The importance of handling high-value biologicals: Physico-chemical instability and immunogenicity of monoclonal antibodies.

The present review specifies the various chemical and physical factors that can influence drug stability and immunogenicity, and the treatment outcomes of antibody biologicals. Although monoclonal antibodies (mAbs) are known to be more resistant to environmental changes compared with other proteins, the molecules themselves can be subjected to chemical and physical processes that promote their degradation and transformation into their specific amino-acid moieties. With increasing use of medicinal products that contain mAbs, and their self-administration by the patients, the issue of the correct manipulation of these drugs is of increasing importance. This review summarises the correct handling of mAb biologicals from the point of view of the pharmacist, clinical biochemist and patient, as is supported by relevant cases from the literature and our own data and experience. In particular, if there is a break in the cold chain, both healthcare professionals and patients need to be aware of the potential pharmacokinetics and pharmacodynamics alterations to these biologicals. Furthermore, any alterations in the protein structure can induce harmful immune reactions, including anaphylaxis and cytokine storms, or result in the production of neutralising or blocking Abs. Overall, considering also that treatment costs usually remain high, drug stability can have a tremendous effect on the clinical, humanistic and economic outcomes of such treatments.