Editorial Article: Protecting against human error: Why documentation and data are important

Mary Kay Bates emphasises the need for robust documentation techniques within laboratories

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Good manufacturing practices (GMP) and documentation are required to maintain efficient and effective processes within a laboratory. Within cell and gene therapy laboratories, they are essential for consistency, regulatory adherence, and proving that therapies are safe. 

Good documentation is also important to ensure that the same processes are being adhered to by everyone. Projects can be damaged and discarded without robust documentation processes. This also applies to equipment and instrumentation itself. Detailed documentation from manufacturers further supports laboratories to know which equipment performs the best for their projects.

We speak with Mary Kay Bates, Senior Global Applications Scientist at Thermo Fisher Scientific, about the importance of GMP and good documentation, as well as the need as manufacturers to go beyond product specifications to also document performance.

The importance of good manufacturing and documentation processes

Good manufacturing practices (GMP) are a requirement of many laboratories, but there is no one way to do it. Bates explains why GMP needs to be planned and tailored for every process, “People new to this topic always want to say, ‘Just tell me how to do it. Just tell me how to comply and I'll do whatever.’ But there's no one prescriptive way to do that, and that's even more true in cell and gene therapy because every new process to produce a therapy is different.”

Documentation can sometimes be arduous, and the importance of rigorous documentation is not always immediately apparent. Bates sees this in the context of the bigger picture, “By one estimate in a production company, 40% of your time is just spent doing documentation to ensure quality, consistency and reproducibility – because ultimately what you're doing is creating a product that will affect somebody's health.”

Documentation is essential to maintain accountability and for regulatory processes, but there are also other important drivers for the need for robust documentation. As Bates explains, “From my perspective, the whole point of GMP is to eliminate human variation in a system. When you’re working in a lab, you get busy and you do the same thing day after day to keep those cells propagating, and culturing cells can be a little monotonous. So, you start to skip steps, thinking you are improving efficiency. That's understandable, natural human behavior, and many people in a basic research lab are tempted to do this. However, when you then get a contamination in your cultures, you've now lost a month, probably more than that. 

“GMP is designed to counter that natural human tendency to get careless. You have to document everything. If you don't follow the procedure, and do it the same way each and every time, or if you skip steps, someone could die.” 

Equipment performance makes the difference

Requirements for rigorous information and testing also extends to the equipment used in cell and gene therapy laboratories. Manufacturers compete to provide equipment with defined specifications. But some go beyond, testing their equipment fully to ensure they work in real-life situations and to demonstrate that their performance is optimal. This can make the difference between a successful cell therapy project or one that fails. “From an equipment perspective, a list of specifications is not the same as performance,” says Bates. 

To illustrate the importance of looking at the performance of equipment beyond its specifications, Bates uses the example of a CO₂ incubator. “Two manufacturers might use ta CO₂ sensor with the same specifications. But how that sensor performs in the incubator is affected by the airflow design, by the heat and the humidity, and where the gas inlet is located,” explains Bates. “The accuracy of the sensor might be plus or minus 0.1%, but CO₂ gas is heavier than air, so it actually sinks unless you're actively circulating it. So, while the accuracy of the sensor might be plus or minus 0.1%, you might, without active airflow, have a higher percentage of CO₂ at the bottom than at the top of the incubator. As a result, the cells could grow differently depending on where you put them in the chamber.”

It is the differences in these performance measurements that can greatly impact cells and the final product. Bates continues, “You need an incubator where your cells are going to spend the maximum amount of time in conditions that are mimicking the microenvironment in the body because otherwise, the cells are going to react differently in culture than in vivo. Maybe you don't think about it that much until your cells stop growing and then everything else in the process stops. And when this is no longer discovery or education, suddenly, you're talking about somebody's health and that performance is then critical.

“When we take a step back and we look at it in these terms, how the incubator performs matters to the ultimate success of the therapy because it determines how the cells grow,” concludes Bates. “For example, at Thermo Fisher Scientific, 100% of our CO₂ incubators undergo end-of-line testing, where all the functions are tested. We run the sterilization, check the temperature control with external probes and other measures before it’s shipped to you. That's all available with end-of-line documentation and factory acceptance test documentation.”

High standards in manufacturing

Equipment performance goes beyond the internal workings and encompasses the whole of the equipment, inside and out. Bates elaborates, “As somebody who's producing cell therapies, you also want to know that the materials used to construct the incubator are high quality. Because you're constantly disinfecting things, some chemical disinfectants can corrode stainless steel and glass over time. Lower quality stainless steel, for example, could degrade, which can cause microscopic particulates to circulate in the production facility, and if those were to enter the cell culture, could put patients at risk. 

“Thermo Fisher Scientific take this very seriously. There's a lot of pride for us that goes into our work. It’s important to us that our laboratory equipment includes such complete documentation, because we understand how critical it is to the end result, which could be a treatment to improve someone’s health or even save a life.”