DI-099 Similarity assessment of reference remicade (infliximab) and its marketed biosimilar inflectra by means of aggregates profile over time and freeze/thaw stress

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Abstract

Background

The Inflectra (infliximab) product monograph indicates slightly higher aggregate proportions than the reference product Remicade.

Purpose

To evaluate the similarity between the reference Remicade and its marketed biosimilar Inflectra by means of tracking the aggregate contained in several solutions prepared in conditions for hospital use, in a stability study over time stored at 4°C. Similarity of reconstituted medicines regarding aggregate content when subjected to freeze/thaw cycles was also assessed.

Material and methods

Two vials of Remicade and Inflectra were used. Three concentrations (10 mg/mL reconstituted with water, and 5 mg/mL and 2 mg/mL in NaCl 0.9%) were analysed. The aggregates profile was obtained by size exclusion high performed liquid chromatography with diode array detection (SE-HPLC-DAD). Samples were analysed immediately after the solutions were prepared and the chromatographic aggregate profiles recorded were compared with those obtained periodically in the samples stored at 4°C for up to 15 days and in the samples which underwent several freeze (−20°C)/thaw cycles.

Results

Aggregate chromatographic profiles clearly indicated the presence of aggregates in reconstituted (10 mg/mL) and diluted 5 mg/mL Inflectra samples as natural infliximab aggregates. No aggregates were detected in the 2 mg/mL dilution. These profiles were unchanged over time, and for the freeze/thaw cycles of the reconstituted samples. For Remicade, no aggregates were detected in the chromatographic profiles until day 15; and no aggregates were detected for the reconstituted samples after the freeze/thaw cycles.

Conclusion

Remicade and its biosimilar Inflectra showed slight differences regarding aggregates, with natural aggregates in Inflectra that persisted in dilutions up to 5 mg/mL and over time when stored at 4°C. Inflectra seemed to be more stable regarding the aggregation process, since the aggregation profiles remained unchanged over the time period. Remicade suffered some degradation that led to the formation of aggregates on day 15 day after preparation of the solutions. No new aggregation was induced in both medicines after five cycles of freeze/thaw. Therefore, and despite the initial slightly higher content of aggregates in Inflectra, in use stabilities of the biosimilar and the reference medicine were similar.

References and/or acknowledgements

Financial support provided by Project PI10/00201, and therefore it was partially supported by the European Regional Development Funds (ERDF).

References and/or acknowledgements

No conflict of interest

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