Imagine you have spent months working with a cell line provider. You are proud to have found this specific one – cheap, fast and seemingly efficient. You already envision the lucrative commercial production of your therapeutic protein. But then reality hits you. You have reached the point at which you need to upscale your production.
Suddenly, you realize that your precious cell line behaves completely different in large scale compared to what you observed in the lab, and your decent titers have vanished. You had merely reached the first stage of your protein production technology, and now you are back at zero. You have lost out on money and lost months of hard work. You have to find a new cell line provider, and this time, you want to do it right.
Selecting a robust cell line to suit your research needs can be a real hassle. Especially, because it all rises and falls with the cell line development provider you choose. Not only should your cells be robust and efficient, but there are several other factors that need to be taken into account.
The importance of selecting the right cell line development provider for your commercialprotein production becomes clear, when one looks at all the mistakes that can be made in the process. We have created a list of five key points for you to avoid disaster and guarantee your success.
Don’t try to save as much money as you can
When it comes to money, don’t we all fight the urge to save as much as we can? Well, sometimes it’s a big mistake. Especially, when you’re choosing your cell line development provider for production of your therapeutic protein. After all, one tiny mistake can set you back months and might make you lose out on much more money than you originally meant to spend.
How is that possible? Easily. Although low cost systems may be enticing, for instance, they most often result in poor applicability for production scale and have limited space for improvement, due to a lack of liquidity. Consequently, one should make sure that the system allows for improvement of titer and variation of product quality attributes.
“You get what you pay for. Therefore, it is important to carefully choose the right provider from the beginning,” explains Hugo De Wit, Managing Director of the cell line development provider Sartorius Stedim Cellca.
“Switching providers can be very expensive. Firstly, because there will be additional costs for the generation of a new cell line. Secondly, the delay in filing will cost extra money and time, as a new cell line requires a new filing process.”
Instead of counting every penny, it is better to plan ahead and consider upscaling as early as possible. “You might be starting in a lab, but if everything goes well you will have to scale up your production,” explains De Wit.
“This is where you will be confronted with surprises and problems, which can take months off your timeline and make you lose money. By taking upscaling into account right from the beginning you can lower your chances of making major mistakes.”
Don’t try to achieve the highest titer you could get
When selecting how much money you want to spend on the titer – or concentration – the middle path is the best way to go. “Don’t invest too much time and money on improving your titer, but rather save it and agree on a 3-4 g/L titer,” deliberates De Wit. Why?
The so-called cost of goods reduction model can be used to explain this phenomenon. Let’s assume that the cost for the production of a biopharmaceutical at a yield of 1 g/L lies at 800 €/g. If the titer is doubled to 2 g/L, you only need half the production capacity, which halves the cost of goods to 400 €/g.
The cost of goods reduction model shows that doubling the titer for a second time – so, from 2 g/L to 4 g/L – can save another 200 €/g. “However, from that point onwards it doesn’t make any more sense to save more money, as it would cost a lot more effort to achieve 8 g/L and you would only save another 100 €/g,” De Wit explains.
“In the end, you’re better off choosing the golden mean. You have the highest titer for the best possible price. Above or below that you either lose money or effort.”
Don’t try to get approval for the most “fancy” non-established technology
Rather than getting regulatory agencies confused, use well-known, state-of-the-art systems, such as Chinese hamster ovary (CHO) cells. This ensures that regulators are already familiar with the benefits and the performance outcome of the system. “Your researcher spirit might be frustrated, but it will delight the authorities’ employees. And always make sure to emphasize the benefits of your technology,” De Wit adds.
CHO cells are one of the most reliable cell types to choose, because they grow fast and remain stable. CHO cells are commonly used for the commercial production of therapeutic proteins, and in basic biological and medical research.
Don’t try to re-invent the wheel
In basic scientific research, cell lines are often developed by focusing on one step after the other, with the use of different hosts and expression vectors. Within this framework, the development process and the media are designed from scratch each time, at the expense of time and money, which involves a high trial-and-error rate.
As a client, you would also have to pay for every step of this approach – cells and media screening, reactor settings, risk assessment and test manufacturing. These are a lot of steps, which again increase costs on the client’s side.
Using standardized methods can reduce time, costs and the risk of failure. Many platforms already have all necessary components established, are immediately available for customer projects and won’t run into problems when it comes to upscaling procedures.
Don’t get lost in the shuffle of bioreactor types and manufacturers
To reduce costs and timelines and to increase efficacy, it is important to also consider the equipment used during research and process development.
“The moment you start the basic research on your therapeutic protein, you should already keep in mind that you want to produce on a larger scale. For example, on a 2000 Litre scale,” De Wit explains. “The ultimate goal when it comes to producing therapeutic proteins in cell lines, would be that everybody uses the same equipment throughout the entire process development. With standardization the cost of drug manufacturing could be reduced from the early development stages onwards.”
Taking all of these variables into account can make it easier for researchers to choose the right cell line provider, as well as avoid unnecessary loss of money and time. Learning the know-how from a trusted advisor can pave the way to success.
Sartorius Stedim Cellca is a cell line development and protein supply company. It has focused its efforts on creating a CHO expression platform that is not only easy to use, but also has the ability to be scaled up. Together with Sartorius Stedim BioOutsource and the parent company Sartorius Stedim Biotech, Cellca offers a broad portfolio of integrated early stage development services. Check our their website and get in touch!