SOP for Preparing Cold-Processed Nasal Sprays

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

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

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

Date	Equipment ID	Cleaning Procedure	Operator Initials	QA Approval
DD/MM/YYYY	Equipment Name/ID	Cleaning Method	Operator Name	QA Name

Date	Equipment ID	Calibration Procedure	Calibration Results	Operator Initials	QA Approval
DD/MM/YYYY	Equipment Name/ID	Procedure	Pass/Fail	Operator Name	QA Name