Inside eXmoor Pharma’s New Cell and Gene Therapy Manufacturing Hub
Technology Networks visited eXmoor Pharma to learn about its journey to becoming a cell and gene therapy CDMO.
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eXmoor Pharma has received a Manufacturing and Import Authorisation for Investigational Medicinal Products (MIA(IMP)) license from the UK’s Medicines and Healthcare products Regulatory Agency (MHRA).
The facility can now offer a full range of good manufacturing practice (GMP) services for cell and gene therapies (CGT), including manufacture, fill/finish, packaging, labeling and shipping to global clinical sites.
eXmoor invited members of the press to a guided tour of the facility, which showcased its sustainable features and highlighted the facility as a flexible and scalable manufacturing hub.
A 20-year journey in cell and gene therapy
The MHRA license marks a major milestone in eXmoor’s 20-year journey from a consultancy into a full-service, global CGT contract development and manufacturing organization (CDMO). The licensure follows a successful inspection of the CGT facility located in Bristol, UK. This marked the end of a 2-year project to design, build and bring online a 65,000 sq ft advanced therapies manufacturing facility.
During a tour of the facility, members of the press were shown the site's integrated process development and analytical labs and the four GMP cleanrooms, each equipped with up to 2 x 200L bioreactors and multiple autologous cell therapy stations per suite.
A series of presentations from eXmoor’s senior leadership team complemented the tour and explored the company’s journey as a CGT manufacturer.
Angela Osborne, CEO at eXmoor, shared how the company was originally set up to support the concept design and build of manufacturing facilities for biological therapies like monoclonal antibodies (mAb). Starting out working predominantly with academia, the team identified a knowledge gap in the industry: many drug developers lacked expertise on how to translate basic discovery research into CMC strategy, development and manufacturing.
“A lot of our early work was with adeno-associated viruses (AAV) and over time we developed expertise in cell therapies, autologous, allogeneic and then, more recently, ribonucleic acid (RNA) therapies. So now we've got the flexibility to work across all types of advanced modalities that are currently of interest in our area,” Osborne explained.
Osborne described how utilizing internal experts from across the company greatly helped expedite the MHRA license for clinical manufacturing. Collaborative dialogue and building relationships between eXmoor, inspectors and regulators help the company to stay ahead of the latest regulatory guidelines.
“If this industry is to be successful it needs everyone to work together whether this be through client partnerships, supplier partnerships and meeting with like-minded CDMOs to see where can collaborate,” said Osborne.
A seamless transition from process development to manufacture
David Vincent, head of process and analytical development at eXmoor, described the company’s journey in the gene therapy space and beyond. In 2016, eXmoor invested heavily in its process development labs with a focus on AAV gene therapies.
Before 2016, AAV development had been mainly constrained to academia following the death of Jesse Gelsinger from complications of vector administration in a liver gene therapy trial. The field eventually rebounded with innovations such as CRISPR, leading the way to safe gene therapies. Vincent explained how eXmoor has worked with vendors since the resurgence of AAVs to help drive innovation in this space.
“Supply chain in all of its guises is critical […] you want to work with your suppliers so they understand what you need and at the same time you understand their constraints and that’s what guides innovation,” said Vincent.
AAVs are a success story for the biopharma industry and eXmoor is now placed to help develop the manufacturing process of a whole host of therapies. Vincent used induced pluripotent stem cells (iPSCs) as an example of an evolving technology that eXmoor is now supporting in its process development laboratories.
“iPSCs are a difficult cell type to work with and we are now looking at how we can differentiate iPSCs to scale and formulate this in such a way that it can go into a patient,” said Vincent. “For this, we are using an engineering approach similar to that taken for AAVs.”
With the addition of the GMP cleanrooms at eXmoor, the process development group can now seamlessly transition a process from development into manufacturing. “Because we now have the manufacturing facility […] as we develop this process, we understand the scale-up challenges, and we can develop the product to work around any manufacturing constraints,” said Vincent.
“Every single manufacturing facility in the world has constraints but they are all different [...] if you know exactly where the product is going to be manufactured, what equipment and expertise is required, you can build that into the process from the offset,” explained Vincent.
eXmoor utilizes the depth of knowledge in its translation consultancy group to work with clients to help put together an initial target product profile. This initial high-level strategic discussion helps eXmoor define a CMC strategy and identify the areas the process development lab will need to focus its efforts on to help offset any risks from the beginning.
Flexible design for an ever-changing market
In addition to the process development labs, eXmoor now boasts four Grade C cleanrooms including fill/finish capabilities. Touring the facility highlighted the large amount of space in the cleanrooms. This, coupled with the fact that each cleanroom is process-agnostic, enables the company to adapt based on the changing needs of the CGT market.
Inside one of eXmoor's cleanrooms. Credit: eXmoor Pharma.
During her presentation, Emma Ewins, head of GMP Manufacturing at eXmoor, highlighted the safety features in place to ensure zero contamination during the manufacturing process. These features include each cleanroom having its own heating, ventilation and air conditioning (HVAC) system, a unidirectional flow into and out of the labs and controlled access to the labs limited to trained GMP staff only.
The GMP labs played a major role in the inspection that formed part of the recent MHRA license application. “We have just manufactured a 50L vector batch which was one of the initial process transfers from the process development lab,” said Ewins. “This was ongoing during the inspection so we could show the inspectors how we work with the equipment and ensure processes are controlled and safe.”
A sustainable hub for innovation
A standout feature of the facility is its dedication to environmental sustainability. “In the construction, we recycled 98% of the original building back into this facility […] this is something like 2 – 3% above the national average,” stated Gavin Sutton, executive director of capital projects at eXmoor.
The facility also boasts BREEAM excellence status, indicating the sustainable performance of the building. To earn this accreditation, eXmoor had to go through a series of assessments to prove energy efficiency.
Bristol’s strong foundation in academic excellence and the possibilities for expansion of the site fit nicely into eXmoors plans. The facility includes a large amount of space that eXmoor will use for expansion and will adapt based on CGT market needs. The space is large enough to build an additional seven cleanrooms if needed, all while not interfering with any current client projects.
eXmoor has identified that many US-based firms want to run early-phase clinical trials in the UK, which is recognized internationally as having a favorable regulatory environment and considerable CGT expertise. US biotech/pharma also looks to companies like eXmoor when they have a late-stage product and want to bring on board a second manufacturer to supply the product into the UK and Europe.
To further support its customers, eXmoor has set up a strategic partnership with fellow US-based CDMO Kincell Bio to advance development and manufacturing services in Europe and the US to meet growing CGT demands for global clients.
eXmoor plans to continue to build on these strategic partnerships and is currently in the process of applying for a commercial manufacturing license to once again expand its capabilities to service the growing CGT market.
