CDER FDA Letters

The FDA has issued a Complete Response Letter (CRL) for NDA 220049 for vatiquinone, indicating that the application is not ready for approval in its current form. The agency found that the nominally significant findings on exploratory endpoints (Upright Stability Subscale and Modified Fatigue Impact Scale) were not statistically robust or persuasive enough to establish effectiveness, especially given negative results on primary and key secondary endpoints. Concerns were raised regarding statistical observations, handling of missing data, baseline imbalances, and the interpretability of certain outcome assessments. Real-world evidence and biomarker data submitted as confirmatory evidence were deemed insufficient to serve as such without a positive, adequate, and well-controlled study. The FDA requires a new positive, adequate, and well-controlled study to establish effectiveness, suggests a specific study design, and outlines deficiencies related to nonclinical/product quality, labeling, proprietary name, and a comprehensive safety update for any resubmission.

This FDA letter addresses deficiencies in NDA 218923, reserving comment on proposed labeling and proprietary name until the application is otherwise adequate. It mandates a comprehensive safety update, including detailed data presentation, and outlines specific requirements for resubmission within one year, emphasizing that a partial response will not be processed.

This document is a Complete Response Letter (CRL) from the U.S. Food and Drug Administration (FDA) to an applicant for New Drug Application (NDA) 205508. The FDA has determined that the application cannot be approved in its present form due to several deficiencies related to facility inspections, manufacturing process controls (CMC data), and bioequivalence/bioavailability data reliability. The letter outlines specific reasons for non-approval and provides recommendations for addressing these issues, including requirements for resubmission and potential re-inspection of facilities.

This document is a letter from the U.S. Food and Drug Administration (FDA) to an applicant regarding New Drug Application (NDA) 218607. It outlines deficiencies in the application concerning prescribing information, carton and container labeling, proprietary name, and safety updates. The letter provides detailed instructions for addressing these deficiencies, particularly for the safety update, and sets a one-year deadline for resubmission or other actions.

This section outlines requirements for responding to deficiencies identified during inspections and for providing a comprehensive safety update for New Drug Application (NDA) 215644. It details specific content and formatting for the safety update, including new data integration, comparative tables, and narrative summaries for adverse events and trial discontinuations.

This document is a letter from the U.S. Food and Drug Administration (FDA) to an applicant regarding New Drug Application (NDA) 210168. It reserves comment on proposed labeling until the application is otherwise adequate and outlines required actions for the applicant within one year, including resubmission or withdrawal, and emphasizes that the drug cannot be marketed until approved.

The FDA has issued a deficiency letter for NDA 217382 concerning Nutrilipid 20%. Key issues include the lack of an adequate scientific bridge between Nutrilipid 20% and Intralipid 20% due to statistically significant physicochemical differences and insufficient data on comparable drug capture capability. The application also has deficiencies in human factors validation studies, indicating unsafe user interface for critical tasks. The FDA reserves comment on proposed labeling until other issues are resolved and requests comprehensive updates to safety data, benefit-risk assessments, and clarification on the proposed indication, especially for pediatric use and non-life-threatening Local Anesthetic Systemic Toxicity (LAST).

This section serves as a representation of an electronically signed record, detailing the electronic signature and associated metadata such as the signing date, time, and a reference ID.

The FDA has identified significant deficiencies in New Drug Application (NDA) 215244 for elamipretide, concluding that its effectiveness has not been established for traditional approval due to a lack of superiority over placebo in clinical trials (SPIBA-201 Part 1 & 2, SPIBA-001) and concerns regarding bias in endpoint measurements. The proposed surrogate endpoints (LVSV, MLCL:CL ratio, acylcarnitines) are also deemed insufficient for accelerated approval due to various limitations. The FDA suggests exploring muscle strength of knee extensors as a potential intermediate clinical endpoint for accelerated approval, contingent on demonstrating its predictive clinical benefit and proposing a confirmatory postmarketing trial. Additionally, the applicant must resolve facility inspection deficiencies, and address labeling and proprietary name issues.

This FDA letter, dated April 25, 2025, addresses New Drug Application (NDA) 215818, outlining specific requirements and recommendations related to product quality, prescribing information, carton and container labeling, and other general submission procedures. It emphasizes the need for the applicant to address deficiencies, update various data points, and adhere to specific formatting and submission guidelines before the application can be approved and the product legally marketed.

This FDA letter communicates deficiencies in New Drug Application (NDA) 218353 for floretyrosine F 18, requiring the applicant to address issues related to efficacy evidence, dose optimization, prescribing information, carton and container labeling, and a comprehensive safety update. It outlines specific requirements for the safety update data presentation and sets a one-year deadline for resubmission or other actions.

This document is a Complete Response Letter (CRL) from the FDA to an applicant for New Drug Application (NDA) 218592, outlining deficiencies that prevent approval and detailing the necessary actions for resubmission.

The FDA has identified deficiencies in NDA 216442, primarily concerning the robustness of Study 030's primary efficacy endpoint analysis and the statistical methodology used. The agency requires the applicant to conduct at least one additional adequate and well-controlled study to demonstrate positive treatment effects for ocular symptoms of dry eye, without making unapproved protocol or statistical analysis plan changes. Further comments on prescribing information, carton/container labeling, and proprietary name are reserved until the application is otherwise adequate. A safety update is also required upon resubmission, and the applicant must take action within one year to resubmit or risk withdrawal of the application.

This FDA letter provides feedback on NDA 218345, acknowledging revised labeling and carton/container labeling submissions, but reserving further comment until the application is otherwise adequate. It outlines detailed requirements for a safety update, including specific data presentation and analysis, and provides instructions for resubmission or other actions within one year.

This FDA letter for NDA 218571 outlines deficiencies in the application, particularly concerning labeling and safety data, and provides instructions for resubmission and further actions required for approval.

The FDA issued a Complete Response Letter (CRL) for NDA 216586 for rivoceranib tablets, indicating that the application cannot be approved in its present form due to outstanding issues, primarily concerning the co-dependent approval of SHR-1210 and labeling adequacy.

This section outlines the required actions for an applicant following an FDA letter regarding NDA 217719, including deadlines for resubmission or other actions, specific formatting for resubmissions, and conditions for product distribution.

This document from the U.S. Food and Drug Administration (FDA) addresses deficiencies in New Drug Application (NDA) 219112, specifically regarding proposed labeling and the requirement for a comprehensive safety update.

This FDA letter for NDA 218879 outlines deficiencies and requirements for the applicant to address in a resubmission. It details specific instructions for revising prescribing information, updating carton and container labeling, and comprehensively presenting new safety data from clinical studies and worldwide experience. The letter also sets a one-year deadline for resubmission or other actions and clarifies the process for resubmission and potential meetings.

This FDA letter addresses deficiencies in New Drug Application (NDA) 219357, providing instructions for the applicant to resubmit the application. Key areas of focus include labeling, proprietary name, and a comprehensive safety update, along with general resubmission requirements and timelines.

The FDA has issued a Complete Response Letter for NDA 210934 for sotagliflozin, indicating that the application is not approvable. The agency concluded that the submitted data did not support a favorable benefit-risk assessment for sotagliflozin in patients with Type 1 Diabetes (T1D) and eGFR ≥60 ml/min/1.73m2 and UACR ≥30 mg/g, primarily due to the risk of Diabetic Ketoacidosis (DKA) outweighing the modest glycemic and other non-glycemic benefits. The letter outlines deficiencies and suggests potential paths forward, including conducting new clinical safety trials to demonstrate adequate DKA risk mitigation and providing additional data for T1D patients with eGFR <60 ml/min/1.73m2.

The FDA has identified numerous deficiencies in NDA 218828 for glepaglutide, primarily concerning the interpretability and persuasiveness of efficacy results from clinical trials (EASE-1, EASE-2, EASE-3, EASE-4, ZP1848-15073) and limitations in the safety database. Issues include protocol deviations, incomplete documentation, data reliability concerns, inadequate qualitative and quantitative analyses for clinically meaningful change, lack of confirmatory evidence, and inconsistent dose responses. Furthermore, the safety database is deemed insufficient for a new molecular entity intended for chronic administration, with multiple safety concerns identified and significant reliability issues found during a clinical investigator site inspection. The FDA recommends conducting a new, well-controlled trial to address these deficiencies before resubmission.

This document is a letter from the U.S. Food and Drug Administration (FDA) to an applicant regarding New Drug Application (NDA) 212271. It outlines deficiencies and provides instructions for the applicant to address issues related to prescribing information, carton and container labeling, proprietary name, and safety updates. The letter also specifies requirements for resubmission.

This document is a communication from the U.S. Food and Drug Administration (FDA) regarding New Drug Application (NDA) 214610. It outlines specific requirements related to product quality, prescribing information, and safety data, and provides instructions for resubmission or further actions.

This document outlines specific requirements for updating and presenting safety data for NDA 218762, including new clinical trial data, adverse event frequencies, trial discontinuations, and worldwide safety experience. It also sets a deadline for resubmission or other actions.

The FDA has identified significant deficiencies in NDA 219195 for govorestat, concluding that the currently available evidence does not support the drug's effectiveness for treating CG, nor does it validate plasma galactitol as a reasonably likely surrogate endpoint for accelerated approval. The agency requires substantial evidence of effectiveness, including new adequate and well-controlled clinical trials, and comprehensive data to support galactitol's role as a surrogate endpoint.

This document outlines specific requirements for updating safety data in a New Drug Application (NDA), focusing on incorporating new clinical trial findings, adverse event reporting, and global safety information.

This document is a letter from the U.S. Food and Drug Administration (FDA) to an applicant regarding New Drug Application (NDA) 218600. It outlines deficiencies and provides detailed instructions for resubmitting the application, focusing on labeling, proprietary name, and safety updates.

The FDA has reviewed a New Drug Application (NDA 219045) for a naloxone HCl, 4 mg, nasal spray. While the product's efficacy is considered comparable to Narcan, significant safety concerns exist due to its higher systemic exposure, which is greater than Narcan. This higher exposure poses an increased risk of precipitated opioid withdrawal, especially in opioid-dependent individuals and in a nonprescription setting without healthcare guidance. The submitted safety data is deemed inadequate, and communicating this risk effectively on a Drug Facts Label (DFL) is challenging. The FDA recommends either product reformulation to achieve lower systemic exposure or conducting further studies to establish the safety of the current higher-exposure formulation for nonprescription use, along with potential labeling modifications. A comprehensive safety update is also required.

This FDA letter communicates deficiencies in NDA 218923, deferring clinical inspections and reserving comments on labeling and proprietary name until the application is otherwise adequate. It outlines specific requirements for a safety update, including detailed data presentation and analysis, and provides instructions for resubmission within one year, emphasizing that all deficiencies must be addressed.

This letter from the FDA communicates deficiencies found in New Drug Application (NDA) 217724 and outlines requirements for a complete response. Key areas of concern include manufacturing compliance (CGMP), prescribing information (labeling) content and format, proprietary name review, safety updates, and specific clinical data requests related to pediatric dosing, safety, and efficacy, particularly for infants with low body weight or prematurity. The applicant is required to address these deficiencies within one year, with specific instructions for resubmission.

This FDA letter outlines deficiencies for New Drug Application (NDA) 218026 and provides detailed instructions for resubmission, focusing on labeling requirements, safety updates, and administrative procedures.

The FDA issued a complete response letter for NDA 215455, citing substantial concerns regarding the reliability of safety data due to inconsistent adverse event reporting, particularly for 'positive' effects related to abuse potential. The application also failed to demonstrate durable treatment effects for midomafetamine in PTSD, largely due to design issues and potential selection bias in the MAPP1, MAPP2, and MPLONG studies. The FDA recommends a new clinical trial to address durability and safety characterization, including specific design elements to minimize bias and ensure comprehensive AE capture. Additionally, the FDA identified data gaps in laboratory assessments, cardiac safety, and hERG evaluation that need to be addressed in any resubmission, along with recommendations for characterizing psychotherapy's contribution and improving study diversity.

The FDA issued a Complete Response letter for NDA 217338 for naproxen sodium, dextromethorphan hydrobromide, guaifenesin extended-release (ER) tablet, indicating that the application cannot be approved in its current form due to insufficient evidence supporting the proposed 12-hour duration of action and dosing regimen.

This document is a Complete Response Letter (CRL) from the FDA for New Drug Application (NDA) 216195, outlining deficiencies that prevent approval and detailing the requirements for a complete response resubmission, including specific instructions for a safety update and addressing facility issues.

This FDA letter for NDA 217433 outlines deficiencies related to product quality, human factors, prescribing information, carton and container labeling, and safety updates. The primary concern is the user interface's failure to support safe and effective use, as demonstrated by a human factors validation study where participants failed to administer the intended dose. The letter requires the applicant to implement user interface revisions, provide data demonstrating effectiveness, and submit a safety update with detailed new safety data. It also reserves comment on labeling until the application is otherwise adequate and provides instructions for resubmission.

This document is a letter from the U.S. Food and Drug Administration (FDA) to an applicant regarding New Drug Application (NDA) 215029. It outlines deficiencies in the application, reserves comment on proposed labeling, addresses the proprietary name, and provides detailed instructions for a safety update and the resubmission process. The letter also specifies the timeframe for resubmission and options for meetings.

This document is a letter from the U.S. Food and Drug Administration (FDA) regarding New Drug Application (NDA) 218345. It addresses product quality, regulatory aspects, prescribing information, carton and container labeling, and provides detailed instructions for a required safety update.

This document outlines the requirements for submitting a safety update as part of a New Drug Application (NDA) response, detailing specific data presentation and analysis expectations for nonclinical and clinical studies.

This document is a Complete Response Letter (CRL) from the FDA for New Drug Application (NDA) 218506, outlining deficiencies that prevent approval in its current form. It addresses issues related to product quality, proprietary name, facility inspections, and requires a comprehensive safety update.

This FDA letter communicates deficiencies in New Drug Application (NDA) 218698, reserving comment on proposed labeling until the application is otherwise adequate. It outlines specific requirements for a safety update, details for resubmission, and options for meeting requests.

This document is a letter from the U.S. Food and Drug Administration (FDA) to an applicant regarding New Drug Application (NDA) 218317. It outlines deficiencies identified during the review process, particularly concerning facility inspections, safety updates, and labeling, and provides instructions for a complete response and resubmission.

This document outlines requirements for New Drug Application (NDA) submissions, specifically regarding the resubmission of a proprietary name and the provision of a comprehensive safety update when responding to application deficiencies. The safety update must include detailed data from all nonclinical and clinical studies, incorporating new findings, retabulated adverse event frequencies, and narrative summaries for serious events or deaths.

This document is a letter from the FDA regarding New Drug Application (NDA) 216987, outlining deficiencies that need to be addressed before approval. It specifies requirements for labeling revisions, a comprehensive safety update, and procedures for resubmission or other actions.

This section serves as an attestation for an electronic record, confirming it was signed electronically and providing details of the electronic signature, including the date, time, and a reference ID.

This FDA letter communicates deficiencies in New Drug Application (NDA) 218524, primarily concerning prescribing information (PI) and safety updates. It outlines specific requirements for revising labeling, submitting safety data, and the process for resubmission or other actions within one year.

This FDA letter addresses deficiencies in New Drug Application (NDA) 218408, specifically regarding prescribing information, carton and container labeling, and safety updates. It outlines requirements for resubmission and emphasizes that the product cannot be marketed until approved.

This document is a letter from the U.S. Food and Drug Administration (FDA) to an applicant regarding New Drug Application (NDA) 210168. It outlines the required actions for the applicant to take within one year, primarily focusing on resubmission or other actions under 21 CFR 314.110, and details the proper format and content for a resubmission. It also mentions the option to request a meeting with the FDA.

This document from the U.S. Food and Drug Administration (FDA) outlines significant deficiencies in New Drug Application (NDA) 218223 for GA Depot as a treatment for relapsing forms of multiple sclerosis (RMS). The FDA found the Phase 3 trial (Study Mapi GA Depot Phase III – 001) did not provide interpretable or persuasive efficacy findings, failed to establish an adequate scientific bridge to Copaxone, and exhibited numerous issues with trial design, data quality, and reliability. Furthermore, the submitted safety data were deemed inadequate, and the study raised new safety concerns, including severe injection site reactions and systemic injection-related reactions, suggesting important differences from Copaxone.

This letter from the FDA outlines deficiencies in NDA 215749, primarily focusing on the requirement for a comprehensive safety update and instructions for resubmission. It details specific data and documentation needed for the safety update, including new and combined safety data, adverse event comparisons, and worldwide safety experience. The letter also sets a one-year deadline for resubmission or other actions and provides guidance on the format and content of a resubmission.

The FDA has identified several deficiencies in the New Drug Application (NDA) for roluperidone for the treatment of negative symptoms of schizophrenia. Key issues include insufficient evidence for efficacy from Study C07, lack of data on co-administration with antipsychotics, unproven clinical meaningfulness of the observed effect on negative symptoms, and inadequate long-term safety data. Additionally, the proposed strategy for mitigating QTc prolongation risk based on CYP2D6 genotyping is deemed insufficient, requiring a robust companion diagnostic device. The FDA requires the submission of additional studies and data to address these deficiencies before the application can be approved.

This document is an FDA letter regarding New Drug Application (NDA) 217556 for cefepime for injection and taniborbactam for injection. It outlines specific deficiencies and requirements that must be addressed for the application to be approved, including detailed instructions for presenting safety data, clinical pharmacology analyses, and resubmission procedures.

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.