What’s one adjustment that made a big difference in your CM process?

I recently read a two-part study published by Amgen researchers. It described a conversion of the penultimate step of the synthesis of Apremilast, which is the API in Otezla (a PDE4 inhibitor for inflammatory diseases).

The traditional batch process for the penultimate step in apremilast synthesis had three main challenges:

1. Long reaction time (>18 hours).
2. Low solubility of starting materials/intermediates in THF.
3. Multiple post-reaction operations, leading to significant solvent waste.

By switching to continuous mode using a higher temperature plug flow reactor they realized several benefits:

• Plug-Flow Reactor (PFR): Enabled higher reaction temperatures (up to 130 °C), reducing reaction time from >18 hours (batch) to 30 minutes (flow) (*this is huge in my opinion).
• Solvent Switch: Replaced THF with DMSO, greatly improving solubility of 3-acetamidophthalic anhydride and intermediates. (*highly impactful from a distributed manufacturing, diversified supply chain perspective)
• Process Safety: Careful thermal analysis (ARC) and modeling ensured safe operation at elevated temperatures, with built-in safety protocols for lab and production scale. (*always a concern)

The two part study is published in: A Continuous Process for Manufacturing Apremilast. Part I: Process Development and Intensification by Utilizing Flow Chemistry Principles | Organic Process Research & Development

A Continuous Process for Manufacturing Apremilast. Part II: Process Characterization to Establish a Parametric Control Strategy | Organic Process Research & Development

The value of having chemists and chemical engineers together in meetings.  Its a small team action that dramatically accelerates development work.
Also, it's important to have analytical chemists in any meeting for planning a production campaign.  Their input for where and when to sample can provide so much value afterwards.

Another big unexpected positive impact is the significant reduction in cleaning solvent required as more and more unit operations are integrated - one cleans at the end of the campaign instead of after every batch.

Intentional Information, Meaningful Impact: Implementing a deliberate, consistent, and collaborative method for sharing project updates, data insights, literature reviews, and guidelines to strengthen stakeholder engagement and knowledge exchange.