Standard Operating Procedure for Preparing Nasal Sprays for Elderly Patients
1) Purpose
The purpose of this SOP is to provide detailed procedures for the formulation, preparation, and packaging of nasal sprays specifically designed for elderly patients. It ensures that the formulation is tailored to the physiological and pharmacological needs of this age group, taking into consideration factors such as ease of use, reduced dosage, and safety.
2) Scope
This SOP applies to all personnel involved in the formulation, production, and testing of nasal sprays intended for elderly patients at [Company Name]. It ensures that the formulation complies with both internal standards and regulatory guidelines.
3) Responsibilities
- Operators: Responsible for preparing the formulation according to the specifications and ensuring accurate mixing, filling, and packaging.
- Quality Assurance (QA): Ensures that the product meets regulatory standards and quality specifications, including dosage accuracy and safety testing.
- Maintenance Team: Ensures all equipment is cleaned, sterilized, and calibrated regularly to prevent contamination and ensure proper functioning.
4) Procedure
4.1 Selection of Ingredients
4.1.1 Active Ingredient Selection
- Select active pharmaceutical ingredients (APIs) that are appropriate for elderly patients. This includes APIs with known safety and efficacy profiles for this population, considering any possible drug interactions or sensitivities.
- Choose excipients that enhance nasal absorption without irritating the nasal mucosa, which may be more sensitive in elderly patients.
4.1.2 Weighing of Ingredients
- Weigh the API and excipients using a calibrated balance, ensuring accuracy within ±2%. Adjust the API concentration according to the therapeutic needs of elderly patients, who may require lower doses compared to younger populations.
- Record the weighed amounts in the Batch Manufacturing Record (BMR).
4.2 Mixing and Formulation
4.2.1 Preparation of the Aqueous Phase
- Prepare the aqueous phase by dissolving stabilizers, buffers, and other excipients in water for injection (WFI). Maintain the temperature of the solution at 20-25°C.
- Ensure the formulation has a low viscosity to allow easy spraying, as elderly patients may have difficulty generating enough force for higher viscosity solutions.
4.2.2 Incorporation of API
- Slowly add the API to the aqueous phase under continuous stirring. Ensure that the API is fully dissolved or uniformly dispersed, depending on the solubility of the ingredient.
- Use a homogenizer if necessary to ensure a uniform mixture. Record the mixing speed, duration, and temperature in the BMR.
4.2.3 pH and Osmolality Adjustment
- Adjust the pH to the desired level (typically pH 5.5 – 7.0) using pre-approved buffers. The pH should be gentle on the nasal mucosa of elderly patients, which can be more prone to irritation.
- Adjust the osmolality to match physiological levels (around 300 mOsm/kg) to minimize discomfort and ensure proper absorption.
- Record pH and osmolality values in the BMR.
4.3 Sterilization and Filtration
4.3.1 Sterilization of Equipment
- Ensure all mixing vessels, filling machines, and storage containers are sterilized using autoclaving or other validated methods. Document the sterilization process in the cleaning log.
4.3.2 Filtration of the Formulation
- Filter the nasal spray formulation through a 0.22-micron filter to ensure sterility and remove any particulates.
- Record the filtration process in the BMR, including the integrity test of the filter.
4.4 Filling and Packaging
4.4.1 Filling the Nasal Spray Bottles
- Transfer the sterilized formulation to the filling machine. Fill the nasal spray bottles with the required volume (e.g., 100 µL per spray), ensuring that each bottle contains the correct dose for elderly patients.
- Test the fill accuracy by weighing 10 randomly selected filled bottles. The variance must not exceed ±5%. Record the results in the BMR.
4.4.2 Sealing and Packaging
- Seal the filled bottles with sterile spray nozzles and caps. Ensure that the containers are leak-proof and inspect them for any defects.
- Package the nasal spray bottles in clearly labeled containers with batch numbers, expiration dates, and storage instructions. Include easy-to-read labels and instructions suitable for elderly patients with potential visual impairments.
4.5 Quality Control Testing
4.5.1 Microbiological Testing
- Conduct microbiological tests, including sterility and endotoxin tests, to ensure the nasal spray is free from contamination. Record the results in the microbiological testing log.
4.5.2 Dosage Accuracy Testing
- Perform dosage accuracy testing by dispensing a set number of sprays into a graduated cylinder to ensure each spray delivers the intended volume.
- Document the results in the dosage testing log.
4.5.3 Stability Testing
- Conduct stability testing under both room temperature and accelerated conditions to ensure the product remains stable throughout its shelf life. Record all stability test results in the stability testing log.
4.6 Documentation
- Record all formulation steps, including ingredient selection, weighing, mixing, pH adjustment, filtration, and filling, in the BMR.
- Ensure all quality control test results are reviewed and approved by QA before the batch is released for distribution.
4.7 Equipment Cleaning and Calibration
- Calibrate all equipment used in the formulation process according to the calibration schedule. Record calibration data in the calibration log.
- Clean all equipment after each batch following the cleaning validation protocol. Record the cleaning process in the cleaning log to prevent contamination between batches.
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)
- Microbiological Testing Log
- Dosage Testing Log
- Stability Testing Log
- Calibration Log
- Cleaning Log
7) References, if any
- ICH Q1A – Stability Testing Guidelines
- FDA Guidance for Nasal Drug Products
- Geriatric-specific Regulatory Guidelines
8) SOP Version
Version 1.0
Annexure
1. Microbiological Testing Log Template
| Date | Formulation | Microbial Test | Results | Operator Initials | QA Approval |
|---|---|---|---|---|---|
| DD/MM/YYYY | Formulation Name | Microbial Test | Results | Operator Name | QA Name |
2. Dosage Testing Log Template
| Date | Formulation | Dosage Volume (µL) | Test Method | Operator Initials | QA Approval |
|---|---|---|---|---|---|
| DD/MM/YYYY | Formulation Name | Volume | Method | Operator Name | QA Name |
3. 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 |
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 |
5. Cleaning Log Template
| Date | Equipment ID | Cleaning Procedure | Operator Initials | QA Approval | |
|---|---|---|---|---|---|
| DD/MM/YYYY | Equipment Name/ID | Cleaning Method | Operator Name | QA Name | |
