preservatives that enhance the stability of the hydrophilic API without causing irritation to the nasal mucosa.

4.1.2 Weighing and Handling of Ingredients

• Weigh the API and excipients using a calibrated balance. Ensure that all ingredients are weighed to within ±2% of the target weight. Document the measured quantities in the Batch Manufacturing Record (BMR).
• Ensure the formulation area is free from contaminants to prevent cross-contamination during ingredient handling.

4.2 Mixing and Formulation

4.2.1 Preparing the Aqueous Phase

• Dissolve the excipients (e.g., buffers and preservatives) in Water for Injection (WFI). Ensure that the solution is free from air bubbles and foam by stirring gently.
• Maintain the solution at a controlled temperature (20-25°C) to ensure proper dissolution of the excipients.

4.2.2 Incorporating the Hydrophilic API

• Add the hydrophilic API to the aqueous phase. Stir continuously to ensure that the API dissolves completely in the solution. If necessary, use a magnetic stirrer to achieve uniform dissolution.
• Check for the absence of undissolved particles using a visual inspection or filtration method. Record the mixing parameters in the BMR.

4.2.3 pH Adjustment

• Measure the pH of the solution using a calibrated pH meter. Adjust the pH using a buffer solution to match the optimal pH range for nasal administration (typically pH 4.5-7).
• Record the pH adjustment process, including the initial and final pH values, in the BMR.

4.3 Filtration and Sterilization

4.3.1 Sterilization of Equipment

• Ensure that all equipment used in the formulation and filling process, including mixing vessels and filling machines, is sterilized using autoclaving or other validated methods.

4.3.2 Filtration of the Formulation

• Filter the nasal spray formulation through a 0.22-micron filter to remove microbial contaminants and ensure sterility.
• Record the filtration process, including the integrity test of the filter, in the BMR.

4.4 Filling and Packaging

4.4.1 Filling Process

• Transfer the sterile formulation to a filling machine. Fill each nasal spray container with the required volume (e.g., 100 µL per spray), ensuring that each unit is filled accurately and consistently.
• Test the fill accuracy by weighing a sample of 10 filled containers. Ensure that the fill accuracy is within ±5% of the target volume. Record the results in the BMR.

4.4.2 Sealing and Packaging

• Seal the filled containers with sterile spray nozzles or caps. Ensure that the containers are leak-proof and properly labeled with batch numbers, expiration dates, and storage instructions.
• Package the nasal sprays in appropriate secondary packaging that protects the product from environmental factors such as light and humidity.

4.5 Quality Control Testing

4.5.1 API Content Uniformity

• Test the content uniformity of the API in the nasal spray formulation to ensure that each spray contains the appropriate amount of API. Perform this test on a sample of 10 units.
• Record the API content uniformity results in the content uniformity log.

4.5.2 Sterility Testing

• Perform sterility testing on the final product to ensure that it is free from microbial contamination. Use validated methods for sterility testing such as membrane filtration.
• Record the sterility test results in the microbial testing log.

4.6 Documentation

• Document all steps of the formulation, mixing, pH adjustment, filtration, and filling processes in the BMR.
• Ensure QA reviews and approves all documentation before the batch is released for distribution.

4.7 Equipment Cleaning and Calibration

4.7.1 Equipment Calibration

• Calibrate all equipment used in the formulation process, including balances, pH meters, and filling machines, according to the calibration schedule. Record the calibration data in the calibration log.

4.7.2 Cleaning Equipment

• Follow the cleaning validation protocol to clean and sterilize all equipment used in the formulation and filling processes. 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)
• Content Uniformity Log
• Microbial Testing Log
• Calibration Log
• Cleaning Log

7) References, if any

• ICH Q6A – Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products
• FDA Guidance for Nasal Drug Products

8) SOP Version

Version 1.0

Annexure

1. Content Uniformity Log Template

Date	Formulation	API Content (mg/spray)	Test Method	Operator Initials	QA Approval
DD/MM/YYYY	Formulation Name	API Content	Method	Operator Name	QA Name

2. Microbial Testing Log Template

Date	Formulation	Microbial Test	Results	Operator Initials	QA Approval
DD/MM/YYYY	Formulation Name	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