The Why
The sensitive structure of proteins makes the handling of protein drugs complex. Our research can change this.
During the last 20 years the number of protein drugs has increased substantially. One drawback with these drugs is that their chemical and physical stability is considerably more complex than for small molecules.
For example, handling of the proteins such as pumping of solutions (shear), interaction with primary packing material (adsorption) and temperature fluctuation are detrimental to product quality. Therefore, considerable effort has been made to identify triggers that reduce product quality for example during production.
However only a few studies have focused on the effects of handling drug products in hospitals and by patients. There is a strong and urgent need to investigate this area. Inappropriately handled protein drugs may lead to adverse effects, such as immunological reactions due to aggregation, and a need to discard prepared medications due to unintentional mishandling (if noticed) or e.g. visual aggregation. This leads to unnecessary patient suffering and increased cost for health care and medication.
Scientific references for further background reading
Nejadnik et. al., Postproduction Handling and Administration of Protein Pharmaceuticals and Potential Instability Issues, Journal of Pharmaceutical Sciences 107 (2018) 2013-2019
https://doi.org/10.1016/j.xphs.2018.04.005
Jiskoot et. al., Potential Issues With the Handling of Biologicals in a Hospital, Journal of Pharmaceutical Sciences 106 (2017) 1688-1689
https://doi.org/10.1016/j.xphs.2017.02.029
Manning et. al., Stability of protein pharmaceuticals: an update, Pharmaceutical Research, 27 (2010) 544-757
https://doi.org/10.1007/s11095-009-0045-6
Vlieland et. al., The majority of patients do not store their biologic disease-modifying antirheumatic drugs within the recommended temperature range, Rheumatology, 55 (2016) 704-709.
https://doi.org/10.1093/rheumatology/kev394
Wang W. Protein aggregation and its inhibition in biopharmaceutics, Int J Pharm., 289 (2005) 1-30.
https://doi.org/10.1016/j.ijpharm.2004.11.014
Moussa et. al., Immunogenicity of Therapeutic Protein Aggregates, Journal of Pharmaceutical Sciences 105 (2016) 417-430
https://doi.org/10.1016/j.xphs.2015.11.002
Torre et. al. The Pharmaceutical Industry in 2018. An Analysis of FDA Drug Approvals from the Perspective of Molecules, Molecules, 24 (2019) 809
https://doi.org/10.3390/molecules24040809
Her et. al., Effects of Tubing Type, Operating Parameters, and Surfactants on Particle Formation During Peristaltic Filling Pump Processing of a mAb Formulation. Journal of Pharmaceutical Sciences, 109 (2020) 1439-1448
https://doi.org/10.1016/j.xphs.2020.01.009
Funatsu et. al., Impact of Ethylene Oxide Sterilization of Polymer-Based Prefilled Syringes on Chemical Degradation of a Model Therapeutic Protein During Storage, Journal of Pharmaceutical Sciences, 108 (2019) 770-774
https://doi.org/10.1016/j.xphs.2018.09.029
Hawe et. al., Structural properties of monoclonal antibody aggregates induced by freeze-thawing and thermal stress, Eur J Pharm Sci., 38 (2009) 79-87
https://doi.org/10.1016/j.ejps.2009.06.001
Das et. al., Stress Factors in mAb Drug Substance Production Processes: Critical Assessment of Impact on Product Quality and Control Strategy, Journal of Pharmaceutical Sciences, 109 (2020) 116-133. Li et al AAPS J, 21 (2019) 44
https://doi.org/10.1016/j.xphs.2019.09.023
