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US FDA•United StatesAL•Approval Letter

Approval Letter Other 210274 (Jan 1, 2023)

Issued January 1, 2023

Issued

January 1, 2023

Application

Other • 210274

Review center

Other

Stage

Final Decision

Letter type

Approval Letter

Response due January 1, 2024Product may be marketed.

Summary

This is a Complete Response letter from the FDA to Zhejiang Novus Pharmaceuticals Co. Ltd. regarding their New Drug Application (NDA) for Vancomycin Hydrochloride for Injection. The FDA has determined that the application cannot be approved in its present form due to unresolved objectionable conditions at the manufacturing facility, non-conformance of the proposed Prescribing Information with regulations, and a minor error in carton/container labeling. The letter outlines the deficiencies and provides recommendations for addressing them, including a detailed safety update requirement.

Key points

  • Satisfactorily resolve the remaining objectionable conditions at the manufacturing facility (Zhejiang Novus Pharmaceuticals Co., LTD. | FEI: 3013567704) and ensure verification by the FDA.
  • Ensure the proposed Prescribing Information (PI) conforms to the content and format regulations found at 21 CFR 201.56(a) and (d) and 201.57.
  • Review labeling review resources on the PLR Requirements for Prescribing Information and Pregnancy and Lactation Labeling Final Rule websites.
  • Submit draft labeling that addresses FDA's proposed revisions.
  • Use the SRPI checklist to correct any formatting errors in the labeling.
  • Submit updated content of labeling [21 CFR 314.50(l)(1)(i)].
  • Provide a highlighted or marked-up copy showing all changes to the labeling, as well as a clean Word version, with annotations supporting proposed changes.
  • Submit revised draft carton and container labeling.

Cited reasons

  • Unresolved Objectionable Conditions at Manufacturing Facility
  • Non-conformance of Prescribing Information with Regulations
  • Missing Fahrenheit Symbol on Container Label Storage Statement
  • Insufficient Safety Update Submission
  • The application cannot be approved in its current form due to unresolved objectionable conditions at the manufacturing facility, non-conformance of the proposed Prescribing Information with regulatory requirements, a minor error in carton/container labeling, and an incomplete safety update submission.

Recommended actions

  • Satisfactorily resolve the remaining objectionable conditions at the manufacturing facility (Zhejiang Novus Pharmaceuticals Co., LTD. | FEI: 3013567704) and ensure verification by the FDA.
  • Ensure the proposed Prescribing Information (PI) conforms to the content and format regulations found at 21 CFR 201.56(a) and (d) and 201.57.
  • Review labeling review resources on the PLR Requirements for Prescribing Information and Pregnancy and Lactation Labeling Final Rule websites.
  • Submit draft labeling that addresses FDA's proposed revisions.
  • Use the SRPI checklist to correct any formatting errors in the labeling.
  • Submit updated content of labeling [21 CFR 314.50(l)(1)(i)].
  • Provide a highlighted or marked-up copy showing all changes to the labeling, as well as a clean Word version, with annotations supporting proposed changes.
  • Submit revised draft carton and container labeling.

Deficiency summary

The application cannot be approved in its current form due to unresolved objectionable conditions at the manufacturing facility, non-conformance of the proposed Prescribing Information with regulatory requirements, a minor error in carton/container labeling, and an incomplete safety update submission.

Findings

Unresolved Objectionable Conditions at Manufacturing Facility

Severity: critical

Following an evaluation of the last inspection performed at Zhejiang Novus Pharmaceuticals Co., LTD. manufacturing facility, our field investigator observed objectionable conditions. Satisfactory resolution of these conditions and FDA verification are required before approval.

Recommended response: Address all objectionable conditions identified during the facility inspection and obtain FDA verification of satisfactory resolution. Engage with the manufacturing facility to understand and remediate findings.

Non-conformance of Prescribing Information with Regulations

Severity: major

The proposed Prescribing Information (PI) does not conform to the content and format regulations found at 21 CFR 201.56(a) and (d) and 201.57. Revisions are needed based on attached labeling, and the SRPI checklist should be used to correct formatting errors. An updated content of labeling per 21 CFR 314.50(l)(1)(i) is also required, with marked-up and clean versions.

Recommended response: Revise the Prescribing Information to comply with 21 CFR 201.56(a), (d), and 201.57. Utilize the SRPI checklist for formatting and submit updated content of labeling per 21 CFR 314.50(l)(1)(i) with marked-up and clean versions.

Cited: 21 CFR 201.56(a), 21 CFR 201.56(d), 21 CFR 201.57, 21 CFR 314.50(l)(1)(i)

Missing Fahrenheit Symbol on Container Label Storage Statement

Severity: minor

The storage statement on the 5 gram/vial container label, 'Prior to reconstitution, store at 20°C to 25°C (68° to 77°F)…', is missing the Fahrenheit symbol (F) following '68°'. This needs to be added for clarity and consistency.

Recommended response: Correct the storage statement on the 5 gram/vial container label by adding the Fahrenheit symbol (F) after '68°'.

Insufficient Safety Update Submission

Severity: major

A comprehensive safety update, as described at 21 CFR 314.50(d)(5)(vi)(b), is required. This includes data from all nonclinical and clinical studies, detailed descriptions of safety profile changes, new safety data tabulations, case report forms, narrative summaries for deaths and serious adverse events, and updated exposure information.

Recommended response: Provide a comprehensive safety update as per 21 CFR 314.50(d)(5)(vi)(b), including detailed descriptions of safety profile changes, new safety data tabulations, case report forms, narrative summaries for deaths and serious adverse events, and updated exposure information.

Cited: 21 CFR 314.50(d)(5)(vi)(b)

Regulatory context

Submission stage
final decision
Regulatory pathway
505(b)(2)

Impact

Impact score
0.95
Estimated delay
365 days
Estimated rework cost
$0
Subsequent action
resubmission

Strategic insights

The application received a Complete Response due to critical manufacturing facility inspection findings, significant deficiencies in the proposed Prescribing Information and carton/container labeling, and an incomplete safety update, all of which prevent approval.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 5%

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