[Q&A] Scaling cell & gene therapy with the right manufacturing execution system

[Q&A] Scaling Cell and Gene Therapy With the Right Manufacturing Execution System

How to benefit from electronic batch recording, data analytics and artificial intelligence to commercialise cell and gene therapy production
In this interview, we speak with Welf Ludwig, Head of Sales and Marketing Software at Körber Business Area Pharma, about manufacturing execution systems (MES) and their role in delivering scalable cell and gene therapy products. 

Q:  Tell me about Körber, your history and expertise.

WL:  We’re an international technology group, with about 10,000 employees and more than 100 locations worldwide. Our goal is really to turn entrepreneurial thinking into customer success and shape technological change. We help pharmaceutical, biotech, cell and gene companies unlock the potential of their business with our PAS-X Manufacturing Execution Systems – or MES. It provides electronic batch recording, data analytics and artificial intelligence to accelerate things like product commercialisation and uncover business value.

Q:  For those who aren’t familiar with MES, can you maybe explain more about what it enables?

WL: As I mentioned, MES stands for Manufacturing Execution Systems. If you look at the shop floor, there’s tasks that people do. Operators, they’re performing the process of the certain production steps to produce these life-saving medicines. An MES helps that person. An operator would have a tablet, for example, or a PC. And there’s going to be instructions on there that tell them how to produce that batch. And there’s a number of benefits. Traditionally, operators would be using paper-based processes or spreadsheets or Word documents. Those aren’t able to scale and it leads to errors. And it’s not just the instructions, there’s a lot of other things like connecting with your shop floor systems, connecting with your LIMS, connecting with ERP to essentially drive the production. One of the benefits that you get out of an MES is Right First Time. If you look at a typical legacy process, if you have a paper-based batch record, where an operator needs to manually record or perform calculations, you see people with calculators, with pens, performing calculations. When you digitise, we can automatically perform those type of calculations. We can proof or check things after being recorded. So, for example, if you’re recording a pH value or cell density, we will check whether that value falls out of range. And if it does, you’re allowed to proceed. We call that Right First Time.
Review by Exception is another phrase or benefit we talk about a lot. This is one of the big benefits in an autologous process for example. One patient has one batch. But with more patients, all of a sudden, you have a lot more batches and if you were to do that with a paper-based approach, that means you have to hire a lot of quality people to review those batches; those pieces of paper. That can take a lot of time and is error-prone but our patients in this space don’t have a lot of time. So if you implement an electronic solution, you can actually do something called Review by Exception. As we’re executing a batch, we’re in real time able to verify values as they’re being entered and flag them whether they’re right or not. So at the end of the batch, we already know whether exceptions have happened or not. And we only need to look at deviations in the process, we don’t need to look at anything that was correct. In the ideal case, where there haven’t been any deviations, when you’re producing a batch, you can pretty much auto-release that product and that saves time.
Q: Would you say the MES system drastically reduces the need for paper? And have you got an idea of how much by?

WL: Ideally, by 100 percent on the shop floor! There could still be paper from some legacy piece of equipment that prints something out or you need to scan something in. What we’ve seen with COVID-19 over the last year, with people working remotely, you want everything to be digital. You want that data instantly to be in your system, in the cloud, so it can be accessed by anybody in the company to do their job.
Q: What makes what Körber do quite unique in this marketplace?

WL: What’s unique about us is really our focus. Körber – and I’ll note we used to be Werum – have focused on software for pharma and biotech since 1990. At this point, 17 of the top 30 pharmaceutical companies and biotechs use our software. Our PAS-X MES is really tailored for this type of regulated, batch manufacturing industry. We also have a tremendous amount of knowledge of how to run these projects and how to tailor our software to different modalities. We worked e.g. with Dendreon in the early days of the industry. We’re proud to say that the trailblazers in the field like Novartis and Kite are using our software - over 15 leading cell and gene companies are using our PAS-X MES software at the moment.
Q:  MES is a key part of Biopharma 4.0. Can you talk a little bit about what the different components are of that environment? And where does MES sit within it?

WL: Biopharma 4.0 is a spin on Industry 4.0. It provides a framework for adapting digital strategies to the unique context of pharma and biotech manufacturing. So what this means in practical term is connecting all your different systems and devices together. As a result, this improves productivity, simplifies compliance and captures production information to respond to problems as they emerge – not at the end, when the batch is completed. If you think about it, that’s almost like the definition of what an MES system does. 
Q:  Can an MES be a source of competitive advantage that executives should be thinking about?

WL: Even before the decision whether to go with MES, companies need to make the decision whether they are going to manufacture in house or use a CDMO or hybrid approach. Once you decide to take manufacturing in house, you do have to make the decision about going digital. We see more and more companies adopting digital systems or starting digital right from the beginning – and the reason for that is really time to market. A lot of these therapies are getting fast track approval and if you start with that digital footprint from the beginning, you’re setting yourself up for success because you will be able to scale much quicker than if you were to go with a manual paper-based process.
Looking at it from a business perspective, this allows you to produce more and get more treatments to your patients at a faster rate than the competition. We see this quite a bit; before they’ve even started their pivotal studies, companies are already looking at things like MES. One thing that’s quite interesting is we have a couple of customers that are even implementing an MES before they’re implementing an ERP system. Traditionally, an ERP system was always the first. At this point, we see that being flipped because that ability to scale is so important, especially if you’re looking at the vein-to-vein process. 
Q: Can you talk about what some of the barriers are and issues are with adoption?

WL: While cost can be perceived as a barrier, the ROI is pretty quick, usually one or two years. When you implement MES solutions in pharmaceutical environment, there’s a lot validation required. Our cloud model does have less of an upfront investment because it’s SaaS. The main barrier is change management. You want to make sure that people on the production floor adopt and actually use the MES. As such, you need to have a plan in place on how you enable people to use the software. 
Q: What’s the driving force for startups versus late-stage companies to adopt an MES?

WL: The earlier a company is, the fewer restrictions they have and the more flexible they can be. For them, what’s more important is getting the data out and analyzing it and then improving their processes and improving their product, the treatment. That’s the goal of early stages of drug development. As a company moves into phase two, phase three, and then commercial, the more and more restricted the process is and the less flexible the MES will be. Now, it’s going to be more about quality and compliance. 
When a company is looking for IT solutions in that early stage, they want to make sure whatever approach is selected is flexible enough to adapt to the process. Many use traditional MES systems designed for commercial manufacturing, where it is restrictive. As a result, it becomes difficult to adjust to the process. So you want to make sure you pick an approach that matches your particular needs, is flexible and scalable.
Q: To what extent are early-stage companies focused on being “digital first”?

WL: There are many going digital first. It’s rare to just go with paper these days; it wouldn’t make sense. It’s an exponential growth curve for these businesses, and going digital allows you to accelerate more and more. Like we talked about before, speed to market, Right First Time, access to the data; having all of that makes a critical difference. There is no way around digitisation.

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