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2023 ISPE Facilities of the Future Conference: Cell & Gene Therapies, Facilities Planning, & More

Beau Castro
FDA Peter Marks

The second day of the 2023 ISPE Facilities of the Future Conference in North Bethesda, Maryland, included keynotes addressing various facets of the industry and their impact on future facilities planning and development. Key among these included a presentation by the director of FDA’s CBER on cell and gene therapy manufacturing and a range of considerations behind new facility planning from a Janssen Pharmaceuticals executive whose company has been paving the road ahead with its facilities.

Peter Marks, MD, PhD
Director, Center for Biologics Evaluation and Research

Peter Marks, MD, PhD, Director, Center for Biologics Evaluation and Research, US FDA, presented on “The Importance of Manufacturing in Cell and Gene Therapy Development” in an afternoon keynote on 1 February. He discussed the current state of gene therapy development, overcoming manufacturing barriers, and FDA actions facilitating development.

The number of original investigational new drug applications (INDs) peaked in 2020 at 308 and declined slightly in 2021 to 300, which has been a reasonably good rate despite the pandemic, Marks said. Amendments to INDs have been soaring in recent years to a peak of 10,857 in 2021 from 4,473 in 2015. Approvals of gene therapies in the US have continued to climb as well: five new gene therapies were approved in 2022.

Marks noted the importance of gene therapies for disorders that are very rare: gene therapies may address these where small molecule or protein-based therapies won’t be developed. “If we could get gene therapy right on a small scale, we may be able to get it right on a large scale,” Marks said. Successful experience with small populations of rare diseases will make it easier to move to larger populations, he added.

Marks said that the industry is entering the age of individualized medicine, or creating the right drug to treat the patient. These fall into two categories:

  1. Customized products with the same indication and same mode of action. An example: a personalized vaccine for pancreatic cancer using dendritic cells pulsed with an individualized peptide mixture.
  2. Created products with different indications and different mode of action. An example: gene therapies for two different hemoglobin mutations using the same vector backbone.

Individual therapies present challenges, he said, including manufacturing, nonclinical development, clinical development, and product access. And he noted that possibly due to the pandemic, there has been little progress in achieving commercial viability over the past 5 years for these treatments.

Automating vector production is one approach to consider, Marks said. A lot of process in gene therapy production can be automated; downstream process of vector purification is very similar for any adeno-associated virus. He also observed that small batch gene therapy manufacturing may be able to be accomplished on a device platform.

Marks outlined some concepts that could be helpful in manufacturing cell and gene therapies:

  1. Cookbook for development and manufacturing of bespoke therapeutics; FDA is working with the National Institutes of Health on a playbook. The goal is the ability to transfer the technology.
  2. Leveraging of nonclinical and manufacturing data from one application to another. This focuses on the concept of originator and offshoot products leveraging information on file and focusing on distinguishing attributes of offshoot products.

While gene therapies are not devices, Marks said there is a device-like element to gene therapies. For instance, for many adeno-associated virus gene therapies of a certain type, it may be the same elements over and over—the vector, the delivery device. Streamlining and having a series of linked products could help in coming up with therapies for small numbers of people; this could also help with product manufacturing updates since with 20 linked products, updating manufacturing of the originator product could “waterfall” to the rest.

FDA is working to support global collaboration for gene therapy with potential areas including developing preclinical study requirements such as for toxicology studies; environmental assessments; manufacturing information on areas such as identity, purity, and potency; and clinical outcomes. Next steps on convergence that he outlined included convergency of regulatory approaches in high-income countries and encouraging sponsors to consider global development programs that include the US inviting other regulators to early-stage meetings.

FDA has two programs that are helping to support early-stage development, working toward accelerated approval and areas such as advanced manufacturing: INitial Targeted Engagement for Regulatory Advice on CBER ProducTs (INTERACT) and CBER Advanced Technologies Team (CATT).

Planning for Facilities of the Future

The last keynote on 1 February focused on how the industry is moving ahead with planning for facilities of the future and what should be considered. James A. Breen, Jr., PE, Vice President, Lead Biologics Expansion, at Janssen Pharmaceuticals, presented on “Facility of the Future–Considerations, Planning and Realization.” He reviewed and summed up themes addressed during the conference.

Facility of the future considerations discussed by Breen were technology, sustainability, digital, workforce of the future, risk management, and operations. He noted that moving ahead is a journey, and encouraged attendees to look for different flexibility and agility options. “But how do you really do that? Can we as an industry do all this? I think we can. It’s just how we approach this.” He provided more detail on each area.

Technology: Strategy, maturity roadmap, and transformation roadmap are the tools to use. “Cell and gene therapy is constantly changing—how do we think about that?” The industry needs to address how to transform the roadmap to go from step to step; usually looking 10 years down the road with flexibility since we do not know in five to 10 years what may happen is best.

Sustainability: This area is changing a lot, Breen said. The industry is considering how to approach scope 1, 2 and 3 and LEED certification of new buildings. Purchase of renewable energy, product design that is changing, and materials in construction are in consideration, but a lot of product is changing constantly, as is the speed of transformation.

Digital: Breen gave the example of Janssen’s considerations in constructing its facility: they decided at the start that the facility would be all digital, no paper, for a large biologics plant. They followed many concepts from Pharma 4.0™. There was leverage from different plants to support this and gain speed. The facility does a lot of multivariate analysis. Operator training to work in this environment was needed, he noted.

Workforce of the future: Facilities need to be able to train operators, often in all-new technology. Also needed is leadership that can lead teams, have the emotional intelligence to get everyone to work together and work globally. It requires an investment in learning to work digitally, he observed. Sustainability ties in, with younger employees are asking for this. Diversity, equity, and inclusion (DEI) are about having a different workforce with different inputs and views.

Risk management: This area is really interesting right now, Breen said, with how much the world has changed since the start of the pandemic. He noted the World Economic Form’s Global Risks Report 2023 as a source of information about the changes. “We can’t control risk but we can try to mitigate it,” Breen said. “Risks have changed!”

Operation: The Global Lighthouse Network was cited as a good report on what people are working on, Breen said, noting that there are changes each year.

The primary obstacle to successful scaling of industry 4.0 has been lack of resources and capabilities. Investment and leadership commitment are also important, as is speed to be able to go fast and be affordable and flexible.

Conference Highlights