PCT is a CDMO (contract development and manufacturing organization) based in the U.S., serving global clients from two manufacturing facilities in Mountain View, CA, and Allendale, NJ, and is a wholly-owned subsidiary of NeoStem, Inc. NeoStem recently acquired California Stem Cell, gaining an important product candidate, as well as a facility in Irvine, CA that’s exclusively being used for the development of the product candidate. PCT offers services from consulting through manufacturing and distribution of cells for testing in clinical trials for a wide variety of therapeutic indications and the manipulation and storage of cells used for cancer treatments.

Bob is PCT’s co-founder and visionary behind its growth and development strategy over much of the last two decades. Bob built PCT to meet a recognized need for high quality manufacturing and development services in an emerging industry. As the cell therapy field has grown, PCT has now served more than 100 clients and performed more than 30,000 cell therapy procedures. PCT aims to bridge the gap between discovery and patient care through efficient transfer of cell-based therapies from lab into clinical practice.

Bob’s vision for PCT includes expansion of its manufacturing capacity in the U.S. and Europe, as well as the development of new technological and engineering innovations that will help streamline and automate many cell processing techniques, leading to faster scale up, lower cost of goods, and improved robustness for the industry.

“Our focus has always been on the future and where the industry is going. We recently opened an engineering and innovation center that looks at scalability, robustness, sustainability, and cost of goods, and the application of engineering principles to better prepare us as an industry for commercial distribution,” said Mr. Preti.” —KB

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Contract Pharma: What is your typical client and what are the main reasons they outsource?
Robert Preti: We have clients spanning the range from university hospitals to big pharma. Most commonly, they are small biotech companies that have one or more cell therapies or regenerative medicines in their pipeline. 

The reason they outsource is to gain access to technical expertise, along with the vision they have for their product. They recognize the manufacturing process is not where it needs to be. We can accomplish the clinical trial manufacturing for them in its current form, but we can also apply our manufacturing, development, and engineering services to help them develop a process that is lower cost, more robust, more scalable, and sustainable.

There are physical requirements in terms of clean rooms and GMP systems that are very expensive to set up. Additionally, there’s a variety of expertise needed from the quality side, the technical side, and the engineering side, manufacturing, and regulatory, in order to put the whole puzzle together for a clinical trial that could ultimately lead to an approved product.

CP: Where do you see cell therapy heading in the short term and long term?
RP: With respect to the cell therapy industry, we’re looking at something that will shift the paradigm in the way healthcare is delivered to patients. Up to this point, therapies have been palliative. With a medicine or even a biologic, to a large extent, you’re treating symptoms and trying to stop disease progression. With cell therapy, the difference is, we’re trying to affect cures. So, in the short term, we’re looking to try and change that paradigm. As many cell therapies are moving into Phase II and Phase III development, with a number of cell therapies from several companies now in advanced trials, we’re starting to get an indication of just how commercial this industry is today. There is great excitement around the innovation of cell therapy and we feel there’s a tremendous amount of energy now and wind behind the field—part of the reason is that big pharma companies are involved.

We’re seeing that long-term potential with cell therapy lies in transforming medicine. It’s this transformative aspect of the industry that excites us all. The fact that big pharma, which previously sat on the sidelines for many years, is now more heavily investing in cell therapy gives us faith that, in the long term, we’ll be able to lessen the overall burden of disease on patients, as well as the economic burden these diseases impose on society today. While cell therapies are expensive and difficult to make, they can affect cures. So, over the long term, the pharma economics are favored for therapies that can become cures as opposed to long-term treatment.

CP: What therapeutics areas do cell therapies address?
RP: Right now, it’s all over the medical map. There are regenerative medicines used to regenerate tissue, with products such as Organogenesis’ Dermagraft and Apligraf, and Aastrom’s Carticel and TiGenix’s ChondroCelect, which regenerate and replace cartilage.

One of the most exciting areas today is in the immunotherapy area, where T-cells, in particular, are used to bolster the immune system and/or dampen the immune system, depending on what the disease state is. There are also cell therapies for diabetes that use manipulation of the immune system to manage the disease. 

Additionally, there are anti-cancer therapies, such as dendritic cell therapies in commercial production; an example is Dendreon’s Provenge, a personalized treatment for prostate cancer. There are also a number of these therapies in the pipeline in Phase III trials, which will tell us how effective these therapies will be as direct anti-cancer therapies.

In the cardiovascular space, cell therapy focuses on the repair of tissue damaged by a heart attack, for example, or to reinvigorate the heart with blood vessels. There’s also a lot of work with ischemia and peripheral arterial disease. Additionally, a fair amount of work is dedicated to neurological diseases, such as Parkinson’s, Alzheimer’s and spinal cord injury. However, immunotherapies are currently getting the most attention, particularly from big pharma in recent years.

CP: What are the main obstacles to development and commercialization? How could they best be addressed?
RP: There are four criteria we use to address the challenges. Production of cells in a high quality and robust way at a reasonable cost of goods, and in a manner that will scale to meet clinical demand and also be sustainable over the commercial life of the product. Essentially, these are the issues we face today.

We have committed ourselves as an industry to the issue of production of a high quality product, something that is robustly manufactured. PCT has worked hard to address these issues. We’ve broken down the process to what are called unit operations. Within those operations we’ve looked at how to replace some of the manual labor and the interaction of the product with people using engineering solutions. People think of automation as one engineering solution, but there are other solutions one can use. By doing that we can take a tremendous amount of the cost out.

That brings us to the second issue, what we call Development by Design. The first portion is a Quality by Design approach. Once you begin to pull some of the manual labor out and replace that with instruments and engineering solutions integration, you can start to bring the cost of goods down and make the products more scalable at the same time.

There are companies that are starting to see some larger volume production, particularly those that are commercial. The issue with patient-specific cell therapies is that for every patient you need to manufacture a product, so for 100 patients, you need to manufacture 100 different products. If the labor component for one product is 10 hours, for 100 products, it will be ten times that. So there’s economy of scale that’s built into the facilities, and at the end of the day, the real costs are in the disposables and the labor.
The physical interaction with the product is where all the problems lie. Scaling becomes really difficult because you have to continually bring in people to train and it’s highly technical and tedious work, resulting in long lead times and high turnover. There’s always a new influx of people, and scaling to meet demand is an industry challenge, which can be helped with engineering solutions.

Finally, as you replace some of the manual manipulations, you end up with tools and technologies that will be around for the long haul. Today we are in a boutique industry where many of the tools we use are from suppliers that may have one or two tools they sell. The problem arises if enough companies aren’t using the tools, they might not be around anymore.  

For example, Baxter had a number of interesting and useful products on the market for us to use as an industry, but has moved out of the space through its own corporate decisions, and no longer supplies these instruments and enabling technologies. Therefore, if those devices were built into your manufacturing process, you now have to find a way to replace them. We look at that as a sustainability issue.

CP: How do you approach R&D differently, and what is the importance of CMC (chemistry manufacturing and controls)?
RP: We step back and take a holistic view of a manufacturing process using our understanding of this industry. Today, the CMC section and the manufacturing are incredibly critical. The products we produce are very complex and it’s difficult to understand their mechanism of action completely, in part because they are a heterogeneous mixture of cells. We don’t fully understand what each of the cells in this mix does and for how long, which is also part of the beauty of cell therapy. It’s declaring that we may not understand the disease process as well as the cells do. So, we are creating products that have definitions that are not fully mature. If we change the manufacturing process, we have to guarantee we have not changed the end product. While the CMC aspect is incredibly difficult, quality, cost sustainability, and comparability are the end goals.