The Cost and Practicality of Scaling Up and Out in Cell and Gene Therapeutics: An Interview With Mike O’Mara | Corning

This article was originally published by RegMedNet on September 16, 2022

How can automation increase efficiency in therapeutics? In this interview, Mike O’Mara, Chief Operating Officer of Cellipont Bioservices (CA, USA), discusses the factors affecting cost and practicability of scaling up and out. With over 30 years of experience in manufacturing, supply-chain, quality assurance and quality control, Mike sheds light on the benefits of knowledge-sharing with experienced partners.

How have you seen the cell and gene therapy industry expand in the last decade and what new challenges does this bring?

The industry has seen great expansion in numbers of companies, technologies and overall regulatory maturity in the space over the last decade. With over 20 approved cell and gene therapies currently on the market, the industry is encouraged to continue pushing novel advanced cell and gene therapy products forward towards approval. The challenges with this growth that we now all face, first and foremost, is recruiting. We’ve just attended a conference where a common theme among both sponsors and CDMOs alike is the difficulty in finding the right individuals with experience in this part of the industry to fill open roles.

How can automation increase efficiency in therapeutics?

With cell therapies there is a ceiling on how much you can scale up. This is driven by the amount of time it takes to harvest the culture vessel, which has a direct impact on the viability of the cells you are growing. Once you hit that ceiling, then you have to scale out. When scaling out, the aim is to minimize the amount of square footage required in order to keep manufacturing costs low. For example, T-flasks were a go-to culture vessel in cell therapy manufacturing. The more cells you need, the more T-flasks required. At a certain point it is inefficient to simply keep adding more flasks for a number of reasons; cost, labor and space to name a few. When you get to that tipping point, you can move to a stacked vessel, like a Corning® HYPERStack® 36 vessel, which has the same surface area as ~102 T-175 culture flasks, saving labor and space.

How can working with experienced vendors such as Corning Life Sciences help with scale up?

By having an open dialog with trusted vendors, we are able to maintain a two-way communication line and ensure we are always ahead of what is coming in terms of new technologies and platforms. We recently had the opportunity to be beta-testers for the Corning Ascent® Fixed Bed Bioreactor System, a platform that Corning has developed to address the scalability and labor cost challenges associated to culture of adherent cells. In turn, we can give them feedback based on our client’s current needs and what we believe will be needed in the future in the cell and gene therapy manufacturing field.

How can you learn and apply lessons from other SME bioservices?

From the vendor side, I think a great example is working with partners to identify industry gaps and needs that need solving, which was the case with testing the Corning Ascent FBR system. It combines a compact footprint with large surface area of the HYPERStack technology with the precise process control of a bioreactor. With the system also being closed, it allows operations to happen in lower grade environments such as a grade C or even D. Corning was able to work with their customers in this industry to identify and solve a specific problem in upstream bioproduction.

What are the challenges of creating a master cell bank? What considerations should be made to the eventual scale of manufacture?

The challenge of a master cell bank is the starting material: how well understood are those cells prior to making the bank and what tests need to be done in order to determine the characteristics you are looking for? In some cases, donor-to-donor variability can play a role in how the process your master cell bank is used in will perform. I have seen processing steps vary based on growth rate of the cell, which can vary between individuals.

How might quality assurance/control processes differ from research to commercial scale?

The big difference between an academic process and a commercial process is how well understood and characterized the process actually is. In a commercial process you have defined critical quality attributes and critical process parameters; in an academic process, these are still being defined and established. When you get to commercial manufacturing you have numerous runs of data, a process characterization study and process performance qualification. The data, characterization studies and process performance qualification let you know that your process is going to consistently manufacture the drug product intended for the patient.

How can you assess potential time and motion to ensure approval of large batch size manufacture?

Most cell therapies are for the treatment of individuals, so your scale remains relatively small; rather than scale up, you scale out. However, when you scale out, labor becomes a big factor as many things must be run in parallel. This includes receipt of materials and batch record review, in order to manufacture the amount needed for your indication. With allogeneic cell therapy, although you will have to scale up at some point, those volumes are still quite small – less than 200L. In those cases, the unit operation time needed to process the volume is your stumbling block because the longer it takes, the bigger impact it will have on viability.

Other things can impact the cost to manufacture your drug. The cost of manufacturing location can vary – West Coast, East Coast, Europe – but closing your process can help reduce the cost of building your manufacturing plant. If your process is closed already, you could manufacture in a grade C or even D environment instead of grade B or A. It will also reduce operational cost because of less gowning requirements needed for the lower grade area. Whether you are working with a frozen in/frozen out product vs fresh in/fresh out product can also have an impact. A frozen product gives you more flexibility to when the product needs to be released, tested and shipped. A fresh product can lead to complex supply chain and delivery challenges, especially around the collection site and timings of delivery and shipping.

What logistical considerations, such as shipping container or facility space, should also be considered, and how far in advance of moving to commercial scale?

It’s as important to evaluate the final step of your supply chain as it is to establish development and manufacturing processes. We’d recommend establishing a relationship with a knowledgeable specialized logistics provider in the cell and gene space who can guide you on what will be needed to ensure correct shipping solutions, technology within that shipping system and lane mapping as early as phase I protocol planning. If you’re considering global clinical trials, they will also be able to give you an understanding of what will be required to ship your cell therapy into those countries based on individual country guidance and licensing. Cellipont has established relationships with key providers, so we can make the connections for our clients. Most of these providers will arrive with the appropriate shipping container charged and ready to be packed, saving the CDMO or sponsor space in their warehouse.

Where do you see the scale up process of cell and gene therapies in the next 5 years?

The field is moving towards higher levels of automation and closed systems, developing new technologies and platforms to meet scale needs, with minimal scale-up development time, especially for products using adherent cells for allogeneic drug products.

Mike O’Mara is Chief Operating Officer of Cellipont Bioservices (CA, USA), a contract development and manufacturing organization (CDMO) specializing in cell therapy and gene-modified cell therapies. Mike is an industry veteran with over 30 years of experience in manufacturing, supply chain, quality assurance and quality control. His prior roles include Vice President of BioIndustry of North America for Miltenyi Biotec’s (Bergisch Gladbach, Germany) CDMO business unit, which specialized in lentiviral vector and cell therapy manufacturing. Prior to this, he was Senior Vice President of Manufacturing Operations for Cytovance (OK, USA). Mike holds a degree in microbiology from the University of Maryland (USA).


This interview is part of the RegMedNet In Focus on scaling up and out. Discover expert opinions on this topic by visiting the feature homepage.