US FDA ‘Quietly Working Hard’ To Develop Advanced Manufacturing Framework
Executive Summary
Soon-to-be-released white papers will FRAME how FDA plans assess products manufactured with advanced technologies as part of an initiative to reduce uncertainty for sponsors.
The US Food and Drug Administration is “quietly working hard” to develop a regulatory framework for advanced manufacturing, according to Michael Kopcha, the director of the Office of Pharmaceutical Quality.
Speaking at the Association for Accessible Medicines’ Generics + Biosimilars conference on 8 November, Kopcha said that the program, called the Framework for Advanced Manufacturing Evaluation, or FRAME, would “provide clarity and reduce uncertainty for products manufactured with advanced technologies.”
The program will address both current and potential future manufacturing innovations, Kopcha said.
To identify future possibilities, FDA funded a National Academies report which gathered public input on emerging technologies and helped FDA ascertain technologies it might see over the next five to 10 years. (Also see "Advanced Manufacturing May Require US FDA To Think Differently About Guidance" - Pink Sheet, 3 Mar, 2021.)
The FRAME program is one of several advanced manufacturing initiatives the agency has undertaken since COVID-19 relief legislation provided it with an infusion of funding. (Also see "US FDA Would See Cash Windfall In COVID-19 Relief Bill" - Pink Sheet, 10 Feb, 2021.)
Another is the Emerging Technologies Program, which provides manufacturers with the opportunity to interact directly with the FDA throughout a novel technology’s development. (Also see "US FDA Program Adds Staff, Graduation Concept To Help Advance Newer Manufacturing Technologies" - Pink Sheet, 3 Nov, 2021.)
Defining The Technology
While the agency has not yet released information on its website about the initiative, several speakers have offered details about the program over the past few months.
At the FDA Small Business & Industry Assistance Pharmaceutical Quality Symposium on 27 October, FDA’s Adam Fisher provided more information about the effort.
Fisher, who is the Associate Director of Science & Outreach at OPQ, said that the agency gathered information through attending workshops and the Emerging Technology program, in addition to the National Academies report, and narrowed in on four main technologies it believes will play a major role over the next five to 10 years.
The technologies are:
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End-to-end continuous manufacturing: A fully integrated process in which raw materials or chemical intermediates are continuously fed in and then finished drug products are continuously removed;
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Distributed manufacturing: A decentralized mobile manufacturing platform that can be deployed to multiple locations but uses one quality management system;
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Point of care manufacturing: A subset of DM that operates in close proximity to patient care, including places such as hospitals, nursing homes, and physician’s offices; and
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Artificial intelligence: Can perceive the environment through data acquisition, interpret the data, and decide on the best actions.
Steps One And Two Completed: Information Gathered
The FRAME program is proceeding in three stages, Fisher said.
In the first, which the FDA called “Building the Foundation,” the agency brought together top OPQ experts “to assess the existing guidance regulations and statutory authorities to identify any gaps or pain points.”
“Gaps” could refer to missing areas in “provisions, regulations or guidance that govern quality assessment, or inspection that precludes approval of an application proposing to use an advanced manufacturing technology,” while “pain points” are all other regulatory challenges, including ambiguous language, lack of guidance on a specific topic, or lack of technical knowledge on a certain subject.
Examples of things that FDA would consider gaps or pain points include regulatory terminology that may not account for emerging technologies, holes in drug application requirements, and the ability of these technologies to comply with current regulations and standards, Fisher said.
Phase two of the effort focused on making recommendations to address these points, and also planning for the long-term implementation of the framework.
During this period, the FDA conducted an in-depth, two-way impact analysis to inform its potential recommendations, including both the gaps and pain points for new technologies and also how changes to regulatory framework could impact existing technologies.
“Clearly, we don’t want any unintended consequences from something that we’re trying to do here,” Fisher commented.
“This view enabled us to come up with a series of preliminary recommendations for the framework,” he continued.
Agency Poised To Embark On Stage Three: Public Comment
With these preliminary recommendations, the FDA will now be embarking on stage three of the program, which will be a “multi-year effort,” Fisher said.
There will be three main steps that comprise stage three, including:
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Increasing public outreach to share information and provide visibility;
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Gathering input from the public on the gaps and pain points that have been identified to further inform its thinking; and
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Once FDA has had an opportunity to understand the issues, beginning to implement different components of the regulatory framework.
“The crux of our outreach will be public white papers that will share the regulatory gaps and pain points we’ve identified,” Fisher said. “So you can expect to see white papers in the not-too-distant future.”
FDA also plans to take public comments, and post final versions of the white papers after all input has been taken into account.
The white papers and associated recommendations, said Fisher, will inform an overall “internal CDER FRAME roadmap that will be the thing we follow to make sure that we realize this vision.”