Small Molecule Pharma Companies Are Employing These Advanced Technologies To Get Ahead

By Joseph Pategou

Small molecule therapeutics account for over 50 percent of global pharmaceutical sales and nearly 70 percent of new FDA approvals in recent years, underscoring their continued dominance in medicine delivery.¹ Every day, millions rely on small molecule medicines — yet few appreciate the sophisticated processes ensuring each pill’s safety and efficacy. From new continuous-flow reactors that slash production times to AI systems that preempt defects, manufacturing is undergoing a dramatic transformation. This article highlights concrete innovations boosting quality and efficiency and examines remaining challenges and future trends shaping an industry at the heart of global health.

Innovations Driving Efficiency And Quality

In response to cost pressures, regulatory expectations, and supply chain risks, pharmaceutical manufacturers are embracing several transformative innovations. Continuous manufacturing has been adopted by companies such as Janssen and Vertex, where Janssen’s continuous antiviral line reduced overall production time by 40 percent and increased yield by 8 percent, while Vertex halved setup times for its cystic fibrosis therapy, all without extensive revalidation of larger batch equipment.²

Automation and digitalization under the Pharma 4.0 paradigm now sees AI-driven control systems and robotics across the plant. For example, Merck’s AI platform detected early blend nonuniformity, cutting batch rejections by 30 percent and troubleshooting time in half,³ and Roche’s robotic packaging lines delivered a 25 percent reduction in labor costs and a 15 percent throughput increase.⁴

At Eli Lilly, engineers built a digital twin model of their solid dose line with Siemens NX and Aspen Hybrid Models. By testing “what if” scenarios virtually — say, sudden humidity spikes or blender speed shifts — they shaved 30  percent off process development time and avoided three scale‑up deviations in 2024.⁵ In Osaka, Takeda has pushed real‑time release even further: inline NIR and Raman data stream to a cloud‑based multivariate model approved by Japan’s PMDA, allowing tablets to leave the compression room just an hour after manufacture and freeing roughly €4 million in working capital inventory.⁶

Digitalization is also revolutionizing asset care. Sanofi’s Frankfurt site now bristles with IoT vibration and temperature sensors that feed an AWS machine learning stack; early warning alerts for impending granulator gearbox failures have cut unplanned shutdowns by 40 percent and saved about €2 million a year in maintenance costs.⁷

Beyond these, modular and single-use technologies are gaining traction. Catalent’s SmartDose disposable modules allow rapid small-batch production of clinical trial material, shortening setup by 60 percent compared to traditional stainless-steel lines and reducing cleaning validation requirements.⁸ These modular units can be reconfigured quickly for different products, enhancing flexibility and speeding time to clinic.

In the realm of green chemistry and sustainability, Pfizer reported a 19 percent reduction in waste and a 56 percent productivity gain through greener synthetic routes,⁹ while GSK’s solvent recycling initiative cut solvent usage by 40 percent and emissions by 22 percent.¹⁰

Security and sustainability are advancing in parallel. Bayer is piloting a blockchain‑enabled track‑and‑trace ledger that links unit‑level bar codes with warehouse and 3PL data; provenance checks that once took days can now be completed in minutes, tightening defenses against counterfeit product.₁₁ Meanwhile, AstraZeneca has installed a continuous electrochemical oxidation skid — developed with Chemtrix — to make a key quinazoline intermediate without chromium oxidants, cutting the process mass intensity of that step in half and eliminating toxic waste; the greener route was filed with the EMA in 2024.¹²

Flow chemistry reactors represent another leap; rather than large batch reactors, continuous microreactors enable precise temperature and mixing control, improving selectivity and safety for hazardous reactions. Novartis reported using flow chemistry to synthesize a key intermediate with a 30 percent higher yield and a 70 percent reduction in by-products compared to batch processing.¹³

Novartis employs advanced crystallization (AdCryst) software paired with inline focused beam reflectance measurement (FBRM) probes to map supersaturation windows in flow; first‑pass API yield jumped from 82 percent to 94 percent, trimming solvent consumption by 18 percent.¹⁴

Finally, 3D printing and on-demand manufacturing are emerging for personalized dosing. Aprecia Pharmaceuticals’ Spritam (levetiracetam) became the first FDA-approved 3D-printed drug, demonstrating that porous tablet structures can dissolve more rapidly, improving patient compliance — particularly in neurology.¹⁵ This proof of concept opens the door for tailored dosages fabricated at the point of care.

From modular micro‑plants and flow reactors to 3D‑printed tablets, new hardware is making production of small molecule drugs faster, greener, and more flexible. Add digital twins, real‑time release, IoT analytics, smart crystallization, blockchain traceability, and electrosynthesis, and tomorrow’s factories become data‑rich, self‑diagnosing, and supply chain transparent — reinventing how pills reach patients.

Challenges To Tackle And Future Outlook

Despite these advances, manufacturers face ongoing hurdles. Scale-up complexity often uncovers unanticipated heat- and mass-transfer issues at commercial volumes, necessitating iterative process optimization and extensive PAT support to maintain consistency.¹⁶ Regulatory compliance demands rigorous validation for every new technology under cGMP; any deviation can lead to costly inspections or production halts. Quality control — including exhaustive testing for impurities, potency, and dissolution — while essential for patient safety, can become a bottleneck. The WHO estimates that up to one in 10 medicines in certain regions may be substandard or falsified,¹⁷ illustrating the critical need for reliable QC systems. Finally, a globally concentrated supply chain for APIs and raw materials poses risks, driving firms to pursue dual sourcing and onshoring strategies to bolster resilience.¹⁸

Looking ahead, small molecule manufacturing will become even more agile and intelligent. End-to-end continuous lines promise on-demand production; fully autonomous AI-driven facilities will self-optimize; modular, portable plants will enable localized manufacturing; and personalized dosing via 3D printing may complement bulk production for niche therapies. Sustainability will shift from aspiration to standard practice, with metrics like process mass intensity and carbon footprint guiding process design. These trends herald a future where medicines are produced faster, safer, and more responsibly — ensuring patients worldwide have reliable access to essential therapies.

References

1. Van Arnum, P. (2024). Bio/Pharma Watchlist: Small-Molecule Drugs. DCAT Value Chain Insights
2. Smith, J. L. et al. (2022). Case Study: Continuous Antiviral Production at Janssen. BioProcess International, 20(3), 45–52
3. Müller, R. & Patel, S. (2023). AI-Driven Blend Uniformity Control in Tablet Production. Journal of Pharmaceutical Innovation, 18(1), 12–19
4. Roche Annual Report. (2023). Digital Transformation and Automation Highlights. Roche.
5. Eli Lilly & Siemens. “Digital Twin for Solid‑Dose Scale‑Up.” Industry webinar, 2024
6. Takeda. “Real‑Time Release Strategy for Oral Solids.” Osaka Plant Case Study, 2023
7. Sanofi & AWS. “Predictive Maintenance Success at Frankfurt.” White paper, 2023
8. Catalent. (2021). SmartDose Disposable Module Case Study. Catalent White Paper.
9. Pfizer. (2022). Green Chemistry: A More Sustainable Approach to Medicine Development
10. GlaxoSmithKline. (2022). Sustainability Report: Process Intensification in Antibiotic Manufacturing. GSK Publications
11. Bayer. “Blockchain Pilot for Pharma Supply Security.” Company press release, 2024
12. AstraZeneca & Chemtrix. “Continuous Electro‑Oxidation Platform.” Green Chem. Challenge entry, 2024
13. Novartis. (2020). Implementation of Flow Chemistry for Intermediate Synthesis. Novartis Process Innovation
14. Novartis. “Advanced Flow Crystallization in API Manufacturing.” Process Chem. Conf. abstract, 2024.
15. Aprecia Pharmaceuticals. (2015). FDA Approval of Spritam (Levetiracetam) 3D-Printed Tablets. U.S. FDA News Release
16. Pinto Reis, C. (2015). Good manufacturing practices for medicinal products for human use. J. Pharm. Bioallied Sci., 7(2), 87–96
17. World Health Organization. (2024). Substandard and falsified medical products – Key facts
18. April Stanley, A. (2024). A Closer Look at Small Molecule Drug Substance and Drug Product Manufacturing. Pharma’s Almanac.

About The Author:

Joseph Pategou has authored over 30 articles in publications such as Cell and Gene Therapy, The Indian Economist, Labotech.eu, Drug Discovery & Development, and others. A former consultant at Boston Consulting Group in New York, he has held and continues to hold operational roles in biopharma companies. The views expressed are his own. He holds an MBA from New York University and a master’s degree from HEC Paris.