At our annual breakfast event during Phacilitate Cell & Gene Therapy World, we hosted a panel discussion exploring the next grand challenge for the cell and advanced therapies industry: dramatically lowering the cost of manufacturing a (cell) therapy.

Invetech’s Brian Hanrahan was joined by Peter Olagunju (bluebird bio), Rodney Rietze (Novartis Pharmaceuticals) and Dieter Hauwaerts (Celyad) in discussing how the industry can address this goal of achieving cost-effective therapies through automation.

Below are highlights from the presentations. You can also watch the recording here.

Rapid growth in the cell and gene therapy industry is driving the demand for more efficient and cost-effective manufacturing solutions. In opening the discussion, Brian Hanrahan, Manager, Cell Therapy at Invetech, set the scene by referring to a recent industry survey Invetech conducted among more than 70 cell and gene therapy leaders. When asked about their greatest challenges to implementing automation, the two top responses were cost (38 percent) and process complexity (31 percent). Hanrahan stated that these are actually the two reasons why you should want to automate and opened the discussion to the three panel members.

Peter Olagunju, Senior Director of Technical Operations at bluebird bio, looked to the recent past to open the conversation with what he considers ultimately a success story: Dendreon and Provenge, the advanced prostate cancer immunotherapy.

“In my experience, some people view this as a negative story, but domestically Provenge is a success story. When you look at the complex operations involved—the constraint of an 18-hour shelf life both inbound and outbound—the therapy still manages to reach thousands of patients on an annual basis.”

Olagunju continued that, “at a cost of $93,000 upon launch, it was controversial and COGS were greater than 100 percent; but, the product generated $275M in its first 18 months on the market, which is significant. And if we look to 2016 results, this product has now reached close to 3,500 men. This is a great example of a product delivered at scale. And if you consider three cycles of treatment for each patient, that translates to more than 10,000 transactions.”

Since the time of launch, via looking at optimizing unit operations and areas where enabling technology could be deployed, those COGS are now less than 40 percent. This shows that automation can reduce COGS.

Olagunju also briefly explored how to help companies plan for scale-up and invest wisely in automation.

• Strive for organization-wide communication. This includes development, commercial, marketing teams, and particularly insights from the field (patients and physicians). This allows you to tweak unit operations to address some of those needs to enable clinical and commercial manufacture and delivery.
• Know your process and rate limiting steps in development. If we consider lessons learned from the Dendreon experience, the 18-hour shelf life of their product was an issue. This has driven many in the industry to pursue 48 hours.
• Fresh versus thaw. Being able to cryopreserve at certain steps can add more latitude and flexibility.
• Capacity considerations. It is important to understand the lack of CMO storage and transplant capacity and how this factors into your scale-up strategy.

When thinking about where to start with automation, Rodney Rietze, Lead of cGMP Process Automation at Novartis says, “start small, think big. The optimal time to automate is right at the beginning. The more the researcher is using technology that will enable automation, the better it is for everyone.”

Rietze continues, “in the early stages when you are developing and integrating automation and closing the unit operations, look to off-the-shelf automation solutions for immediate value. Targeting specific unit operations lowers risk. And consider your options early. There are off-the-shelf solutions out there to automate wash and volume reduction that are not cost-prohibitive.”

“For a longer-term view, look to new devices but invest in equipment that will have beginning to end impact. For example, when Novartis needed to improve cell capture, this was achieved through investment without affecting the process.”

Further discussion was had around the challenge of: when is the optimal time to automate? Rietze made a key point that automation is the first opportunity to lower variability. “It need not be a one-off event, but rather a strategic decision. Ask questions such as, what is the product, what is the process? Then focus on automating the expensive and highly variable areas.”

Rietze went on to reinforce Olagunju’s suggestion that you must involve all internal stakeholders. “What are the parts of the process that are highly variable, where can we make the most impact, and where do we not have product drift?”

Think about what your product is: how is it defined, how is it produced, where is the variability and how that is controlled? If you don’t know your product, you are at a high risk when you go to automate your process. Remember that the process is the product.

In discussing his position on introducing automation, Dieter Hauwaerts, Vice President of Operations at Celyad, provided a number of thought-provoking discussion points.

When thinking about automation, “do the things you need to do, not just things you can do. You must aim to automate for product success from a clinical, medical and commercial perspective. Therefore, when thinking about where to start, start with the end in mind—the commercialization of your therapy—then work backwards.”

Hauwaerts suggests establishing a framework used to define needs. At Celyad, they have been using the Target Product Profile (or TPP) approach. He points out that while mainly used for pharmaceuticals labelling and product claims, it helps define the process development required to progress your product to a manufacturable commercial scale.

Hauwaerts further explored the TPP approach when he stated, “in focusing on a TPP, ask yourself: what does the product, and the environment in which it will be placed, need? For example, is it a product that has value in being cryopreserved? Will you do multiple infusions? If the product has to be infused in a setting that has high capacity constraints, having flexibility is critical. But if your patients are in urgent need of product, a 48 to 96-hour shelf life means you can get it there quickly and fresh and so the cryopreservation step might not be useful in your setting. By ensuring there is no disconnect between clinic expectations, sales and marketing, what you develop will be the most appropriate product for your circumstance.”

Another example that can be driven by the TPP is cell selection, according to Hauwaerts. “Wanting cell selection for both CD4 and CD8 is a nice-to-have feature. But if your TPP says there is no specific requirement for both CD4 and CD8 cell selection, don’t do it.”

In closing, Hauwaerts sets everyone a challenge to dream big. Dare to challenge engineers, scientists and clinical teams to aim for a high goal.

“Set yourselves a far-reaching goal. It is better to aim for the stars and achieve 60 percent, rather than merely plan for next week and achieve 100 percent!”