The public doesn’t always have a good view of the pharma industry, but truly this is an industry of heroes. In particular, there is a constant desire to improve rather than allowing a status quo for patient treatments. In the last issue of The Medicine Maker, Vijay Chudasama (https://themedicinemaker.com/issues/0516/better-together) discussed the subject of antibody drug conjugates (ADCs). Most of us reading this publication are technical, but we’re not experts in every single area; there are times when I think we need to sit back and remind ourselves of the incredible work done by scientists and engineers outside our own area of expertise. I mainly focus on facility design, but I’m a self-confessed fanatic of progress in our industry, so I like to see what is bubbling in other areas of drug development – and to shout out when I see something successful. I think we should all do the same.
ADCs fascinate me because their formulation is all about making good drugs work better, which links back to the desire to improve. Cytotoxic drugs can be highly effective against cancer cells – but can also damage healthy cells and lead to severe side effects. As Chudasama explained, ADCs consist of three components: an antibody that is built to target specific spots on the surfaces of cells, an active drug (often a chemotherapy), and a linker that is in place to prevent release of the drug until it is in exactly the right location. Only a small number of ADCs have received regulatory approval, but there is a great deal of excitement about the potential of these therapies – and much ongoing research. But the complexity doesn’t end with research and development; from a manufacturing perspective, each component of an ADC has a vastly different manufacturing method, which can lead to each piece of the ADC puzzle being made in different facilities. The antibody is a biotech product, the drug is usually a small-molecule API and the linker must be made via organic synthesis. The antibodies used in ADCs are manufactured using a monoclonal cell culture production that consists of cell culture reactions, harvesting and purification – the result is a bulk container of biologically active antibodies. The payload of the ADC is often made as an API in a classic chemical reaction and separation production train that results in a container of dried active drug product. Sometimes, this API is highly hazardous, which is an extra burden in manufacturing because the API must then be handled with extreme care and specialized equipment. As the conjugate is purified, the risk of exposure is reduced, but it is not completely eliminated. Each step requires special consideration – and you can never be too careful. Of course, you also need to think about any potential impact on end users too, such as patients or healthcare practitioners, who may handle the finished drug. The final piece of the ADC, the linker, is usually an organic chemical reagent with activity to create strong crosslinking between the antibody and the payload. All of the pieces tend to come together at yet another facility that finalizes the conjugation of the antibody to the payload using the linker, followed by more purification steps and final sterile filtration into the dosage form. Oftentimes, the conjugate is stable but then lyophilized to improve its shelf life. Bringing the ADC puzzle to completion is a complex activity, but despite the challenges and obstacles, I find it remarkable that such progress is being made – not just on the R&D side but also in terms of manufacturing. Companies are constantly looking to make the process as streamlined as possible. It takes many heroes to bring all of these complex areas together to create a new drug that could make treating a disease less painful and more effective than the treatments of even 10 years ago. Most of us will know someone who has suffered cancer (in my case, it was my grandfather). At some point, perhaps I will have to face it too, but it’s positive to know that drugs are being reformulated all of the time to make them better. Where will ADCs and cancer treatments be in another 10 years’ time? It’s an exciting thought. I’d like to offer my personal thanks to everyone working in this area. You’re making the world a better place.
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