Analysis of Downstream Process Controls to Assure the Quality of Recombinant Granulocyte-Colony Stimulating Factor

by Natacha Pérez, Mónica Navarro, Lázaro Estenoz, Ernesto Urrutia, Denis Alvarez, Oscar Cruz, Yunaisy Jiménez, Yodelis Calvo, Regla Somoza, Neyda Hernández, Lázaro Betancourt, and Rodolfo Valdés
Volume 14, Issue 2 (Summer 2015)

Human granulocyte colony-stimulating factor (GCSF) is produced by biotech laboratories and production facilities for reducing neutropenia duration and sequels in patients with myelosuppressor treatments, among other applications. However, real challenges for these laboratories started in 2015 when the PEGylated-GCSF patent expired, opening alternatives for developing biomanufacturing processes and new applications. Thus, the purpose of this study was to analyze downstream process controls designed to ensure recombinant human GCSF (rh-GCSF) quality and to provide some evidence of the downstream process validation status. Study outcomes proved that the rh-GCSF expression system was stable and chromatographic profiles were reproducible among samples. Also, rh-GCSF purity determination demonstrated an increased purity, step-by-step, reaching maximum value after ion exchange chromatography. The rh-GCSF characterization by mass spectrometry, biological and specific activity, immunodetermination, isoelectrofocusing, sterility, endotoxin level, host cell protein, and DNA content also showed high rh-GCSF molecular integrity and purity. Therefore, rh-GCSF quality was demonstrated, and the purification process was consistent for rh-GCSF industrial production...

Pérez N, Navarro M, Estenoz L, Urrutia E, Alvarez D, Cruz O et al. Analysis of downstream process controls to assure the quality of recombinant granulocyte-colony stimulating factor. BioProcess J, 2015; 14(2): 39–48.

Posted online July 10, 2015.