Assessment of process validation program in batch production of stresomix premix™: A focus on operational qualification procedures within the herbal industry

Regulatory bodies throughout the world have ensured that formulations must be manufactured to the highest quality levels. The Food and Drug Administration (FDA) has a large-scale development program that is currently testing continuous production processes. Powder mixing is an important operation routinely used in many industries, including herbal medicine industry. The PAT (Process Analytical Technology) initiative requires the implementation of process validation, including in-process monitoring systems and controls, in the blending or mixing process. The quality of products depends on certain operating conditions, such as equipment, technical parameters, and formulation. In this work, an operational qualification for the blending process in the manufacturing of Stresomix Premix™ during large-scale production was performed. Blender operation was tested to illustrate the effect of mixing time on the homogeneity of the phytoconstituents in the herbal formulation, demonstrating that this parameter can be used as a secure parameter to control this process. A simple and practical operational qualification procedure has been proposed to investigate the blending operation on a large-scale production of Stresomix Premix™. Using an authentic analytical method that reliably profiles the phytoactives helped in validating the manufacturing process. The effects of mixing time have been quantified, and the behaviour of the dry powder mass was evaluated. A relation between theoretical concepts and real conditions that are applied in routine industrial production allowed the association of the critical operational aspects with the practical effects. The observed results illustrate that the homogeneity of powder in the blender depends on mixing time; it is important to consider this parameter to avoid segregation, mainly in formulations with a more complex composition and elevated powder mass. Additionally, results of this study demonstrates that the manufacturing process stands validated as it met acceptance criteria.