SOP for Lyophilization of Nasal Powders

Standard Operating Procedure for Lyophilization of Nasal Powders

1) Purpose

The purpose of this SOP is to outline the procedures for lyophilizing nasal powder formulations. Lyophilization (freeze-drying) ensures the stability and shelf life of temperature-sensitive or moisture-sensitive ingredients by removing moisture under low temperature and pressure.

2) Scope

This SOP applies to all personnel involved in the preparation, lyophilization, and packaging of nasal powders at [Company Name].

3) Responsibilities

Operators: Responsible for operating lyophilization equipment, ensuring correct freeze-drying conditions.
Quality Assurance (QA): Ensures that the lyophilized product meets quality and stability specifications.
Maintenance Team: Responsible for maintaining and calibrating lyophilization equipment.

4) Procedure

4.1 Preparation of Formulation

4.1.1 Ingredient Selection

Select APIs and excipients suitable for freeze-drying. Ensure that the ingredients maintain stability under freezing conditions.

4.1.2 Weighing and Mixing

Weigh the API and excipients accurately using a calibrated balance. Ensure the quantities fall within ±2% of the target weight.
Mix the ingredients to create a uniform blend. Record the mixing parameters, including speed and time, in the Batch Manufacturing Record (BMR).

4.2 Lyophilization Process

4.2.1 Freezing the Formulation

Transfer the blended formulation into pre-sterilized trays. Place the

trays in a pre-cooled chamber at -40°C or lower, depending on the formulation’s freezing point.

Monitor the freezing process until the formulation is completely frozen. Record the temperature and freezing duration in the BMR.

4.2.2 Primary Drying

Initiate primary drying by reducing the pressure in the lyophilizer to a vacuum of less than 100 millitorr. Slowly raise the temperature to sublimate the frozen water from the formulation.
Monitor the chamber pressure and shelf temperature throughout the process to ensure effective sublimation. Record all parameters in the BMR.

4.2.3 Secondary Drying

After the primary drying phase, increase the temperature to remove any bound water. Maintain the vacuum throughout the process.
Continue secondary drying until the residual moisture content falls below the target level (typically less than 1%). Record the final moisture content in the BMR.

4.3 Post-Lyophilization Testing

4.3.1 Moisture Content Testing

Test the moisture content of the lyophilized powder using the Karl Fischer method or another validated method. Ensure that the moisture content falls within the acceptable range for nasal powders (typically less than 2%).
Record the moisture content results in the moisture content log.

4.3.2 Particle Size Testing

Perform particle size analysis on the lyophilized powder using laser diffraction or another suitable method. Ensure the particle size is within the target range for nasal delivery (typically 1-10 microns).
Record the particle size distribution in the particle size testing log.

4.4 Packaging

4.4.1 Filling Process

Fill the lyophilized nasal powder into pre-sterilized containers using a powder filling machine. Ensure that the powder is filled in an environment with low humidity to prevent moisture absorption.
Record the fill weight for 10 random samples, ensuring that the fill volume is within ±5% of the target weight. Document the results in the BMR.

4.4.2 Sealing and Packaging

Seal the filled containers with pre-sterilized caps or nozzles. Store the containers in a moisture-controlled environment (e.g., desiccated packaging) to maintain the stability of the lyophilized powder.
Label the containers with batch numbers, expiration dates, and storage instructions.

4.5 Quality Control Testing

4.5.1 Stability Testing

Conduct stability testing on the lyophilized powder under different temperature and humidity conditions to ensure long-term stability.
Record the stability testing results in the stability testing log.

4.6 Documentation

Document all steps of the lyophilization process, including freezing, primary drying, secondary drying, and post-lyophilization testing, in the BMR.
Ensure QA reviews and approves all documentation before the product is released for distribution.

4.7 Equipment Cleaning and Calibration

4.7.1 Equipment Calibration

Calibrate all equipment used in the lyophilization process, including lyophilizers, balances, and particle size analyzers, according to the calibration schedule.
Record calibration data in the calibration log.

4.7.2 Cleaning Equipment

Clean all equipment used in the lyophilization process according to the cleaning validation protocol. Document the cleaning process in the cleaning log.

5) Abbreviations, if any

API: Active Pharmaceutical Ingredient
QA: Quality Assurance
BMR: Batch Manufacturing Record

6) Documents, if any

Batch Manufacturing Record (BMR)
Moisture Content Log
Particle Size Testing Log
Stability 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. Moisture Content Log Template


  
    Date
    Formulation
    Moisture Content (%)
    Test Method
    Operator Initials
    QA Approval
  
  
    DD/MM/YYYY
    Formulation Name
    Moisture Content
    Method
    Operator Name
    QA Name

Date	Formulation	Moisture Content (%)	Test Method	Operator Initials	QA Approval
DD/MM/YYYY	Formulation Name	Moisture Content	Method	Operator Name	QA Name

2. Particle Size Testing Log Template


  
    Date
    Formulation
    Particle Size (µm)
    Test Method
    Operator Initials
    QA Approval
  
  
    DD/MM/YYYY
    Formulation Name
    Particle Size
    Method
    Operator Name
    QA Name

Date	Formulation	Particle Size (µm)	Test Method	Operator Initials	QA Approval
DD/MM/YYYY	Formulation Name	Particle Size	Method	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

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. 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