Luxturna Maker Spark Therapeutics' Flexible Platform Approach

A conversation with Chris Stevens, Spark Therapeutics

The platform concept, by strict definition, suggests rigidity. But making complex molecules or nucleic acids, with all of their variability, demands the opposite.

Officials at Spark Therapeutics think they found a Goldilocks combination at their Gene Therapy Innovation Center in Philadelphia, with just enough structure to achieve efficiencies but technologically fueled flexibility to adapt to changing demands.

Spark’s Chief Patient Supply Officer Chris Stevens will talk about the company’s approach to the flexible platform at the 2024 International Society for Pharmaceutical Engineering (ISPE) Annual Meeting & Expo.

Before the conference, we asked him for a preview of his talk and had some questions about Spark’s approach. Here’s what he said.

When you're developing a flexible gene therapy platform, what functional groups or skillsets are working at the whiteboard together?

STEVENS: We think of the term “platform” as a holistic term in that it encompasses the potential therapy as a fully integrated complete asset.

Because of this holistic point of view and perspective, all of the key groups in the value stream — ranging from research and development (which includes process, analytical, and clinical) to manufacturing and commercial — are critical to developing a flexible and fully integrated gene therapy platform.

Practically speaking, how are you using digital twins to design flexible manufacturing spaces?

STEVENS: When you operationalize a new technology, there is significant uncertainty due to the nascency of the technology.

By “building” a digital version of your facility, you can simulate many operational strategies, process options, and resourcing plans in advance of the facility being operational. This ensures that what you are building will be able to effectively operate under a variety of conditions that may be of interest to you.

Examples could include various shift structures for the operations teams, the impact of new process technologies like producer cell lines for AAV, or sharing of portable, single-use equipment across manufacturing suites.

This technology sounds ideal for facility design applications. Does it have any shortcomings to watch out for?

STEVENS: As with any modeling exercise, the quality of the inputs is highly correlated to the quality of the outputs.

By developing a questions-of-interest list, you can help drive toward the right level of detail on the inputs, which ensures you can answer the highest-value questions appropriately.

What are your priorities as chief patient supply officer and how do they fit into Spark's mission?

STEVENS: While Spark’s mission is to unlock the power of gene therapy to accelerate healthcare transformation, our Patient Supply organization is key to achieving and enabling that mission by reliably delivering our products — and potential products — to patients.

Beyond reliable supply — which is foundational — we have several other priorities critical to the acceleration element of our mission. These priorities include building and operationalizing our new Gene Therapy Innovation Center (GTIC), which is located in West Philadelphia in the heart of the University City neighborhood.

This 500,000-square-foot, multistory facility will serve as a Roche center of excellence for gene therapy manufacturing globally. The new space will allow cross-functional teams to come together and work side by side to create a world where no life is limited by disease.

The underlying digital systems that will allow us to operate the GTIC in a flexible and efficient manner are another key priority for our team. These digital capabilities start at the enterprise resource planning (ERP) level and extend to the full integration of the instruments for each piece of process equipment. Our focus this year is on delivering the ERP system for the GTIC, which is expected to be completed in 2026.

What's your approach to scaling?

STEVENS: From a macro perspective, scaling must be viewed in the context of products and their individual needs. For example, because gene therapies generally target specific tissues, some smaller tissue areas are reached via relatively low doses that don’t require scaling up or out.

Other potential products — such as those delivered systemically — may require larger doses and therefore drive the need for scaling. In this case, we can learn from and leverage the highly effective process and analytical development efforts in large molecule manufacturing relative to process productivity vs. scale and the amount of investment required in each.

In 2017, former FDA Commissioner Scott Gottlieb called Luxturna's approval a "turning point" for novel therapies and promised a regulatory framework to support innovation. From your perspective, how has that played out?

STEVENS: The development life cycle of any medicine is measured in years, so we are just starting to see a wave of gene therapy approvals that stemmed from investments made in the 2017-19 timeframe.

These companies saw — and learned from — the Luxturna approval as well as a few other early approvals in gene therapy. The regulatory authorities have done quite a bit to keep pace with industry and fully engage, which is encouraging. It’s also important to consider that we are all learning in this nascent space, so being able to work with health authorities that are continually and quickly evolving their frameworks to support innovation based on those learnings is equally encouraging and promising.

So many companies have unproven platforms. Spark has a unique viewpoint as a company that has done it from start to finish and produced a commercial product. What are some of the biggest lessons Luxturna taught you?

STEVENS: Luxturna is now approved in approximately 50 countries around the world. While there have been many lessons learned throughout its life cycle, one of the primary learnings relates back to why we think of the platform holistically.

The platform has to be fully integrated, proactively incorporating commercial, regulatory, and access considerations in order to develop and deliver products that can help as many patients around the world as possible.

About The Expert:

Chris Stevens is chief patient supply officer at Spark Therapeutics, which he joined in 2017 to lead all internal and external drug product and drug substance manufacturing. Previously, he was a senior director at GSK and before that he worked at Bristol-Myers Squibb. He received his M.S. in industrial management at the University of Southern Indiana and a B.S. in chemical engineering from Purdue University.