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Inhalation Drug Product Monographs: Removal of Performance Tests

Type of Posting: Notice of Intent to Revise
Posting Date: 25-June-2021
Target Official Date: TBD, Interim Revision Announcement
Expert Committee: Small Molecules 5

In accordance with the 2020–2025 Rules and Procedures of the Council of Experts, this is to provide notice that USP and the Small Molecules 5 Expert Committee intend to revise multiple inhalation drug product monographs to remove the performance quality tests. Specifically, the Expert Committee intends to remove of both the Aerodynamic Size Distribution test, also known as Particle Size Distribution by Cascade Impaction test, and the Delivered Dose Uniformity test in the impacted monographs. It is anticipated that the proposed revisions will be published as Proposed Interim Revision Announcement (IRA) in a future Pharmacopeial Forum. A list of the impacted monographs and test names is provided at the end of this Notice.

Rationale for removing performance tests
Recent comments from both FDA and industry stakeholders have noted that the performance tests providing detailed test procedures and acceptance criteria in some inhalation drug product monographs are product-specific/device-specific.  As such, these tests are not effective at ensuring uniformity (or consistency) in product performance among different manufacturers of the same drug product. Additionally, FDA has suggested that the inclusion of detailed performance tests in inhalation drug product monographs adds a regulatory burden that potentially impedes the approval of generic drug products already in development, as manufacturers are required to demonstrate their product’s conformance (or to address non-conformance) to the performance test requirements in the public standard. 

The Agency has further communicated that they no longer support the inclusion of multiple performance test procedures in these monographs to address differences in FDA-approved applications.

The decision to remove performance tests from inhalation product monographs at this time is a stop-gap measure to address the emerging compliance risk posed to those manufacturers with approved inhalation drug products or products currently in registration that do not conform to the current monograph performance test standards. This measure should not be interpreted to imply that performance quality tests are unnecessary for inhalation drug products. These tests remain a critical aspect of the overall quality controls for these complex dosage forms. The importance of performance quality tests is specifically addressed in USP General Chapter <5> Inhalation and Nasal Drug Products–General Information and Product Quality Tests.  Additionally, standardized apparatus and procedures for the conduct of these tests are described in USP General Chapter <601> Inhalation and Nasal Drug Products: Aerosols, Sprays, and Powders–Performance Quality Tests.

The future of performance tests
USP will engage with stakeholders to explore new ways of addressing these important performance quality tests for inhalation drug products within the public standard in a manner that will not impede generic development. Future action will be determined based on the outcome of that engagement.

Refer to the related Compendial Notice, posted on the USP website- Update: New Inhalation Product Monographs; Proposed Approach for Performance Tests Employing Non-standard Apparatus for additional information.

List of impacted inhalation drug product monographs [performance test names targeted for removal]

  • Fluticasone Propionate Inhalation Aerosol
    • [Particle Size Distribution by Cascade Impaction and Delivered Dose Uniformity]
  • Fluticasone Propionate Inhalation Powder
    • [Particle Size Distribution by Cascade Impaction and Delivered Dose Uniformity]
  • Fluticasone Propionate and Salmeterol Inhalation Aerosol
    • [Aerodynamic Size Distribution and Delivered Dose Uniformity]
  • Fluticasone Propionate and Salmeterol Inhalation Powder
    • [Aerodynamic Size Distribution and Delivered Dose Uniformity]
  • Salmeterol Inhalation Powder
    • [Particle Size Distribution by Cascade Impaction and Delivered Dose Uniformity <601>]

Should you have any questions, please contact Shankari Shivaprasad, Ph.D. (