Standard Operating Procedure for Use of Cryoprotectants in Lyophilized Formulations

1) Purpose

The purpose of this SOP is to establish guidelines for selecting and incorporating cryoprotectants into lyophilized formulations to protect biological molecules during the freezing and drying processes.

2) Scope

This SOP applies to the formulation development team, production operators, and QA teams involved in lyophilized products that require the use of cryoprotectants.

3) Responsibilities

• Formulation Scientists: Responsible for selecting appropriate cryoprotectants based on product characteristics.
• Operators: Responsible for incorporating cryoprotectants into formulations as per the batch manufacturing record (BMR).
• QA: Responsible for verifying the incorporation process and ensuring the cryoprotectant addition is documented.

4) Procedure

4.1 Selection of Cryoprotectants

4.1.1 Criteria for Selection

• 4.1.1.1 Select cryoprotectants that are non-toxic and do not interfere with the lyophilization process.
• 4.1.1.2 Ensure that cryoprotectants provide adequate protection against freezing damage for sensitive molecules.
• 4.1.1.3 Common cryoprotectants include sugars like sucrose, trehalose, and amino acids like glycine.

4.2 Incorporation of Cryoprotectants

4.2.1 Weighing and Dispensing

• 4.2.1.1 Weigh the cryoprotectants accurately as per the formulation specifications in the BMR.
• 4.2.1.2 Dispense the cryoprotectant into the formulation solution prior to freezing.

4.2.2 Mixing Procedure

• 4.2.2.1 Stir the solution containing cryoprotectants until they are fully dissolved.
• 4.2.2.2 Ensure no particles are visible in the solution, which could indicate improper