Mapping Cell And Gene Therapy Processes: A Common Frame Of Reference For Scientists And Engineers

Collaboration in the fledgling cell and gene therapy sector is crucial to its success and helps identify critical challenges and best practice solutions. Here, two experts discuss how coordinated industry dialog and joint working have helped develop cell and gene therapy process maps that will educate, bring consistency and drive clear communication in these unique operations.

Cell and gene therapy has only recently started being commercialized and standard methods for generating therapeutic products are continuing to change. Many companies are therefore developing their own procedures following general biologics processes, which often do not directly apply to cell and gene therapy.

These divergent processes mean there may be confusion and inconsistency – made worse by significant gaps in publicly available information on the industrial practices used to produce cell and gene therapies.

To fill these gaps, BioPhorum’s Commercialization Workstream, part of its Cell & Gene Therapy Phorum, has generated a series of cell and gene therapy process maps containing example processes, unit operations and platform technologies being used in manufacturing. The maps form a common frame of reference for scientists and engineers working within the field. They also encourage collaboration on process improvements that will benefit future cell therapy patients by supporting the acceleration of commercialization of novel modalities.

The cell therapy process maps reflect the current state of selected manufacturing processes within the cell therapy field. They form a common frame of reference for scientists and engineers and support collaboration to enable process improvements benefitting future cell therapy patients. Example process maps include a number of autologous and allogeneic cell therapy process variants.

The gene therapy process maps introduce readers to the in vivo gene therapy manufacturing processes and act as an educational tool for people new to the field. The baseline maps can also help drive discussions and identify specific areas that require further expansion. Example process maps include processes for generating precursor materials, different AAV expression platforms, and downstream drug substance manufacturing.

Industry collaboration

BioPhorum is a trusted setting where senior leaders gather to discuss emerging industry trends and challenges. It comprises more than 90 manufacturers and suppliers deploying their top 3,500 leaders and subject matter experts to work in eight focused Phorums. These develop best practices in cell and gene therapy, drug substance, drug development, fill finish, IT, supply partner, technology roadmapping and medical technology.

In each Phorum, facilitators bring leaders together to create future visions, mobilize teams of experts, create partnerships to enable change and provide the quickest route to implement best practice solutions. The Cell & Gene Therapy Phorum comprises 31 companies with more than 400 participants. Its Commercialization Workstream is one of its sub-groups and focuses on all commercializing aspects of cell and gene therapy manufacture.

From the 10 companies involved in the process mapping sub-team, 15 subject matter experts worked on the cell therapy map and 13 focused on the gene therapy map.

While the two maps resulted from a series of meetings over 18 months (both face-to-face and virtual), there are some important intangible benefits of being involved in the discussions. Conversations ranged from sharing best practices and real-world challenges, to giving advice and directing industry thinking. As ever, collaboration and sharing are crucial to success and mean that Workstream members can influence and drive change.

Now that the maps have been published and are being used in the industry, two of the lead authors discuss what value they gained from the process and how they are using the maps in their businesses. Scott Probst is Unit Head of Technical Development and Support at Bayer Pharma. John Kerwin worked with Gene Therapy Manufacturing Sciences at Biogen at the time of the activity and is now Director of Viral Vector Process Development at Resilience.

1. Why were the creation of the cell and gene therapy manufacturing process maps a priority for the group?

Creating the maps became a priority for the Workstream because of the rapid growth in cell and gene therapy products being developed with diverse processes across the industry, and the lack of standard technology platforms.

“When we started these maps the group was new, so we agreed they were a great starting place for members to articulate and appreciate the diversity of the approaches that we’re facing within cell and gene therapy manufacturing,” said Kerwin. “We’re all approaching the space a little differently and this was a great way to document not only the similarities but also differences of our manufacturing strategies.”

Soon after coming together, the Workstream members realized that a common language and terminology for the manufacturing processes were needed to improve familiarity, understanding and communication. This became an important part of the map development process.

“There are a wide variety of therapy types manufactured by member companies, and within each therapy type there are many different technology platforms or possible unit operations,” explained Probst. “Participants from each company also join with very different backgrounds, knowledge and experiences. It was necessary to define a common context in which we could discuss development or manufacturing challenges.”

2. What benefit have you obtained from being part of the Cell & Gene Therapy Phorum mapping Workstream?

While the process mapping originally started as an internal exercise in his organization to provide education about the different therapeutic areas, Probst suggested the maps “were something we could do as a Cell & Gene Therapy Phorum team exercise as this would bring extra value through more people looking at them from different perspectives and with different experiences.”

Developing the maps has been a rewarding experience for the Workstream members and has broadened their understanding of cell and gene therapy approaches. “We have an opportunity to really move the needle and I think the BioPhorum group helps us to appreciate the large steps we have already taken, not only as individuals but also as a collaborative group,” said Kerwin.

3. How will you be using the maps? 

“The maps can be a tool for focusing on a new topic or even for identifying what those topics might be,” said Probst. “They could be used in an exercise to work through each block in the map and then brainstorming what type of challenges are in a particular process step. They are a platform for driving future communications and identifying project ideas.”

Kerwin envisions the maps to be a standard tool not only for internal communication, road mapping and the external dissemination of technology, but also to help facilitate discussions. “With the diverse approach industry is applying to cell and gene therapy manufacturing, the maps can at least provide a standard language and terminology for manufacturing practices. There’s still a lot of sensitivity around sharing information but we acknowledge there are multiple ways we’re approaching the same unit operation. This could be a good opportunity for us to do a technical deep dive into some of these unique unit operations.”

4. How do you see the mapping publications benefiting the cell and gene therapy industry?

“The maps attempt to represent the spectrum of processes used within our cell and gene therapy community and serve as a communication platform for our future collaborations,” explained Probst.

They will enable the similarities and differences of manufacturing strategies to be seen and will benefit a broad group of people across the industry by serving as an educational resource and an initial guide for deep-dive approaches.

Kerwin agreed that the maps are a standard tool that will help communication and added, “They will also help drive a standard way that we’re visually connecting manufacturing platforms.”

5. Who do you feel will benefit the most from the creation of the maps?

“For novices, the maps are a good place to start when trying to learn about manufacturing processes with which they are unfamiliar. They provide a preliminary orientation to folks who are just getting started and can help individuals start asking insightful questions faster,” said Probst.

Those with more experience in cell and gene therapy will also benefit from the maps. “Experts will be able to appreciate the diversity of the approaches described in the maps and start to leverage best practices, orthogonal approaches or different platforms and fold these into their current strategy for further optimization,” explained Kerwin.

Probst added that the maps could help other teams on a site. “For example, in a multi-product facility, it would help teams to know what different types of processes might be running in the same facility.” He suggested that they could also be used in the other activities being discussed by the Cell & Gene Therapy Phorum, such as raw materials, analytics, regulatory strategy, validation, commercialization of cell and gene therapy manufacture, and environmental health and safety and biosafety.

6. What are the benefits of doing this work in collaboration with the other companies in the Cell & Gene Therapy Phorum?

“Working with other folks in BioPhorum expands the experience base and increases our exposure to different types of processes and technologies. It is also helpful to get the perspectives of others and benefit from the diversity of the group,” said Probst.

The collaborative aspect of the BioPhorum work is, as ever, an essential aspect of how the Cell & Gene Therapy Phorum works to develop agreed industry-level approaches. “We’re all doing this a little bit differently but, ultimately, we’re all facing a really exciting and difficult scientific challenge,” added Kerwin. “I think for a scientist or an engineer this is a great space to be in.”

The above Q&A shows the value of industry-wide discussions and how these support the accelerated commercialization of novel modalities. However, creating the maps is just the start, not the end of the conversation. Further benefits will be gained from the discussions of subject-matter experts using the maps to identify future challenges and potential mitigation strategies to drive improvement and standardization in cell and gene-modified cell therapy manufacturing.