FDA Letters Issued in January 2024

This FDA letter acknowledges receipt of a draft labeling for NDA 218470 and reserves further comment until the application is otherwise adequate. It provides detailed instructions for a required safety update, outlines specific data presentation requirements for adverse events and clinical trial information, and sets a one-year deadline for resubmission or other actions under 21 CFR 314.110. The letter also specifies formatting for resubmissions and states that the product cannot be marketed until approved.

This document is a deficiency letter from the U.S. Food and Drug Administration (FDA) regarding New Drug Application (NDA) 214315. It outlines several deficiencies related to human factors, prescribing information, carton and container labeling, proprietary name, and safety updates. The FDA found that the proposed product's user interface does not support safe and effective use due to identified use errors and close calls during human factors validation studies. The letter requests specific actions and data from the applicant to resolve these deficiencies before the application can be approved.

This document is a letter from the U.S. Food and Drug Administration (FDA) to an applicant regarding New Drug Application (NDA) 218528. It outlines specific requirements and recommendations concerning prescribing information, carton and container labeling, medication guides, proprietary name resubmission, and a comprehensive safety update. The letter also includes additional Chemistry, Manufacturing, and Controls (CMC) comments.

This is a Complete Response Letter from the FDA to Hikma Pharmaceuticals USA, Inc. for New Drug Application (NDA) 218258 for phenobarbital sodium injection. The FDA has determined that the application cannot be approved in its present form due to deficiencies in clinical data, abuse potential assessment, facility inspections, and other areas, and provides recommendations for addressing these issues.

This FDA letter for NDA 215291 outlines deficiencies that must be resolved before the application can be approved. It provides detailed requirements for labeling revisions, proprietary name resubmission, and a comprehensive safety update, including specific data presentation formats for clinical trial safety information. It also sets a one-year deadline for resubmission or other actions and advises on meeting requests.

This FDA letter, identified as NDA 217294, outlines requirements for a safety update and procedures for resubmission following deficiencies. It mandates specific data presentation for safety information, including adverse events, discontinuations, and worldwide experience, and sets a one-year deadline for resubmission or other actions under 21 CFR 314.110.

This is a Complete Response Letter from the FDA to Delcath Systems, Incorporated, for their New Drug Application (NDA) 201848 for Melblez Kit. The FDA has determined that the application cannot be approved in its present form due to deficiencies related to clinical effectiveness, clinical pharmacology, and product quality. Key issues include a lack of substantial evidence of effectiveness where benefits outweigh risks, insufficient pharmacokinetic characterization for the proposed commercial product, and an inadequate toxicological risk assessment of leachables and extractables from the device components of the commercial configuration.

The FDA issued two Complete Response Letters for NDA 204311 for Abacavir and Lamivudine Tablets for Oral Suspension, indicating that the application cannot be approved in its current form. The primary reasons for non-approval include unresolved deficiencies from facility inspections at Mylan Laboratories Limited Unit-8 and requirements for revisions to prescribing information, carton/container labeling, and the medication guide. The letters provide detailed instructions for addressing these issues and for resubmitting the application.

This document is a Complete Response letter from the FDA to AFT Pharmaceuticals, Ltd. regarding New Drug Application (NDA) 209471 for COMBOGESIC. The FDA has determined that the application cannot be approved in its present form due to various deficiencies across clinical, statistical, nonclinical, product quality, and facility inspection areas. The letter outlines specific requirements for revising labeling, providing safety updates, addressing data quality issues, justifying drug substance specifications, analyzing elemental impurities, and confirming process validation. It also details the process and timeline for resubmission or other actions.

This is a Complete Response letter from the FDA to Braeburn Inc. for their New Drug Application (NDA) 210136 for BRIXADI (buprenorphine) extended-release injection. 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, safety update requirements, and mandated postmarketing studies.

The FDA issued a Complete Response letter for New Drug Application (NDA) 210852 for Cyclophosphamide Injection, indicating that the application cannot be approved in its current form due to deficiencies related to facility inspections and requiring a comprehensive safety update.

The FDA issued a Complete Response letter for NDA 211413 for Cefazolin for Injection USP, indicating non-approval due to deficiencies primarily related to the inadequate safety qualification of identified leachables and incomplete safety updates. The letter provides specific recommendations for addressing these issues and outlines the process for resubmission or further action.

This document contains two FDA letters concerning NDA 211566 for Sitagliptin Tablets. The first letter, dated March 3, 2023, details extensive requirements for updating safety data in a resubmission, including incorporating new clinical trial data, comparing adverse event frequencies, providing worldwide safety experience, and translating foreign labeling. It mandates resubmission or other actions within one year. The second letter, dated September 2, 2021, grants tentative approval for Sitagliptin Tablets for type 2 diabetes, contingent on the resolution of patent protection and exclusivity issues, specifically a patent infringement suit related to a Paragraph IV certification. It outlines the conditions for lifting the 30-month stay and the process for requesting final approval, which includes a safety update and confirmation of any changes to the application's conditions.

The FDA issued a Complete Response letter for NDA 212849 for Rykindo (risperidone) for extended-release injectable suspension, indicating that the application cannot be approved in its present form. The FDA identified deficiencies primarily related to clinical and clinical pharmacology concerns regarding unexplained concentration spikes and potential dose dumping, disagreeing with the applicant's root-cause analysis. Additional deficiencies include biopharmaceutics issues, pending labeling comments, and the need for a comprehensive safety update.

This document is a Complete Response Letter (CRL) from the FDA to Verrica Pharmaceuticals Inc. for New Drug Application (NDA) 212905, indicating that the application for cantharidin topical solution, 7% cannot be approved in its present form. It outlines specific deficiencies and provides detailed instructions for resubmission, focusing on updated labeling, proprietary name resubmission, and a comprehensive safety update.

This is a Complete Response Letter from the FDA to Teva Neuroscience, Inc. regarding New Drug Application (NDA) 213586 for risperidone extended-release injectable suspension. The FDA has determined that the application cannot be approved in its present form due to deficiencies related to clinical data quality, syringe and carton labeling, and proprietary name submission. The letter outlines specific reasons for non-approval and provides recommendations for addressing these issues, including requirements for a safety update and options for resubmission or further action.

This is a Complete Response Letter from the FDA to Ardelyx, Inc. regarding their New Drug Application (NDA) for tenapanor hydrochloride tablets. The FDA has determined that the application cannot be approved in its present form due to insufficient evidence of a clinically relevant treatment effect on serum phosphorus, despite acknowledging the drug's efficacy in reducing serum phosphorus. The letter outlines specific deficiencies and requirements for resubmission.

The FDA issued a Complete Response letter for NDA 213972 for sulopenem etzadroxil and probenecid tablets, indicating that the application cannot be approved in its current form due to a lack of substantial evidence of effectiveness from clinical trials and other deficiencies related to labeling, barcodes, safety updates, and nonclinical PK/PD studies.

This is a Complete Response letter from the FDA to Takeda Pharmaceuticals U.S.A., Inc. for their New Drug Application (NDA) 213976 for Eohilia (budesonide oral suspension) for the treatment of eosinophilic esophagitis (EoE). The FDA determined that the application cannot be approved in its current form due to insufficient evidence of effectiveness, citing deficiencies in clinical and statistical data, and provides recommendations for resolution.

The FDA issued a Complete Response letter for NDA 214927 for arimoclomol capsules, indicating that the application cannot be approved in its present form due to a lack of substantial evidence of effectiveness. Key concerns include issues with the 5-domain NPC Clinical Severity Scale (5DNPCCSS) as a primary endpoint, the statistical analysis (hypothetical estimand vs. while-on-treatment estimand), and weak/contradictory confirmatory evidence from in vitro and animal studies.

This document is a Complete Response letter from the FDA to CMP Development LLC regarding their New Drug Application (NDA) for sildenafil oral suspension, 10 mg/ml. 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, and safety updates.

This is a Complete Response Letter from the FDA to Galephar Pharmaceutical Research Inc. regarding their New Drug Application (NDA) 215040 for Legubeti (acetylcysteine) for oral solution. The FDA has determined that the application cannot be approved in its present form due to several deficiencies related to clinical data, regulatory compliance, and safety information.

The FDA issued a Complete Response letter for NDA 215064 for Filsuvez (birch triterpenes) gel, indicating that the application cannot be approved in its current form due to insufficient evidence of effectiveness for the proposed indication of treating wounds associated with inherited epidermolysis bullosa (EB). The letter details specific deficiencies in clinical data and outlines requirements for a safety update and other submissions.

The FDA issued a Complete Response letter for Shilpa Medicare Limited's New Drug Application (NDA 215179) for Pemetrexed Injection, indicating that the application cannot be approved in its current form due to unresolved product quality issues, facility inspection deficiencies, and outstanding safety update requirements. The letter outlines specific actions and data submissions required for potential approval.

This document is an 'Other Action Letter' from the FDA to an applicant regarding New Drug Application (NDA) 215151. It outlines deficiencies and required actions for the applicant to address within one year to move the application towards approval. Key areas of focus include labeling updates, proprietary name resubmission, and a comprehensive safety update.

The FDA issued a Complete Response Letter for Akebia Therapeutics, Inc.'s New Drug Application (NDA) 215192 for vadadustat tablets. The application was not approved in its current form due to an unfavorable benefit-risk assessment, citing major safety concerns including major adverse cardiac events (MACE), thromboembolic events, and drug-induced liver injury (DILI), which were deemed to outweigh the benefits for the proposed indication of anemia associated with chronic kidney disease (CKD) in adults not on dialysis and on dialysis.

The FDA issued a Complete Response Letter for NDA 215212 for Meropenem for Injection 2 g/vial, indicating that the application cannot be approved in its current form due to deficiencies in nonclinical, product quality, and safety update sections. The letter outlines specific issues and provides recommendations for resolution, requiring the applicant to address all deficiencies within one year for resubmission.

This is a Complete Response Letter from the FDA to AFT Pharmaceuticals Ltd. regarding their New Drug Application (NDA) 215320 for Combogesic (acetaminophen/ibuprofen) solution for injection. The FDA has determined that the application cannot be approved in its present form due to several deficiencies related to nonclinical data (toxicological risk assessment for leachables), prescribing information, carton and container labeling, medication guide, proprietary name, and the need for a safety update.

This is a Complete Response letter from the FDA to Braintree Laboratories, Inc. regarding New Drug Application (NDA) 215344 for Suflave (polyethylene glycol 3350, sodium sulfate, potassium chloride, magnesium sulfate, and sodium chloride) for oral solution. The FDA has determined that the application cannot be approved in its present form due to product quality/facility inspection deficiencies, issues with prescribing information, carton and container labeling, and the need for a comprehensive safety update.

This is a Complete Response letter from the FDA to Almatica Pharma, LLC, for their New Drug Application (NDA) 215721 for zolpidem tartrate capsules. The FDA has determined that the application cannot be approved in its present form due to deficiencies related to product quality, prescribing information, medication guide, and safety updates. The letter outlines specific requirements and recommendations for the applicant to address these issues.

This is a Complete Response letter from the FDA to Liqmeds Worldwide Limited regarding New Drug Application (NDA) 216482 for mycophenolate mofetil oral suspension. The application cannot be approved in its present form primarily due to the lack of a required Risk Evaluation and Mitigation Strategy (REMS). The letter outlines specific deficiencies and provides recommendations for addressing them, including detailed requirements for a safety update and submission procedures.

This is a Complete Response letter from the FDA to Ascendis Pharma Bone Diseases A/S regarding their New Drug Application (NDA) 216490 for palopegteriparatide injection. The FDA has determined that the application cannot be approved in its present form due to unresolved deficiencies related to product quality/device, labeling, and requires specific safety updates and postmarketing studies.

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.

This is a Complete Response letter from the FDA to Botanix SB Inc. regarding their New Drug Application (NDA) 217347 for sofpironium bromide. The FDA has determined that the application cannot be approved in its present form due to deficiencies primarily related to human factors study results and the need for a safety update.

The FDA issued a Complete Response letter for Takeda Pharmaceuticals' Biologics License Application (BLA) 761133 for MLN0002 SC, indicating that the application cannot be approved in its current form due to various deficiencies. The letter details specific recommendations across product quality, human factors, labeling (device, carton, container, prescribing information, medication guide), proprietary name, and facility inspections.

This document is a Complete Response Letter from the FDA to Bio-Thera Solutions Ltd. regarding their Biologics License Application (BLA) 761198 for BAT1706. The FDA has determined that the application cannot be approved in its present form due to various deficiencies across clinical pharmacology, product quality, labeling, and safety updates. The letter outlines specific issues and provides recommendations for addressing them.

This is a Complete Response Letter from the FDA to Hugel, Inc. regarding their Biologics License Application (BLA) for letibotulinumtoxinA injection. The FDA has determined that the application cannot be approved in its present form due to several deficiencies, including unresolved facility inspection issues, pending labeling comments, and requirements for a comprehensive safety update.

This letter from the FDA's Center for Drug Evaluation and Research outlines deficiencies in Biologics License Application (BLA) 761248 for Kisunla and provides detailed requirements for a resubmission. Key areas addressed include long-term safety characterization, prescribing information, carton and container labeling, proprietary name, a comprehensive safety update, and product quality specifications. The applicant is required to address all deficiencies within one year to avoid withdrawal of the application.

This is a Complete Response Letter from the FDA to Fresenius Kabi USA, LLC, for their Biologics License Application (BLA) 761275 for MSB11456. The FDA has determined that the application cannot be approved in its present form due to deficiencies related to facilities, and requires a comprehensive safety update and other technical revisions before approval.

The FDA issued a Complete Response letter for Biologics License Application (BLA) 761299 for AVT02, indicating that the application cannot be approved in its current form due to deficiencies. The letter outlines specific requirements for resubmission, including resolving facility inspection issues, updating labeling, resubmitting the proprietary name, and providing a comprehensive safety update.

This is a Complete Response Letter from the FDA to Eli Lilly and Company regarding their Biologics License Application (BLA) for lebrikizumab injection. The FDA has determined that the application cannot be approved in its present form due to unresolved product quality issues related to manufacturing facility deficiencies, data reliability concerns, and pending labeling and proprietary name reviews. The letter outlines specific deficiencies and provides recommendations for resolution, including a comprehensive safety update.

The FDA issued a Complete Response letter for Biologics License Application (BLA) 761343 for AVT04, indicating that the application cannot be approved in its present form due to outstanding deficiencies related to facility inspections, labeling, safety updates, product quality, and microbial quality.

This letter from the FDA's Center for Drug Evaluation and Research addresses deficiencies in Biologics License Application (BLA) 761365 for IMAB362 drug product. It outlines specific requirements related to analytical methods, manufacturing, labeling, proprietary name, and a comprehensive safety update, instructing the applicant on necessary actions for potential approval.

This is a Complete Response Letter from the FDA to Regeneron Pharmaceuticals, Inc. regarding their Biologics License Application (BLA) 761355 for Eylea HD (aflibercept) Injection. The FDA has determined that the application cannot be approved in its present form due to deficiencies in manufacturing facilities and controls, specifically non-compliance with current good manufacturing practice (cGMP) regulations.