Standard Operating Procedure for Preparing Cold-Processed Nasal Sprays
1) Purpose
This SOP outlines the procedures for the preparation of cold-processed nasal sprays, ensuring that sensitive ingredients are preserved, and no heat is applied during the formulation process.
2) Scope
This SOP applies to all personnel involved in the preparation, formulation, and testing of cold-processed nasal sprays at [Company Name].
3) Responsibilities
- Operators: Responsible for weighing, mixing, and testing ingredients under cold conditions as outlined in the batch manufacturing record (BMR).
- Quality Assurance (QA): Ensures that the cold-processing conditions are maintained and that the nasal spray meets the required quality specifications.
- Maintenance Team: Responsible for ensuring that refrigeration and cooling equipment are calibrated and maintained.
4) Procedure
4.1 Preparation of Materials
4.1.1 Selection of Ingredients
- Select the active pharmaceutical ingredient (API) and excipients that are sensitive to heat or require cold processing. Document the selected ingredients in the BMR, ensuring their compatibility with cold processing.
4.1.2 Weighing of Ingredients
- Weigh the required quantities of the API and excipients using a calibrated balance, ensuring accuracy within ±2% of the target weight. Record the weights in the BMR.
- Store the weighed ingredients in a refrigerator at 4°C until ready for mixing.
4.2 Cold Mixing Process
4.2.1 Mixing in Cold Conditions
- Transfer the weighed ingredients to a cooled mixing vessel, ensuring the temperature does not exceed 10°C throughout the mixing process.
- Mix the ingredients using a mechanical stirrer or homogenizer, maintaining the cold temperature throughout. Record the mixing speed, time, and temperature in the BMR.
4.2.2 pH Adjustment
- Adjust the pH of the formulation using pre-cooled buffers or pH-adjusting agents. Use a pH meter to ensure the pH falls within the specified range for nasal administration (typically pH 4.5-7).
- Record the pH measurements and adjustments in the BMR.
4.3 Filling and Packaging
4.3.1 Filling Process
- Transfer the cold-processed formulation into a nasal spray filling machine. Ensure that the machine and the containers are pre-cooled to avoid raising the formulation temperature.
- Fill the nasal spray containers with the required dose (e.g., 100 µL per spray). Test the fill accuracy by weighing 10 filled containers, ensuring the variation does not exceed ±5% of the target volume.
4.3.2 Packaging
- Seal the filled containers with sterile nasal spray nozzles or caps. Ensure that the containers are free of leaks or defects before packaging.
- Label the containers with the batch number, expiration date, and storage instructions. Store the filled containers in a refrigerated environment (4°C) until they are ready for shipment.
4.4 Quality Control Testing
4.4.1 Cold Stability Testing
- Conduct stability testing of the cold-processed nasal spray by storing samples at 4°C and testing them at regular intervals (e.g., 1 month, 3 months, 6 months) for physical, chemical, and microbiological stability.
- Document the stability results in the stability testing log and ensure the product remains stable under cold conditions.
4.5 Documentation
- Document all steps of the cold-processing procedure, including ingredient weighing, mixing, pH adjustment, and filling, in the BMR.
- Ensure QA reviews and signs off on all documentation before releasing the product for distribution.
4.6 Equipment Calibration and Cleaning
- Calibrate all refrigeration and mixing equipment according to the calibration schedule and document the results in the calibration log.
- Clean and sterilize the equipment used for cold processing according to the cleaning validation protocol.
5) Abbreviations, if any
- API: Active Pharmaceutical Ingredient
- QA: Quality Assurance
- BMR: Batch Manufacturing Record
6) Documents, if any
- Batch Manufacturing Record (BMR)
- Stability Testing Log
- pH Adjustment 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 Conditions | Time Interval | Stability Results | Operator Initials | QA Approval |
|---|---|---|---|---|---|---|
| DD/MM/YYYY | Formulation Name | Temperature and Humidity | 1 month, 3 months, etc. | Pass/Fail | Operator Name | QA Name |
2. pH Adjustment Log Template
| Date | Formulation | pH Value | pH Adjusting Agent | Operator Initials | QA Approval |
|---|---|---|---|---|---|
| DD/MM/YYYY | Formulation Name | pH Value | Adjusting Agent | 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 |