Approval Letter Other (Nov 13, 2025)

Summary

The FDA has issued a provisional determination that Pyzchiva (ustekinumab-ttwe) is interchangeable with Stelara (ustekinumab) for various formulations, but cannot approve the applications (BLA 761373/Original 2 and BLA 761425/Original 2) due to an unexpired period of exclusivity for the first interchangeable biosimilar biological products. The letter outlines the steps required for future approval once the exclusivity period expires, including submitting an amendment with updated information and fulfilling postmarketing commitments.

Key points

• Specify the BLA number and Original number for all future submissions to BLA 761373 and BLA 761425.
• Submit an amendment no more than six months prior to the date the application is believed to be eligible for approval, clearly identified as 'REQUEST FOR APPROVAL'.
• The amendment must provide the legal/regulatory basis for the request for approval and include a copy of relevant supporting documentation.
• The amendment must include a safety update.
• The amendment must identify any changes in the application, such as updated labeling, chemistry, manufacturing, and controls data, and risk evaluation and mitigation strategy (REMS), or clearly state if there are no changes.
• Fulfill postmarketing commitment 4651-1 to develop an endotoxin testing method for the 5 mg/mL drug product that mitigates the low endotoxin recovery (LER) effect, submit method qualification results with 3 lots, and provide results of a LER study performed with the updated method using 3 lots of drug product, with a final report submission by January 2026.
• Submit clinical protocols to IND 136959 for this product.
• Submit nonclinical and chemistry, manufacturing, and controls protocols and all postmarketing final reports to the respective BLA.

Cited reasons

• Agency deficiencies
• The agency has provisionally determined that the 351(k) application meets interchangeability criteria and has not identified any deficiencies that would justify a complete response action. However, final approval cannot be granted at this time due to an unexpired period of first interchangeable exclusivity. The letter also reminds the applicant of a postmarketing commitment related to endotoxin testing.

Recommended actions

• Specify the BLA number and Original number for all future submissions to BLA 761373 and BLA 761425.
• Submit an amendment no more than six months prior to the date the application is believed to be eligible for approval, clearly identified as 'REQUEST FOR APPROVAL'.
• The amendment must provide the legal/regulatory basis for the request for approval and include a copy of relevant supporting documentation.
• The amendment must include a safety update.
• The amendment must identify any changes in the application, such as updated labeling, chemistry, manufacturing, and controls data, and risk evaluation and mitigation strategy (REMS), or clearly state if there are no changes.
• Fulfill postmarketing commitment 4651-1 to develop an endotoxin testing method for the 5 mg/mL drug product that mitigates the low endotoxin recovery (LER) effect, submit method qualification results with 3 lots, and provide results of a LER study performed with the updated method using 3 lots of drug product, with a final report submission by January 2026.
• Submit clinical protocols to IND 136959 for this product.
• Submit nonclinical and chemistry, manufacturing, and controls protocols and all postmarketing final reports to the respective BLA.

Deficiency summary

The agency has provisionally determined that the 351(k) application meets interchangeability criteria and has not identified any deficiencies that would justify a complete response action. However, final approval cannot be granted at this time due to an unexpired period of first interchangeable exclusivity. The letter also reminds the applicant of a postmarketing commitment related to endotoxin testing.

Findings

Regulatory context

Submission stage

final decision

Regulatory pathway

Interchangeable Biosimilar (PHS Act sections 351(i) and 351(k))

Impact

Impact score

0.75

Estimated delay

180 days

Estimated rework cost

$0

Subsequent action

resubmission

Strategic insights

Provisional determination of interchangeability for Pyzchiva (ustekinumab-ttwe) has been made, indicating the application meets criteria. However, final approval is pending the expiration of an unexpired first interchangeable exclusivity period, which is an external regulatory barrier, not a deficiency in the application itself. A reminder for an existing postmarketing commitment regarding endotoxin testing is also included.

Regulatory change impact: Pending sponsor mitigation plan

Approval likelihood after response: 25%