Green chemistry: how enzymes and cleaner processes are changing API manufacturing
Biocatalysis and greener solvents cut steps and waste. The world’s leading drug makers are investing — and the tools are openly shared.
In this article
Making an active pharmaceutical ingredient can take many chemical steps, large volumes of solvent and a lot of waste. Green chemistry aims to do the same job with fewer steps and less waste — often by using enzymes as catalysts.
Biocatalysis in practice
Merck & Co. received a 2025 Green Chemistry Challenge Award for a biocatalytic process that replaces a multi-step route with a single enzyme cascade — its eleventh such award. The company says it has invested in biocatalysis for more than 25 years, including developing new enzymes.
An industry effort
The ACS Green Chemistry Institute Pharmaceutical Roundtable, a partnership between global drug makers and the American Chemical Society, marked its 20th year in 2025. Its year in review reports:
| 2025 | Figure |
|---|---|
| Stakeholders engaged | 4,912 |
| Countries reached | 45 |
| Research grants | $480,000, eight projects from 266 proposals |
| Active focus teams | 21 |
Funded topics included greener catalysis, biocatalysis, manufacturing technologies and greener peptides. The Roundtable’s own 2025 awards went to Merck, Corteva, Pfizer and contract manufacturer Olon.
Tools anyone can use
The Roundtable publishes practical tools, including a Solvent Selection Guide and calculators for process mass intensity (PMI) — the total mass of materials used per kilogram of product, a simple measure of efficiency.
The principles behind it
Green chemistry is often summarised by twelve principles set out by chemists Paul Anastas and John Warner in 1998. The most relevant for API manufacturing are simple to state: prevent waste rather than treat it; design routes in which as much of the starting material as possible ends up in the product; use safer solvents and reagents; use catalysts rather than large amounts of reagents; avoid unnecessary steps such as protecting and deprotecting groups; and design processes that use less energy.
Measuring waste
Two measures are widely used. Process mass intensity (PMI) counts all the materials used — reagents, solvents, water — per kilogram of product. The E-factor counts the waste produced per kilogram of product. Pharmaceutical processes traditionally have much higher values than bulk chemicals, because molecules are complex and made in many steps. Solvents are often the largest single contributor, which is why solvent choice and recovery receive so much attention.
Why enzymes help
Enzymes are nature’s catalysts. They work in water or mild solvents, at moderate temperatures, and are highly selective — they can make exactly the bond or stereochemistry required without affecting the rest of the molecule. That selectivity can replace several chemical steps with one. A well-known example is Merck’s process for the diabetes drug sitagliptin, in which an engineered enzyme replaced a metal-catalysed step under high pressure, earning a US Presidential Green Chemistry Challenge Award in 2010. Advances in enzyme engineering now let companies design enzymes for specific reactions, widening the range of processes that can use them.
Greener does not mean costlier
| Change | Environmental gain | Business gain |
|---|---|---|
| Fewer steps | Less waste | Lower cost, faster production |
| Solvent recovery | Less effluent | Lower solvent purchases |
| Safer reagents | Lower hazard | Simpler plant and permits |
Starting points for a new plant
- Choose solvents with recovery and reuse in mind, using published solvent selection guides.
- Measure process mass intensity from the first development batch, so improvements can be tracked.
- Ask technology partners whether enzymatic or catalytic steps are available for the route.
- Design effluent treatment together with the process, not as an afterthought.
Why it matters for Pakistan
- Cost: fewer steps and less solvent mean lower production cost — important for new API plants.
- Environment: less effluent is easier to treat and permit.
- Exports: buyers increasingly ask about sustainability.
As Pakistan plans to make more APIs at home, building new plants around greener processes from the start is an opportunity. Process and environmental technology suppliers exhibit at Pharma Asia 2026.
