4.1.2 Weighing of Ingredients

• Weigh APIs and excipients using a calibrated balance, ensuring the accuracy of measurements within ±1%. Record all measured quantities in the Batch Manufacturing Record (BMR).

4.2 Mixing and Formulation

4.2.1 Preparing the Aqueous Phase

• Dissolve excipients in Water for Injection (WFI) under gentle stirring to avoid air bubble formation, which may compromise nasal delivery.
• Ensure the solution is at room temperature (20-25°C) and is free of foam.

4.2.2 Incorporating the API

• Add the API to the aqueous phase while maintaining constant stirring. For hydrophobic APIs, use a surfactant to help disperse the API uniformly in the solution.
• Record all mixing parameters such as stirring speed, time, and temperature in the BMR.

4.2.3 pH and Osmolality Adjustment

• Measure the pH of the solution and adjust it to fall within the physiological range for nasal sprays (pH 5.5-7.0), which is safe for elderly nasal mucosa.
• Ensure the osmolality is close to isotonic levels (280-320 mOsm/kg) to minimize irritation.
• Document the pH and osmolality adjustment process in the BMR.

4.3 Filtration and Sterilization

4.3.1 Filtration Process

• Filter the nasal spray formulation through a sterile 0.22-micron filter to ensure it is free from microbial contamination. Use a low-pressure filtration system to preserve the integrity of sensitive APIs.
• Perform a filter integrity test post-filtration and record the results in the BMR.

4.4 Filling and Packaging

4.4.1 Filling Process

• Fill the sterile formulation into calibrated nasal spray containers using a filling machine. Set the machine to dispense an appropriate dose volume for elderly patients (e.g., 100 µL per spray).
• Check the fill accuracy by weighing 10 random filled containers. Ensure that the fill variance is within ±2% of the target volume. Record the results in the BMR.

4.4.2 Sealing and Packaging

• Seal the containers with pre-sterilized caps or nozzles. Ensure that the packaging is easy to open, but child-resistant if necessary, as elderly patients may struggle with complex packaging.
• Store the product in secondary packaging labeled with the appropriate storage conditions, batch number, and expiration date.

4.5 Quality Control Testing

4.5.1 API Content Testing

• Test the content uniformity of the API in the nasal spray to ensure each dose delivers the correct amount of API. Perform this test on 10 randomly selected units.
• Record the API content test results in the content uniformity log.

4.5.2 Stability Testing

• Conduct stability testing under various environmental conditions (e.g., 25°C/60% RH and 40°C/75% RH) to ensure the formulation remains stable over its shelf life.
• Document the stability test results in the stability testing log.

4.6 Documentation

• Document all steps of the formulation, mixing, filtration, filling, and packaging processes in the BMR.
• Ensure that 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, including balances, pH meters, osmometers, and filling machines, as per 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 process. Document the cleaning process in the cleaning log to ensure traceability and compliance.

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
• Stability Testing Log
• Calibration Log
• Cleaning Log

7) References, if any

• FDA Guidance for Drug Products for the Elderly
• ICH Q1A – Stability Testing Guidelines

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. 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