The bioassayist

At the very west end of the Biberach site is the home of the new Potency Assay Skill Center. As I visit what were once the facilities for non-clinical drug safety, I now find modern laboratories where Dr Caterina Giorno analyzes active ingredients and cells. Access to the building is restricted; only supervised visits to the realm of the safety labs are permitted.

Manufacturing biopharmaceutical products involves countless complex technologies. The scientists work with living cells that are not only tiny, but also extremely sensitive. “In theory, it’s quite simple to explain many basic functions. However, it’s quite another matter to employ them technically,” Dr Giorno explains. That goes for bioassays, too. The term is short for “biological assay” and involves analyzing the effects that specific active ingredients have on living organisms. Bioassays are standardized tests for verifying the substances in a sample or measuring the efficacy of drug products on living cells, for example.

The whole nine yards

And these are also the primary tasks at the Potency Assay Skill Center. The center’s team of 45 checks every batch from biopharmaceutical production to see whether the cells in the bioreactors have produced the right proteins with the right effects. “Living cells are the ‘factories’ for our active ingredients, but they don’t always behave in the same way, since biological processes simply have a certain variability ,” Dr Giorno explains.

For this reason, specialists are brought in when the time comes to develop the test methods, or bioassays, in short. “Every one of our biopharmaceutical products has a specific Mechanism Of Action, and needs to have a corresponding bioassay developed for it. You also need specific cells for every bioassay, which are cultivated in the Potency Assay Skill Center for conducting bioassays,” she continues.

Caterina Giorno did her doctoral work in this very area. In a cooperation between Boehringer Ingelheim and the University of Konstanz, she investigated whether the effect of an antibody against cancer cells changes when the molecule lacks particular sugar chains, or when they are introduced. For her work, she had to use a “factory” that was rather unusual for the company: moss cells. These cells can produce the protein without synthesizing specific sugar residues. Her work also included developing the corresponding bioassays.

“We have developed a total of 53 different assays here at the Potency Assay Skill Center. We actively use over 30 of them, and at the same time we’re still thinking ahead and already have the next five to ten in the works,” she remarks.

Poison for cancer cells

And cancer cells come back into play here: The active ingredients that are being tested are for example targeted towards destroying cancer cells, with the help of ADCC (antibody dependent cellular cytotoxicity). “We use real tongue twisters sometimes,” she smiles as she gives the German translation: “Antikörper-abhängige zelluläre Zytotoxizität.” As I’m still stumbling over the German, she explains the active principle: “Antibodies look like the letter ‘y.’ The upper arms dock onto the cancer cells and the lower part binds to the surface of an endogenous killer cell, which is how the antibody brings both cells really close together. This direct contact is needed for the cytotoxic granula to hit their target. The enzymes penetrate the cancer cell, dissolve the cell membrane, and it is lights out for the cancer cells.”

This method and its strengths can be analyzed with one of her bioassays. Cultivated cancer cells are for example brought together with killer cells and the antibody. The team then analyzes how many of the unwanted cells are eradicated. “With this procedure, we mirror the mode of action. In the biopharmaceutical development of drug molecules, bioassays are the only kind of analytical method that can verify mechanisms of action directly on living cells,” Dr Giorno explains.

The Potency Assay Skill Center does more than just analyze active ingredients from Biberach. The team is part of a global network, and they analyze samples from Vienna or Shanghai, too. “Here, we support our colleagues in Ingelheim and Fremont with bioassays for our biosimilars projects, for example,” she continues. “I think it’s exciting to work with people from all over the world, who often have a different perspective on the processes.”

Detective work

Because processes in the biological “factories” can vary, the Potency Assay Skill Center is brought in to help with identifying errors and problem solving. Dr Giorno and her team then get to work figuring out where the deviations came from. “Many parameters can influence the antibodies’ biological activity. Small variations in temperature or pH values in fermentation can lead to the resulting proteins looking a bit different. And that can really influence their efficacy,” she explains.

This process characterization is one of the responsibilities of the Potency Assay Skill Center. “At the Center, we pool expertise in the complex test procedures into a range of lab groups and profit from having communally used labs in a single building,” Dr Giorno enthuses. The labs offer all business sectors tailor-made services and thereby support the contract manufacturing business as a shared services unit within the Innovation Unit.

Caterina Giorno loves the variety that comes with her job. “I can develop new methods, improve existing ones, and do some detective work in looking for the solutions when something isn’t going the way we’d planned. This variety makes my work really exciting,” she enthuses. Her dream: “To accompany one drug from the early phase right up to its administration to the patient, and see how I can contribute to their well-being.“

And when she is not in the lab? “My young son constantly keeps me on my toes,” she laughs. “I enjoy being both a mother and a scientist.” She does have some set boundaries, however: Her day in the lab ends when it’s time to pick up her four-year-old from daycare.