Type of Posting: General Announcement
Posting Date: 28-Aug-2020
Comment Deadline: 30-Nov-2020
This notice describes a proposed approach for the inclusion of informational performance tests employing non-standard apparatus in new inhalation product monographs. Any existing inhalation product monographs having a non-standard performance test will not be affected by this proposal. The purposes of this approach are: (1) to continue publishing quality standards based on legacy approvals (i.e., products approved by FDA before the adoption of the current USP performance test standards); (2) to facilitate the future development of generic drug products exclusively using standardized performance tests; and (3) to discourage the adoption of non-standard performance tests by manufacturers.
USP publishes standards for evaluating the in vitro performance of complex inhalation drug products, including inhalation aerosols delivered via metered dose inhalers (MDIs) and inhalation powders delivered via dry powder inhalers (DPIs). These standards help manufacturers ensure uniformity (or consistency) within a specific inhalation drug product and among different manufacturers of the same drug product. USP performance standards for inhalation products include drug product monographs as well as USP General Chapter <601> Inhalation and Nasal Drug Products: Aerosols, Sprays, and Powders ̶ Performance Quality Tests, which describes standardized performance test apparatus (standardized apparatus) and well-established test procedures.
USP faces a compendial challenge when sponsors of FDA-approved inhalation products provide methods for inclusion in the USP-NF that utilize solely in-house or formerly standardized apparatus, collectively referred to as “non-standard apparatus.” An example of a non-standard apparatus is one that uses a modified induction port for a cascade impactor in aerodynamic particle size distribution measurements. If USP includes only non-standardized apparatus in a monograph, this may place generic development at a disadvantage, particularly as regulatory authorities seek to encourage development based on standardized performance tests.
History of Stakeholder Feedback and Engagement
Beginning in 2018, USP received comments from FDA and industry stakeholders that the inclusion of detailed performance tests employing non-standard apparatus in inhalation product monographs created a potential burden for industry and was inconsistent with the agency’s inhalation product specific guidance documents, which encouraged – but did not require – the use of the standardized apparatus. FDA noted that the burden would be particularly acute when the only performance test in the monograph specified the use of a non-standard apparatus, as this would necessitate that the applicant procure the non-standard apparatus and validate the performance test with the non-standard apparatus in order to demonstrate product equivalence.
Proposed Compendial Approach
To address the challenge described above, USP is proposing a new approach intended to ensure the efficient development of new inhalation product monographs. This approach will support generic developers by providing a complete public standard, including details related to all relevant performance tests, but would hold any performance test employing non-standard apparatus in abeyance (i.e., in a postponed status), thus making it informational at the time of publication. This is intended to provide a public quality standard while promoting unencumbered development of new products with performance tests employing the standardized apparatus. The proposed approach is briefly outlined below with descriptions of: (1) how the information will appear in the Pharmacopeial Forum (PF); (2) how the information will appear in the USP-NF; and (3) the mechanism for making the postponed test official.
- For new inhalation product monograph proposals appearing in PF:
USP will continue to include detailed performance tests reflecting the sponsor’s approved application. However, when the performance test employs a non-standard apparatus as the only available option, the following conditions will apply:
- The PF Briefing will highlight the fact that the test employs non-standard apparatus and will encourage the submission of additional procedures employing standardized apparatus from other manufacturers with approved applications;
- Any non-standard component of the apparatus shall be described within the test procedure for the specific drug product making its applicability monograph-specific; and
- The target official date for the performance test’s implementation will not be specified, i.e., the performance test will be tagged “(Official TBD).”
- For new inhalation product monographs once they have been approved and published in the USP-NF:
Where the performance test in the new inhalation product monograph employs a non-standard apparatus as the only available option, the test will be tagged “(Postponed on XX-XXX-XXXX),” with the date coinciding with the official date of the rest of the monograph. The postponement of the performance test employing non-standard apparatus will render this test informational and not essential for regulatory compliance. In addition, USP will specify that the performance test employing non-standard apparatus is not eligible for early adoption, to avoid encouraging reliance by generic product developers.
- Mechanism for making the postponed test official:
When USP receives a monograph revision from an approved applicant requesting the inclusion of a performance test employing standardized apparatus (or upon the regulatory approval of an applicant utilizing the Pending Monograph process meeting the same requirements), postponement of the non-standard performance test will no longer be necessary. Both the new performance test(s) employing standardized apparatus and the previous non-standard performance test will be made official via the same revision vehicle.
Request for Feedback and Intent to Publish Comments
USP is seeking public comments on the approach described above. Stakeholders are encouraged to provide their feedback and recommendations. After the comment period closes on November 30, 2020, USP will review the comments and post an updated Compendial Notice.
In order to provide full context for conversations with stakeholders, USP plans to publish the comments received from stakeholders in their entirety and with attribution. The transparency of comments will be beneficial to that conversation. If any stakeholder would prefer that their comment not be published in its entirety or published without attribution, we request that you specifically designate information as confidential in your submission.
Should you have any questions or comments, please contact Nicholas Garito, Senior Scientific Liaison, at firstname.lastname@example.org.