Standard Operating Procedure for Preparing Cold-Processed Nasal Sprays
1) Purpose
The purpose of this SOP is to provide the step-by-step procedure for preparing nasal sprays using a cold-processing technique, which helps to maintain the integrity of temperature-sensitive active pharmaceutical ingredients (APIs) and excipients.
2) Scope
This SOP applies to all personnel involved in the preparation, testing, and quality control of cold-processed nasal spray formulations at [Company Name].
3) Responsibilities
- Operators: Responsible for executing the cold-processing formulation process to ensure the correct handling of temperature-sensitive ingredients.
- Quality Assurance (QA): Ensures the final product meets the quality and sterility requirements.
- Maintenance Team: Responsible for the maintenance and calibration of cold-processing equipment.
4) Procedure
4.1 Preparation of Materials
4.1.1 Selection of Ingredients
- Choose active pharmaceutical ingredients (APIs) and excipients that are temperature-sensitive and require cold processing for optimal stability.
- Store ingredients in cold storage prior to formulation to prevent degradation. Record the storage conditions in the Batch Manufacturing Record (BMR).
4.1.2 Weighing of Ingredients
- Weigh APIs and excipients using a calibrated balance, ensuring accuracy within ±2%. Weigh materials in a controlled environment to maintain cold storage requirements.
- Document the
weighed quantities in the BMR.
4.2 Cold Processing
4.2.1 Preparation of the Aqueous Phase
- Prepare the aqueous phase by dissolving excipients in cold Water for Injection (WFI) at 2-8°C. Keep the mixing vessel in a chilled environment to maintain temperature.
- Ensure the solution is free from foam by stirring gently. Maintain the temperature of the aqueous phase throughout the entire process.
4.2.2 Incorporating the API
- Slowly add the API to the cold aqueous phase while stirring continuously to prevent clumping or aggregation.
- Use a cold homogenizer to achieve a uniform mixture. Monitor the temperature closely, ensuring it does not exceed 8°C during the entire mixing process.
- Record the mixing parameters, including time, speed, and temperature, in the BMR.
4.2.3 pH Adjustment
- Measure the pH using a calibrated pH meter. Adjust the pH as necessary using a cold buffer solution to maintain nasal compatibility (typically pH 5.5-7.0).
- Record the pH adjustments and the final pH in the BMR.
4.3 Filtration and Sterilization
4.3.1 Cold Sterilization
- Filter the formulation using a sterile 0.22-micron filter to remove microbial contaminants. Ensure that the filtration is performed under cold conditions (2-8°C).
- Record the filtration process in the BMR, including the filter integrity test results.
4.4 Filling and Packaging
4.4.1 Filling the Nasal Spray Containers
- Transfer the sterile formulation to a filling machine pre-calibrated for cold operation. Fill the containers at low temperatures to ensure that the API remains stable throughout the filling process.
- Check the fill accuracy by weighing 10 filled units. Record the fill weight and ensure it is within ±5% of the target volume.
4.4.2 Sealing and Packaging
- Seal the filled containers with pre-sterilized nozzles or caps. Store the final product in a temperature-controlled environment (2-8°C) until packaging.
- Package the nasal sprays in labeled containers, ensuring the labels include cold storage instructions. Record the packaging details in the BMR.
4.5 Quality Control Testing
4.5.1 Stability Testing
- Conduct stability testing on the cold-processed nasal spray formulation under different temperature conditions to ensure that the product remains stable during storage and transportation.
- Record all stability test results in the stability testing log.
4.5.2 Microbial Testing
- Perform microbial testing to ensure sterility of the final product. Record the results in the microbial testing log.
4.6 Documentation
- Document all steps of the cold-processing, filtration, filling, and packaging in the BMR.
- Ensure QA reviews and approves all documents before the product is released for distribution.
4.7 Equipment Cleaning and Calibration
4.7.1 Equipment Calibration
- Calibrate all equipment used in cold-processing, including temperature-controlled vessels, balances, and filling machines. Record calibration data in the calibration log.
4.7.2 Cleaning Equipment
- Clean all equipment using a validated cold-cleaning procedure to prevent contamination. Record the cleaning process in the cleaning log.
5) Abbreviations, if any
- API: Active Pharmaceutical Ingredient
- QA: Quality Assurance
- BMR: Batch Manufacturing Record
- WFI: Water for Injection
6) Documents, if any
- Batch Manufacturing Record (BMR)
- Stability Testing Log
- Microbial 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. Stability Testing Log Template
| Date | Formulation | Storage Temperature | Time Interval | Stability Results | Operator Initials | QA Approval |
|---|---|---|---|---|---|---|
| DD/MM/YYYY | Formulation Name | Temperature | 1 month, 3 months, etc. | Pass/Fail | Operator Name | QA Name |
2. Microbial Testing Log Template
| Date | Formulation | Microbial Test | Results | Operator Initials | QA Approval |
|---|---|---|---|---|---|
| DD/MM/YYYY | Formulation Name | Microbial Test | Results | Operator Name | QA Name |
3. 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 |
4. Cleaning Log Template
| Date | Equipment ID | Cleaning Procedure | Operator Initials | QA Approval | |
|---|---|---|---|---|---|
| DD/MM/YYYY | Equipment Name/ID | Procedure | Operator Name | QA Name | |
