Abstract
Various kinds of treatments on the surface of the elastomeric components can have impacts on the quality of protein therapeutics. We compared the effects of bare (non-siliconized and non-laminated), siliconized and fluoropolymer laminated elastomeric components on the stability of β-Lactoglobulin, human serum albumin, adalimumab, abatacept and immunoglobulin antibodies. The study was conducted in two main parts. Part I was to evaluate the stability of proteins under agitation induced stress. Protein aggregate formation, turbidity and protein recovery were analyzed using dynamic fluid imaging, absorbance @350 nm and SE-HPLC, respectively. Proteins were found to be more stable with laminated stoppers as compared to bare or siliconized stoppers. Part II was to identify chemical modifications when proteins were stored in contact with the same three stoppers. cIEF analysis of the adalimumab samples showed formation of acidic variants in siliconized and bare stoppers. RP-HPLC suggested chemical changes to human serum albumin. Analysis of tryptic human serum albumin by LC/MS/MS indicated that the amino acids most susceptible to oxidation (cysteine, tryptophan and methionine) were also the ones which were modified. Part III of this study investigated the barrier property of the fluoropolymer film with no drug product. Our results are consistent with the suggestion that the fluoropolymer lamination provides a barrier that prevents leachables from the elastomeric components into the protein therapeutics. Our work provides an in-depth understanding of the effects of elastomeric surface treatments on the biophysical and chemical stability of protein drugs.
- Drug delivery systems
- biotherapeutics, ß-lactoglobulin, human serum albumin, mAb, antibody, monoclonal antibody, abatacept
- elastomers, stoppers,
- lamination, fluoropolymer
- protein stability, protein aggregation, protein modification
- siliconization
- Received July 1, 2020.
- Accepted October 15, 2020.
- Copyright © 2020, Parenteral Drug Association
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