No, One Size Does Not Fit All

So many ways to go wrong and no clear path to getting it right – nobody said launching a gene therapy platform was easy… But to help us get to grips with the problem, we spoke to David Smith, the Vice President of Technical Operations at Ori Biotech.

Describe the essence of the problem…
 

In both gene-modified cell therapies and vector-based gene therapies, we are failing to provide access to addressable patient populations. Forcing researchers and developers to change their processes to fit the constraints of currently available technology can reduce the quality of a gene-edited cell therapeutic product and directly impacts cost and speed of clinical programs, regulatory submissions, and ultimately patient access.

This industry is still learning, evolving, and pushing existing technology to its limits, and therefore the need to bend, flex, and be agile is crucial.

And now some of the specifics…
 

We, as a field, have to reckon with problems concerning closed and open processes, automation, scalability, cost, and supply chains, to name but a few.

Completely closed processes, whilst a commonly discussed topic, remain an elusive solution. Many parts of processing still require open operations. And that’s especially true of small volume fluid transfers, such as vector additions and protein supplements. Given the stability and cost of these reagents, manually pipetting in a Grade A environment remains a common feature of most processes.

The need for automation often goes hand-in-hand with closed processing. Automation is crucial not only to lowering costs, but also to increasing accessibility. The current manual operations require extensive training of highly paid professionals to perform highly skilled manipulations. Unsurprisingly, this renders the process expensive and complicated, and therefore harder to scale up and industrialize.

And that leads to the challenge of scalability, which is still very much overlooked - or dismissed offhand as a challenge that a developer will tackle at some point in the future. Given the need for rapid development and clinical trial schedules to deliver speed to market, therapy developers are looking for platforms that can be used from development through to commercialization more than ever. As the industry moves away from testing, our task must now be to produce therapies that are commercially viable; cost, scalability, and sustainability must factor into technology adoption decisions much earlier in the development process.

Given the advancement of gene-edited cell therapy in the last years, technology providers have found it hard to keep up with the demand for their products. No thanks to global crises and political instability, the vulnerable level of sustainability in supply chains and materials has had a considerably negative effect on clinical trials and an even more severe effect on commercial products. As the industry continues to bring more products to market and to service more patients, our fragile supply chains continue the great trial by fire of the 2020s. If we don’t strengthen those chains, we may well see them break…

What kind of groundwork should a company lay out at the very beginning, when designing a new technology for the field? 
 

When developing technology for the cell and gene therapy field, understanding manufacturers’ needs is critical. Far too often, the tech developed solves a perceived need rather than the actual need. We can see this when players assess one section of the industry and assume the same limitations are in place industrywide. For example, assessing only academic CAR T developers will reveal one particular need completely different from the need revealed when one speaks to late-stage iPSC developers.

Differences are omnipresent. Among the stakeholders there are academics, developers, and service providers. The stages of development are threefold: preclinical, clinical, and commercial. Products can be allogeneic, autologous, large scale, small scale, adherent, or suspension-based. The complexity and variation is almost endless, so a one size technology does not fit all.

What has your experience taught you?
 

Keep it simple. It will be close to impossible to create a manufacturing platform or solution that can service the entire gene-edited cell therapy industry, so look to segment the industry and identify where a need isn’t being met, or where a technology fits best. Alongside this, never stop asking questions to your network of potential customers and partners. These are the people that will best inform your ideas. Use partner organizations to continually assess your progress and make sure it’s still meeting a true need, and don’t be afraid to pivot if you find out that it doesn’t.

As with any nascent industry, it’s incredibly hard to know where our field is going. On top of that, developing any technology is a multi-year project – so you’ll need to verify whether the need you chose to address three years ago still exists…

What changes are likely in the years to come?
 

Over the last decade, more investors and large pharmaceutical companies have joined the field. And that’s inspired interest from other players, such as service providers and companies selling enabling technology. For example, there is a lot of focus right now on using AI technology to streamline manufacturing.

The other major boom will be the integration of information technology and operational technology. Process automation will have a profound effect within the cleanroom, but this digital infrastructure can also vastly improve quality, speed to market, and safety. Investigating supply chain, quality control, and quality assurance may reveal new areas where investing in a digital infrastructure will pay dividends in resources and quality.

What is your top advice for newcomers to the field? 

Protecting and possessing your own ideas won’t help you in the long run.

The most successful technology we’ve produced as an industry has come about through collaboration. Making these therapies is hard, but doing it alone is even harder. It’s important to keep in mind that the end goals are patient access and improved clinical outcome. We are all working so diligently to create a better outcome for millions of people, and without working collaboratively the challenges will not be overcome quickly enough to bring these life changing therapies to the patients that need them.

What is your ultimate vision for the future of gene therapy manufacturing?
 

My vision is accessibility to anyone that can benefit from a gene-edited cell therapy treatment.

Right now, we have an industry that produces life changing therapies that only a handful of lucky patients have access to. At the heart of the accessibility issue is the huge unmet need in manufacturing technology platforms with digital infrastructure and partner ecosystems that work together to deliver widespread patient access.