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

Area of Science:

• Biopharmaceutical Manufacturing
• Process Chemistry
• Analytical Chemistry

Background:

• Recombinant human growth hormone (rhGH) production requires stringent purification to meet pharmacopeial standards.
• Existing downstream processes may face challenges in impurity removal and maintaining product quality.

Purpose of the Study:

• To optimize the downstream processing of rhGH using a Quality by Design (QbD) approach.
• To establish in-process controls for minimizing impurities and degradation by-products.
• To meet higher quality specifications for the final active pharmaceutical ingredient (API).

Main Methods:

• Implementation of a QbD strategy for process optimization.
• Utilizing capillary zone electrophoresis (CZE), reverse-phase chromatography (RPC), and size-exclusion chromatography (SEC).
• Establishing critical process parameters (CPPs) for solubilization, capture, and intermediate purification steps.

Main Results:

• Minimized presence of impurities and degradation by-products through in-process controls.
• Successfully established new CPPs for key purification steps.
• Achieved optimized specific recovery and purification of rhGH without compromising quality.
• Demonstrated stringent removal of remaining impurities in polishing stages.

Conclusions:

• The QbD-driven optimization enhances rhGH downstream processing efficiency and product quality.
• The established in-process controls and CPPs ensure consistent production meeting pharmacopeial specifications.
• This optimized process yields a high-quality rhGH API with significantly reduced impurities.