Standard Operating Procedure for Lyophilization of Nasal Powders
1) Purpose
The purpose of this SOP is to outline the procedure for the lyophilization (freeze-drying) of nasal powders, which enhances stability and prolongs shelf life by removing water through sublimation, without the need for heat.
2) Scope
This SOP applies to personnel involved in the formulation and preparation of nasal powders using the lyophilization process at [Company Name].
3) Responsibilities
- Operators: Responsible for preparing and loading the samples for lyophilization and ensuring the correct parameters are followed.
- Quality Assurance (QA): Ensures that the lyophilization process meets required specifications and that final products meet stability and quality standards.
- Maintenance Team: Responsible for ensuring that the lyophilizer is maintained, cleaned, and calibrated as required.
4) Procedure
4.1 Preparation of Materials
4.1.1 Selection of Ingredients
- Select the active pharmaceutical ingredient (API) and excipients suitable for lyophilization, ensuring that the API is stable in a freeze-dried state. Document the selection in the batch manufacturing record (BMR).
- Common excipients used for lyophilization include mannitol, trehalose, and lactose, which act as bulking agents and protectants for the API during freeze-drying.
4.1.2 Weighing of Ingredients
- Weigh the required amount of API and excipients using a calibrated balance. Document the weights in the BMR, ensuring that all components are within ±2% of the target weight.
4.2 Lyophilization Process
4.2.1 Equipment Setup
- Set up the lyophilizer according to the manufacturer’s instructions. Ensure the chamber is clean, sterile, and free of contaminants. Perform a pre-operation check to verify that all controls are functional.
- Calibrate the temperature and pressure controls according to the BMR, ensuring that they are within the required range for the specific formulation.
4.2.2 Freezing the Samples
- Transfer the prepared formulation (API and excipients) into suitable vials or trays for lyophilization. Pre-freeze the samples at a temperature below the formulation’s glass transition temperature (typically -40°C or lower).
- Document the freezing parameters, including temperature and time, in the BMR.
4.2.3 Primary Drying (Sublimation)
- Once frozen, apply a vacuum to the lyophilizer chamber to initiate the sublimation process, where water in the frozen state (ice) is directly converted into vapor. Maintain the chamber temperature below the critical point of the formulation (typically -20°C to -40°C).
- Monitor the pressure and temperature throughout the process and adjust as necessary to maintain a controlled rate of sublimation. Record the parameters in the BMR.
4.2.4 Secondary Drying (Desorption)
- After the primary drying phase, increase the temperature gradually (e.g., to 20-30°C) to remove any residual water from the formulation through desorption. Maintain the vacuum during this phase.
- Monitor the residual moisture content in the samples using a moisture analyzer. Record the final moisture levels in the BMR.
4.3 Quality Control Testing
4.3.1 Residual Moisture Content
- Test the final product for residual moisture content using a Karl Fischer titrator or other validated method. Ensure that the moisture content falls within the specified range (typically less than 3%).
- Record the test results in the moisture testing log.
4.3.2 Particle Size Distribution
- Test the particle size distribution of the lyophilized nasal powder using a particle size analyzer. Ensure that the particle size falls within the target range for nasal delivery (typically 1-10 microns).
- Record the particle size test results in the particle size testing log.
4.4 Packaging and Storage
4.4.1 Filling and Sealing
- Once lyophilization is complete, seal the vials or trays under vacuum or an inert gas (e.g., nitrogen) to prevent moisture from re-entering the product. Ensure that the containers are leak-proof and labeled with the batch number, expiration date, and storage instructions.
4.4.2 Storage
- Store the sealed containers in a cool, dry environment (e.g., 25°C and 60% RH) until they are ready for use. Document the storage conditions in the BMR and ensure that the product remains stable during storage.
4.5 Documentation
- Document all steps of the lyophilization process, including freezing, primary drying, secondary drying, and quality control tests, in the BMR.
- Ensure that QA personnel review and sign off on the documentation before the product is released for distribution.
4.6 Equipment Cleaning and Calibration
- Calibrate the lyophilizer as per the calibration schedule and document the results in the calibration log.
- After completing the batch, clean and sterilize the lyophilizer according to the cleaning validation protocol to prevent contamination of future batches.
5) Abbreviations, if any
- API: Active Pharmaceutical Ingredient
- QA: Quality Assurance
- BMR: Batch Manufacturing Record
6) Documents, if any
- Batch Manufacturing Record (BMR)
- Moisture Testing Log
- Particle Size Testing Log
- Calibration Log
- Cleaning Log
7) References, if any
- ICH Q1A – Stability Testing Guidelines
- FDA Guidance for Nasal Drug Products
8) SOP Version
Version 1.0
Annexure
1. Moisture Testing Log Template
| Date | Formulation | Residual Moisture (%) | Test Method | Operator Initials | QA Approval |
|---|---|---|---|---|---|
| DD/MM/YYYY | Formulation Name | Moisture (%) | Method | Operator Name | QA Name |
2. Particle Size Testing Log Template
| Date | Formulation | Particle Size (µm) | Test Method | Operator Initials | QA Approval |
|---|---|---|---|---|---|
| DD/MM/YYYY | Formulation Name | Particle Size | Method | Operator Name | QA Name |
3. Cleaning Log Template
| Date | Equipment ID | Cleaning Procedure | Operator Initials | QA Approval | |
|---|---|---|---|---|---|
| DD/MM/YYYY | Equipment Name/ID | Cleaning Method | Operator Name | QA Name | |
4. Calibration Log Template
| Date | Equipment ID | Calibration Procedure | Calibration Results | Operator Initials | QA Approval |
|---|---|---|---|---|---|
| DD/MM/YYYY | Equipment Name/ID | Procedure | Pass/Fail | Operator Name | QA Name |
