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 Therakind Limited regarding New Drug Application (NDA) 212479 for Jylamvo (methotrexate) oral solution. The FDA has determined that the application cannot be approved in its present form due to product quality issues related to a manufacturing facility and deficiencies in labeling and safety update submissions.

Key points

Satisfactorily resolve objectionable conditions at the manufacturing facility (e.g., preapproval inspection and/or adequate facility responses).
Revise labeling using the Selected Requirements for Prescribing Information (SRPI) checklist to conform with format items in regulations and guidances.
Submit updated content of labeling in structured product labeling (SPL) format as described at FDA.gov.
Submit the November 18, 2021 draft carton and container labeling based on the FDA's proposed revisions dated November 12, 2021.
Include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b) with the resubmission.
Describe in detail any significant changes or findings in the safety profile within the safety update.
Present new safety data from studies/clinical trials for the proposed indication using the same format as in the original submission.
Present tabulations of the new safety data combined with the original application data.

Cited reasons

Unsatisfactory Manufacturing Facility Conditions
Required Carton and Container Labeling Revisions
Comprehensive Safety Update Deficiencies
The application cannot be approved in its present form due to objectionable conditions at the manufacturing facility, required revisions to carton and container labeling, and the need for a comprehensive safety update including clinical and nonclinical data.

Recommended actions

Satisfactorily resolve objectionable conditions at the manufacturing facility (e.g., preapproval inspection and/or adequate facility responses).
Revise labeling using the Selected Requirements for Prescribing Information (SRPI) checklist to conform with format items in regulations and guidances.
Submit updated content of labeling in structured product labeling (SPL) format as described at FDA.gov.
Submit the November 18, 2021 draft carton and container labeling based on the FDA's proposed revisions dated November 12, 2021.
Include a safety update as described at 21 CFR 314.50(d)(5)(vi)(b) with the resubmission.
Describe in detail any significant changes or findings in the safety profile within the safety update.
Present new safety data from studies/clinical trials for the proposed indication using the same format as in the original submission.
Present tabulations of the new safety data combined with the original application data.

Deficiency summary

The application cannot be approved in its present form due to objectionable conditions at the manufacturing facility, required revisions to carton and container labeling, and the need for a comprehensive safety update including clinical and nonclinical data.

Findings

Unsatisfactory Manufacturing Facility Conditions

Severity: critical

During a review of records requested under section 704(a)(4) of the Federal Food, Drug, and Cosmetic Act, the FDA noted objectionable conditions at the manufacturing facility. Satisfactory resolution of these conditions (e.g., preapproval inspection and/or adequate facility responses) is required before approval.

Recommended response: Address all objectionable conditions at the manufacturing facility, potentially requiring a preapproval inspection or submission of adequate facility responses to the agency.

Cited: section 704(a)(4) of the Federal Food, Drug, and Cosmetic Act

Required Carton and Container Labeling Revisions

Severity: major

Submit the draft carton and container labeling based on FDA's proposed revisions dated November 12, 2021. This includes updated content of labeling in structured product labeling (SPL) format.

Recommended response: Revise carton and container labeling according to FDA's proposed revisions and resubmit in SPL format.

Cited: 21 CFR 314.50(l)(1)(i)

Comprehensive Safety Update Deficiencies

Severity: major

A comprehensive safety update is required as described at 21 CFR 314.50(d)(5)(vi)(b). This includes detailing significant changes in the safety profile, presenting new and combined safety data from all nonclinical and clinical studies, retabulating reasons for premature trial discontinuation, providing case report forms and narrative summaries for deaths and serious adverse events, updating exposure information, summarizing worldwide safety experience, and providing English translations of current approved foreign labeling.

Recommended response: Compile a comprehensive safety update, including all requested data and analyses, adhering strictly to 21 CFR 314.50(d)(5)(vi)(b) and the specific requests outlined in the letter.

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

Regulatory context

Submission stage: final decision
Regulatory pathway: 505(b)(2) New Drug Application (NDA)

Impact

Impact score: 0.95
Estimated delay: 545 days
Estimated rework cost: $0
Subsequent action: resubmission

Strategic insights

Approval is withheld due to critical manufacturing facility issues, required revisions to carton and container labeling, and the need for a comprehensive update of safety data from all studies.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 5%

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