Approval Letter Other 213260 (Jan 1, 2023)

Summary

This document is a Complete Response Letter from the FDA to an applicant for New Drug Application (NDA) 213260, indicating that the application cannot be approved in its current form due to various deficiencies. It outlines the specific issues that need to be addressed before approval can be granted, including manufacturing facility observations, product reformulation, bioequivalence studies, labeling updates, safety updates, and environmental assessment requirements.

Key points

• Satisfactorily resolve objectionable conditions, which may include preapproval inspection and/or adequate facility responses.
• Satisfactorily resolve observations noted at the manufacturing facility.
• List communications submitted to or held with the Agency to facilitate resolution of observed objectionable conditions or deficiencies at the facility.
• Reformulate the proposed product and conduct additional relative bioavailability studies to demonstrate bioequivalence to the listed drug, or conduct a clinical study to support effective and safe use of the proposed atorvastatin oral suspension product.
• Review labeling review resources on PLR Requirements for Prescribing Information and Pregnancy and Lactation Labeling Final Rule websites.
• If revising labeling, use the SRPI checklist to ensure conformity with format items in regulations and guidances.
• Include updated content of labeling in Structured Product Labeling (SPL) format [21 CFR 314.50(l)(1)(i)].
• Resubmit the proposed proprietary name when responding to application deficiencies.

Cited reasons

• Unresolved Manufacturing Facility Observations
• Lack of Bioequivalence or Clinical Support for Atorvastatin Oral Suspension
• Inadequate Safety Update and Data Presentation
• Incorrect Environmental Assessment Exemption Request
• Proprietary Name Review Terminated
• Missing English Translations of Foreign Labeling
• The application for atorvastatin oral suspension received a Complete Response Letter due to unresolved manufacturing facility observations, lack of bioequivalence data or clinical support for the proposed formulation, inadequate safety update documentation, an incorrectly submitted environmental assessment exemption request, and missing English translations for foreign labeling. The proprietary name review was also terminated pending resolution of these issues.

Recommended actions

• Satisfactorily resolve objectionable conditions, which may include preapproval inspection and/or adequate facility responses.
• Satisfactorily resolve observations noted at the manufacturing facility.
• List communications submitted to or held with the Agency to facilitate resolution of observed objectionable conditions or deficiencies at the facility.
• Reformulate the proposed product and conduct additional relative bioavailability studies to demonstrate bioequivalence to the listed drug, or conduct a clinical study to support effective and safe use of the proposed atorvastatin oral suspension product.
• Review labeling review resources on PLR Requirements for Prescribing Information and Pregnancy and Lactation Labeling Final Rule websites.
• If revising labeling, use the SRPI checklist to ensure conformity with format items in regulations and guidances.
• Include updated content of labeling in Structured Product Labeling (SPL) format [21 CFR 314.50(l)(1)(i)].
• Resubmit the proposed proprietary name when responding to application deficiencies.

Deficiency summary

The application for atorvastatin oral suspension received a Complete Response Letter due to unresolved manufacturing facility observations, lack of bioequivalence data or clinical support for the proposed formulation, inadequate safety update documentation, an incorrectly submitted environmental assessment exemption request, and missing English translations for foreign labeling. The proprietary name review was also terminated pending resolution of these issues.

Findings

Regulatory context

Submission stage

final decision

Regulatory pathway

NDA

Impact

Impact score

0.95

Estimated delay

365 days

Estimated rework cost

$0

Subsequent action

resubmission

Strategic insights

Key themes include significant manufacturing quality issues, fundamental clinical/bioequivalence concerns requiring reformulation or new studies, and substantial deficiencies in safety data reporting and administrative documentation, all preventing approval.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 5%