US FDA’s OPQ Aims To Clear The Way For Further Manufacturing Technology Advances in 2023
Executive Summary
As the agency's Office of Pharmaceutical Quality releases its annual report highlighting last year's efforts to advance distributed and point-of-care manufacturing, OPQ director Kopcha tells the Pink Sheet of plans to focus on activities advancing the use of artificial intelligence in manufacturing process control this year.
The Office of Pharmaceutical Quality in the US Food and Drug Administration’s Center for Drug Evaluation and Research is building on last year's efforts to help strengthen the continual quality improvement and supply chain resilience of drug products by facilitating use of advanced manufacturing technologies, OPQ director Michael Kopcha told the Pink Sheet.
The move is part of the agency’s efforts to pivot from its historically reactive and punitive compliance approach to an anticipatory process focused on continually improving and preventing problems.
Instead of remaining mired in lagging GMP compliance indicators, “the FDA and forward-looking companies understand the importance of transitioning to a system that reflects wider philosophies of continual improvement,” Kopcha said.
“Regulation should become more pragmatic, more proactive, and we should be looking to reward companies that actually take that kind of an approach,” he said in an interview on the release of OPQ’s 2022 annual report.
Advanced Manufacturing Advances
The increased focus on advanced manufacturing technologies in 2022 is something Kopcha had highlighted upon release of OPQ’s 2021 annual report. (Also see "How US FDA’s Pharma Quality Office Fared In Pandemic’s Second Year" - Pink Sheet, 23 Feb, 2022.)
CDER’s OPQ-led Emerging Technology Program held 12 meetings with emerging technology adopters and supported approval of three applications for drug products to be manufactured using emerging technologies last year, according to the report.
Several meetings focused on transportable drug manufacturing processes that could be deployed closer to patients, even to the point of care.
But that was just part of the story.
“In terms of where we stand with distributed and point-of-care manufacturing, in 2022 we heavily engaged stakeholders developing these technologies by releasing a discussion paper for public comment and holding a three-day public workshop,” Kopcha said.
The discussion paper asked industry a variety of questions on the topic. (Also see "Twenty Questions: How Should The US FDA Regulate Distributed Drug Manufacturing?" - Pink Sheet, 14 Oct, 2022.)
The paper elicited responses from industry groups like the Pharmaceutical Research and Manufacturers of America, Biotechnology Innovation Organization and ISPE, and from distributed manufacturing pioneers like Aprecia Pharmaceuticals, G-CON CEO Maik Jornitz and Gilead Sciences, Inc.’s Kite unit.
“We’re now analyzing the comments and feedback that we’ve gotten from these engagements,” Kopcha told the Pink Sheet.
He added that OPQ is working on a follow-up paper that will examine how, in light of the input received, the process should work to advance these technologies.
The annual report also explains that the office is relying on feedback to inform its evaluation of the existing regulatory framework and prepare for the new manufacturing technologies.
Artificial Intelligence And Other Next Steps
Connected to the advance of novel continuous and distributed manufacturing technologies is the advent of artificial intelligence that could be used, for example, to adjust manufacturing processes in real time for closer control.
Kopcha said OPQ expects to produce a discussion paper soon that explores the potential of artificial intelligence in pharmaceutical manufacturing.
“We are going to have a similar workshop later in the year around that, again, to get stakeholder input,” he added.
Kopcha also elaborated on drug shortage, mitigation and prevention work, emphasizing efforts to strengthen supply chain resilience by improving quality management maturity and taking advantage of advanced manufacturing technologies.
The report states OPQ expedited 303 quality assessments in 2022 to prevent or mitigate drug shortages.
“We need to use the same type of innovative thinking that we’ve used to address COVID to realize a future where we are more immune … to supply chain disruptions.”
The 2022 annual report said OPQ continued to rely on alternative tools to supplement inspection activities that remained somewhat curtailed due to the COVID-19 pandemic. The office relied on remote regulatory assessments to act on 85 regulatory submissions.
The Role Of The Growing Sampling And Testing Program
OPQ also continued to strengthen its program of sampling and analyzing drug products collected during inspections, presented for import or through retail purchases.
This program mushroomed during the pandemic with testing of suspect hand sanitizers obtained at the border with Mexico. Many were found to contain subpotent levels of the active ingredient and potentially deadly levels of methanol, an unapproved ingredient.
The report noted that CDER began fine-tuning that program in 2018 using data analytics to focus the effort. In July 2022, OPQ reviewed the 2018-2021 results, “which showed that this data-driven, risk-based approach has effectively targeted products that fail quality tests.”
Kopcha stressed that manufacturers are responsible for the quality of their marketed drug products, reiterating that it is not possible for the FDA or anyone else to test all 140,000 drug products on the market.
Still, he said there is some value in growing the FDA’s testing program.
“The information we gain through testing can be used to better understand the overall state of quality, identify defective products and provide evidence for compliance actions, and inform guidance to the industry,” Kopcha said.
More important is work to develop artificial intelligence for manufacturing process control, he said.
“This way, we make sure that the processes are in control, so we don’t have to test once it’s to the market,” Kopcha said.