Issued January 1, 2018
Issued
January 1, 2018
Application
Other • 207987
Review center
Other
Stage
Final Decision
Letter type
Approval Letter
This is a Complete Response Letter from the FDA to Belcher Pharmaceuticals, LLC, for their New Drug Application (NDA) 207987 for Ablysinol (Dehydrated Alcohol Injection, USP). The FDA has determined that the application cannot be approved at the present time due to various deficiencies related to clinical data, product quality (CMC), prescribing information, proprietary name, and facility inspections. The letter outlines specific issues and provides suggestions for addressing them, including a mandatory postmarketing study.
The application cannot be approved due to significant deficiencies across Chemistry, Manufacturing, and Controls (CMC), inadequate clinical safety data requiring a postmarketing study, non-conformance of labeling to regulatory requirements, and the manufacturing facility not being ready for inspection. A comprehensive safety update is also required upon resubmission.
Insufficient information on instructions for use (particularly dose) and expected rates for adverse events. A proposed postmarketing study design was received but needs to be initiated.
Recommended response: Initiate the proposed postmarketing registry while addressing other issues.
Provide CMC information concerning the validated analytical methods to be included in the revised drug product specification.
Recommended response: Provide validated analytical methods for the revised drug product specification.
Inadequate drug product stability data due to the absence of quantitative analytical methods for monitoring product attributes. New stability data using the revised product specification and validated quantitative analytical methods are required.
Recommended response: Generate new stability data using the revised product specification, including validated quantitative analytical methods for critical quality attributes.
Inadequate specification of the number and types of tests for the revalidation/requalification program. Inadequate validation information for the chromogenic kinetic endotoxin testing method.
Recommended response: Adequately specify microbiological tests for revalidation/requalification and provide adequate validation for endotoxin testing.
Revise the carton and container labels using the approved trade name.
Recommended response: Update carton and container labels with the approved trade name.
Proposed prescribing information (PI) must conform to content and format regulations (21 CFR 201.56(a) and (d) and 201.57). Formatting errors need correction using SRPI checklist. Updated content of labeling (21 CFR 314.50(l)(1)(i)) in SPL format is required.
Recommended response: Revise PI to conform to regulations, use SRPI checklist, and submit updated content in SPL format.
Cited: 21 CFR 201.56(a), 21 CFR 201.56(d), 21 CFR 201.57, 21 CFR 314.50(l)(1)(i)
The proposed proprietary name was found acceptable pending approval, but needs to be resubmitted with the response to application deficiencies.
Recommended response: Resubmit the proposed proprietary name with the complete response.
The manufacturing facility was not ready for inspection, which is a prerequisite for application approval.
Recommended response: Notify the agency in writing when the facility is ready for inspection.
A comprehensive safety update is required upon resubmission, including significant changes, new safety data, retabulations, case reports for deaths/serious AEs, updated exposure, worldwide experience, and foreign labeling translations.
Recommended response: Prepare a detailed safety update as per 21 CFR 314.50(d)(5)(vi)(b) for resubmission.
Cited: 21 CFR 314.50(d)(5)(vi)(b)
A registry of patients undergoing PTSMA with Ablysinol is required under Section 505(o)(3) of the FDCA to assess known serious risks (heart block, cardiac arrhythmias, MI, coronary artery dissection) due to limited safety information in the application and insufficiency of spontaneous reporting.
Recommended response: Establish a prospective registry of patients undergoing PTSMA with Ablysinol to collect peri/post-procedural adverse event data.
Cited: Section 505(o)(3)
The application for Ablysinol faces significant hurdles to approval, primarily stemming from unresolved CMC issues, inadequate clinical safety data requiring a postmarketing study, non-compliant labeling, and a manufacturing facility not ready for inspection. The agency emphasizes the need for robust data, validated methods, and full regulatory compliance before approval can be granted.
Regulatory change impact: Pending sponsor mitigation plan
Approval likelihood after response: 5%
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