Single-use technology – products or solutions that are made from various forms of disposal plastic and intended for one-time use – has emerged as an important solution for biopharmaceutical companies. There are many advantages, including: elimination of cleaning needs and in-house sterilization requirements; reduced use of cleaning chemicals; fewer storage requirements; increased process flexibility and optimization; reduced cross contamination risks; and lower investment costs. But there are also challenges.
Ruud Verstegen, process engineer at Byondis, a Nijmegen-based clinical-stage biopharmaceutical research and development company, discusses his experience with single-use materials.
Byondis creates precision medicines targeting intractable cancers and autoimmune diseases. The company focuses on the development and production of monoclonal antibodies (mAbs), antibody-drug conjugates (ADCs) and small molecules. Verstegen is mainly involved in the production of investigative ADCs, therapies composed of a mAb that is linked via a chemical linker to a cytotoxic drug. The mAb binds to receptors found on cancer cells and the linked drug enters these cells, killing them without harming healthy cells.
The switch to single-use: flexibility, speed, EHS
Verstegen cites production process optimization as the main reason for Byondis’ increased use of single-use solutions over time. “In 2013, when we started producing monoclonal antibodies and antibody-drug conjugates, we didn’t employ many different single-use materials,” says Verstegen. “Later on, with the addition of several production processes, we expanded our single-use options considerably.”
“Single-use materials provided more flexibility. For example, if we wanted to design a slightly different process, or switch to the production of new or different batches of medicines, we could do it faster,” he explains.
The risk of cross-contamination also played a role, according to Verstegen. “With single-use materials, our employees were better protected against the dangers of the toxic substances they often handle.” The cytotoxic drug in ADCs is delivered in powder form coupled to a linker-drug, which must first be dissolved in an organic solvent because it is poorly soluble in water. This can be a risky step for employees and is done in an isolator.
“Once dissolved, the risk is more manageable,” says Verstegen. “Then the conjugation part, in which the linker-drug is linked to the antibody and purified, can take place. As much as possible, these steps occur in fume hoods with single-use materials. These materials can be disposed of after use in special drums that are subsequently destroyed. In this way, employees do not have to clean and are therefore not in contact with hazardous materials.”
Single-use materials and the elimination of cleaning steps also optimizes production and benefits the environment. “Cleaning produces a lot of liquid waste streams that have to be collected and destroyed, with all the EHS (Environmental Health & Safety) requirements that this entails. After that, everything needs to be sterilized again. With single-use products, we eliminate all that,” Verstegen explains.
The challenges: continuity, compatibility
While the benefits of single-use systems far outweigh the risks, Verstegen identified some challenges that he and his team have encountered over the years, as well as solutions.
“You have to be flexible with your production plan. Before start, everything is carefully engineered. When introducing single use materials – for example, for certain filter steps, a mixing vessel or transfer to another vessel – we need to connect everything together. Not all the connections are the same and fit together so we have to find a solution. Moreover, there is usually little space in a fume hood and you really have to think and engineer carefully how to outline the production plan.”
“Another thing to take into account is that the organic solvent for dissolving the linker-drug is sometimes incompatible with the plastic in the single-use product and can therefore lead to leachables. To prevent this, we always request information from the manufacturer, but we also conduct tests ourselves,” says Verstegen.
Finally, there could be supply issues. According to Verstegen: “When choosing complex single-use products, you can become dependent on the supplier. And if that supplier is temporarily unable to supply a product or product component like we have seen during the Covid period, or if they make a component change, you have a problem. So you have to figure out the consequences for your production process and come up with a solution.”
“Single-solution technology can save time, money, avoid risks and benefit the environment,“ says Verstegen. “While it requires careful planning, coordination and at times, troubleshooting, it’s well worth the effort,” he concludes.
