Type of Posting: Notice of Intent to Revise
Posting Date: 11–Feb–2025; updated 25-Apr-2025
Targeted Official Date: 01-Dec-2025
Expert Committee: Packaging and Distribution Expert Committee
In accordance with the Rules and Procedures of the Council of Experts, the General Chapters–Packaging and Distribution Expert Committee (PDEC) announces its intent to revise <381>Elastomeric Components in Injectable Pharmaceutical Product Packaging/Delivery Systems and <382> Elastomeric Component Functional Suitability in Parenteral Product Packaging/Delivery Systems.
Background
On June 1, 2020 USP published the new general chapter <382> Elastomeric Component Functional Suitability in Parenteral Product Packaging/Delivery Systems. This chapter is scheduled to become official on December 1, 2025. In alignment with the scope of this new chapter the Expert Committee also recently proposed a revision to general chapter <381> Elastomeric Components in Injectable Pharmaceutical Product Packaging/Delivery Systems in PF50 (4) [Jul.-Aug. 2024] to remove section 4.3 Functionality Tests from <381>, which includes information on fragmentation tests, as this topic is now covered as part of the scope of the new general chapter <382> under section 5.1 Fragmentation.
Comments from the FDA
USP received public comments from FDA on <382> and the proposed revisions to <381> indicating concerns with the impact of differences in the fragmentation test in <382> from the fragmentation test in <381>. FDA also submitted letters to USP dated June 14 and July 30, 2024, in which they expressed specific concerns with section 5.1 Fragmentation in <382>. These concerns are related to the increase in the particle size threshold for fragmentation detection in <382> (from 50 µm in <381> to 150 µm in <382>); a lack of sufficient supporting safety data was cited as the basis for this concern. Additionally, the FDA opposed broadening the acceptance criteria beyond NMT 5 for specific applications, stressing the need to maintain the 50-µm detection limit and to introduce microscopic examination along with an acceptance criterion of NMT 5 to ensure patient safety.
Intended Revisions to <382>
In response to the recent FDA letters the PDEC, which includes government liaisons from FDA, has engaged in an extensive review of all the comments received on <382> and <381>. As an outcome of these deliberations, the Expert Committee intends to revise the current to be official text of <382> to remove section 5.1 Fragmentation from the general chapter before it becomes official on December 1, 2025. Removal of the tests will provide additional time for USP to engage with industry stakeholders and elastomer suppliers to gather data and establish more appropriate particle detection limits and acceptance criteria.
Correspondingly, the Expert Committee does not intend to adopt the proposed revision to remove section 4.3 Functionality Test from <381>, which was published for comment in PF50 (4) [Jul.-Aug. 2024]. The revision to chapter <381>, expected to become official on December 1, 2025, would retain the fragmentation test but omit the penetrability and self-sealing capacity tests, which can be found in <382>.
The intent of these revisions is to address the safety concerns raised by the FDA and to ensure alignment with regulatory expectations while allowing time for thorough data collection and analysis. It is anticipated that the revision to <382> will be published as a Revision Bulletin on April 25, 2025 with an official date of December 1, 2025.
For further questions or comments, please contact Desmond G. Hunt, Scientific Liaison to the General Chapters–Packaging and Distribution Expert Committee, at 301–816–8341 or dgh@usp.org.
This Notice was updated on April 25, 2025 to correct the target official date listed in the header