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US FDA•United StatesAL•Approval Letter

Approval Letter Other (Nov 13, 2025)

Issued November 13, 2025

Issued

November 13, 2025

Application

Other

Review center

Other

Stage

Final Decision

Letter type

Approval Letter

Response due November 13, 2026Product may be marketed.

Summary

This is a Complete Response letter from the FDA to Eli Lilly and Company regarding their Biologics License Application (BLA) 761215/Original 2 for Rezvoglar (insulin glargine-aglr) injection, seeking interchangeability with U.S.-licensed Lantus. The FDA cannot approve the application in its current form primarily because the regulatory exclusivity period for the reference product has not yet expired, as stipulated by section 351(k)(6) of the Public Health Service Act. The letter also outlines specific requirements for a comprehensive safety update, potential labeling revisions, and the necessary next steps for resubmission or other actions.

Key points

  • Await the expiration of the reference product's exclusivity period as per section 351(k)(6)(A)-(C) of the PHS Act before an interchangeability determination can be made.
  • If labeling is revised, use the Selected Requirements for Prescribing Information (SRPI) checklist to ensure Prescribing Information conforms with format items in regulations and guidances.
  • Include updated content of labeling in Structured Product Labeling (SPL) format (21 CFR 601.14(b)) in any response.
  • Provide a comprehensive safety update when responding to deficiencies.
  • The safety update must detail significant changes or findings in the safety profile and their relevance to clinically meaningful differences between the proposed biosimilar and the reference product.
  • Present new safety data from clinical studies for the proposed indication in the same format as the original BLA submission.
  • Present tabulations of new safety data combined with original BLA data.
  • Include tables comparing frequencies of adverse events in the original BLA with retabulated frequencies.

Cited reasons

  • Interchangeability Exclusivity Period Not Expired
  • Incomplete Safety Update for Resubmission
  • Labeling Review Deferred; Future Revisions Expected
  • The application for interchangeability cannot be approved due to an unexpired exclusivity period for a prior interchangeable biological product. Additionally, a comprehensive safety update with detailed clinical data, worldwide experience, and translations is required upon resubmission, and labeling comments are reserved for future revisions.

Recommended actions

  • Await the expiration of the reference product's exclusivity period as per section 351(k)(6)(A)-(C) of the PHS Act before an interchangeability determination can be made.
  • If labeling is revised, use the Selected Requirements for Prescribing Information (SRPI) checklist to ensure Prescribing Information conforms with format items in regulations and guidances.
  • Include updated content of labeling in Structured Product Labeling (SPL) format (21 CFR 601.14(b)) in any response.
  • Provide a comprehensive safety update when responding to deficiencies.
  • The safety update must detail significant changes or findings in the safety profile and their relevance to clinically meaningful differences between the proposed biosimilar and the reference product.
  • Present new safety data from clinical studies for the proposed indication in the same format as the original BLA submission.
  • Present tabulations of new safety data combined with original BLA data.
  • Include tables comparing frequencies of adverse events in the original BLA with retabulated frequencies.

Deficiency summary

The application for interchangeability cannot be approved due to an unexpired exclusivity period for a prior interchangeable biological product. Additionally, a comprehensive safety update with detailed clinical data, worldwide experience, and translations is required upon resubmission, and labeling comments are reserved for future revisions.

Findings

Interchangeability Exclusivity Period Not Expired

Severity: critical

The application for a second or subsequent biological product under section 351(k)(6) cannot be determined interchangeable until the exclusivity period for the first interchangeable product has expired. A determination of interchangeability under 351(k)(4) cannot be made at this time.

Recommended response: Monitor the Purple Book for the expiration date of the first interchangeable product's exclusivity period and resubmit the application for interchangeability once eligible.

Cited: section 351(k) of the Public Health Service Act, section 351(k)(6), section 351(k)(4)

Incomplete Safety Update for Resubmission

Severity: major

The safety update for resubmission must include detailed changes in safety profile, case report forms and narrative summaries for deaths/adverse event discontinuations, narrative summaries for serious adverse events, updated exposure information, a summary of worldwide safety experience including immunogenicity and updated use estimates, and English translations of current approved foreign labeling.

Recommended response: Thoroughly compile and present all requested safety data, ensuring comprehensive updates on clinical study exposure, adverse events, worldwide experience, and provide all necessary translations. Integrate new data with original BLA data and compare frequencies.

Labeling Review Deferred; Future Revisions Expected

Severity: minor

FDA reserves comment on the proposed labeling until the application is otherwise adequate. Upon resubmission, updated content of labeling in Structured Product Labeling (SPL) format is required, and adherence to FDA labeling resources and guidances is encouraged.

Recommended response: Proactively review FDA's labeling resources, including the SRPI checklist and relevant guidances, and prepare updated labeling in SPL format for the eventual resubmission.

Cited: 21 CFR 601.14(b)

Regulatory context

Submission stage
final decision
Regulatory pathway
351(k) interchangeable biosimilar BLA

Impact

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

Strategic insights

The primary reason for the Complete Response is the unexpired interchangeability exclusivity period for a prior biological product. Additionally, the submission requires a comprehensive safety update with detailed clinical data, worldwide experience, and translations, along with future labeling revisions in SPL format.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 5%

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