Standard Operating Procedure for Formulation Optimization for Lyophilized Proteins
1) Purpose
This SOP outlines the procedure for optimizing formulations for lyophilized proteins to ensure maximum stability, bioactivity, and ease of reconstitution.
2) Scope
This SOP applies to formulation scientists, production operators, and QA personnel involved in the development, preparation, and testing of lyophilized protein formulations.
3) Responsibilities
- Formulation Scientists: Responsible for optimizing protein formulations, selecting stabilizers, and ensuring reconstitution performance.
- Operators: Responsible for preparing the protein formulations as outlined in the Batch Manufacturing Record (BMR).
- QA: Responsible for verifying protein stability, bioactivity, and proper documentation.
4) Procedure
4.1 Formulation Design
4.1.1 Criteria for Protein Stability
- 4.1.1.1 The formulation should ensure that proteins do not denature or aggregate during lyophilization. Common stabilizers include trehalose, mannitol, and PEG.
4.2 Preparation and Lyophilization
4.2.1 Solution Preparation
- 4.2.1.1 Weigh the required proteins and stabilizers as per the BMR.
- 4.2.1.2 Dissolve the proteins in a suitable buffer, ensuring full dissolution and homogeneity.
4.2.2 Sterile Filtration and Filling
- 4.2.2.1 Filter the solution through a sterile 0.22-micron filter to ensure sterility.
- 4.2.2.2 Aseptically fill the vials with the protein solution and freeze at -80°C before starting the lyophilization cycle.
4.3 Lyophilization and Reconstitution Testing
- 4.3.1 Transfer the vials to the lyophilizer and run the lyophilization cycle as specified in the BMR.
- 4.3.2 After lyophilization, reconstitute the protein formulation using a suitable diluent and perform bioactivity tests to ensure protein functionality is retained.
4.4 Documentation
Record all steps, including protein solution preparation, filtration, and lyophilization parameters, in the Protein Lyophilization Logbook. Ensure that QA verifies all reconstitution and bioactivity test results.
5) Abbreviations
- BMR: Batch Manufacturing Record
- PEG: Polyethylene Glycol
6) Documents
- Protein Lyophilization Logbook
7) References
- Pharmacopoeial guidelines for protein stability and bioactivity testing in lyophilized formulations
8) SOP Version
Version 1.0
Annexure
Protein Lyophilization Logbook Template
| Date | Protein Name | Batch No. | Stabilizer Used | Reconstitution Test | Bioactivity Test | Operator Initials | QA Verification |
|---|---|---|---|---|---|---|---|
| DD/MM/YYYY | Protein Name | Batch Number | Stabilizer Name | Pass/Fail | Pass/Fail | Operator Name | QA Initials |