The U.S. Food and Drug Administration has published a proposed rule that would create a new registration pathway for drug manufacturers using a hub-and-spoke model, while also aligning foreign establishment registration and listing requirements with changes made by the PREVENT Pandemics Act. The rule was published in the Federal Register on July 13, 2026 (Docket No. FDA-2025-N-6075, RIN 0910-AI94).
For drug manufacturers exploring decentralized or advanced manufacturing strategies, and for foreign establishments involved anywhere in a U.S.-bound drug supply chain, the proposal introduces changes that could affect how facilities register and list with FDA.
What the Proposed Rule Covers
The rule has two distinct parts. The first addresses distributed manufacturing establishments (DMEs), which use a hub-and-spoke model: manufacturing activities take place at one or more “distributed manufacturing units” (DMUs) overseen by a single quality unit at a central “hub” with a unified pharmaceutical quality system (UPQS).
Currently, each DMU and the hub must register separately, even though they function as one establishment. The proposed rule would let a DME register as a single establishment, treating the addition, removal, or relocation of a DMU as an expedited update rather than a new registration.
The second part updates registration and listing requirements for foreign establishments, consistent with section 2511 of the PREVENT Pandemics Act. It would clarify that foreign establishments manufacturing a drug, including an active pharmaceutical ingredient (API), must register and list that drug even if it’s only distributed to another foreign establishment before being imported into the United States.
FDA notes that nearly 60% of registered drug establishments are now located outside the U.S., and that gaps in foreign registration have limited its supply chain visibility.
Registration Details and Timelines
For DMEs, initial registration would be required no later than 5 calendar days after the first domestic DMU begins manufacturing for commercial distribution, or before a drug from a foreign DMU is imported or offered for import, whichever comes first. Relocating a mobile DMU would require advance notice to FDA, 30 calendar days for moves within or into the United States, and 120 calendar days for moves to or within a foreign country.
Comment Period and Timeline
The proposed rule has a 60-day comment period, closing September 11, 2026. FDA has proposed an effective date of 30 calendar days after a final rule is published, and has not indicated a target date for finalization.
What This Means for Your Business
Drug manufacturers, considering or currently using decentralized manufacturing strategies, should review whether their operations would meet the proposed definition of a DME, particularly the requirements around equivalent design and operations across units, and prior preapproval inspection tied to a decentralized manufacturing strategy.
Notably, the proposed rule would also permit a DME to manufacture certain OTC monograph drugs alongside application-based drugs, provided the OTC product shares the same profile class as an application-based drug already made at that DME. This could give companies manufacturing both prescription and OTC products under one decentralized strategy a path to consolidate registration across their full product line.
Foreign establishments involved in manufacturing APIs or intermediates destined for the U.S. market, even indirectly through another foreign facility, should assess whether the clarified registration and listing requirements would newly apply to their operations. Finished product manufacturers relying on foreign API suppliers should also confirm that those suppliers understand their registration obligations, since an unregistered upstream establishment can result in a finished product being deemed misbranded.
Frequently Asked Questions
Does this rule apply to all drug manufacturers?
No. The DME registration pathway is optional and applies only to establishments using a decentralized, hub-and-spoke manufacturing strategy tied to an approved application. The foreign establishment provisions apply more broadly to any foreign establishment manufacturing a drug that is ultimately imported or offered for import into the United States.
Does registering as a DME change CGMP requirements?
The proposed rule addresses registration and listing, not CGMP requirements directly. FDA has indicated it intends to issue separate guidance addressing CGMP considerations specific to distributed manufacturing.
What happens if a foreign establishment does not register under the clarified requirements?
A drug manufactured, prepared, or processed at an unregistered establishment, including one that only distributes to another foreign establishment before U.S. import, would be considered misbranded under section 502(o) of the FD&C Act.
Key Takeaways
- FDA’s proposed rule would let distributed manufacturing establishments (DMEs) register as a single establishment instead of registering the hub and each unit separately.
- The rule also clarifies that foreign establishments manufacturing drugs or APIs must register and list, even when distributing only to another foreign establishment before U.S. import.
- DMEs could also manufacture certain OTC monograph drugs under the same registration, provided the product shares a profile class with an application-based drug made at that establishment.
- The comment period closes September 11, 2026.
- Manufacturers using or considering decentralized manufacturing strategies, and foreign API suppliers in a U.S.-bound supply chain, should assess how the proposed definitions and timelines would apply to their operations.
Next Steps
Whether your company is exploring a distributed manufacturing strategy, managing a foreign API supply chain, or simply confirming your current registration status is airtight, understanding how this proposed rule applies to your specific operations now can prevent costly gaps later. Quality Smart Solutions supports drug manufacturers and foreign establishments through registration strategy, regulatory assessments, and ongoing compliance support with FDA drug establishment requirements.
Reach out to our team through our contact page to discuss how this proposed rule may affect your registration status or visit our U.S. Drug Registration services page to learn how we can support your FDA drug establishment registration and listing needs.
