Development of Biotechnology Products in Pre-filled Syringes: Technical Considerations and Approaches

Abstract

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 prefilled syringe presentations for biotechnology-based compounds has been highlighted.

Strengths, weaknesses, opportunities and challenges for long acting injectable therapies: Insights for applications in HIV therapy

“…Innovation using injectable micro or nanoparticles and high concentration liquids may lead to the introduction of specialised processing needs with subsequent development of new quality controls. The recent trends towards the production of pre-filled sterile syringes for administration of biopharmaceutical products may offer opportunities to advanced LA products and minimise concerns during drug administration [85]. …”

Antibody adsorption on the surface of water studied by neutron reflection

“…4,5 The latter is encountered by mAbs exposed to air/liquid, solid/liquid and silicone oil/liquid interfaces as present during filling (pumping) and storage in primary packaging, such as glass vials with rubber stoppers and plastic/glass prefilled syringes. 6,7 Aggregation leading to particulate formation may be accelerated during manufacturing processes, in particular, fill-finish activities wherein the mAb is exposed to interfacial stresses. 8 Particulate limits are set by the pharmacopeias: for each unit dose referred to here, there must be less than 6000 particles > 10 mm and less than 600 particles > 25 mm (USP <787> and EP 2.9.19).…”

Gelation of a Monoclonal Antibody at the Silicone Oil–Water Interface and Subsequent Rupture of the Interfacial Gel Results in Aggregation and Particle Formation

“…The silicone oil–water interface is commonly encountered by therapeutic proteins during storage in drug product containers . Silicone oil is widely used as a lubricant for the plunger in prefilled syringes, and for stoppers for glass vials .…”

“…The silicone oil–water interface is commonly encountered by therapeutic proteins during storage in drug product containers . Silicone oil is widely used as a lubricant for the plunger in prefilled syringes, and for stoppers for glass vials . In prefilled syringes, formation of protein particles has been linked to the presence of silicone oil, and conformational changes have been observed in a number of monoclonal antibodies upon adsorption to the silicone oil–water interface .…”