FDA Letters Issued in January 2022

The FDA issued a Complete Response letter for DURECT Corporation's New Drug Application (NDA) 204803 for POSIMIR (bupivacaine extended-release solution), indicating that the application cannot be approved in its current form. The primary reasons for non-approval are insufficient clinical data to demonstrate the safety of POSIMIR, specifically regarding adverse events related to shoulder joints, skin/underlying tissues (bruising, hematoma, pruritus, dehiscence), and neurologically related adverse events (dizziness, dysgeusia, headache, hypoesthesia, paresthesia, somnolence). The letter outlines specific additional studies required to characterize the risk profile and details requirements for a comprehensive safety update.

This is a Complete Response letter from the FDA to Hospira, Inc. regarding their New Drug Application (NDA) 210282 for Daptomycin for Injection. The FDA has determined that the application cannot be approved in its present form due to deficiencies related to facility inspections, product quality (elemental impurities), and prescribing information. The letter outlines specific requirements for addressing these issues, including a comprehensive safety update, and provides instructions for resubmission or other actions.

The FDA issued a Complete Response letter for New Drug Application (NDA) 210526 for Dyanavel XR (amphetamine) extended-release tablets, indicating that the application cannot be approved in its current form. The letter outlines deficiencies related to manufacturing facility inspections, prescribing information, medication guide requirements, proprietary name resubmission, and the need for a comprehensive safety update.

The FDA issued a Complete Response letter for AuroMedics Pharma LLC's New Drug Application (NDA) 210735 for Cyclophosphamide Injection, indicating that the application cannot be approved in its current form due to several deficiencies. These deficiencies include unresolved issues from a facility inspection, non-conformance of proposed Prescribing Information (PI) with regulatory requirements, and incomplete safety update information.

This is a Complete Response letter from the FDA to Clearside Biomedical, Inc. regarding their New Drug Application (NDA) 211950 for XIPERE (triamcinolone acetonide ophthalmic suspension). The FDA has determined that the application cannot be approved in its present form due to several deficiencies related to manufacturing, product safety data, process robustness, and compliance with patent certification regulations.

This document is a Complete Response Letter from the FDA to Heron Therapeutics, Inc. regarding their New Drug Application (NDA) 211988 for Zynrelef. The FDA has determined that the application cannot be approved in its present form due to several nonclinical and other deficiencies, and provides recommendations for addressing these issues.

This letter from the FDA's Center for Drug Evaluation and Research outlines deficiencies found in New Drug Application (NDA) 212304. It provides specific instructions for revisions to labeling, packaging, and submission content, including a comprehensive safety update, to address these deficiencies.

This document is a Complete Response letter from the FDA to Adamis Pharmaceuticals Corporation regarding their New Drug Application (NDA) for Naloxone HCl Injection, 5 mg/0.5 mL. The FDA has determined that the application cannot be approved in its present form due to several deficiencies related to clinical data, device design, risk analysis, human factors, and statistical validation of manufacturing processes and device performance.

This letter from the FDA's Center for Drug Evaluation and Research addresses an applicant regarding deficiencies in application number 213218Orig1s000. It requests the submission of draft carton and container labeling, resubmission of the proposed proprietary name, and a comprehensive safety update. The safety update must include detailed new safety data from clinical studies, comparisons with original data, retabulation of trial discontinuations, case report forms for adverse events, updated exposure information, a summary of worldwide safety experience, and English translations of foreign labeling. The applicant is required to resubmit or take other actions within one year, fully addressing all deficiencies, or the application may be considered withdrawn. The drug cannot be marketed until approved.

This is a Complete Response Letter from the FDA to Esteve Pharmaceuticals, S.A. regarding their New Drug Application (NDA) 213426 for celecoxib and tramadol hydrochloride tablets. The FDA has determined that the application cannot be approved in its present form due to deficiencies related to facility inspections, prescribing information, proprietary name resubmission, Risk Evaluation and Mitigation Strategy (REMS) requirements, and safety updates.

This letter from the FDA addresses the New Drug Application (NDA) 213478, outlining deficiencies that prevent its approval. It provides instructions regarding labeling, proprietary name resubmission, facility inspection requirements (specifically for TOYO PHARMACEUTICAL CO. LTD. in Japan, which was delayed due to travel restrictions), and a comprehensive safety update. The applicant is required to address these deficiencies within one year, with specific guidance on resubmission and the option to request a meeting.

The FDA issued a Complete Response letter for New Drug Application (NDA) 213645 for DAPZURA RT (daptomycin) for Injection, indicating that the application cannot be approved in its present form. The primary reasons for non-approval include inadequate non-clinical safety qualification for several detected leachables, deficiencies in the proposed Prescribing Information and carton/container labeling, and the need for a comprehensive safety update.

This is a Complete Response Letter from the FDA to Xellia Pharmaceuticals, ApS, for their New Drug Application (NDA) 213895 for Vancomycin Injection. The FDA has determined that the application cannot be approved in its present form due to deficiencies related to product quality, nonclinical toxicology, and safety updates. The letter outlines specific issues and recommendations for addressing them.

The FDA issued a Complete Response Letter for New Drug Application (NDA) 213953 for testosterone undecanoate, citing that the application cannot be approved in its present form due to unreliable pharmacokinetic (PK) data from the pivotal efficacy and safety trial (MRS-TU-2019EXT). The unreliability stems from inadequate documentation of PK sample handling and processing at multiple clinical sites, which raised significant uncertainties about the integrity of the entire study's PK data.

This is a Complete Response Letter from the FDA to Novartis Pharmaceuticals Corporation regarding New Drug Application (NDA) 214012 for inclisiran injection. The FDA has determined that the application cannot be approved in its present form due to objectionable conditions noted during a review of records at a manufacturing facility and other outstanding issues.

This is a Complete Response Letter from the FDA to United Therapeutics Corp. regarding their New Drug Application (NDA) 214324 for treprostinil inhalation powder. The FDA has determined that the application cannot be approved in its present form due to deficiencies related to facility inspections, prescribing information, proprietary name resubmission, and the need for a comprehensive safety update.

This is a Complete Response Letter from the FDA to CMP Development LLC regarding their New Drug Application (NDA) for NORLIQVA (amlodipine) Oral Solution 1 mg/mL. The FDA has determined that the application cannot be approved in its present form due to deficiencies related to facility inspections, proprietary name resubmission, and required safety updates.

This is a Complete Response Letter from the FDA to Novitium Pharma LLC regarding their New Drug Application (NDA) 214581 for Hydroxychloroquine Sulfate Tablets. The FDA has determined that the application cannot be approved in its present form and outlines specific deficiencies and recommendations.

This is a Complete Response letter from the FDA to Nevakar, Inc. for their New Drug Application (NDA) 214628 for Norepinephrine Bitartrate in Sodium Chloride Injection. The FDA has determined that the application cannot be approved in its present form due to unresolved facility inspection deficiencies, additional CMC deficiencies, and requirements for a comprehensive safety update.

This document is a Complete Response letter from the FDA to Accord Healthcare, Inc. regarding their New Drug Application (NDA) 215000 for Carmustine for injection. The FDA has determined that the application cannot be approved in its present form due to deficiencies related to product quality, prescribing information, and safety updates. The letter outlines specific actions required for resubmission.

This is a Complete Response letter from the FDA to Santen, Inc. regarding their New Drug Application (NDA) for Omlonti (omidenepag isopropyl ophthalmic solution), 0.002%. The FDA has determined that the application cannot be approved in its present form due to several deficiencies, including manufacturing facility issues, inadequate clinical safety data regarding corneal endothelial cell loss, and requirements related to the product's classification as a drug-led combination product. The letter outlines specific actions and information required for resubmission and potential approval.

The FDA issued a Complete Response Letter for Biologics License Application (BLA) 761082 for Theragrastim, indicating that the application cannot be approved in its current form due to several deficiencies, including the need for a facility inspection, issues with stability protocols and analytical methods, and requirements for labeling and safety updates.

This is a Complete Response Letter from the FDA to Kashiv BioSciences, LLC regarding their Biologics License Application (BLA) 761084 for TPI-120. The FDA has determined that the application cannot be approved in its present form due to various deficiencies across microbiology, labeling, facility inspections, safety data, stability, shipping validation, and immunogenicity.

This is a Complete Response Letter from the FDA to Revance Therapeutics, Inc. regarding their Biologics License Application (BLA) 761127 for daxibotulinumtoxinA for injection. The FDA has determined that the application cannot be approved in its present form due to unresolved manufacturing facility deficiencies and pending labeling issues. The letter outlines the required actions for resubmission, including resolving manufacturing issues, revising prescribing information and carton/container labeling, resubmitting the proprietary name, and providing a comprehensive safety update.

This is a Complete Response Letter from the FDA to Spectrum Pharmaceuticals, Inc. regarding their Biologics License Application (BLA) for SPI-2012. The FDA has determined that the application cannot be approved in its present form due to deficiencies related to product quality (manufacturing facility inspections), prescribing information, carton and container labeling, proprietary name resubmission, and the need for a comprehensive safety update.

This is a Complete Response letter from the FDA to Bioverativ USA, Inc. regarding their Biologics License Application (BLA) for sutimlimab. The FDA has determined that the application cannot be approved in its present form and outlines specific deficiencies and recommendations that must be addressed for approval.

This letter from the FDA's Center for Drug Evaluation and Research addresses deficiencies in Biologics License Application (BLA) 761180, specifically requesting a resubmission of the proposed proprietary name and a comprehensive safety update.