Stability Testing of Reference Listed Drug (RLD)
Purpose
The purpose of this Standard Operating Procedure (SOP) is to outline the process for placing the Reference Listed Drug (RLD) on stability testing. This is to ensure that the RLD is evaluated under specified conditions to generate stability data necessary for regulatory submissions and comparison with test products.
Scope
This SOP applies to all activities related to the placement of the RLD on stability for drug substances and drug products intended for regulatory approval and market comparison in the US.
Responsibilities
- Stability Manager: Ensure the proper placement of the RLD on stability and compliance with regulatory guidelines.
- Stability Technicians:
Implement the stability protocol as specified and ensure proper documentation and monitoring.
Quality Assurance (QA) Team: Review and approve stability protocols and ensure adherence to documentation and regulatory standards.
Procedure
- Preparation for Stability Study:
- Obtain the Reference Listed Drug (RLD) and ensure it is within its expiration date.
- Document the batch number, expiration date, and other relevant information of the RLD.
- Determine Stability Conditions:
- Review regulatory guidelines (e.g., ICH Q1A(R2), FDA) to determine appropriate stability conditions.
- Set up storage conditions based on the climatic zones relevant to the US market:
- Long-term Storage: 25°C ± 2°C / 60% RH ± 5% RH
- Accelerated Storage: 40°C ± 2°C / 75% RH ± 5% RH
- Intermediate Storage (if needed): 30°C ± 2°C / 65% RH ± 5% RH
- Labeling of Samples:
- Assign a unique identifier to each RLD sample.
- Label samples with storage conditions, study identifiers, batch numbers, and time points.
- Placement of Samples:
- Place labeled RLD samples in designated storage units under specified conditions.
- Ensure proper organization of samples within the storage units by study, batch, and time point.
- Monitor Storage Conditions:
- Regularly monitor and record storage conditions (e.g., temperature, humidity).
- Set up alarms and alerts for deviations from specified conditions.
- Document any deviations and corrective actions taken.
- Sampling and Testing Intervals:
- Establish testing intervals based on regulatory guidelines:
- Accelerated Testing: 0, 1, 3, and 6 months
- Long-term Testing: 0, 3, 6, 9, 12, 18, and 24 months, then annually thereafter until the end of the proposed shelf life
- Intermediate Testing (if applicable): 0, 3, 6, 9, and 12 months
- Conduct stability testing at each interval and document results.
- Establish testing intervals based on regulatory guidelines:
- Documenting and Reporting Results:
- Record all stability data in the stability protocol and associated logs.
- Ensure all documentation is reviewed and approved by the Stability Manager and QA Team.
- Report stability data in regulatory submissions and compare with test products as needed.
- Review and Approval:
- Submit the stability protocol and results to the Stability Manager and QA Team for review and approval.
- Make any necessary adjustments based on feedback and finalize the stability study documentation.
- Communication:
- Communicate the stability study plan and results to all relevant stakeholders, including Stability Technicians, QA Team, and project managers.
Abbreviations Used
- QA: Quality Assurance
- RH: Relative Humidity
- SOP: Standard Operating Procedure
- ICH: International Council for Harmonisation
- RLD: Reference Listed Drug
Documents
- Stability Protocol
- Storage Unit Calibration and Validation Records
- Storage Condition Monitoring Logs
- Stability Testing Results
- Audit Reports
- Regulatory Guidelines
References
- ICH Q1A(R2) Stability Testing of New Drug Substances and Products
- FDA Guidance for Industry: Stability Testing of Drug Substances and Drug Products
SOP Version
Version 1.0 – Effective Date: [Insert Date]