Through the proposal, the FDA could clear barriers to distributed manufacturing approaches intended to enhance emergency preparedness and supply chain resilience.
The FDA has proposed streamlining regulatory requirements for drugmakers operating “hub-and-spoke” manufacturing models.
Traditionally, establishments registered with the FDA reside at one location and are overseen by a quality unit based at the site. Distributed manufacturing represents a shift away from that centralized model. In a distributed system, the team overseeing operations is based at a “hub” establishment and implements a unified pharmaceutical quality system across multiple “spoke” units in different locations.
Current regulations require manufacturers to register the hub and each spoke separately, even though they operate as one establishment. The requirement is “unnecessarily burdensome for industry” and could impede the adoption and implementation of distributed manufacturing, the FDA said.
Seeking to avoid that outcome, the agency on July 10 shared a proposed rule designed to create a streamlined registration pathway for distributed manufacturing. If finalized, the rule will allow biopharma companies to register distributed manufacturing networks as single establishments. The FDA will treat the addition or removal of spoke units—or the relocation of mobile production sites—as expedited registration updates.
The proposal applies to distributed manufacturing networks operating as a single legal entity. The FDA considered whether to open the streamlined registration pathway to companies that outsource the production of a drug to multiple third-party sites. However, the lack of one team with direct authority over the quality system at each site led the FDA to exclude the third-party model from its proposed rule.
Finalizing the proposal could address concerns that have emerged in recent years. In 2021, the National Academies of Sciences, Engineering, and Medicine predicted that the FDA was “likely to see substantial innovations in integrated, flexible and distributed manufacturing” in the next 5 to 10 years, adding that regulatory challenges could slow the deployment and use of highly portable manufacturing units.
In 2023, Amgen manufacturing leaders questioned the necessity and sustainability of imposing full data requirements on multiple sites producing the same or similar drugs. The rules are “increasingly arduous” in the context of distributed manufacturing and stop companies from using “robust platform data” to get relief from regulatory requirements, the leaders said.
The FDA envisions its proposed rule allowing companies to combine and collectively evaluate data from multiple sites to develop a validation strategy for a newly established manufacturing process. The data could reduce the extent of validation activities needed when a new site is added to the network, the FDA said.
That more agile validation strategy could be especially important for companies commissioning mobile units to make products during emergencies, like the mobile modular manufacturing unit BioNTech developed to produce its COVID-19 vaccine during the pandemic.
The proposed rule also affects registration and listing requirements for foreign establishments that make drugs and ingredients for distribution to other overseas plants. Currently, such establishments might not be registered with the FDA, limiting the agency’s oversight of drugs and ingredients that may ultimately reach U.S. patients. The agency wants the establishments to register and list the drugs they make.
The proposed rule is open for comment until Sept. 11.
