ADC manufacturing process
Antibody drug conjugate manufacture involves the aggregation of three key compounds through bioconjugation techniques:
- a monoclonal antibody
- a payload, typically a cytotoxic drug or small molecule, and
- a stable linker.
Through the combination of the tumor targeting quality of the monoclonal antibody and the drug, it becomes possible to deliver effective cytotoxins directly to cancer cells without the risk of damaging healthy ones.
The steps to manufacture ADCs each bear their own challenges.
MAb production and characterization is an important step in the successful outcome of ADC production. The antibody needs to have specific binding qualities to recognize the cancerous cells and deliver the drug to its target. mAbs are sensitive protein structures which are prone to contamination and product loss during production. Producing them on a large scale requires the right equipment and expertise, often involving the use of a cell line optimized for the production of the monoclonal antibody.
The purification process is a critical part of ADC manufacturing, with tangential flow filtration (TFF), a form of ultrafiltration, playing a key role in separating and purifying the desired substances from impurities. This ensures high-quality mAbs and other ADC components are used in the production process.
Managing drug development and bioconjugation through a drug-linker presents similar challenges. The combination of the drug and linker creates intermediates that must be carefully managed to ensure the stability and efficacy of the final ADC product. There are many details which have to be considered before an ADC enters the market.
ADCs are a novel solution for cancer or autoimmune diseases and its market is growing. Many ADCs are currently in preclinical development or in ADC clinical trials waiting for their FDA approval, as well as many assays in validation.
In most cases different parties and departments are involved in the production and these steps are carried out by different biopharmaceutical manufacturing services as they require specific equipment, manufacturing environments and in-depth knowledge. Due to this instance, it is often necessary to transport ADC bulks from one manufacturing facility to another.
To provide safe handling of ADCs it is important to decrease risk of product loss through breakage, of temperature deviations at ultra-low temperatures and of disruptions of the supply chain. To make this possible, they have to be kept at -80 degrees.