Issued January 1, 2024
Issued
January 1, 2024
Application
Other • 217202
Review center
Other
Stage
Final Decision
Letter type
Approval Letter
The FDA issued a Complete Response letter for NDA 217202 for landiolol injection, indicating that the application cannot be approved in its current form due to deficiencies related to product quality, manufacturing, prescribing information, proprietary name, and safety updates. The letter also outlines a postmarketing requirement to assess drug transporter inhibition.
The application for landiolol injection cannot be approved in its current form due to unspecified manufacturing deficiencies, significant issues with the formatting and content of the prescribing information, an unacceptable proprietary name, and the lack of an in vitro assessment for drug transporter inhibition potential, which is required as a postmarketing commitment. A comprehensive safety update is also required upon resubmission.
The letter indicates issues under 'PRODUCT QUALITY Drug Product Manufacturing' but does not provide specific details within this complete response letter. It implies that manufacturing issues contribute to the non-approvability of the application.
Recommended response: Address all outstanding manufacturing-related deficiencies, potentially referencing previous communications or requesting clarification from the agency.
The submitted draft labeling contains formatting errors and does not conform to the SRPI checklist. Updated content of labeling must be submitted in Structured Product Labeling (SPL) format. The proposed Prescribing Information (PI) does not conform to content and format regulations found at 21 CFR 201.56(a) and (d) and 201.57.
Recommended response: Revise the Prescribing Information to comply with SRPI checklist, 21 CFR 201.56(a), (d), 201.57, and 21 CFR 314.50(l)(1)(i). Submit in SPL format with marked-up and clean versions.
Cited: 21 CFR 314.50(l)(1)(i), 21 CFR 201.56(a), 21 CFR 201.56(d), 21 CFR 201.57
The proposed proprietary name for landiolol injection was previously deemed unacceptable. A new proposed proprietary name must be submitted upon resubmission if the sponsor wishes to have one for the product.
Recommended response: Propose and submit a new proprietary name that meets FDA's naming conventions and guidelines.
A comprehensive safety update is required upon resubmission, as described at 21 CFR 314.50(d)(5)(vi)(b). This update must include data from all nonclinical and clinical studies/trials, detailed changes in the safety profile, updated adverse event tabulations, case report forms for deaths/serious adverse events, updated exposure information, and worldwide safety experience.
Recommended response: Compile and submit a complete safety update as per 21 CFR 314.50(d)(5)(vi)(b), ensuring all specified data points and formats are included.
Cited: 21 CFR 314.50(d)(5)(vi)(b)
The application lacks investigation into the inhibitory effect of landiolol and its M1 metabolite on multiple drug transporters (P-glycoprotein, BCRP, OATP1B1, OATP1B3, OCT2, MATE1, MATE2-K, OAT1, and OAT3). FDA has determined that an in vitro assessment of this potential is required as a postmarketing requirement under section 505(o)(3) of the FDCA.
Recommended response: Conduct the required in vitro assessment of landiolol and M1 metabolite's drug transporter inhibition potential and submit the results as part of the resubmission or as a commitment for post-approval.
Cited: Section 505(o)(3) of the FDCA
The application received a Complete Response Letter primarily due to deficiencies in product quality (manufacturing), significant issues with labeling content and format, an unacceptable proprietary name, and a critical gap in drug interaction assessment requiring a postmarketing commitment. A comprehensive safety update is also mandated for resubmission.
Regulatory change impact: Pending sponsor mitigation plan
Approval likelihood after response: 5%
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