Can Development Time be Cut 50% From Covid Lessons?

CBER director Peter Marks wants to continue the “Operation Warp Speed” attention and quick approval process given to Covid-19 vaccines after the public health emergency has ended and apply the processes to certain priority products. Speaking at an Alliance for a Stronger FDA briefing 5/10, Marks said a likely pilot program in the near future will look to demonstrate whether it is possible to speed up product development and approvals, perhaps as much as 50% faster than current development timelines, then the Center could “make the case for staffing up to be able to do so.”

Operation Warp Speed for Covid vaccines benefited from CBER’s attention to work “in parallel,” for example performing manufacturing reviews while preclinical work was going on, Marks said. “One of the most important pieces that’s underappreciated that facilitated rapid vaccine development was the level of interaction between the sponsors who were developing the vaccines and the agency,” he said. “There was a constant line of communication and we did not have the normal bounds. Questions came in in the morning and they were oftentimes answered by the evening. So this was something really fundamentally different, and I can't promise that this will change because of Covid.”

Marks told the Alliance that CBER has a goal to get back on track by year end to catch up on its application backlog, particularly where the Center has been lagging behind in getting sponsors feedback on their applications. For example, he said CBER will also be looking to enhance its gene therapy interactions and expediting feedback and reviews for gene therapies. “Now, there's been a lot said about whether the Center is taking a more cautious attitude or a more liberal attitude towards gene therapy, but I think at the end of the day, we view this as an incredibly exciting field, which obviously will require a lot of nurturing as any nascent field does when it’s growing. And so we will continue to work diligently with sponsors and with stakeholders to try to move this forward.”

Another priority for CBER this year is to explore whether an intermediate pathway could be established for certain cellular therapy products. Marks said there are cell therapy products that do not fall clearly into the box requiring submission of a full biologics license applications, “and so we're going to explore whether there is some intermediate pathway that might be appropriate there.”

In terms of future budget request priorities, Marks said resources are needed to advance safety surveillance systems, which can also be used in some cases for looking at effectiveness. He said the agency would like to start implementing more work with artificial intelligence, including using natural language processing to be able to start to let computers process adverse event reports received to sort through and detect signals more readily. Marks admitted that FDA’s information technology systems are 10 or 20 years behind industry standards. Applying supercomputing to adverse event reporting could eliminate 99% of reports now needed to be seen by a human, “and what's even more is the computer could probably identify trends that the humans simply would never identify,” he said.

In reflecting how Covid-19 has transformed CBER and FDA as a whole, he said virtual work from home will continue post-Covid. He couldn’t speculate as to what percentage of staff will be virtual and what percentage will be staffed in person in the office, but he did say: “we are not going to go back to February 2020… and I suspect that going forward we will see a larger mix of in-person and virtual meetings.” He said meetings will be flexible since some sponsors like virtual meetings because they save money and time, whereas others value in-person meetings.

Asked to comment on the need to conduct in-person inspection versus remote audits, Marks pointed to current headlines about baby formula contamination as to why inspections are still very important. “You see what happens when things don't go well in manufacturing, and inspections help detect problems hopefully before they get out of hand and lead them to be corrected,” he said adding that “it’s really important for us to keep up on our inspectional capabilities.”