Development of biotechnology products in pre-filled syringes: technical considerations and approaches

AAPS PharmSciTech. 2011 Jun;12(2):564-72. doi: 10.1208/s12249-011-9617-y. Epub 2011 May 4.

Abstract

A monoclonal antibody (mAb) product development case study is presented to address some of the issues faced during developing a pre-filled syringe (PFS) product for a biotherapeutic. In particular, issues involving incompatibility with silicone oil and a stability-based approach for selection of PFS barrel and tip cap components have been discussed. Silicone spiking studies followed by exposure to agitation stress or accelerated temperature conditions were used to check for incompatibilities of the mAb with silicone oil, a necessary product contact material in PFS. In addition, screening studies to compare various closure materials as well as syringe barrel processing methods were used to select the optimum closure materials as well as the correct syringe processing method. Results indicate that the model mAb formulation used was sensitive to high levels of silicone oil especially under accelerated temperature conditions resulting in formation of protein-silicone particles in the solution for samples that were spiked with the silicone oil. Agitation stress did not have any significant impact on the quality attributes tested. Samples stored in syringe barrels that were processed with sprayed-on silicone had higher levels of subvisible particles as compared to those that were processed with the baked-on process. The tip cap comparability study resulted in one tip cap material having superior compatibility among the three that were tested. The quality attribute that was most impacted by the tip cap materials was mAb oxidation. An approach for evaluation of primary packaging components during the development of pre-filled syringe presentations for biotechnology-based compounds has been highlighted.

Publication types

  • Comparative Study

MeSH terms

  • Antibodies, Monoclonal / chemistry*
  • Biotechnology / methods*
  • Biotechnology / standards
  • Biotechnology / trends
  • Drug Discovery / methods*
  • Drug Discovery / standards
  • Drug Packaging / methods*
  • Drug Packaging / standards
  • Drug Packaging / trends
  • Drug Stability
  • Silicone Oils / chemical synthesis*
  • Silicone Oils / standards
  • Syringes* / standards
  • Syringes* / trends

Substances

  • Antibodies, Monoclonal
  • Silicone Oils