Standard Operating Procedure for Use of Cryoprotectants in Lyophilized Products

1) Purpose

The purpose of this SOP is to establish the procedures for selecting and incorporating cryoprotectants into lyophilized formulations, ensuring the protection of active ingredients during the freezing and drying stages.

2) Scope

This SOP applies to all staff involved in the formulation and production of lyophilized products, including operators, formulation scientists, and QA teams.

3) Responsibilities

• Formulation Scientists: Responsible for selecting suitable cryoprotectants.
• Operators: Responsible for accurate incorporation of cryoprotectants as per the Batch Manufacturing Record (BMR).
• QA: Responsible for verifying cryoprotectant use and documentation.

4) Procedure

4.1 Selection of Cryoprotectants

Selection of cryoprotectants is based on the product’s stability and the sensitivity of the active pharmaceutical ingredient (API) during the freezing and lyophilization processes.

4.1.1 Criteria for Selection

• 4.1.1.1 Choose cryoprotectants that are compatible with the formulation and do not interfere with the API.
• 4.1.1.2 Typical cryoprotectants include sugars (e.g., sucrose, trehalose) and polyols (e.g., mannitol, glycerol).

4.2 Incorporation of Cryoprotectants

4.2.1 Weighing and Dispensing

• 4.2.1.1 Weigh the cryoprotectants as specified in the BMR using calibrated equipment.
• 4.2.1.2 Dispense the cryoprotectant into the formulation solution before the freezing step.

4.2.2 Mixing Procedure

• 4.2.2.1 Ensure complete dissolution of the cryoprotectant by stirring or using a homogenizer if necessary.
• 4.2.2.2 Ensure the solution