Reshored and Reassured?

INTRODUCTION

Dear Community,

First of all, I’d like to thank our visionary CEO, Thomas Loewald, for stepping in to introduce Issue 5 of Synthesis in my absence (if you missed all the peptide action, catch up here).

For this month’s issue, we zoom out for a high-level view of outsourcing strategy, which is not as predictable as it used to be…

Right now, it seems to me that a lot of folks are exploring the ability to manufacture “in country, for country” or at least “in region, for region.” Phrases like Europe-for-Europe manufacturing and US-for-US manufacturing are suddenly commonplace.

Although such conversations started during COVID-19, there was little traction. Fast forward to 2026 and we’ve seen much more change, with companies increasingly focused on diversifying supply chains and manufacturing drugs where they want to sell them.

For a leading global CDMO, such (shifting) trends are clearly important. A couple of years ago, we conducted a survey to explore the views and intent of senior-level executives in the space (see THE LEAD REACTION for topline results and a link to the resulting infographic).

Clearly, we’re in a different place today, so it’s time for another pulse check.

Would you consider helping us? We only ask for two minutes of your attention: please complete the survey here.

Many thanks in advance,

Matt Bio

P.S. To further express our gratitude, we’ll be sure to share the survey results with Synthesis readers as soon as we have them!

THE LEAD REACTION

The times, are they a-changin’?

Back in 2023, we surveyed senior-level executives about the whats, whens, wheres, and whys of outsourcing, noting a distinct trend towards onshoring.

View the full infographic here.

The standout stats?

• 32% had already onshored internationally outsourced operations.
• 29% had plans to change CDMO locality within 18 months.
• 33% preferred domestic partnerships (versus 22% international).
• 58% were dual sourcing CDMOs for commercialization (and up to 55% were dual sourcing for clinical trials).
• Top three benefits of CDMO partnerships were cost-efficiency (52%), process optimization (47%) and larger manufacturing capacity (43%); however, the number one driver for onshoring was quality assurance.

As Matt Bio notes above, a great deal can change in just a few short years. At Cambrex, we believe the onshoring/reshoring trend has deepened. But we want to know what you think, so we can draw a fuller picture of manufacturing strategy in 2026 and beyond.

Please complete the two-minute survey here.

THE METHOD

Lessons learned from tech transfer in tight timeframes

Back in 2018, Cambrex Charles City was selected by Achillion to assist with a two-stage technology transfer and the process development of danicopan, a small-molecule API with a big chemical name: (2S,4R)-1-{[3-acetyl-5-(2-methylpyrimidin-5-yl)-1H-indazol-1-yl] acetyl}-N-(6-bromopyridin-2-yl)-4-fluoropyrrolidine-2-carboxamide.

The deep collaboration continued through three process iterations, two acquisitions (by Alexion and then AstraZeneca), and one global pandemic, ultimately resulting in success: Danicopan was approved as Voydeya in Japan, the US, and Europe in 2024.

Later that year, scientists from both teams joined forces again to co-author a detailed perspective article in Organic Process Research & Development. Within, they share successes, discuss lessons learned (on both sides), and outline their approach to collaboration using “Step 4” of the process – a Suzuki-Miyaura coupling – as a specific case study.

Three key successes?

1. Safety, sustainability and efficiency of the process were all improved. Process validation was conducted at two scales to enable global regulatory submission.
2. The small-scale validation campaign satisfied commercial demand for the initial indication.
3. The large-scale validation and commercial campaigns highlighted the benefits of an early awareness of process scalability, offering flexibility to target an unforeseen indication.

Three key lessons learned?

1. Early and continued alignment are prerequisites for success.
2. There is a big difference between “must-have” and “nice-to-have” when it comes to prioritization on ambitious timelines.
3. A “go slow to go fast” approach resulted in the maximum degree of flexibility in manufacturing scale.

By the numbers?

• 562 experiments performed across Cambrex’s Charles City, High Point, and Durham sites.
• 7 DoE studies, with 58 factors, 61 responses and 170 unique process parameters fully characterized across 6 synthetic steps.

Read the full story in Organic Process Research & Development

THE CATALYST

What we are reading…

Thinking about supply chains reminded me of a paper¹ from a few years ago by Stéphan Caron at Pfizer that answered the question “Where does the fluorine come from?” Re-reading that paper, I was reminded that nearly all fluorine ultimately comes from calcium fluoride. The mineral fluoride is then converted to hydrofluoric acid (HF) on a scale of millions of tons annually. That HF is ultimately converted to all the fluoride containing building blocks that ultimately make their way into more than 20% of all marketed drugs.

The paper reviews the various protocols developed for introducing fluorine. What is striking about the list is the challenging supply chain for many of the reagents required. Perfluoro-1-butanesulfonyl fluoride is PFAS and thus a regulatory challenge both as input and byproducts in waste stream. Most alternative reagents derive from SF₄ which is a reactive gas produced by only a handful of suppliers. Supply chain challenges indeed!

¹ Org. Process Res. Dev. 2020, 24, 470-480.

THE SIDEBAR

Bridging development and commercial manufacturing

The technology transfer process is an effort of multiple departments, including chemical development, analytical development, process engineering and production. Together, we look for opportunities to reduce cycle time and improve the overall process.