Is your active pharmaceutical ingredient (API) manufacturable—or just technically feasible?
In small molecule drug development, manufacturability doesn’t always get the attention it deserves. It’s often treated as a downstream concern—something to think about once the route is established and the molecule has advanced into later clinical phases.
But by the time a process reaches validation, the chemistry is largely fixed. Reworking it that late introduces cost, delays, and regulatory risk. And what looked efficient in a lab setting can become a liability under commercial pressures.
That’s the quiet failure point in many development programs: the chemistry works on paper, but it can’t be made consistently, economically, or at scale.
Manufacturability isn’t about what’s possible. It’s about what holds up.
Designing for manufacturability means asking hard questions early. Is the route scalable with minimal rework? Are the reagents cost-effective and available at commercial volumes? Does the process rely on excessive purification or high-risk steps that will slow production or raise safety flags?
These questions can’t wait until late-phase development. The earlier they’re addressed, the more freedom there is to refine the chemistry, improve yields, simplify steps, and build a process that performs—not just once, but at every stage of scale-up.
It also means breaking down silos between process design, analytical control, sourcing strategy, and plant operations. Manufacturability isn’t owned by a single function. It’s a continuous loop between disciplines, shaped by real-time feedback and close collaboration.
What does that look like in practice?
At Thermo Fisher Scientific’s API center of excellence in Cork, Ireland, manufacturability is a driving principle from the start. The site is structured specifically to support the complex realities of small molecule development—especially when scale-up, cost pressure, or high-potency compounds are in play.
The technical model at Cork brings together development chemists, analytical development chemists, process chemists, and process engineers in an integrated environment. This cross-functional collaboration ensures that every process is shaped not just by sound chemistry, but by practical insight into how that chemistry will perform at commercial scale.
This isn’t theoretical. The team has applied this approach successfully across a wide range of customer programs—identifying issues early, improving synthetic routes, and setting up processes that perform consistently through validation and launch. That depth of experience matters, especially when the molecule is complex or timelines are compressed.
Cork combines early development and commercial production within a single facility, so processes can evolve seamlessly from lab scale through kilo-scale and pilot operations to commercial manufacturing. Each transition builds on the last, reducing the risk of surprises as batch sizes grow or regulatory milestones approach.
The infrastructure is designed for flexibility and depth:
- Development, scale-up, and manufacturing assets are co-located, enabling efficient knowledge transfer and process continuity.
- Dedicated high-potency API suites (up to category 3B) and large-scale reactors (up to 16,000L) support both complexity and scale.
- On-site capabilities include analytical development, solid-state assessment, spray drying, multiple milling technologies, and real-time process monitoring.
- The team of more than 500 scientists, engineers, analysts, and operators works across functions to stress-test and strengthen each process before it reaches validation.
- Safety, sustainability, and quality are built into site operations, with practices like green chemistry integration, on-site waste treatment, and renewable energy use.
This structure allows process decisions to be made in context—not just for lab success, but for long-term viability.
A better route forward starts upstream
Too often, manufacturability becomes a reactive process—something to fix when it starts to break. But for programs with commercial potential, the question should come much earlier: Is this chemistry truly built to scale?
At Cork, that question shapes everything. Because the difference between a program that’s technically feasible and one that’s truly manufacturable often comes down to when—and how—that question gets answered.
