Issued January 1, 2023
Issued
January 1, 2023
Application
Other • 216686
Review center
Other
Stage
Final Decision
Letter type
Approval Letter
This is a Complete Response letter from the FDA to Spes Pharmaceuticals Inc. regarding their New Drug Application (NDA) 216686 for fosaprepitant injection. The FDA has determined that the application cannot be approved in its present form due to deficiencies identified in product quality/facility inspections, prescribing information, carton and container labeling, and clinical safety data.
The application for fosaprepitant injection received a Complete Response due to unresolved manufacturing facility deficiencies, issues with prescribing information and carton/container labeling, and significant deficiencies in the presentation and completeness of clinical safety data, including worldwide experience and adverse event reporting.
Satisfactory resolution of deficiencies conveyed during a recent inspection of the Pharmaceutics International, Inc. manufacturing facility (FEI 3006503102) is required before this application may be approved.
Recommended response: Address all deficiencies identified during the inspection of the manufacturing facility and provide evidence of satisfactory resolution.
Satisfactory resolution of deficiencies conveyed during a recent inspection of the Pharmaceutics International, Inc. manufacturing facility (FEI 1000513101) is required before this application may be approved.
Recommended response: Address all deficiencies identified during the inspection of the manufacturing facility and provide evidence of satisfactory resolution.
Submit draft labeling responsive to electronic communications (August 23, 2022 PI; August 24, 2022 PPI). Correct formatting errors using SRPI checklist. Submit updated content of labeling in SPL format. Proposed PI must conform to 21 CFR 201.56(a), (d) and 201.57.
Recommended response: Revise Prescribing Information and Patient Package Insert according to FDA's electronic communications, ensuring compliance with formatting guidelines (SRPI checklist) and regulatory requirements (21 CFR 201.56, 201.57, 314.50(l)(1)(i)) and submit in SPL format.
Cited: 21 CFR: 314.50(l)(1)(i), 21 CFR 201.56(a), 21 CFR 201.56(d), 21 CFR 201.57
Submit draft carton and container labeling responsive to electronic communication (August 23, 2022). Revise the container label as specified.
Recommended response: Update carton and container labeling as per FDA's electronic communication and specified revisions.
Present new safety data from studies/clinical trials for the proposed indication using the same format as the original submission. Present tabulations of new safety data combined with original application data. Include tables comparing frequencies of adverse events.
Recommended response: Re-present all new clinical safety data in a consistent format, combined with original data, and provide comparative tables of adverse event frequencies.
Present a re-tabulation of reasons for premature trial discontinuation, incorporating dropouts from newly completed trials, and describe any new trends or patterns identified.
Recommended response: Provide a comprehensive re-tabulation of premature trial discontinuations, including new trial data, and analyze for trends.
Provide case report forms and narrative summaries for each subject who died during a clinical trial or did not complete a trial because of an adverse event. In addition, provide narrative summaries for serious adverse events.
Recommended response: Submit all requested case report forms and narrative summaries for deaths and serious adverse events from clinical trials.
Describe any information that suggests a substantial change in the incidence of common, but less serious, adverse events between the new data and the original application data.
Recommended response: Analyze and report any significant changes in the incidence of common, less serious adverse events compared to original data.
Provide updated exposure information for the clinical studies/trials (e.g., number of subjects, person time).
Recommended response: Update and submit complete clinical exposure information for all studies.
Provide a summary of worldwide experience on the safety of this drug. Include an updated estimate of use for drug marketed in other countries.
Recommended response: Compile and submit a comprehensive summary of worldwide safety experience and drug use estimates.
Provide English translations of current approved foreign labeling not previously submitted.
Recommended response: Submit English translations for all current approved foreign labeling not yet provided.
The application for fosaprepitant injection received a Complete Response due to critical manufacturing facility deficiencies, significant issues with the content and format of both prescribing information and carton/container labeling, and numerous deficiencies in the presentation, completeness, and analysis of clinical safety data, including adverse event reporting, exposure information, and worldwide safety experience.
Regulatory change impact: Pending sponsor mitigation plan
Approval likelihood after response: 5%
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