Issued January 1, 2021
Issued
January 1, 2021
Application
Other • 206610
Review center
Other
Stage
Final Decision
Letter type
Approval Letter
This document is a Complete Response letter from the FDA to Mylan Laboratories Limited regarding their New Drug Application (NDA) 206610 for Acetaminophen for Injection, 1 g/vial. The FDA has determined that the application cannot be approved in its present form due to deficiencies related to facility inspections, regulatory requirements (patent certifications), prescribing information, and safety update requirements.
The application cannot be approved in its present form due to unresolved manufacturing facility inspection deficiencies, outstanding regulatory issues concerning patent certifications and third-party documentation, and significant deficiencies in the submitted safety update, including inadequate presentation of clinical data, missing case report forms, and incomplete worldwide safety information.
Deficiencies were conveyed during a recent inspection of the Mylan Laboratories Limited manufacturing facility. Satisfactory resolution is required for approval.
Recommended response: Address all identified manufacturing facility deficiencies and ensure satisfactory resolution to enable approval.
Updated letters from Mallinckrodt are required to clearly indicate a specific date upon which your application can be approved.
Recommended response: Obtain and submit updated letters from Mallinckrodt specifying a clear approval date for the application.
Provide appropriate patent certification, recertification, or statement for U.S. patent 9,399,012, listed in the Orange Book with new use codes, following the January 24, 2017, paragraph IV certification for NDA 022450 (Ofirmev).
Recommended response: Submit the required patent certification, recertification, or statement for US Patent 9,399,012.
Cited: patent certification
Provide an appropriate patent certification or recertification for the new condition of use (new dosing instructions for neonates and infants) proposed in your draft labeling.
Recommended response: Submit the necessary patent certification or recertification for the proposed new dosing instructions for neonates and infants.
Cited: patent certification
Proposed Prescribing Information (PI) must conform to the content and format regulations found at 21 CFR 201.56(a) and (d) and 201.57.
Recommended response: Revise the Prescribing Information to ensure full compliance with 21 CFR 201.56(a), (d), and 201.57.
Cited: 21 CFR 201.56(a), 21 CFR 201.56(d), 21 CFR 201.57
A comprehensive safety update, as described at 21 CFR 314.50(d)(5)(vi)(b), is required, including data from all nonclinical and clinical studies/trials regardless of indication, dosage form, or dose level.
Recommended response: Provide a complete safety update encompassing all nonclinical and clinical data as mandated by 21 CFR 314.50(d)(5)(vi)(b).
Cited: 21 CFR 314.50(d)(5)(vi)(b)
Specific requirements for safety data presentation include providing separate tables for adverse event frequencies for indications other than the proposed one, presenting new safety data in the original format, tabulating new data with original data, and comparing frequencies.
Recommended response: Restructure and present adverse event data as specified, including separate tables for different indications and comparative analyses.
Cited: safety update
Provide case report forms and narrative summaries for all patients who died or discontinued trials due to adverse events, and for all serious adverse events.
Recommended response: Compile and submit all required case report forms and narrative summaries for deaths and serious adverse events.
Cited: safety update
Provide updated exposure information for all clinical studies/trials, including details such as number of subjects and person-time.
Recommended response: Submit updated and comprehensive clinical exposure data for all relevant studies.
Cited: safety update
Provide a summary of worldwide experience on the safety of this drug, including an updated estimate of use for drug marketed in other countries, and English translations of current approved foreign labeling not previously submitted.
Recommended response: Compile and submit a summary of worldwide safety experience, updated usage estimates, and English translations of all relevant foreign labeling.
Cited: safety update
Peer companies: Mallinckrodt
Historical frequency: 0 similar letters
The application received a Complete Response due to critical manufacturing facility issues, unresolved administrative and patent-related regulatory deficiencies, and substantial gaps in the clinical safety data and its presentation, requiring a comprehensive resubmission.
Regulatory change impact: Pending sponsor mitigation plan
Approval likelihood after response: 5%
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