The next generation of advanced therapies is creating increasingly complex supply chains, according to Matthew Lakelin, PhD, vice president of scientific affairs, and a founder of TrakCel, which supplies supply chain orchestration software. Lakelin says he saw an  “inflexion point” in their business around 2018, after advanced therapies Yescarta and Kymriah were first approved by the FDA.

“After Kymriah and Yescarta, there was a pathway for companies to commercialize and now, there are more of these therapies in development,” he adds.

Moreover, he explains, early advanced therapies that focused on orphan diseases are now being replaced by a new generation of drugs designed to treat indications with much larger patient populations, possibly in the tens or hundreds of patients at a time.

“It forced companies to think about their supply chain in great detail,” he continues. “From a demand side, we’ve had an increasing number of companies developing advanced therapies.”

But they are also seeing therapies that require multiple patient-derived cells or tissues, each with their own supply chain, he points out. “These supply chains aren’t complex for the sake of complexity. They’re addressing clinical needs around solid tumors, which the first generation of CAR-T were unable to address.”

According to Lakelin, advanced therapy supply chains have always been more complex than earlier therapies. As he explains, the supply chain is circular–beginning with a patient-specific starting material and passing through manufacturing before returning to the patient.

In contrast, traditional pharmaceutical supply chains are linear. A tablet, or other formulation, is distributed to wholesalers, pharmacies, and then onto patients.

“These [advanced] therapies can also have short shelf lives,” he says. “The starting material or drug product might only have a shelf life of 48 hours and that adds additional complexity to the supply chain.”

Moving forward, he highlights work on advanced therapies for stress-related and rectal incontinence.

“The interesting thing about these indications is that there are maybe hundreds of thousands of these patients,” he says. “The industry needs to get ready for this next wave where it’s not just about complexity but treating wider patient populations–and that’s going to drive digitization and the need to harmonize activities to deliver at that scale.”

Lakelin also threw caution on the speed of delivering point-of-care manufacturing for advanced therapies. “I don’t foresee this happening in the next five to ten years,” he maintains. “There are too many regulatory challenges.”

Another risk, he adds, is process drift where the characteristics of products manufactured in different locations can diverge over time.