The Right Route Can Deliver Fewer Steps, More Consistent Batches, Cleaner Processes…and Cost Savings

With drug development and manufacturing processes becoming more complex, alternate synthetic route design is often a critical step where existing methods are impractical for large scale production.

Custom synthesis and route scouting is a big part of what we do at Neuland Labs. Synthesis scouting has grown in importance as the benefits of taking action (and the downsides to convoluted, difficult and lengthy synthesis processes) become more apparent.

Route Steps – Combine, Reorder, Reduce, Modify and Simplify
Synthetic route scouting brings together a number of disciplines, including medicinal-, synthetic- and preparative-chemistry. All aspects of the drug’s chemistry must be thoroughly explored. Then we must understand what happens at each step in the route – before any step is combined and an alternate, shorter route can be designed.

In other cases, alternate route design considers the order of events. In a previous post, we referenced the importance of when certain chemicals or reagents are added to the process. As I mentioned in that post, the order of events can spell the difference between a successful drug and a failed candidate.

Rethink the Route
There are a number of specific reasons to develop alternate synthesis routes, many of which can directly impact safety, efficacy, and manufacturing efficiency & sustainability. Here are two key aspects to “Rethinking the Route,” both of which can contribute to significant advantages – whether cost-, safety or infrastructure based.

Solvent Selection
The chemicals and reagents used to synthesize a molecule invariably come under the microscope during alternate route scouting. Solvent selection can have a wide-ranging impact on manufacturing cost and hazardous waste manufacturing infrastructure, and can add additional processing steps in order to clear toxic compounds or byproducts.

In many cases, front loading any potentially toxic or hazardous chemicals as early in the process as possible is a good option to allow sufficient clearance time.  Early introduction is a fundamental strategy in cases where the number of processing steps is significantly reduced, since the solvents may still require multiple steps to allow for sufficient contaminant clearance.

At Neuland we try – as much as possible – to use universal solvents (including water) that have well-characterized safety profiles, and that tend to be:

• Less toxic
• Easier to manage or treat
• Widely available
• Less expensive

By selecting the proper solvent and introducing it at the optimal processing step, a route change can deliver big benefits, including a shorter process, cost savings and cleaner, more consistent batches.

Cleaner processing with fewer or less-toxic solvents also deliver “green” savings on the back end, with hazardous waste management, treatment & disposal, safety, and other EHS-related subjects.

Take the Shorter Route
Route shortening is almost always a key objective of alternate route scouting. Fewer processing steps can have an enormous impact in terms of time, regulatory challenges, cost and infrastructure (including waste handling – discussed above).

A shorter route is often an efficient route.  Fewer steps mean fewer critical control points. It means potentially improved consistency, with fewer opportunities for out-of-spec product. It means less processing infrastructure – equipment, utilities, manpower, time, and more. It can bring unwieldy processes in-line with the ever-increasing price pressures on drugs.

Route scouting is critically important to the design of effective, economical and efficient manufacturing processes that help improve drug company or pipeline sustainability.

To learn more about the benefits of route scouting, contact us.