Why CMC Tech Transfer Should Begin With The End In Mind

By Katie Anderson, Chief Editor, Pharmaceutical Online

As pipelines become more differentiated, regulatory requirements more complex, competition more intense, and demand continues to rise, sponsors can easily become consumed by the immediate tasks of CMC technology transfer. Yet, the end goals must remain top of mind throughout the process. In part one of this interview, I spoke with Tuneer Ghosh, president of CMC at Sai Life Sciences, about how to build a successful technology transfer. In part two, we explore the endpoints that should shape the conversation from the outset.

Don’t Forget Scale

You may be more focused on speed than scale-up in early development, but it is important to be mindful of it early, according to Ghosh. “Understanding scale is something which we often do not keep in mind when we start working in the laboratory.  I call it beginning with the end in mind, and that's very important for us. So when I'm working on a five milligram scale or a 10 gram scale, do I have at the back of my mind that at the end of the day, I've got to run a 1,000 kilogram batch in the plant. That's very important for the scientist and the engineer to understand,” explained Ghosh.

Early CDMO Involvement

How early you should involve a CDMO varies by size of the manufacturer, according to Ghosh. However, he noted that the CDMO ideally should be involved before the process becomes more robust. This would place the interaction before phase two occurs.

At that point, Ghosh adds that the manufacturers should look beyond commercialization into lifecycle management. “It's not only launching the drug, because even before you launch the drug, there is a pre-approval inspection. So, you've got to be regulatory, competent enough to get through the inspection with FDA. And then post-commercialization, lifecycle management in terms of cost of goods improvement, making the process greener, reducing solvents, recovering solvents and recovering catalysts. There are so many things one does post-commercialization. So, you actually have to select the right partner who can help you with all of this as well,” continued Ghosh.

Differentiate Supply

The process and scale-up are just two parts of the transfer process with a CDMO. It is also important to select a partner that differentiates the raw material supply.

Ghosh recommended choosing two or three different suppliers based on the quantity of material, and to always choose suppliers from different geographies. He continued, “Now, what we also do is the suppliers that we choose, we have partnered with seven or eight companies in and around the place where we operate.”

This supplier differentiation isn’t just protecting the safety and security of the supply, according to Ghosh. “It’s also getting in that element of competition amongst your suppliers, because if your suppliers know that they're the only ones, then you don't have any negotiation margin over there. So, it helps you on many counts, essentially,” he explained.

Work With Suppliers on Processes

Furthering the discussion on material suppliers, Ghosh advised validating the process before requesting the material. His reason behind this is that some material manufacturers may have more capabilities in manufacturing than they do in science.

“We often use our scientists to help them develop those processes for the starting material, and then transfer those processes back to them,” he continued.

Whenever his team validates a process, they use at least two suppliers. “So, if you're taking three validation batches, we would use one supplier for two batches, and then we would use a second supplier for the third batch. If the commercial quantity requirements are higher, then we would also use a third supplier,” Ghosh explained further.

Identify Regulatory Regions Early

It is important to establish commercialization targets early to ensure the process can be approved in that area. Ghosh added that every regulatory agency is different, and each country in Europe has its own set of regulatory requirements.

Ghose explained further, “When you define a particular intermediate as a registered starting material in the U.S., there's no guarantee that Europe will consider it as the registered starting material. It might push you back one or two steps behind, and we've seen that happening very often, more often than we are comfortable with. So, what we do is we adopt a strategy where we ask customers that, "Hey, are you planning only U.S. or is Europe also part of your plan?"

If a broader reach is desired by the manufacturers, Ghosh’s team advises them to include the full GMP process as part of the scope to make sure they have data in a GMP environment for regulatory approval in that region.

Process Safety Study

One of the steps Ghosh insisted his team would not compromise on was a process safety study. This is done before the process goes to the pilot plant to ensure complete safety.

“We've got primary screens. We've got secondary screens. We have everything, and we would not compromise on process safety before we take a process to the plant,” he emphasized.

Share Learned Lessons

Mistakes and failures are going to happen during technology transfer, but that is where lessons are learned. What you do with that learning is important, according to Ghose. “Whenever there's a failure, whenever there's a learning, we do not tactically apply that learning to only that process. But, we are strategic in ensuring that we have a holistic approach in ensuring that that is then disseminated within the entire team,” he added.  

The Larger Objective

In a complex CMC technology transfer, immediate milestones can easily overshadow the larger objective. Beginning with the end in mind keeps decisions about scale, lifecycle management, regulatory approvals, supply safety and process adjustments aligned with capacity needs. By defining those endpoints early, sponsors can build a transfer strategy that is not only faster, but also safer, more resilient, and better prepared for what comes next.

Bio

Tuneer Ghosh is President of CMC (Chemistry, Manufacturing & Controls) Services at Sai Life Sciences. He leads process development, scale-up, and manufacturing strategy, integrating analytical and technical capabilities to support regulatory compliance and reliable supply.