Stability of monoclonal antibodies after simulated subcutaneous administration

Changes in the environment from the drug product to the human physiology might lead to physical and/or chemical modifications of the protein drug, such as in vivo aggregation and fragmentation. Although subcutaneous (SC) injection is a common route of administration for therapeutic proteins, knowledge on in vivo stability in the SC tissue is limited. In this study, we developed a physiologic in vitro model simulating the SC environment in patients. We assessed the stability of two monoclonal antibodies (mAbs) in four different protein-free fluids under physiologic conditions. We monitored protein stability over two weeks using a range of analytical methods, in analogy to testing purposes of a drug product. Both mAbs showed an increase of protein aggregates, fragments, and acidic species. mAb1 was consistently more stable in this in vitro model than mAb2, highlighting the importance of comparing the stability of different mAbs under physiologic conditions. Throughout the study, both mAbs were substantially less stable in bicarbonate buffers as compared to phosphate-buffered saline. In summary, our developed model was able to differentiate stability between molecules. Bicarbonate buffers were more suitable compared to phosphate-buffered saline in regards to simulating the in vivo conditions and evaluating protein liabilities.     

Ectopic thyroid in presumed thyroglossal duct cyst

We report a case of an eight year old female child with a midline neck mass for seven years. Since its early presentation, this midline mass has recently increased in size. A presumptive diagnosis of thyroglossal duct cyst was made clinically & planned for surgery. Preoperative evaluation revealed hypothyroidism, hence she was referred to us for the management of the same prior to excision. On further evaluation ⁹⁹Tc-thyroid scan showed that this midline mass was in fact the only functioning thyroid tissue & ultrasonography revealed no thyroid tissue in usual location, therefore no surgery was performed. This case demonstrates the essential role of a thyroid scan and ultrasonography in the preoperative evaluation of a midline neck mass.