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

Abstract

Abstract. 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. IntroductionMonoclonal antibodies (mAbs) have revolutionised the treatment of oncological and autoimmune diseases over the past 10 years. Moreover, they are also successfully used in the management of asthma, hypersensitivity reactions, osteoporosis, skeletal-related events in patients with bone metastases from solid tumours, neovascular (wet) age-related macular degeneration, hyperlipidaemia, and many others. According to data from the U.S. National Institutes of Health and other publications, various ongoing clinical studies look promising for indications like Alzheimer's disease, infections, and type-1 diabetes (1,2).According to our local drug registration database (EU-Slovenia), there are currently 64 medical products that contain 40 active mAbs (data retrieved in November 2017). Among these, 39 are intended for intravenous administration, 22 for subcutaneous, and one each for intramuscular and intravitreal administration. For their pharmaceutical forms, 50 are solutions or concentrates for solution, 13 are in the form of powder for solutions, and one is a kit for radiopharmaceutical preparations for infusion. The data from the Agency for Medicines and Medical Devices of the Republic of Slovenia show a wide spectrum of the designs, forms and routes of administration of pharmaceutical drugs. In the earlier years of clinical use, these preparations were compounded by healthcare professionals in controlled environments, and administered in healthcare facilities. However, with the introduction of TNF-α inhibitors in pre-filled syringes in the last 10 years, medicin...

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