Standard Operating Procedure for Formulation Optimization for Lyophilized Proteins

1) Purpose

This SOP describes the procedure for optimizing protein formulations to maintain stability, bioactivity, and ease of reconstitution during and after lyophilization.

2) Scope

This SOP applies to formulation scientists, operators, and QA personnel responsible for the formulation, preparation, and testing of protein-based lyophilized products.

3) Responsibilities

• Formulation Scientists: Responsible for selecting stabilizers and designing protein formulations that remain stable throughout the lyophilization process.
• Operators: Responsible for executing the preparation and lyophilization steps as detailed in the Batch Manufacturing Record (BMR).
• QA Personnel: Responsible for ensuring the quality of the lyophilized protein formulation through documentation and verification of all process steps.

4) Procedure

4.1 Formulation Design

4.1.1 Criteria for Protein Stability

• 4.1.1.1 The formulation should prevent protein denaturation and aggregation during freeze-drying. Common stabilizers such as trehalose, mannitol, or polyethylene glycol (PEG) may be used.

4.2 Preparation and Lyophilization

4.2.1 Solution Preparation

• 4.2.1.1 Weigh the required protein and stabilizers as per the BMR, ensuring accurate measurements.
• 4.2.1.2 Dissolve the protein and stabilizers in a suitable buffer, ensuring that the protein is fully dissolved and the solution is homogeneous.

4.2.2 Sterile Filtration and Filling

• 4.2.2.1 Sterile filter the protein solution using a 0.22-micron filter to remove particulates.
• 4.2.2.2 Aseptically fill sterile vials with the