[Q&A] Protecting High-Value Therapeutics: Designing Single-use Cryopreservation Solutions for Cell Therapy image

[Q&A] Protecting High-Value Therapeutics: Designing Single-use Cryopreservation Solutions for Cell Therapy

In this interview, Georgi Makin spoke with Beth San Segundo, President and CEO of OriGen, about collaborating with cell therapy customers to identify and customize single-use solutions for cryopreservation.

Q: Tell me about the history of OriGen Biomedical.

A: OriGen was founded almost 25 years ago with our first product line in the lifesaving critical respiratory care space of ECMO. In 2003, we launched our CryoStore product line for cryopreservation. When our cell and gene therapy customers started their initial bench testing of our products, we were there to help them, and as they’ve scaled, we’ve kept pace. We’ve even added an additional manufacturing facility to increase our capabilities in late 2020. Our mission is to create medical products that improve patients’ lives and we think we’re well situated to do that.
   

Q: What is it in the history or experience of the company that put you in such a strong position to be able to offer single use disposables for cell and gene therapy manufacturing?

A: We’ve been supplying cell therapy labs and hospitals for almost 20 years. When the Baxter cryobag formally left the market in 2010, we became the preferred provider. OriGen has the experience to understand the unique challenges faced by the cell and gene therapy industry. We’re also globally inspected and audited by our customers and regulatory agencies. We hold clearances from ISO, FDA, MDSAP, NMPA in China, and other countries. These accreditations matter as our customers scale; it means we’re able to support entry into new markets and partner with customers globally. The approval of a customer’s products within a specific geography often requires approval of the containers that are used to store and process those 1 products, and we understand that process and can keep up with it.
 

Q: How are single-use bags currently used in a cell and gene therapy workflow?

A: Our product is intended to be used after apheresis and through cell culture and on to cryopreservation. Customers can maintain a functionally closed system from end to end and utilize our products throughout the entire process. Cells can be frozen for weeks or years, as needed, before or after the completion of the cell therapy manufacturing process. Our products are able to scale with the customer and we work with them from initial design to commercial release.
 

Q: Why is it important to select the right partner when you’re looking for a component of the workflow?

A: It’s incredibly important to pick the right provider who can partner with you, understands what’s happening in the geography in which you are in or are entering, and understands how you are going to be using that product. The customer needs to know that the product is regulated, that the product is approved, and that the product performs as expected. And that is why we consider ourselves to be critical for our customers’ success.
 

Q: To what extent are custom products required by the industry and what aspects can be customized?

A: Customization at OriGen is largely customer-driven and we’ve created a pipeline to facilitate that conversation. We start with our catalog to determine one of our existing 150 SKUs will meet their requirements and through that conversation ensure an understanding of the customer’s process. The regulations that need to be considered are also pulled in at that time. Every customer within this industry has a unique approach to cryopreservation and cell culture. 2 OriGen can create variants of our products to assist in streamlining the customer’s procedure and process. This includes something as simple as changing a pinch clamp to a roller clamp to as complex as a 10-bag set of cryopreservation bags for the efficient fill of a multi-dose product. We also have expertise in sterile fill for cryopreservation solutions into bags, vials, and syringes. Finding the right configuration of OriGen products can minimize waste and allow for GMP alignment in the customer’s facilities. Packaging of the products can also simplify the process to ensure that you’re not having to throw away bags that have been exposed to the clean room space. It can also save time to create a more consistent process for cell manufacturing. As the customer’s unique needs have changed, additional products and parts have been developed and launched to make repeatable and robust processes for our customers.
 

Q: For someone focused on process development, what would be the key regulatory challenges to consider with this level of customization?

A: Most of the plastic products used in the cell and gene therapy are regulated medical devices. They hold a classification that is individual and unique to each geography. The regulations in the US versus Canada are slightly different and the regulations between EU and the UK are also different. We understand the regulations, how our products are classified and how we create those filings.
 

Q: Is there a particular way that you’re working with standards bodies to address these challenges and considerations?

A: Yes, our internal regulatory team is partnered with regulatory agencies around the world. With the recent change in May to MDR requirements, our team has kept up with regulatory agencies to ensure we are meeting those requirements.
 

Q: I’d like to just come back to the idea of customization. You mentioned that you customize products specifically to customer needs. How does that collaboration work? What does that workflow look like?

A: The customer typically approaches OriGen with a problem statement or an initial concept for the product. At that point, a product development engineer will take those inputs and drive the product design. We’ll talk through the regulatory requirements to ensure timeliness of product release. OriGen will evaluate the feasibility of the product as a whole and notify the customer of the next steps in the process. If the project fits within our capabilities, we feel confident we’ll meet the needs and expectations of the customer, we will then proceed with the process. Ultimately, we will provide the customer with a project proposal that includes concept drawings, pricing, sample options, lead times, etc. Then we’ll integrate the customer’s feedback from that proposal. And once all parties are agreed we’ll move forward.
 

Q: How is OriGen supporting the move to automate processes like cell culture and fill and finish for example?

A: Automation of cell culture and cryopreservation has been a hot topic for quite some time. But the process at commercial scale is just beginning. Our partnership with customers and automation providers is a bridge between the manual and automated processes currently. We have partnered with automation providers who are looking to have a single use disposable set provided with their equipment. So, it’s the best of both worlds for companies that make it to commercialization because they can leverage our bag within an automated system. At commercialization, the requirement for repeatable and proven processes is why automation is so important. The ingenuity of the automation equipment providers is what pulls our bags into 4 that automated system. And so we provide the single use disposables within that system and they provide the mechanics.
 

Q: What’ s next for the field when it comes to single use disposables in cell and gene therapy and what is OriGen’s approach to innovation?

A: Innovation at OriGen is largely driven by our single use disposables. As the industry grows and the cell dose requirements change based on efficiency of the advanced therapy, I believe that the doses will become more variable; what that means is there’s a desire to continue to use our bags. However, the volume dosing to the patient is what may change as the cells become more efficient; either the cells scale down or the cells scale up. Either way we’ve created a bag that will partner with our existing CryoStore product line. It’s called the CryoStore FLEX bag. It has five chambers and each of those chambers holds between four and six milliliters. If your patient needs fewer cells you can give them fewer chambers. If they need more, you can give them more; it’s designed for scalable dosing. The bag segments can be used to increase doses by incremental amounts. We believe this bag can also be a solution for cell and gene therapy to replace cryovials holding the representative QC sample product in another freezer and in a different rack configuration. This product is made from the same EVA as our existing CryoStore product line. It fits in the same cassettes as our existing CryoStore product line and can be stored in the same rack, same tank as the customer final product. It provides an accurate representation of how the CryoStore bag performed while stored in cryopreservation.
 

Q: Are there any further expansion plans in the OriGen pipeline?

A: We’ve opened an additional facility and we now have five clean rooms to build products. We also have additional internal automation that we’re bringing online. We are set to keep pace 5 with the growth the industry is expecting to see.