FDA PreCheck pilot draws industry support as questions on execution remain

As the Food and Drug Administration’s PreCheck program prepares to launch its pilot phase, the agency is outlining a framework intended to accelerate U.S.-based pharmaceutical manufacturing by increasing regulatory predictability and facilitating the development of new facilities. However, questions remain around how consistently the model can function at scale, leaving industry stakeholders cautiously optimistic as the pilot progresses.

The PreCheck program — a response to President Donald Trump’s Executive Order 14293 aimed at expanding domestic production of critical medicines — was created to address facility readiness and manufacturing-related issues earlier in the development process, before a specific product application is submitted. The initiative is ultimately designed to reduce costly delays and late-stage regulatory surprises, including Complete Response Letters (CRLs) tied to manufacturing and facility issues.

The initiative takes a two-phase approach intended to “frontload” facility and chemistry, manufacturing, and controls (CMC) evaluation earlier in the development lifecycle. At a public meeting held by the FDA last September, industry representatives broadly supported the goals of the program, particularly its emphasis on earlier engagement between manufacturers and regulators and improving regulatory predictability around facility readiness.

While the key concepts behind PreCheck have largely been welcomed by the industry, uncertainty remains around how the FDA plans to operationalize and sustain the program over time, particularly as the initiative depends heavily on ongoing collaboration, coordination, and consistent feedback through lengthy facility development timelines.

The foundation of early engagement

The first phase of the PreCheck program — facility readiness — allows manufacturers to engage with the FDA early on before facilities become operational. According to the agency, Phase 1 is designed to provide early engagement and support for new pharmaceutical manufacturing facilities through two integrated components: the Pre-Operational Review (POR) and the Type V Drug Master File (DMF).

Under the framework, manufacturers would receive structured FDA feedback from initial facility design through pre-production activities during the POR process, while simultaneously building a facility-specific information repository through the Type V DMF.

The FDA has outlined several engagement mechanisms within the pilot framework, including dedicated agency points of contact, milestone-based check-ins, and pre-submission meetings. Interactions during the POR phase may occur through teleconferences, email correspondence, remote assessments, or site visits depending on the facility’s development timeline and the complexity of the issues under review.

Despite providing an outline of how PreCheck would interface with manufacturers, more specific questions remain around the cadence, scope, and consistency of those interactions as the pilot moves into implementation.

“Is there going to be a regular cadence of meetings? How often will those meetings take place? What exactly will be discussed in each of those meetings?” said Michael Varrone, partner in FDA Practice at Sidley Austin LLP and former senior counsel at the FDA. “Those are some of the details that need to be worked out.”

Beyond the mechanics of interactions, consistency will become increasingly important as the program expands across different facility types, manufacturing technologies, and product categories. Because the pilot is intended to support a broad range of manufacturing environments, maintaining consistent expectations across that diversity will be critical to preserving the predictability the program is designed to provide. 

“Managing that variability will be important because it goes into the aspects of predictability,” says Varrone. “I expect the FDA will develop internal processes like certain procedures and documentation templates, and issue escalation pathways and things like that, for both review and inspectional staff. So, it would facilitate coordination to keep decisions as consistent as possible.”

Because the program spans facility design reviews, compliance considerations, and eventual inspection readiness, PreCheck will require coordination across multiple FDA functions. 

“We’re talking about different groups within FDA that need to implement those,” Varrone said. “You’re dealing with the review division, you’re dealing with the Office of Compliance, and you’re also dealing with the Office of Inspections and Investigations. So, there’s coordination among different offices.”

Stakeholders at the public meeting last year viewed DMF V as one of the more strategically important aspects of the framework because it creates a reusable repository of facility information that can be referenced across future applications, while stressing the importance of reducing the maintenance burden of Type V DMFs. For manufacturers operating multi-product facilities, the approach could reduce repetitive facility reviews while helping promote consistency across applications.

Questions on scalability and agency capacity

As the FDA works to implement the pilot, a lingering question is whether the agency has the staffing and operational capacity needed to meet the expectations of the program, following broader workforce reductions across the agency over the past year.

Some questions surround the FDA’s ability to sustain ongoing interactions with manufacturers while simultaneously managing existing review obligations and user fee deadlines tied to programs such as PDUFA and BSUFA.

The concerns are underscored by broader workforce reductions across these divisions of the FDA. Since the first quarter of fiscal year 2025, both the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) have reported consistent quarter-over-quarter declining staffing levels. Comparing the start of each fiscal year, CDER began FY25 Q1 with 6,044 employees and landed at 4,951 employees at the start of FY26 Q1, while CBER staffing declined from 1,373 employees in FY25 Q1 to 1,149 in FY26 Q1.

“There’s definitely a possibility that the resources at the agency are going to be limited to support some of these interactions, particularly with CBER,” says Christopher Shilling, chief regulatory officer at Forge Biologics, who attended the FDA meeting last September. “CDER is such a large organization that may be able to run that, but we’ve seen such an impact on some of their workforce that it will be a challenge.”

Questions surrounding agency capacity become even more significant as stakeholders like Shilling wonder whether interactions with the industry could eventually extend beyond early-stage meetings and written correspondence into more hands-on facility engagement, as suggested by language in the pilot program.

As part of the Pre-Operational Review (POR), the FDA has stated that the process “may also include remote site assessment(s) and site visit(s) as appropriate.” However, there are questions on whether the agency has sufficient resources to support more extensive on-site involvement as the program expands.

“We on the manufacturers and developer side would love to have more interactions and engagement with the agency, but a constant pushback is they aren’t staffed for that, they don’t have that availability,” said Shilling. “One of the big discussion points at the meeting in September was whether we could move beyond just conversations and actually bring reviewers and inspectors into facilities earlier in the process. A lot of people think that would be a significant value-add for the industry, particularly before the inspections that typically occur during a BLA review.”

Measuring if PreCheck works

Moving into the second phase of the program — application submission — will ultimately provide some of the clearest indicators of whether the broader PreCheck model is functioning as intended.

According to Varrone, one of the most meaningful metrics will be whether the initiative successfully reduces manufacturing- and CMC-related deficiencies that later surface through CRLs related to NDA and BLA applications.

“But if demand outpaces its capacity, you’re just going to go back to seeing CMC-related issues being issued under Complete Response Letters,” Shilling said. “That’s a very measurable and meaningful metric that we are keeping our eye on.”

Varrone also said consistency in feedback throughout the process will serve as another important indicator of how effectively the program is functioning.

“Will the FDA be able to stick to their original recommendations and policies going forward when it gets closer to approval of the application?” Varrone added. “That’s also something that I’d be looking at.”

Another long-term indicator will be whether the program meaningfully reduces repetitive facility review work across multiple applications and enables earlier inspection readiness determinations within the review cycle, particularly for facilities utilizing reusable Type V DMFs. 

Beyond operational efficiency, the program’s value will also be judged by how well it supports emerging manufacturing technologies and product modalities. Shilling suggested that one measure of success will be whether the program proves useful for rapidly evolving fields such as cell and gene therapy, where manufacturing processes often advance alongside clinical development.

“The manufacturing of biologic products has consistently been a challenge,” Shilling said. “We see a lot in cell and gene therapy where the clinical outcomes quickly outpace the development on the manufacturing side.” 

He added earlier FDA engagement could help manufacturers align more quickly on evolving production approaches and reduce uncertainty as programs move toward commercialization.

What about CDMOs?

At the same time, questions remain about how applicable the current PreCheck framework will ultimately be for pure-play contract development and manufacturing organizations (CDMOs). Several aspects of the program appear geared toward manufacturers developing products internally, while longstanding challenges unique to outsourced manufacturing remain unresolved.

A longstanding challenge for CDMOs is the disconnect between facility construction and regulatory review. Manufacturers frequently invest in new capacity before securing programs linked to an NDA or BLA, while FDA inspections typically occur only in connection with a specific product application. That can leave some sites waiting extended periods before receiving regulatory scrutiny.

Shilling noted that Forge has already invested heavily in regulatory capabilities and maintains dedicated personnel focused on FDA engagement, but for smaller manufacturers and newer CDMOs resource demands associated with ongoing FDA engagement could prove more challenging. Stakeholders say it remains unclear whether the pilot’s eventual participant selection process will meaningfully accommodate a broad range of CDMO-operated facilities.

“There are CMOs out there that potentially have current space in their facility that could be doing this, but that wouldn’t necessarily apply because the FDA wants a new facility, they don’t want expansion, or even tech transfer,” Varrone said.

Stakeholders say the pilot cohort may provide the first indication of how broadly PreCheck can be applied across different manufacturing models and whether the framework can ultimately accommodate both innovator companies and outsourced manufacturing partners.