Those results in vaccine development clearly transfer to human development, as do the lessons learned from presenting other new therapeutics to regulatory agencies. “FDA is eager to bring new approaches to unmet medical needs; approaches that are safe and effective,” noted E.J. Brandreth, vp of quality and regulatory affairs at Althea Technologies. The issue, he said, is that, for new approaches, “The rules aren’t yet written.”
Knowledge regarding impurity profiles, safety, and other parameters must be based upon data from related products and good scientific judgment, and augmented over time with data from long-term studies and analyses. The company that introduces the therapy or diagnostic sets the bar.
“FDA is extremely easy to work with in situations like this,” Brandreth said. “The systems have come a long way.” This often occurs under FDA’s Orphan Drug program and under a rolling biologic license application, in which clinical data is separated from manufacturing data, letting companies provide partial submissions as the data becomes available. That approach could speed the process by six months, he said.
New vaccines are benefiting from manufacturers’ decisions not to use mammalian cell lines for production. That approach eliminates the risk of adventitious viral contamination, and thus makes production faster and easier than the traditional processes that use animal-derived components.
In terms of DNA vaccines, Brandreth suggested that the differences between linear and super-coiled fragments need to be understood as they relate to the particular vaccine. If the different forms affect potency, “setting up meaningful specifications regarding the percent of supercoiled DNA that is needed is important,” he said.
The bottom line, Brandreth insists, is to break down each step and understand its clinical and manufacturing ramifications during process characterization and validation studies. Be aware that changes made in Phase III “can’t simply meet the specifications from earlier clinical previous processes. We’ll be expected to meet tighter specifications. Therefore, avoid changes in Phase III. Also,” Brandreth said, “it’s extremely beneficial to manufacture the Phase III material in the actual facility to be used for the commercial launch. Plan ahead.”