//     May 23, 2022

The manufacturing trap (by Marcos Valadares)

https://www.europeanpharmaceuticalreview.com/news/107546/investment-in-uk-cell-and-gene-therapy-manufacturing-set-to-continue/

Previously, we have discussed here that cell therapies hold great promisses but are currently limited in their potential by manufacturing problems, that is, even successful (read approved) cell therapies are only treating thousands of patients a year, not millions. Think about this: as of today, there are many patients that could potentially be treated by an approved game changing curative cell therapy but they cannot access it because the manufacturer has no means to actually produce and deliver that therapy for all patients. Whenever a process cannot reach the volume we need it to reach we say that the process is not scalable.

You might think: why would a drug/cell therapy manufacturer develop an unscalable process? This is a great question that begs for a more in-depth answer.

Let’s just get the perspective of small molecules here as a therapeutic product. Whenever you found a new molecule, you found an entity that can be protected (patented) and there might be many routes of chemical synthesis to produce it. Regardless of the route of synthesis, if you end up with that molecule, you have the same product. After all, this new entity is chemically defined.

Now when working with biologics (proteins or cells) that is not the case at all. It turns out that the process with which you produce your biological product defines your product. So if you make changes to your process, you are very likely to change your product too. This reality gave birth to what is generally assumed to be a truth statement in the CMC space for biologics: the manufacturing process IS the product.

Now let’s go back to the previous question: why would a therapeutic company develop a non-scalable process to produce a cell therapy product? Because to develop a scalable solution, the company needs to spend millions of dollars in process development to make sure their processes are scalable even BEFORE they try their products in clinical trials. This means, if their product fails in clinical trials, they would have spent large sums of money that can’t be recovered now. So, to avoid this, these companies generally tend to disregard how expensive or complex (read unscalable) their manufacturing process really is in order to advance their clinical programs and get true human data (which is the most important piece of info a therapeutic company really needs). You can probably guess the results by now: many companies do fail indeed (the odds of success are small) but the ones that do succeed, are now bound to their unscalable high-cost manufacturing process that can only be deployed for very small patient population (and very high price tags). Even if they wanted to change their manufacturing process, they wouldn’t be able without needing to shoulder the costs for another clinical trial to prove their therapy remains effective in despite of the changes they made in their manufacturing process. After all, the process is the product. If you change the process, you very likely changed the product too. They fell prey for the manufacturing trap.

Don’t get me wrong: the company owning the successful therapy will very likely and justifiably reap the benefits of developing such a successful therapy. Patients too will benefit. However, just a small portion of them. This is the upsetting part.

In order to break that cycle, we need to think on scalable process from the beginning. The only answer we need to answer prior to this is: do we really believe cell therapies will have a prominent role in the future? If no, then we don’t have a pressing need. If yes, than it is safe to assume we should be working on scalability of these therapies ASAP. At LizarBio the answer for us is a loud YES and therefore we are building the first platform to produce any cell type in the body at industrial scale for therapeutic applications fro 1% of the cost. We hope that in the future, no patient will be underserved because of manufacturing constraints. Stick around to know more on how are doing this.

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