Antibody-drug conjugates (ADCs) combine the specificity of monoclonal antibodies (mAbs) with the potency of cytotoxic molecules, thereby taking advantage of the best characteristics of both components. Along with the development of the mAbs and cytotoxins, the design of chemical linkers to covalently bind these building blocks is making rapid progress but remains challenging. Recent advances have resulted in linkers having increased stability in the bloodstream while allowing efficient payload release within the tumor cell.

50 % of reactions in the fine chemical/pharmaceutical industry could benefit from a continuous process based mainly on microreactor technology. However, the frequent presence of a solid phase still hinders the widespread application of such a technology as a multi-purpose solution. For small scale and pilot productions, speed in process R&D, as well as the avoidance of scale-up issues, are the main drivers. On the other hand, for large scale productions, a gain in yield and safety are the main motivations for the use of micoreactor technology. The gain in yield must be significant in order to cope with the increase in capital expenditure associated with the development of a new technology.

Scaled‐down approach: The nitration of phenol is an autocatalytic, strongly exothermic reaction and is thus difficult to handle on an industrial scale. Continuous nitration in a microreactor (see picture) affords higher yields and enhanced process safety, thanks to good heat exchange and mixing properties, as well as rapid radical propagation under sufficiently harsh conditions.

The reduction of methyl butyrate into butyraldehyde with Dibal-H in microreactors is described. Running the reaction continuously in a microreactor afforded results similar to those of batch experiments, but very low temperatures are not necessary and the reaction may be scaled-up without selectivity decrease. Different microreactors were used, and their mixing performances were compared. Increasing the reaction concentration and thus the throughput showed that even when working with microreactors, heat management should not be underestimated. Multi-injection was tested as a way to better control the temperature at the mixing point(s).

Advances in antibody-drug conjugates (ADCs) will permit sensitive discrimination between healthy and cancer cells. Promising clinical results generated much hope that this targeted prodrug therapy will offer more effective treatment options to patients. Manufacturing such highly potent biopharmaceuticals presents a series of unique challenges. Some specific skills required for the process development and production of ADCs are discussed. In addition to the accuracy and reliability needed to handle these potent and costly materials, coworker safety and equipment cleaning are of particular importance. The ideas and concepts shared in this article are based on the experience that Lonza has gained in the ADC field since 2004.