Pichia pastoris has been used as an expression system for multiple biotherapeutic products due to the unique advantages it offers with respect to cell density, protein titer, extracellular expression, and other such advantages. However, clarification of cell broth presents a significant challenge, primarily due to the high cell density (up to 50% W/V). Additionally, the abundance of host cell proteins complicates secondary clarification, impacting subsequent chromatographic, and filtration steps. In this study, a flocculation-based cell clarification method has been developed for the primary recovery of protein therapeutic products from Pichia broth. Human serum albumin (HSA) has been used as a case study. Unlike polymer-based flocculants, which introduce challenges in process clearance, the proposed method employs process-compatible salts. The approach has been designed and optimized using Quality by Design (QbD) principles, achieving a clarification efficiency with up to 90% recovery and a reduction of host cell proteins by up to 30%. The proposed methodology would be applicable to other biotherapeutic applications involving protein production in P. pastoris.