Analytical Sieving

Q4B Annex 12 Analytical Sieving

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Q4B Annex 12 Analytical Sieving General Chapter

1. Introduction: Analytical Sieving

Analytical Sieving: The document at hand represents the outcome of the Q4B process regarding the Analytical Sieving General Chapter. The proposed texts, which are the result of deliberations and discussions within the Pharmacopoeial Discussion Group (PDG), aim to harmonize the approach to analytical sieving across various international pharmacopoeial standards.

2. Outcome of the Q4B Evaluation

The ICH Steering Committee, in consultation with the Q4B Expert Working Group (EWG), has evaluated the analytical procedures as laid out in official pharmacopoeial texts. Following their review, they have provided recommendations regarding the interchangeability of methods across different ICH regions.

2.1 Analytical Procedures

The official pharmacopoeial texts that have been reviewed include the European Pharmacopoeia (Ph. Eur.) 2.9.38 on Particle-size Distribution Estimation by Analytical Sieving, Japanese Pharmacopoeia (JP) 3.04 on Particle Size Determination, and the United States Pharmacopeia (USP) General Chapter <786> on Particle Size Distribution Estimation by Analytical Sieving. After careful evaluation by the EWG, the ICH Steering Committee concluded that these methods can be considered interchangeable in the ICH regions. This decision enables global consistency and facilitates international trade and regulatory compliance by ensuring that these methodologies are recognized equivalently across different regions.

2.2 Acceptance Criteria

During the evaluation process, it was noted that the reviewed texts did not specify formal acceptance criteria. This lack of defined criteria has implications for the way these methods are adopted and applied in various regions and regulatory contexts.

3. Timeline for Annex Implementation

The timing for the implementation of this annex may vary across regions, with each jurisdiction incorporating the guidance at different times. Once incorporated into the regulatory framework in any given region (following the ICH Step 5 process), the contents of this annex will be applicable for use within that region. It is important to monitor local regulatory updates to stay informed about the exact timelines for adoption.

4. Considerations for Implementation

4.1 General Considerations

When manufacturers or sponsors decide to update or modify their existing methods in line with the Q4B-evaluated pharmacopoeial texts referenced in Section 2.1, they must adhere to the established regional regulatory mechanisms. This could involve submitting notifications or variations, obtaining prior approvals, and complying with specific procedures as mandated by the respective regulatory authorities. This ensures that any changes in analytical methods, whether for the sake of harmonization or innovation, align with existing regulatory requirements.

4.2 FDA Considerations

For the U.S. Food and Drug Administration (FDA), the recommendations of the Q4B annex confirm the interchangeability of the referenced pharmacopoeial methods. However, the FDA may require that companies provide additional data to demonstrate that the chosen analytical sieving method is suitable for a particular material or product. Despite the overarching recommendation of interchangeability, the FDA retains the discretion to request supplementary evidence to ensure the method’s applicability in specific contexts.

4.3 EU Considerations

For the European Union, regulatory authorities will accept references to the pharmacopoeial texts cited in this annex when included in a marketing authorization application, renewal application, or variation application. This is contingent on meeting the conditions set forth in the annex. In such cases, a declaration of interchangeability will be required to demonstrate that the methods meet the compliance standards of the European Pharmacopoeia, specifically Ph. Eur. Chapter 2.9.38 on particle-size distribution estimation by analytical sieving.

4.4 MHLW Considerations

In Japan, the Ministry of Health, Labour, and Welfare (MHLW) has endorsed the use of the methods referenced in Section 2.1 as interchangeable, based on the conditions outlined in the annex. However, detailed implementation requirements will be provided by the MHLW when the annex is formally incorporated into the Japanese regulatory process. This ensures that any regulatory actions related to method changes are consistent with national requirements.

4.5 Health Canada Considerations

In Canada, the regulatory authorities will accept any of the pharmacopoeial texts cited in Section 2.1 of the annex as interchangeable, provided that they are used in accordance with the conditions specified. This harmonization is in line with global efforts to standardize analytical procedures and ensure consistency across international borders, thereby simplifying regulatory processes for pharmaceutical manufacturers operating in Canada.

5. References Used for the Q4B Evaluation

The Q4B evaluation process relied on various key references to assess the suitability and equivalence of the analytical sieving methods from different pharmacopoeial sources. These references provided the foundation for the decisions made by the Expert Working Group.

5.1 PDG Stage 5B Sign-off Document

The PDG Stage 5B sign-off document, as published in the Japanese Pharmacopoeial Forum (Volume 16, Number 2, June 2007), was a primary reference for the evaluation. This document provided an official endorsement of the harmonization efforts among the different pharmacopoeias.

5.2 Pharmacopoeial References for the Analytical Sieving General Chapter

The key pharmacopoeial texts that were examined during the Q4B evaluation include:

  • European Pharmacopoeia (Ph. Eur.): Supplement 6.2, published December 11, 2007, and made official by July 2008. This included the section on “Particle-size Distribution Estimation by Analytical Sieving” (reference 07/2008:20938).
  • Japanese Pharmacopoeia (JP): The version in Supplement II to the JP Fifteenth Edition, published on September 30, 2009, under Ministerial Notification No. 425. An English version of the JP text was published on June 4, 2010, and can be accessed at the official website of the Pharmaceuticals and Medical Devices Agency (PMDA).
  • United States Pharmacopeia (USP): General Chapter <786> on “Particle Size Distribution Estimation by Analytical Sieving,” which appeared in USP 32 Supplement 2 (official December 1, 2009). Additionally, there were errata published in the Interim Revision Announcement to USP 32, which were released on September 1, 2009, and became official on October 1, 2009.

These pharmacopoeial references served as the basis for determining the compatibility and interchangeability of analytical sieving methods across the ICH regions, ultimately leading to the recommendations that were adopted in the Q4B annex.

Conclusion

The Q4B process for the Analytical Sieving General Chapter represents a significant step toward global harmonization in pharmaceutical analysis. By establishing the interchangeability of methods from different pharmacopoeias (Ph. Eur., JP, USP), the annex facilitates smoother international trade and regulatory approval processes. Manufacturers and regulatory bodies must stay informed of the specifics laid out in the annex and adhere to regional guidelines when implementing these methods. While the core principle of interchangeability has been accepted, each region retains its ability to request additional evidence or documentation as necessary to ensure that the adopted methods are suitable for the specific circumstances of local products or materials.