title: 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.
authors.affiliation: a Unidad de Investigación y Desarrollo , Probiomed S.A. de C.V., Cruce de carreteras Acatzingo-Zumpahuacán, Tenancingo , Estado de México , México.
authors.forename: Carolina
authors.initials: C
authors.lastname: Ortiz-Enriquez
authors.affiliation: a Unidad de Investigación y Desarrollo , Probiomed S.A. de C.V., Cruce de carreteras Acatzingo-Zumpahuacán, Tenancingo , Estado de México , México.
authors.forename: Alexis de Jesús
authors.initials: AJ
authors.lastname: Romero-Díaz
authors.affiliation: a Unidad de Investigación y Desarrollo , Probiomed S.A. de C.V., Cruce de carreteras Acatzingo-Zumpahuacán, Tenancingo , Estado de México , México.
authors.forename: Ana V
authors.initials: AV
authors.lastname: Hernández-Moreno
authors.affiliation: a Unidad de Investigación y Desarrollo , Probiomed S.A. de C.V., Cruce de carreteras Acatzingo-Zumpahuacán, Tenancingo , Estado de México , México.
authors.forename: Hugo F
authors.initials: HF
authors.lastname: Cueto-Rojas
authors.affiliation: a Unidad de Investigación y Desarrollo , Probiomed S.A. de C.V., Cruce de carreteras Acatzingo-Zumpahuacán, Tenancingo , Estado de México , México.
authors.forename: Mariana P
authors.initials: MP
authors.lastname: Miranda-Hernández
authors.affiliation: a Unidad de Investigación y Desarrollo , Probiomed S.A. de C.V., Cruce de carreteras Acatzingo-Zumpahuacán, Tenancingo , Estado de México , México.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: López-Morales
authors.affiliation: a Unidad de Investigación y Desarrollo , Probiomed S.A. de C.V., Cruce de carreteras Acatzingo-Zumpahuacán, Tenancingo , Estado de México , México.
authors.forename: Néstor O
authors.initials: NO
authors.lastname: Pérez
authors.affiliation: a Unidad de Investigación y Desarrollo , Probiomed S.A. de C.V., Cruce de carreteras Acatzingo-Zumpahuacán, Tenancingo , Estado de México , México.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Salazar-Ceballos
authors.affiliation: a Unidad de Investigación y Desarrollo , Probiomed S.A. de C.V., Cruce de carreteras Acatzingo-Zumpahuacán, Tenancingo , Estado de México , México.
authors.forename: Norberto
authors.initials: N
authors.lastname: Cruz-García
authors.affiliation: a Unidad de Investigación y Desarrollo , Probiomed S.A. de C.V., Cruce de carreteras Acatzingo-Zumpahuacán, Tenancingo , Estado de México , México.
authors.forename: Luis F
authors.initials: LF
authors.lastname: Flores-Ortiz
authors.affiliation: a Unidad de Investigación y Desarrollo , Probiomed S.A. de C.V., Cruce de carreteras Acatzingo-Zumpahuacán, Tenancingo , Estado de México , México.
authors.forename: Emilio
authors.initials: E
authors.lastname: Medina-Rivero
mesh_terms: D002850:Chromatography, Gel / Q000379:methods; D056148:Chromatography, Reverse-Phase / Q000379:methods; D019075:Electrophoresis, Capillary / Q000379:methods; D013006:Growth Hormone / Q000302:isolation & purification*; D006801:Humans; D011994:Recombinant Proteins / Q000302:isolation & purification; D012995:Solubility
chemical_list: D011994:Recombinant Proteins; D013006:Growth Hormone
keywords: Critical process parameters; critical quality attributes; process optimization; purification process; quality by design; recombinant human growth hormone