Why FDA PreCheck is a game-changer for small & mid-sized pharma — and how these companies should lean in

On August 7, 2025 the U.S. Food and Drug Administration announced FDA PreCheck, a voluntary initiative aimed at strengthening the domestic pharmaceutical manufacturing base by streamlining regulatory interactions during facility planning, construction and early manufacturing stages. The program is explicitly designed to give manufacturers earlier, more frequent, and better-targeted engagement with the agency — using a two-phase approach that covers both facility readiness and early chemistry/manufacturing/controls (CMC) feedback. That combination — earlier agency feedback plus a structured pathway for pre-application engagement — is precisely the kind of regulatory innovation that can radically lower the cost, risk and timeline hurdles that typically hit small and mid-sized drug companies the hardest. Below we explore why PreCheck matters for smaller companies, how it shifts the competitive landscape, practical ways to get ready, and why investors and policy makers should welcome it. I’ll draw lessons from prior FDA “pre-cert” style pilots (notably in digital health), the new PreCheck design, and pragmatic realities in pharma manufacturing.

The problem small and mid-sized companies face today:  Small and mid-sized biotechs and specialty pharma firms routinely shoulder the steepest portion of the regulatory and manufacturing risk curve:

• Capital intensity + uncertainty. Building or qualifying a manufacturing process and facility can consume tens of millions of dollars of non-dilutive and dilutive capital. Delays or repeated questions from regulators magnify that burn and shorten the company’s runway.
• Asymmetric access to regulators. Larger firms can dedicate regulatory affairs teams and in-house manufacturing experts who have long relationships with FDA reviewers. Smaller firms usually don’t have that bandwidth, leading to “surprise” requests at submission time that force expensive re-work or additional studies.
• Tech transfer and scale-up pain. Taking a process from lab scale or a contract manufacturer to a dedicated facility frequently uncovers manufacturing, formulation, or analytical issues that require time-consuming fixes — again, harder to absorb for smaller sponsors.
• Investor nervousness. Investors price in regulatory and CMC uncertainty as valuation discounts. Each unknown item at filing is a negotiation point that can derail fundraising or acquisition deals.

That set of realities is why any program that reduces uncertainty, accelerates meaningful early dialogue with FDA, and provides a predictable pathway for facility readiness quickly becomes high value for smaller enterprises.

What FDA PreCheck actually does — the mechanics that matter: FDA PreCheck (as described in the agency’s August 7 announcement) uses a two-phase model:

1. Facility Readiness Phase — structured, earlier communication touching on facility design, construction, and pre-production planning. That gives firms the chance to spot regulatory pitfalls before they are built into the plant or process. 
2. CMC / Pre-application Phase — earlier, focused interactions on chemistry, manufacturing and controls so that a company can refine testing strategies, control strategies, and regulatory approaches well before submission. The goal is to reduce late-stage CMC requests and shorten review uncertainty. 

Those two elements — front-loaded FDA engagement + structured pre-application CMC dialogue — are the concrete features that make PreCheck meaningfully different from the typical “ask at submission and respond” dynamic.

Five core benefits for small and mid-sized companies

1. Lowered development and capital risk through earlier detection of problems: Early engagement reduces the chance that a design choice (ventilation, containment, segregation, utilities, or control strategy) will trigger a major regulatory question later. That single change can prevent months of rework and tens of millions in unplanned capital expenditure — exactly the kind of financial shock that kills small programs. The PreCheck facility readiness track is explicitly aimed at this kind of upstream risk reduction.  Practical impact: fewer stop-work orders, fewer expensive redesigns, and a smoother validation timeline — giving management predictable burn and a clearer path to product-launch milestones.
2. Faster commercialization timelines from reduced application-stage back-and-forth: When CMC conversations happen earlier, companies can build the right datasets into their submissions from the start. That reduces cycles of information requests and supplements that add months to review. For small firms, every month saved can be decisive: it cuts financing needs, speeds revenue realization, and preserves valuation. FDA’s stated goal of providing early feedback on manufacturing and quality control processes directly targets that bottleneck. Practical impact: shorter time-to-market, which translates to earlier cash flows and improved investor confidence.
3. Improved capital efficiency — better use of scarce funds: Capital allocation decisions in small companies are zero-sum: a dollar spent fixing a manufacturing issue is a dollar not spent on R&D, clinical development, or commercial readiness. By surfacing and resolving manufacturing and regulatory friction points earlier, PreCheck helps companies allocate capital more efficiently and reduce “surprise spend.” That benefit compounds when a firm scales from pilot to commercial production. Practical impact: less dilution, improved runways, and a higher probability of achieving value inflection points before the next financing.
4. Stronger negotiating position with CDMOs and partners: When a smaller sponsor brings clearer regulatory expectations and a vetted facility/CMC plan to the table, it negotiates from strength. Contract manufacturers and engineering firms prefer clients who understand requirements and have engaged regulators: projects run more predictably, timelines are tighter, and contingency costs fall. PreCheck gives smaller firms the documentation and regulatory context to secure better terms, priority slots, and clearer tech-transfer timelines. Practical impact: better CDMO pricing and scheduling, fewer change orders, and faster scale-up.
5. An opportunity to build a sustained quality culture (and long-term competitiveness): Pre-certification or pre-engagement models tend to favor organizations that demonstrate robust quality systems and a commitment to continual improvement. As the FDA’s prior experience with the digital health Pre-Cert pilot showed, the agency rewards organizational excellence and the ability to monitor real-world performance. Smaller firms that internalize these quality practices early position themselves not only to benefit from PreCheck’s immediate advantages but also to be treated as credible long-term suppliers or partners. Practical impact: stronger operational performance, fewer post-approval compliance headaches, and an improved reputation with regulators and partners.

Why PreCheck is especially well-suited to benefit small biotechs (versus incumbent big pharma): 

• High marginal value of predictability. Big pharma has diversified portfolios and organizational slack; a delay in one program is survivable. For small biotech, unpredictability is existential. PreCheck’s focus on reducing unknowns is therefore disproportionately valuable to smaller players.
• Scale of impact. The same 3-month reduction in time-to-market delivers much higher ROI for a company that depends on a single program for survival.
• Leveling the playing field. Early engagement democratizes access to FDA expertise. When smaller teams can get structured, documented FDA input on design and CMC, they can avoid the advantage typically held by players with long regulatory relationships.
• Encourages onshore capacity growth. Many small biotech s are now considering onshore manufacturing to avoid supply chain risk. PreCheck reduces first-mover risk for these investments by making feedback predictable during plant design and ramp stages. The agency explicitly framed PreCheck as part of a strategy to boost domestic drug manufacturing. 

Lessons from the FDA’s earlier “pre-cert” pilots (digital health) — what to emulate and what to avoid:  FDA’s Software Precertification (Pre-Cert) pilot — focused on digital health products — provides a helpful precedent. The pilot showed that pre-qualifying organizations on the basis of quality culture and real-world performance can reduce per-product review burden and accelerate market entry. But it also revealed pitfalls: measuring organizational quality objectively is hard, and one-size-fits-all metrics can miss device- or product-specific risks. 

What small biotechs should emulate from digital health lessons:

1. Invest in measurable quality metrics and data systems early (deviation rates, CAPA performance, batch disposition metrics).
2. Build capabilities to monitor post-production performance and close the loop — regulators reward demonstrable real-world surveillance.
3. Treat the engagement as an operational accelerator, not merely a regulatory checkbox.

What to avoid: Over-relying on “status” (i.e., assuming PreCheck enrollment eliminates all downstream scrutiny). PreCheck’s value is in front-loading dialogue and reducing surprises — it does not replace sound science, robust process control, or a solid QC/QA program.

Practical checklist — how small biotech should prepare to make the most of PreCheck

If you lead a small or mid-sized drug company, treat PreCheck as an operational project with deliverables. Below is a practical starter checklist:

1. Map the CMC narrative early. Create a succinct story that ties process choices to product quality attributes and patient risk. Have your analytical methods, stability plan, and control strategies sketched before formal engagement. (This makes early FDA feedback actionable.)
2. Build or document quality metrics. Start collecting basic quality KPIs (e.g., batch release timelines, OOS rates, CAPA closure times). These will demonstrate readiness and a culture of quality.
3. Assemble a facility readiness dossier. Even if you use a CDMO, document how facility design choices (cleanrooms, HVAC, segregation) meet the intended control strategy. Identify potential design questions ahead of a PreCheck interaction.
4. Identify critical tech-transfer risks. Prepare a risk register for scale-up (mixing, wet granulation, dissolution, lyophilization, sterile fill/finish, etc.) and propose mitigation plans to discuss with the agency.
5. Budget for a focused engagement team. Appoint a cross-functional PreCheck lead (regulatory + CMC + engineering) who can quickly turn agency feedback into work packages.
6. Engage investors and CDMOs early. Share the PreCheck plan with partners so that any design or contractual changes triggered by FDA feedback can be implemented swiftly.
7. Invest in data systems for traceability. Good documentation practices will accelerate any subsequent inspections or submissions.

These steps turn PreCheck from a regulatory interaction into a disciplined project management approach that reduces surprises and avoids late rework.

Ready to take the next step towards a successful PreCheck? Connect with us today to schedule a free consultation with our experts. Let’s discuss how we can help you map your CMC narrative, develop and monitor quality KPIs, and prepare a comprehensive facility readiness dossier – making your pathway to approval smoother and faster.

Further Reading:

FDA press announcement: FDA Announces New FDA PreCheck Program to Boost U.S. Drug Manufacturing (Aug 7, 2025). 

Reuters coverage of the program and public meeting plans (Aug 7–8, 2025). 

FiercePharma industry analysis of the facility-readiness and CMC phases. 

American Hospital Association summary of key program features.