Approval Letter Other 215212 (Jan 1, 2024)

Summary

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.

Key points

• Conduct the planned '14-Day Repeat Dose Toxicity Study via Intravenous Injection in Beagle Dogs with a 14-Day Recovery Period' using the cefazolin drug product to qualify the identified leachables.
• Submit the final, complete study report for the nonclinical qualification study for identified leachables in a future NDA resubmission.
• Conduct and provide results of a study to justify the proposed overfill and to demonstrate that the labeled drug amount can be consistently withdrawn from the vial according to the labeling reconstitution instructions.
• Adjust and justify any changes to the range and/or the labeling reconstitution instructions based on the results of the overfill studies.
• Review labeling review resources on the Prescription Drug Labeling Resources and Pregnancy and Lactation Labeling Final Rule websites.
• Ensure that the Prescribing Information conforms with format items in regulations and guidances using the SRPI checklist if labeling is revised.
• Include updated content of labeling [21 CFR 314.50(l)(1)(i)] in structured product labeling (SPL) format in the response.
• Include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b) when responding to deficiencies.

Cited reasons

• Inadequate Nonclinical Qualification of Identified Leachables
• Insufficient Justification for Proposed Drug Product Overfill
• The application received a Complete Response Letter due to inadequate nonclinical qualification of identified leachables and insufficient justification for the proposed drug product overfill amount. Additional studies and data are required to address these issues.

Recommended actions

• Conduct the planned '14-Day Repeat Dose Toxicity Study via Intravenous Injection in Beagle Dogs with a 14-Day Recovery Period' using the cefazolin drug product to qualify the identified leachables.
• Submit the final, complete study report for the nonclinical qualification study for identified leachables in a future NDA resubmission.
• Conduct and provide results of a study to justify the proposed overfill and to demonstrate that the labeled drug amount can be consistently withdrawn from the vial according to the labeling reconstitution instructions.
• Adjust and justify any changes to the range and/or the labeling reconstitution instructions based on the results of the overfill studies.
• Review labeling review resources on the Prescription Drug Labeling Resources and Pregnancy and Lactation Labeling Final Rule websites.
• Ensure that the Prescribing Information conforms with format items in regulations and guidances using the SRPI checklist if labeling is revised.
• Include updated content of labeling [21 CFR 314.50(l)(1)(i)] in structured product labeling (SPL) format in the response.
• Include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b) when responding to deficiencies.

Deficiency summary

The application received a Complete Response Letter due to inadequate nonclinical qualification of identified leachables and insufficient justification for the proposed drug product overfill amount. Additional studies and data are required to address these issues.

Findings

Regulatory context

Submission stage

final decision

Regulatory pathway

505(b)(2)

Impact

Impact score

0.75

Estimated delay

365 days

Estimated rework cost

$0

Subsequent action

resubmission

Strategic insights

The application was not approved due to critical gaps in nonclinical safety data for leachables and inadequate justification for the drug product's overfill, necessitating further studies and data submission for resubmission.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 25%