SOP for Conducting Long-Term Stability Studies on Liposomes

Conducting Long-Term Stability Studies on Liposomes

1) Purpose

The purpose of this SOP is to outline the procedure for conducting long-term stability studies on liposomal formulations. These studies assess the physical, chemical, and microbiological stability of liposomes over extended periods under various storage conditions, ensuring the product’s quality and efficacy throughout its shelf life.

2) Scope

This SOP applies to personnel involved in the formulation, quality control, and stability testing of liposomal products. It provides guidance for preparing and storing samples, conducting periodic testing, and analyzing the stability data over time.

3) Responsibilities

Formulation Scientists: Responsible for preparing liposome batches for stability testing and ensuring that all relevant data is documented.
QC Team: Responsible for conducting stability tests, including particle size analysis, zeta potential measurements, and chemical stability tests, at specified time intervals.
QA Team: Responsible for reviewing and approving the stability study results and ensuring compliance with GMP and regulatory guidelines.

4) Procedure

4.1 Sample Preparation

4.1.1 Prepare liposomal formulations as per the approved batch manufacturing procedure. Ensure that the samples are representative of the production batch.
4.1.2 Label each sample with the batch number, date of preparation, and storage conditions.
4.1.3 Divide the samples into groups to be stored under different conditions, such as

25°C/60% RH, 30°C/65% RH, and 40°C/75% RH, as per the stability protocol.

4.2 Parameters for Stability Testing

The following parameters should be monitored at regular intervals during the long-term stability study:

4.2.1 Particle Size Distribution: Measure the average particle size and distribution using dynamic light scattering (DLS) or another suitable technique. Record any significant changes over time.
4.2.2 Zeta Potential: Measure the zeta potential of the liposomal formulation to assess colloidal stability. A higher absolute zeta potential typically indicates better stability.
4.2.3 pH: Measure the pH of the liposome suspension at each testing interval. Significant fluctuations may indicate instability.
4.2.4 Encapsulation Efficiency: Use HPLC or another appropriate method to assess the encapsulation efficiency of the active pharmaceutical ingredient (API) over time.
4.2.5 Visual Inspection: Perform visual inspections at regular intervals to check for any signs of aggregation, precipitation, or phase separation.

4.3 Testing Schedule

4.3.1 Initial Test: Conduct the initial stability tests immediately after preparing the liposomal formulation to establish a baseline for the stability parameters.
4.3.2 Interim Tests: Conduct stability tests at specified intervals (e.g., 1 month, 3 months, 6 months, 12 months) depending on the storage conditions.
4.3.3 Final Test: Perform the final stability tests at the end of the designated study period (e.g., 24 months).

4.4 Data Recording and Analysis

4.4.1 Record all test results in the Stability Study Report (see Annexure 1 for the template).
4.4.2 Compare the test results over time to assess any trends in stability. Document any significant changes in particle size, zeta potential, or encapsulation efficiency.
4.4.3 Analyze the data to determine if the liposome formulation is stable under the specified conditions throughout the study period.

4.5 Criteria for Stability

The liposomal formulation is considered stable if it meets the following criteria throughout the study period:

4.5.1 Particle size remains within acceptable limits, with no significant aggregation or size increase.
4.5.2 Zeta potential values remain stable, indicating good colloidal stability.
4.5.3 pH remains within an acceptable range, with no significant shifts that would indicate instability.
4.5.4 Encapsulation efficiency remains above the predefined threshold, indicating minimal loss of the API.

5) Abbreviations

DLS: Dynamic Light Scattering
HPLC: High-Performance Liquid Chromatography
QC: Quality Control
QA: Quality Assurance

6) Documents

Batch Manufacturing Record (BMR)
Stability Study Report
Particle Size Analysis Report
Zeta Potential Measurement Report
pH Measurement Report
Encapsulation Efficiency Report

7) References

ICH Q1A: Stability Testing of New Drug Substances and Products
FDA Guidelines for Liposomal Drug Products

8) SOP Version

Version 1.0

Annexure

Annexure 1: Stability Study Report Template


  
    Time Point
    Storage Condition
    Particle Size (nm)
    Zeta Potential (mV)
    pH
    Encapsulation Efficiency (%)
    Visual Inspection
    Operator Initials
  
  
    Initial
    25°C/60% RH
    100-200 nm
    -30 to -50 mV
    7.0
    90%
    No aggregation
    Operator Name
  
  
    3 Months
    30°C/65% RH
    100-200 nm
    -30 to -50 mV
    7.0
    88%
    No aggregation
    Operator Name

Time Point	Storage Condition	Particle Size (nm)	Zeta Potential (mV)	pH	Encapsulation Efficiency (%)	Visual Inspection	Operator Initials
Initial	25°C/60% RH	100-200 nm	-30 to -50 mV	7.0	90%	No aggregation	Operator Name
3 Months	30°C/65% RH	100-200 nm	-30 to -50 mV	7.0	88%	No aggregation	Operator Name