Understanding Regulatory Requirements for Autoinjector Shelf Life Extensions
By Rhizome Team
For pharmaceutical companies managing combination products like autoinjectors, determining the appropriate regulatory pathway for shelf life extensions can significantly impact product lifecycle management. While regulatory professionals might assume a specific submission type is required, the FDA's approach to device-drug combination products has evolved over time, creating potential ambiguity.
The question of whether a Prior Approval Supplement (PAS) or a Changes Being Effected (CBE) pathway is appropriate for extending autoinjector shelf life has meaningful implications for timeline planning, resource allocation, and market strategy. With PAS reviews typically taking 4-6 months versus the immediate or 30-day implementation timeline for CBE submissions, understanding the correct regulatory approach can save considerable time and resources.
Here we ask Rhizome to provide clarity on the required submission type for autoinjector shelf life extensions.
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What type of BLA supplement has been required by CDER in the last five years to extend the labeled shelf life or expiry of an autoinjector?
Answer
Based on the review of FDA public datasets from the last five years, CDER has required a Prior Approval Supplement (PAS) to extend the labeled shelf life or expiry of an autoinjector.
Key findings:
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Prior Approval Supplement (PAS) is the standard pathway:
- For combination products like autoinjectors, when a sponsor seeks to extend the labeled shelf life or expiry, CDER requires submission of a Prior Approval Supplement. This is evident in multiple recent approvals for autoinjector presentations, where shelf life extensions or new expiry periods are supported by updated stability data and reviewed as PAS submissions.
- For example, the supplement approval letter for BIMZELX (bimekizumab-bkzx) explicitly states:
"This Prior Approval supplemental biologics license application provides for a new primary container, the 2mL prefilled syringe, which is assembled into two new 2mL device presentations, a single-dose prefilled syringe and a single-dose prefilled autoinjector."
This supplement, which includes new device presentations and associated shelf life, was reviewed and approved as a PAS 30.
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Requirement for updated stability data and post-approval commitments:
- CDER expects sponsors to submit updated real-time and/or accelerated stability data for the autoinjector presentation as part of the PAS. The data must demonstrate that the device maintains its essential performance requirements (EPRs) throughout the proposed extended shelf life 118265663.
- For example, in the case of IDACIO (adalimumab-aacf), the FDA required the sponsor to update post-approval stability protocols and commitments for both the prefilled syringe and autoinjector presentations to support shelf life claims 118.
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Annual Reportable Changes are not sufficient for shelf life extension:
- While some changes to packaging components or minor manufacturing updates may be handled as annual reportable changes, shelf life extensions for combination products like autoinjectors require a PAS due to the need for comprehensive review of new stability data and potential impact on product performance 13.
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Post-approval stability protocols are often updated as part of the PAS:
Summary Table:
| Product (Year) | Supplement Type | Purpose/Change | Source |
|---|---|---|---|
| BIMZELX (2024) | PAS | New autoinjector presentation, shelf life extension | 30 |
| IDACIO (2023/2024) | PAS | Shelf life extension, updated stability protocol | 118 |
| ZEGALOGUE (2021) | PAS | Shelf life justification for autoinjector | 5663 |
| ENTYVIO (2024) | PAS | 18-month shelf life for autoinjector | 4857 |
Conclusion:
- A Prior Approval Supplement (PAS) is required by CDER to extend the labeled shelf life or expiry of an autoinjector. This supplement must include updated real-time and/or accelerated stability data demonstrating that the autoinjector maintains its essential performance requirements throughout the proposed new shelf life. The PAS also typically updates post-approval stability protocols and commitments for ongoing monitoring.