Major Pharma Companies Push FDA to Modernize Manufacturing Regulations to Support US Drug Production
Key Insights
Leading pharmaceutical companies including AbbVie (search), Amgen, and Eli Lilly are calling on the FDA to update decades-old post-approval manufacturing change regulations that currently hinder domestic drug production.
Industry executives argue that the current "one-size-fits-all" regulatory framework for biologics is overly restrictive and creates unnecessary delays for establishing new US manufacturing facilities.
Companies are also pushing for the FDA to decouple pre-approval inspections from drug approval applications to reduce regulatory burdens and prevent complete response letters caused by inspection timing issues.
Leading pharmaceutical companies are mounting a coordinated effort to convince the FDA to overhaul manufacturing regulations that they say are blocking efforts to bring drug production back to the United States. During recent consultations about the FDA's PreCheck program, executives from AbbVie (search), Amgen, Eli Lilly, Johnson & Johnson, and Merck (search) identified regulatory barriers as major obstacles to establishing domestic manufacturing facilities.
Post-Approval Changes Create Manufacturing Bottlenecks
Simon Hotchin, vice president of regulatory affairs at Amgen, told the FDA that the lack of an updated framework for post-approval management of biologics represents "the most significant hurdle to establishing domestic manufacturing facilities." The current regulatory approach treats all biologics with the same level of scrutiny, despite significant advances in manufacturing technology for established products.
"There are some common modalities, things like monoclonal antibodies (search), 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 explained during the PreCheck meeting.
Julia Edwards, senior vice president of global regulatory affairs at Eli Lilly, echoed these concerns, describing the current post-approval submission categories as "relatively inflexible" and "extremely restrictive." In written feedback to the FDA, Amgen argued that biologics-specific requirements create unnecessary delays to bringing supply and innovation to the U.S.
Kevin Fitzpatrick, senior vice president for quality assurance at AbbVie (search), pointed to the age of the FDA's scale-up and post-approval changes (SUPAC) guidance documents as evidence for the need for modernization. These guidance documents were published in the late 1990s and have not been substantially updated since.
Inspection Timing Creates Approval Delays
The industry is also pushing for fundamental changes to how the FDA conducts pre-approval inspections. Currently, manufacturing facilities undergo FDA inspection when they are used to make medicines submitted for approval, creating timing pressures that can lead to complete response letters (CRLs).
Fitzpatrick cited a specific example of these challenges: "We brought on a new U.S. manufacturing facility two years ago and the PAI for that facility was weeks prior to our PDUFA date. At that point, we're under a lot of pressure. Any questions or comments or observations that come up [during the PAI] are very difficult to resolve in that time frame."
Miguelina Matthews, head of quality intelligence at Sanofi, told the FDA that the unpredictability of inspections is a factor that can lead to CRLs. The industry's proposed solution is to decouple inspections from drug approval applications, allowing the FDA to check facility compliance before authorization applications are filed.
Contract Manufacturing Faces Unique Challenges
Contract manufacturers face particular difficulties with the current inspection system. Karen Wolfrom, global head of regulatory affairs at Lonza, described the "dance" required to align manufacturing runs with FDA inspections when facilities produce different products for different clients.
"In the meantime, we have other important medicines that are coming into the suite. Do we delay them going into the suite so that we can keep it open and idle to do an inspection for this particular product?" Wolfrom asked during the September meeting. "It's terrible to have a submission delayed because we have to be in active manufacturing at the time."
Christopher Shilling, chief regulatory officer at gene therapy manufacturer Forge Biologics (search), noted that the alignment challenge is particularly acute for rare disease treatments, where companies may only need a few batches, requiring "jumping through hoops" to coordinate inspections with manufacturing schedules.
Industry Proposes Risk-Based Approach
Companies are advocating for a more sophisticated, risk-based regulatory approach. Shilling suggested the FDA could "risk assess some of these facility additions, facility changes or copy-and-paste type of facility construction" using historical evidence and prior inspection records to determine whether new inspections are warranted.
The Alliance for Regenerative Medicine has proposed phased or modular inspections, where different parts of a facility would be inspected as they become ready rather than waiting to inspect the entire facility at once. Johnson & Johnson has made similar proposals in its written feedback to the FDA.
Generic Drug Industry Seeks Coordination
The Association for Accessible Medicines, representing generic and biosimilar manufacturers, supports efforts to accelerate regulatory processes for post-approval changes. The organization highlighted the burden of undergoing inspections by both FDA and state-level authorities, suggesting that cooperation between agencies could reduce redundancy.
The group recommended extending SUPAC guidance beyond its current scope of immediate-release, modified-release and nonsterile semisolid dosage forms to "promote consistency and facilitate post-approval flexibility across a wider range of products." Currently, manufacturers of products outside SUPAC's scope, such as sterile injectables, must rely on broader post-approval changes guidance that often requires prior approval supplements, which can take months for FDA review.