Optimization of a recombinant human growth hormone purification process using quality by design

ABSTRACT

This work describes a strategy to optimize a downstream processing of a recombinant human growth hormone (rhGH) by incorporating a quality by design approach toward meeting higher quality specifications. The optimized process minimized the presence of impurities and degradation by-products during manufacturing by the establishment of in-process controls. Capillary zone electrophoresis, reverse phase, and size-exclusion chromatographies were used as analytical techniques to establish new critical process parameters for the solubilization, capture, and intermediate purification steps aiming to maintain rhGH quality by complying with pharmacopeial specifications. The results indicated that the implemented improvements in the process allowed the optimization of the specific recovery and purification of rhGH without compromising its quality. In addition, this optimization facilitated the stringent removal of the remaining impurities in further polishing stages, as demonstrated by the analysis of the obtained active pharmaceutical ingredient.

KEYWORDS:

• Critical process parameters
• critical quality attributes
• process optimization
• purification process
• quality by design
• recombinant human growth hormone

Acknowledgments

The authors thank to Rocío Zamora-Flores, Lidia Esmeralda Ramírez-Ramos, and Francisco Sánchez-Perales for their valuable contribution to the present work. Carolina Ortiz-Enriquez, Alexis de Jesús Romero-Diaz, Ana V. Hernández-Moreno, Hugo F. Cueto-Rojas, Mariana P. Miranda-Hernández, Carlos Augusto López-Morales, Nestor O. Pérez, Rodolfo Salazar-Ceballos, Norberto Cruz-García, Luis Flores-Ortiz, and Emilio Medina-Rivero are employees of Probiomed S.A. de C.V., which is developing, manufacturing, and marketing biosimilar products.