Pfizer and FDA: Expedited regulatory pathways ignore manufacturing burdens

The flexibility of clinical development for products on designated accelerated pathways is leading to at-risk investments in commercial manufacturing, say Pfizer and the FDA.

For products which demonstrate the potential to significantly improve lives in areas where the standard of care is inadequate, expedited pathways can shave the time it takes to bring a drug by over two years, delegates at the AAPS meeting in Denver, Colorado were told yesterday.

According to senior medical advisor at the US Food and Drug Administration (FDA) Jonathan Jarow, certain features within the four US programmes - Fast track, Breakthrough, Priority and Accelerated designations - offer drugmakers flexibility throughout the clinical development stage and the regulatory review, disrupting the traditional development model and in some cases bringing about approval during Phase I.

“This creates the major challenge on the manufacturing side,” he said. “All these programmes are orientated to facilitate expedition of clinical development, not toxicology, pharmacology and manufacturing – they take the hit!”

Alan Poirier, in charge of regulatory policy and global intelligence at Pfizer, also spoke during the session and agreed that while such programmes are undoubtedly beneficial for the patient and the drugmaker, they fail to accommodate Chemistry, Manufacturing, and Controls (CMC) strategy.

“Sponsors may have to make at-risk investment as commercial manufacturing programmes have to be ready to go,” he said. As such, sponsors have to create their manufacturing strategy and build their infrastructure during early development phases, when the odds of approval are low.

“The CMC part of the process is by far the most expensive so therefore there is a need for a company to have important discussions about triggering an at-risk investment.”

Blossoming interest

Since 2008, 302 products - including 109 for rare disease drugs – have been approved by the US FDA through expedited pathways.

According to Poirier, one of the major benefits of such programmes for drugmakers is closer regulator interactions, which can often bring around advice on trial design and may even change the direction of a product’s development, cutting costs.

However, despite him saying there is “a blossoming interest” in attaining such a designation, Jarow warned of both the pathways and the FDA’s limitations.

“The message is loud and clear: regulatory standards have not been reduced [through these programmes]. FDA resources are strained and can’t give this sort of attention to every product that comes in through its door.”