Pfizer: Global regulatory divergence restricted continuous manufacturing ambition

Continuous manufacturing was cited as one of a number of innovations which could transform the drug industry, reducing manufacturing costs while increasing quality, by Pfizer’s head of global CMC Roger Nosal in a conference session at Interphex Japan.

But while the drug giant first began developing such platforms in 2006, regulatory burdens and global variance halted early ambitions and turned Pfizer away from large scale continuous manufacturing.

“We did develop continuous dry granulation for one product and a continuous wet granulation design space and invited regulators to our sites to evaluate these before we decided to pursue them for regulatory approval,”​ he told delegates in Tokyo yesterday.

“After they visited, we started to add up the amount of work it would take to meet the expectations they had put before us, and we decided to abandon continuous manufacturing for large volume products at that time.​

“It wasn’t so much one regulatory body that was causing us such concern, but it was the need for global registration – in other words making sure continuous manufacturing as an innovative manufacturing platform could become globalised. And when we calculated the costs, it was costing us almost twice as much, which gave us very little benefit at the end of the day.”​

Pods and regulatory nods​

The firm’s foray into continuous manufacturing was not to be wasted as it forms the basis of Pfizer’s portable, continuous, miniature and modular (PCMM) system – a 'pod-based' platform being developed with a number of other firms​, including GSK, GEA and G-CON for small volume precision medicine products, many in oncology.

“We hope that it will actually transform [the continuous manufacturing] equation from being a burden to being a benefit, not only in terms of cost but in terms of speed and efficiency, and also in terms of quality assurance,”​ Nosal said.

And ten years on from Pfizer’s first efforts, regulators globally have begun to embrace continuous manufacturing. For example, just this week​ the US FDA called for feedback on a public docket which will help reinforce previous calls to industry to adopt continuous manufacturing.

But according to Nosal there remain a number of challenges relating to how what drug companies put into regulatory submissions reflect what they are doing at their manufacturing sites.

These include the ability to change batch size, which is a significant issue to some regulators but not to others “and would require specific evaluation of that change before it could be implemented.”​

Furthermore, questions remain about adaptive process controls (APC) vs process analytical technology (PAT) monitoring which Pfizer sees as two opportunities going forward, while other concerns from a global regulatory perspective include managing controls of raw materials (which can change through the life cycle of a product), site transfers, inspections, companion criteria, and the volume of data that would have to be submitted to numerous agencies.