NASEM-Led Study for FDA is Helping Drive Industry/Regulator Agenda on Innovation Needs

An FDA-commissioned study carried out through the National Academies of Sciences, Engineering, and Medicine (NASEM) is helping drive the industry/regulator agenda on advancing innovation in pharmaceutical manufacturing.

In 2020, CDER’s Office of Pharmaceutical Quality (OPQ) engaged NASEM to help FDA look beyond what it has been seeing in its Emerging Technology Program (ETP) towards the manufacturing technologies the agency might expect to review in the next five to ten years, with the aim of assuring that the regulatory framework can support their use.

A series of workshops were convened to solicit input from industry, academic and government experts, and a 120-page report was produced outlining the technical and regulatory challenges and opportunities in enabling the “innovations in pharmaceutical manufacturing on the horizon.”

NASEM and FDA then held a “dissemination” workshop in late October 2021 to bring stakeholder thought leaders together to discuss the report. The workshop was divided into five sessions over two days, addressing in turn: ● advances in manufacturing innovation ● existing mechanisms to enable innovation ● challenges and opportunities ● potential solutions and actions, and ● a path forward.

The four-part story that follows has the NASEM report and discussions as a central reference point as it explores the current industry/regulator dialogue on prominent areas on the innovation agenda, including continuous manufacturing, distributed/point-of-care manufacturing, and digitalization and artificial intelligence (AI).

PART I: The NASEM Study and FDA Reflections

The story opens with a review of the aim and process of the NASEM study, what it covered, the group of experts and organizations involved, and the observations and recommendations that were provided in the report.

The NASEM/FDA workshop began with a summary of the study and the report by Purdue University’s Gintaras Reklaitis, who chaired the study committee. OPQ’s Michael Kopcha then shared his thoughts on the findings of the report and the initiatives his office is engaged in that are addressing the recommendations, including the Emerging Technology Program (ETP) and the Framework for Regulatory Advanced Manufacturing Evaluation (FRAME). Observations were shared at the opening session by members of the NASEM study committee on the study experience and the outcomes of their work.

PART II: The Existing Mechanisms to Enable Innovation

Following the opening remarks, the first workshop session closed with industry perspectives from GSK’s Narendra Bam and Thermo Fisher’s Jessica Settimi on the benefits experienced from innovation and their company’s engagement with FDA’s ETP.

Exploring further the different mechanisms to enable innovation from the regulator and industry perspectives, the second session led off with OPQ’s Larry Lee and Joel Welch explaining how the ETP program was evolving to address the NASEM report recommendations and the pathway forward marked out by the ETP 2.0 roadmap.

Following a review by Biogen’s Rohin Mhatre of existing industry mechanisms to enable innovation in pharmaceutical manufacturing and how Biogen is deploying them, GSK’s Sarah Arden explored the broader opportunities for FDA and global regulatory engagement. Arden had just moved to GSK from FDA, where she was a thought leader in the advanced manufacturing/Pharma 4.0 arena.

PART III: Challenges and Opportunities

The third part of the story builds on the discussion around the “challenges and opportunities” that took place in the third NASEM workshop session.

Resilience’s Tom Ransohoff addressed the challenge of evolving the pharma mindset from one reflecting decades-long development timelines to one receptive to more rapid technology innovation. Echoing that theme, EMA’s Dolores Hernan then pointed to the initiatives going on in the EU to overcome that resistance, which are supported in its strategy papers. These initiatives include EMA’s Innovation Task Force, interface with the Quality and Biologics Working Parties, and collaborations with academic/research institutions and with regulators outside Europe.  

International Academy of Automation Engineering (IAAE) lead Mike Hourigan echoed industry consultant and former UK MHRA assessor Malcolm Barratt-Johnson on the importance of manpower and education needs in advancing pharma manufacturing and the related initiatives underway through NIIMBL and other organizations – a topic that also drew attention in the engaging panel discussion that followed, which explored the themes raised in the session presentations. Hourigan described the collaborative initiatives IAAE is engaged in with FDA support to develop resources for advancing the use of digital twins and other digital and platform technologies and the adoption of medical product “smart manufacturing.”

IV: The Path Forward

The second day of the NASEM/FDA workshop included sessions focused on “solutions and actions” and “a path forward.” Perspectives were offered by OPQ’s Adam Fisher and Tom O’Connor, NIIMBL’s Kelvin Lee, Rutgers University’s Fernando Muzzio, and Duke-Margolis Center for Health Policy’s Gillian Sanders Schmidler and Stephen Colvill.

Fisher focused heavily on the FRAME initiative – explaining its current focus on developing the regulatory framework to support end-to-end continuous manufacturing, distributed and point-of-care (POC) manufacturing, and artificial intelligence, in particular, as the initiative shifts from the foundation and planning phases into the implementation phase. O’Connor followed with insights on how FDA’s collaborative research and training programs were informing application assessments, and policy, workforce and guidance development. Included in Part IV is an update provided by O’Connor at the IFPAC June 2022 conference on FRAME’s outreach activities. These include a series of papers that are nearing release on distributed and POC manufacturing and AI, intended to further stakeholder engagement on the regulatory issues involved.

Lee provided his insights on: ● how business risk concerns, along with a fragmented global regulatory environment, are creating resistance to implementing manufacturing innovations, and ● the need for stakeholders to join with FDA in overcoming the hurdles and assuring that the needed resources are in place. Muzzio discussed Rutgers collaborative work on continuous direct compression and the support it has gotten from FDA in creating a “knowledge base for CDC.” An effort is now underway with USP to develop a “Knowledge Center for Pharmaceutical Continuous Manufacturing,” intended to facilitate PCM adoption. The Duke-Margolis experts added their ideas on the opportunities for strengthening biopharma innovation and supply chain resilience, including funding to develop “Centers of Excellence.”

The panel discussion that concluded the workshop focused on how the key issues in advanced manufacturing implementation could be addressed. A summary by the workshop committee of those discussions is included.

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