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Reviewing the effects of monoclonal antibody formulations, with relevance to rheumatoid arthritis

Presentation abstract:

Introduction:  

Monoclonal antibodies (mAbs) are a class of biological therapeutic agents used in oncology or autoimmune diseases like Rheumatoid arthritis (RA). Its sensitivity in ambient conditions causes instability during manufacturing, storage and administration. Employing certain conditions and excipients may improve the mAbs’ pharmaceutical stability. 

Materials and Methods: 

Samples (1mg/ml and 6mg/ml of Immunoglobulin, IgG, from human serum, in citrate buffer) were tested in the absence and presence of β-cyclodextrin (CD), 1:1 weight ratio. Solutions were tested using Solution Differential Scanning Calorimetry (SDSC) from 20-90oC at 60oC/hr.  

Results and Discussion: 

From literature, the effectiveness and suitability of common (amino acids, silicone oil) and novel (dipicolinic acid, quinolinic acid, arginine-glutamate) excipients in countering challenges such as viscosity, opalescence and aggregation have been established.  The findings (Singh, 2011) were used to discuss and account for the safety and efficacy of Tocilizumab, used in RA. Findings demonstrated that amino acids have concentration dependent stabilising and destabilising effects whereas silicone oil induces aggregation and protein instability. Stress induced the most aggregation, leading to colloidal instability, as demonstrated also by our experiment, where the SDSC thermograms showed that CD increased Transition temperature (Tm) by 2oC for the 1mg/ml solution, indicating some stabilising effect. At high IgG concentrations, Tm was reduced by 8oC and solutions after SDSC runs showed aggregation. Based on our in-vitro experiments, CD showed promise as an effective stabiliser, similar to amino acids, however more research is needed to strengthen its use. 

Conclusion: 

In conclusion, the literature creates more potential for research to be conducted in terms of evaluating mAb therapeutics in different patient types (Maggio, 2017). According to our research, using different CD concentrations on IgG solutions should be considered for a more comprehensive evidence base. 

References: 
  1. Edward Maggio (2017) Polysorbates, Biotherapeutics, and Anaphylaxis: A Review, Available at: https://bioprocessintl.com/manufacturing/formulation/polysorbates-biotherapeutics-and-anaphylaxis-a-review/ (Accessed: 22/12/2018).
  2. Satish Kumar Singh (2011) 'Impact of product‐related factors on immunogenicity of biotherapeutics', Journal of Pharmaceutical sciences, 2011,[Online]. Available at: https://onlinelibrary.wiley.com/doi/10.1002/jps.22276 (Accessed: 3/3/2019).