Standard Operating Procedure for Manufacturing Nasal Sprays for Pediatric Use
1) Purpose
The purpose of this SOP is to outline the procedures for formulating and manufacturing nasal sprays specifically designed for pediatric use. Pediatric nasal sprays must meet stricter safety, dosage, and formulation requirements due to the sensitivity of young patients.
2) Scope
This SOP applies to all personnel involved in the formulation, preparation, and testing of nasal sprays for pediatric patients at [Company Name].
3) Responsibilities
- Operators: Responsible for following pediatric-specific formulation guidelines and preparing nasal sprays according to the approved formulation.
- Quality Assurance (QA): Ensures the product meets pediatric safety and efficacy standards, including proper dosage, sterility, and stability.
- Maintenance Team: Ensures that all equipment is calibrated and sanitized appropriately for pediatric formulations.
4) Procedure
4.1 Selection of Ingredients
4.1.1 Pediatric-Safe API and Excipients
- Select active pharmaceutical ingredients (APIs) that have been tested and approved for pediatric use. Ensure that the API is appropriate for nasal administration in children and is at a pediatric-safe dosage.
- Choose excipients that are non-toxic and non-irritating to pediatric nasal mucosa. Avoid preservatives that are not recommended for children under 12 years of age.
4.1.2 Weighing of Ingredients
- Weigh APIs and excipients using a calibrated balance, ensuring accuracy within ±1% for pediatric formulations. Document the weight in the Batch Manufacturing Record (BMR).
4.2 Mixing and Formulation
4.2.1 Preparing the Aqueous Phase
- Dissolve the selected excipients in Water for Injection (WFI) at room temperature. Avoid heating the solution to preserve the integrity of sensitive ingredients.
- Ensure the solution is free from foam and air bubbles by gently stirring.
4.2.2 Incorporating the API
- Slowly add the API to the aqueous phase under constant stirring. If necessary, use a homogenizer to ensure uniform dispersion of the API.
- Record the mixing parameters, such as speed, time, and temperature, in the BMR.
4.2.3 pH Adjustment
- Measure the pH using a calibrated pH meter. Adjust the pH to match the physiological range for pediatric nasal formulations (pH 5.5-7.0).
- Record the pH adjustment process in the BMR.
4.3 Filtration and Sterilization
4.3.1 Filtration Process
- Filter the formulation through a 0.22-micron sterile filter to ensure that the product is free of microbial contaminants.
- Perform a filter integrity test after filtration to ensure the effectiveness of the filtration process.
- Document the filtration process in the BMR.
4.4 Filling and Packaging
4.4.1 Filling the Nasal Spray Containers
- Transfer the sterile formulation to a calibrated filling machine. Set the machine to dispense an accurate pediatric dose (e.g., 50 µL per spray).
- Weigh 10 random filled containers to check the fill accuracy, ensuring it is within ±2% of the target volume. Record the results in the BMR.
4.4.2 Sealing and Packaging
- Seal the filled containers with pre-sterilized nozzles and caps. Ensure that the packaging is child-resistant and properly labeled with pediatric dosing instructions.
- Store the containers in labeled packaging with batch numbers, expiration dates, and storage instructions.
4.5 Quality Control Testing
4.5.1 Pediatric Dose Accuracy
- Test the dose accuracy of the nasal spray to ensure it delivers the correct volume for pediatric use. Perform this test on 10 random units.
- Record the dose accuracy results in the dosing accuracy log.
4.5.2 Stability Testing
- Conduct stability testing under different environmental conditions (e.g., 25°C/60% RH and 40°C/75% RH) to ensure that the formulation remains stable during storage and use.
- Record stability test results in the stability testing log.
4.6 Documentation
- Document all steps of the formulation, mixing, filtration, filling, and packaging in the BMR.
- Ensure QA reviews and approves all documentation before the product is released for distribution.
4.7 Equipment Cleaning and Calibration
4.7.1 Equipment Calibration
- Calibrate all equipment used in the pediatric formulation process, including balances, pH meters, and filling machines, according to the calibration schedule.
- Record calibration data in the calibration log.
4.7.2 Cleaning Equipment
- Follow the cleaning validation protocol to clean and sterilize all equipment used in pediatric formulations. Document 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)
- Dosing Accuracy Log
- Stability Testing Log
- Calibration Log
- Cleaning Log
7) References, if any
- FDA Pediatric Drug Development Guidelines
- ICH Q1A – Stability Testing Guidelines
8) SOP Version
Version 1.0
Annexure
1. Dosing Accuracy Log Template
| Date | Formulation | Dose Volume (µL) | Test Method | Operator Initials | QA Approval |
|---|---|---|---|---|---|
| DD/MM/YYYY | Formulation Name | Volume | Method | Operator Name | QA Name |
2. 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 |
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 | |