SOP Guide for Pharma

SOP for Preparing Cold-Processed Nasal Sprays




SOP for Preparing Cold-Processed Nasal Sprays



Standard Operating Procedure for Preparing Cold-Processed Nasal Sprays

1) Purpose

The purpose of this SOP is to provide the step-by-step procedure for preparing nasal sprays using a cold-processing technique, which helps to maintain the integrity of temperature-sensitive active pharmaceutical ingredients (APIs) and excipients.

2) Scope

This SOP applies to all personnel involved in the preparation, testing, and quality control of cold-processed nasal spray formulations at [Company Name].

3) Responsibilities

  • Operators: Responsible for executing the cold-processing formulation process to ensure the correct handling of temperature-sensitive ingredients.
  • Quality Assurance (QA): Ensures the final product meets the quality and sterility requirements.
  • Maintenance Team: Responsible for the maintenance and calibration of cold-processing equipment.

4) Procedure

4.1 Preparation of Materials

4.1.1 Selection of Ingredients

  • Choose active pharmaceutical ingredients (APIs) and excipients that are temperature-sensitive and require cold processing for optimal stability.
  • Store ingredients in cold storage prior to formulation to prevent degradation. Record the storage conditions in the Batch Manufacturing Record (BMR).

4.1.2 Weighing of Ingredients

  • Weigh APIs and excipients using a calibrated balance, ensuring accuracy within ±2%. Weigh materials in a controlled environment to maintain cold storage requirements.
  • Document the
weighed quantities in the BMR.

4.2 Cold Processing

4.2.1 Preparation of the Aqueous Phase

  • Prepare the aqueous phase by dissolving excipients in cold Water for Injection (WFI) at 2-8°C. Keep the mixing vessel in a chilled environment to maintain temperature.
  • Ensure the solution is free from foam by stirring gently. Maintain the temperature of the aqueous phase throughout the entire process.

4.2.2 Incorporating the API

  • Slowly add the API to the cold aqueous phase while stirring continuously to prevent clumping or aggregation.
  • Use a cold homogenizer to achieve a uniform mixture. Monitor the temperature closely, ensuring it does not exceed 8°C during the entire mixing process.
  • Record the mixing parameters, including time, speed, and temperature, in the BMR.

4.2.3 pH Adjustment

  • Measure the pH using a calibrated pH meter. Adjust the pH as necessary using a cold buffer solution to maintain nasal compatibility (typically pH 5.5-7.0).
  • Record the pH adjustments and the final pH in the BMR.

4.3 Filtration and Sterilization

4.3.1 Cold Sterilization

  • Filter the formulation using a sterile 0.22-micron filter to remove microbial contaminants. Ensure that the filtration is performed under cold conditions (2-8°C).
  • Record the filtration process in the BMR, including the filter integrity test results.

4.4 Filling and Packaging

4.4.1 Filling the Nasal Spray Containers

  • Transfer the sterile formulation to a filling machine pre-calibrated for cold operation. Fill the containers at low temperatures to ensure that the API remains stable throughout the filling process.
  • Check the fill accuracy by weighing 10 filled units. Record the fill weight and ensure it is within ±5% of the target volume.

4.4.2 Sealing and Packaging

  • Seal the filled containers with pre-sterilized nozzles or caps. Store the final product in a temperature-controlled environment (2-8°C) until packaging.
  • Package the nasal sprays in labeled containers, ensuring the labels include cold storage instructions. Record the packaging details in the BMR.

4.5 Quality Control Testing

4.5.1 Stability Testing

  • Conduct stability testing on the cold-processed nasal spray formulation under different temperature conditions to ensure that the product remains stable during storage and transportation.
  • Record all stability test results in the stability testing log.

4.5.2 Microbial Testing

  • Perform microbial testing to ensure sterility of the final product. Record the results in the microbial testing log.

4.6 Documentation

  • Document all steps of the cold-processing, filtration, filling, and packaging in the BMR.
  • Ensure 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 used in cold-processing, including temperature-controlled vessels, balances, and filling machines. Record calibration data in the calibration log.

4.7.2 Cleaning Equipment

  • Clean all equipment using a validated cold-cleaning procedure to prevent contamination. Record 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)
  • Stability Testing Log
  • Microbial Testing 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 Temperature Time Interval Stability Results Operator Initials QA Approval
DD/MM/YYYY Formulation Name Temperature 1 month, 3 months, etc. Pass/Fail Operator Name QA Name
           

2. Microbial Testing Log Template

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


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