In the world of API (Active Pharmaceutical Ingredient) development, one of the earliest and arguably most critical decisions lies in selecting the right synthetic route. This isn’t just a technical choice; it’s a strategic one that determines everything from cost of goods (COGs) and regulatory robustness to scalability, sustainability, and time-to-market.
Welcome to the art and science of route scouting, a high-stakes exercise in process design that can define the fate of a molecule well before it reaches commercial production.
In this blog, we explore why route scouting matters, the key factors to consider, and how expert CDMOs approach it to drive success for their partners.
What Is Route Scouting and Why Is It Important?
Route scouting refers to the systematic evaluation of different chemical pathways to synthesize a target API molecule. It’s typically performed in the early development phase, right after a lead compound has been identified and validated for biological activity.
However, here’s the catch: the shortest or most obvious synthetic route is rarely the best one. It might work in the lab, but fail at scale. Or it might involve expensive or hazardous reagents. Or it might generate impurities that are hard to control.
The ideal synthetic route must be:
- Safe
- Cost-effective
- Scalable
- Regulatory compliant
- Environmentally sustainable
A well-designed route can reduce cost of goods by 20-40%, minimize regulatory hurdles, and enable faster tech transfer across development phases. Conversely, a poor route can derail the entire development program.
How to Evaluate and Choose the Right Synthetic Route
Let’s break down the core factors that chemists and process engineers must evaluate during route selection:
1. Atom Economy & Yield Efficiency
A good route maximizes atom economy – how many atoms of the starting materials end up in the final product. Low-yielding or multi-step reactions increase waste, time, and cost.
- Target: >80% overall yield is desirable for commercial viability
- Watch out for: Complex protecting group strategies or steps requiring exotic catalysts
2. Availability & Cost of Raw Materials
Can the route be supported by readily available and cost-effective starting materials? Or are the intermediates rare, proprietary, or geopolitically sensitive?
- Risk factor: Depending on a single supplier or region
- Smart play: Dual sourcing and use of commoditized intermediates
3. Environmental and Safety Considerations
In the age of green chemistry and ESG expectations, a sustainable route is a competitive advantage.
- Avoid Class I solvents, heavy metals, or energetic reagents
- Prioritize low E-factor (kg of waste per kg of product)
- Incorporate process intensification or continuous flow techniques
4. Impurity Profile and Regulatory Tolerance
Some routes look great until you discover they produce a toxic impurity that’s hard to purge.
- Regulatory agencies like the US FDA or EMA expect full impurity characterization
- Routes must avoid creating genotoxic impurities (GTIs) or require validated controls
5. Scalability and Tech Transfer Potential
Can the route move from gram to kilo to ton scale without major redesigns?
- Consider mixing, heat transfer, solvent handling, and filtration constraints
- Evaluate whether specialized equipment is needed (e.g., cryogenic, high-pressure)
6. Time and Speed to Clinical Trials
In drug development, time is currency. The route must support fast delivery of toxicology batches and clinical supplies.
- A more efficient but time-consuming route may be unsuitable for Phase I
- Early routes may be optimized later for Phase III and commercial scale
Case-in-Point: LMS’s Approach to Route Scouting
At Lupin Manufacturing Solutions (LMS), route scouting is not a single event rather it’s a dynamic, iterative collaboration between our R&D scientists, process engineers, and customers.
Here’s how we help pharma innovators navigate route selection:
- Early route feasibility assessments for synthetic accessibility, cost, and risk
- Design of Experiments (DoE) to test variables quickly and cost-effectively
- Use of chemo- and region-selective strategies to reduce purification burden
- Route comparison matrix that balances safety, yield, cost, and complexity
- Integration of green chemistry principles and sustainability metrics
Whether it’s a complex chiral intermediate or a high-potency API (HPAPI), we bring decades of synthetic expertise and a flexible mindset to help our partners choose and validate the best way forward.
Conclusion: Route Design is Drug Design
In the rush to bring new molecules to market, route scouting is often underappreciated. But make no mistake as the route you choose today will shape your costs, compliance, and competitiveness tomorrow.
A great route doesn’t just make good chemistry. It makes great business sense.
Looking to optimize your molecule’s journey from lab to launch?
Talk to LMS where route design meets real-world execution.