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Brainstorming Poster from France ECOP 2012/Budapest

Pneumatic Conveying Systems and Physical Stability of Monoclonal Antibodies – Example of Rituximab

1, K Rilcy12, A Bellanger2, A Astier1, M Paul1

1Henri Mondor Hospital Group APHP, Pharmacy Department, Creteil, France
2Pitié Salpétrière Hospital Group APHP, Paris, France

Background: Proteins such as monoclonal antibodies (mAb) are sensitive products which could undergo complex degradation pathways during the various manipulation steps also during transport. Aggregation can be induced by mechanical stresses which can occur during manipulations and transport and could induce loss of efficacy and/or toxic effects such as immunogenicity. Currently pneumatic conveying systems are in place in some hospitals but are not currently used for transport of proteins since no stability data under this specific stress is available. Manufacturer’s drug information is not useful giving only sentences such as ‘avoid shaking’. The objective of this study was to verify if the pneumatic conveying systems could be used to send bags containing the mAb rituximab to the clinical services.

Material and method: Various protein characterisation methods: size exclusion chromatography (SEC), dynamic light scattering (DLS) describing submicronic populations and corresponding mean diameters, turbidity (350 nm) and infra-red spectroscopy (FTIR) were used to determine changes in physical properties of Rituximab aggregation mechanically induced. Several conditions were tested: presence of residual air in bags, travel time, number of travel cycles (1 to 8). One concentration was tested (1 mg/mL). All experiments were performed on the same day.

Results and discussion: Up to 8 travel cycles and without head space or bubbles into the bags, no modification was noticed in comparison with the control (no run). Indeed, we observed only one peak by SEC, a monodisperse population (polydispersity index < to 0.1) of 11.34 + 0.03 nm by DLS, a slightly increased of optical densities (OD) at 350 nm (0.0019 up to 0.004) and no modification of the FT-IR spectra (similarity coefficients were close to one). In the opposite, in presence of air, significant modifications were found after 4 cycles since OD reached to 0.007 and 2 populations were found by DLS with a polydispersity index of about 0.24. Moreover, modifications of FTIR spectra were also observed (similarity coefficient < 1) suggested alteration of the secondary structure. These results demonstrate that aggregation during the pneumatic is strongly dependant on the presence of air/ liquid interfaces.

Conclusion: In practice, a pneumatic system can be safely used for the transport of diluted rituximab (and probably other mAbs), but the presence of air into the bags must be avoided.

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This entry was posted on December 28, 2012 by .

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