Drugmakers told the FDA that inflexible post-approval change requirements are among the top regulatory barriers to the reshoring of pharmaceutical manufacturing.
Manufacturing and regulatory leaders at companies including AbbVie, Amgen and Eli Lilly have flagged the FDA’s approach to post-approval changes to the manufacturing process as a barrier to establishing new pharmaceutical production facilities in the U.S.
Leading drugmakers used an in-person meeting about the FDA’s PreCheck program and an associated call for written feedback to push for change in two main areas. One entreaty was to decouple pre-approval inspections from applications for marketing authorization.
The other request was for the FDA to revise its approach to post-approval changes, which include the relocation of production from foreign to domestic facilities. Doing so would reduce regulatory burdens and accelerate reshoring, executives said.
Simon Hotchin, vice president of regulatory affairs at Amgen, told the FDA at the PreCheck meeting that the lack of an updated framework for the post-approval management of biologics is the most significant hurdle to establishing domestic manufacturing facilities. Compared to small molecules, biologics face additional requirements for manufacturing changes due to their complexity. Hotchin argued that certain types of biologics are now mature, established technologies that can be transferred between production sites reliably.
“There are some common modalities, things like monoclonal antibodies, that are very well understood at this point. But the current framework for post-approval changes is somewhat one-size-fits-all, across biologics in particular,” Hotchin said.
Julia Edwards, senior vice president of global regulatory affairs, CMC and devices at Eli Lilly, agreed with Hotchin, calling the current post-approval submission categories “relatively inflexible.” Edwards said the existing requirements are “extremely restrictive.”
In written feedback, Amgen similarly told the FDA that the biologics-specific requirements create unnecessary delays to bringing supply and innovation to the U.S. Amgen wants the FDA to move away from a regulatory framework that treats all biologics as though they have the same level of risk.
Kevin Fitzpatrick, senior vice president for quality assurance at AbbVie, told the FDA he strongly supports modernizing the post-approval process. Fitzpatrick pointed to the age of the FDA’s scale-up and post-approval changes (SUPAC) guidance documents, which the agency published in the late 1990s, to make the case for modernization.
Christopher Shilling, chief regulatory officer at gene therapy manufacturer Forge Biologics, left the meeting with ideas about how the FDA can address the challenges facing companies.
“Is there a scenario where the agency would be able to risk assess some of these facility additions, facility changes or copy-and-paste type of facility construction?” Shilling told BioSpace. “There may already be enough historical evidence, prior inspection records and experience with the facilities to say those sorts of changes may not warrant an inspection.”
Shilling said the approach could reduce regulatory burdens on drug companies and allow the FDA to direct resources to other priority areas. The proposal is in line with calls made at the PreCheck meeting.
The Off-Patent Perspective
Off-patent drugmakers joined the call for the FDA to rethink its post-approval change requirements. A spokesperson for the Association for Accessible Medicines (AAM) told BioSpace that the generics and biosimilars industry group supports efforts to accelerate regulatory processes for post-approval changes.
To illustrate the potential to improve the process, the spokesperson described a hypothetical example of a company that wants to move production of a drug from Canada to the U.S. Currently, moving drug production between sites is quite expensive and time-consuming, in part because of FDA requirements. The AAM spokesperson sees opportunities to accelerate transfers between facilities that are in good standing with regulators.
AAM fleshed out the idea in written feedback, calling for the agency to consider extending the principles outlined in a 2025 guidance document to post-approval changes. The guidance sets out alternative tools, such as remote assessments and reliance on recent inspectional history, for evaluating manufacturing facilities. AAM said extending the guidance to post-approval changes could support site transfers.
The industry group also recommended broadening the scope of SUPAC guidance. AAM said extending the scope beyond immediate-release, modified-release and nonsterile semisolid dosage forms would “promote consistency and facilitate post-approval flexibility across a wider range of products.”
Manufacturers of immediate-release formulations can read the relevant SUPAC guidance to check, for example, what documentation is needed to support the relocation of production to a different campus. The guidance states companies can file a changes-being-effected (CBE) supplement and specifies the chemistry and dissolution documentation that is needed. Changes covered by CBE-30 notifications must be disclosed to the FDA at least 30 days before the product is distributed.
By contrast, manufacturers of dosage forms outside of the scope of SUPAC, such as sterile injectables, rely on FDA’s broader post-approval changes guidance. Under this guidance, many site changes require companies to file prior approval supplements (PAS). The FDA can take months to review PAS.
The FDA has yet to respond publicly to the industry feedback beyond the comments its employees made at the PreCheck meeting, which was focused on collecting rather than providing information. Reshoring has remained high on the agenda in the interim, with the Trump administration ending 2025 with nine more drug pricing deals that include provisions related to domestic manufacturing and supply chain resilience. Last week, Johnson & Johnson announced its own deal with the White House, announcing that the company would build two new facilities, in North Carolina and Pennsylvania, as part of the $55 billion investment in U.S. manufacturing announced last year.
