The revision now includes cases where the Δ⁹-THC zone may appear very faint or even absent.
This change acknowledges that freshly harvested or recently dried THC-dominant cannabis may have low detectable Δ⁹-THC, as it primarily forms through decarboxylation of Δ⁹-tetrahydrocannabinolic acid (THCA) during storage or processing.
Foreign Matter: The acceptance criteria now allow a wider range of immature seeds and small leaves in herbal drug preparations prescribed as medicinal products.
Immature seeds and leaves longer than 1.0 cm, while sometimes present, are considered acceptable within quality limits. According to general chapter 2.8.2 (Foreign matter), such leaves are classified as foreign organs, and the 2% overall limit for foreign matter ensures adequate control.
Implications:
This update reflects a more experience-driven understanding of medicinal cannabis, keeping the monograph focused on the core quality attributes of the product while making the acceptance criteria more flexible. It recognizes that certain natural variabilities do not affect product quality and allows laboratories to assess compliance based on scientifically relevant characteristics rather than visual differences alone.
Identification and Control of Residual Solvents (General Chapter 2.4.24)
Reference: PA/PH/Exp. MG/T (25) 2 ANP
This chapter has been completely revised, though most modifications are editorial and structural. The revision improves clarity and reflects the latest analytical practices for residual solvent analysis using static head-space gas chromatography (GC).
Key updates include:
- Clear distinction between non-targeted and targeted analysis: The revised text explicitly differentiates between these two analytical approaches.
- Non-targeted analysis involves screening for unknown residual solvents through identification, confirmation, and potential quantitation.
- Targeted analysis focuses directly on quantitation or limit testing for known solvents.
- New system suitability solution: A dedicated system suitability solution derived from Class 2 residual solvents has been introduced to improve the verification of analytical performance.
- Updated chromatograms: Chromatographic profiles have been revised to include cyclopentyl methyl ether and tert-butyl alcohol, expanding the scope of detectable Class 2 residual solvents.
Implications:
The revised chapter facilitates more transparent validation practices and harmonizes testing across QC laboratories. By explicitly distinguishing analytical intent, it prevents misapplication of screening methods for limit testing, a common compliance gap identified during inspections. The inclusion of additional solvents further supports ICH Q3C-aligned residual-solvent control across active substances, excipients, and finished products.
Related Article: Residual Solvents – Classes, Guidelines and Testing
Rubber Closures for Containers for Aqueous Parenteral Preparations (General Chapter 3.2.9)
Reference: PA/PH/Exp. 16/T (24) 18 ANP
The chapter on rubber closures used in parenteral containers has been updated to clarify several analytical and terminology aspects:
- Reducing Substances: The volumetric solution of 0.01 M sodium thiosulfate, used to calculate the titration difference, is now explicitly mentioned for clarity.
- Extractable Zinc: The procedure has been modified to specify that acidification of the sample solution is mandatory. This ensures accurate measurement of extractable zinc by atomic absorption spectrometry (AAS).
- Terminology Update – “Rubber” replaced by “Closure”: The term “rubber” has been replaced with “closure” throughout the text to encompass coated and bi-layer closure systems better, reflecting current industry terminology and practices.
Implications:
The changes promote analytical reproducibility and align terminology with evolving pharmaceutical packaging technologies. The explicit requirement for acidification prevents underestimation of extractable metal levels, a parameter increasingly scrutinized under extractables/leachables (E&L) risk assessments.
SEE ALSO: Primary vs Secondary Packaging in Pharma Industry
Implications for Industry and Stakeholder Comments
The publication of these drafts highlights EDQM’s strategic aim to make the European Pharmacopoeia both scientifically robust and operationally practical. For industry professionals, the revisions present several takeaways:
- For Quality Control Laboratories: Clearer analytical instructions reduce ambiguity during method transfer and audit review. The changes to 2.4.24 and 3.2.9 directly affect system suitability testing, sample preparation, and analytical verification under GMP.
- For Manufacturers and Formulators: The updates to the Cannabis Flower monograph and the Rubber Closures chapter ensure that product characterization and container compatibility testing remain aligned with current market and regulatory expectations.
- For Regulators and Inspectors: Improved definitions and expanded acceptance criteria will facilitate more consistent interpretation of compliance outcomes across Europe.
EDQM invites all stakeholders, including industry experts, national authorities, and academia, to submit comments on these draft texts via the Pharmeuropa consultation platform. Feedback received during this phase will guide the final revisions before adoption into the official Ph. Eur.
Conclusion
The updates featured in Pharmeuropa 37.4 demonstrate EDQM’s continued focus on refining analytical methods and aligning pharmacopeial texts with real-world practices.
Stakeholders, including manufacturers, testing laboratories, and regulatory authorities, are encouraged to review the drafts and provide comments before their adoption into the European Pharmacopoeia.
For further details and consultation deadlines, visit the official publication:
Pharmeuropa 37.4 – EDQM
