Guidelines for Stability Testing of Drug Substances as per US FDA
1) Purpose
The purpose of this Standard Operating Procedure (SOP) is to define the procedure for conducting stability studies for drug substances in accordance with US FDA guidelines. This SOP ensures that the stability data generated is adequate to demonstrate the quality, safety, and efficacy of drug substances throughout their shelf life under intended storage conditions.
2) Scope
This SOP applies to all personnel involved in the design, execution, and documentation of stability studies for drug substances intended for the US market.
3) Responsibilities
Stability Testing Team: Responsible for conducting stability studies, collecting data, and documenting results as per US FDA guidelines.
Quality Assurance (QA) Team: Responsible for reviewing and approving stability protocols and reports, ensuring compliance with regulatory requirements.
Regulatory Affairs Team: Responsible for ensuring the study design and results meet the regulatory expectations of
4) Procedure
4.1 Preparation for Stability Testing
4.1.1 Obtain and review the latest version of the US FDA guidelines for the stability testing of drug substances.
4.1.2 Identify the drug substance to be tested and determine the type of stability study required (e.g., long-term, accelerated, or intermediate).
4.1.3 Develop a stability protocol that includes study design, testing schedule, storage conditions, and testing parameters as per US FDA guidelines.
4.2 Selection of Batches and Samples
4.2.1 Select representative batches of the drug substance, typically three primary batches manufactured using the proposed production process.
4.2.2 Prepare sufficient samples to cover the entire study duration, considering the number of time points and tests to be conducted.
4.3 Defining Storage Conditions and Time Points
4.3.1 Define the storage conditions according to the characteristics of the drug substance, including:
- Long-term storage conditions (e.g., 25°C ± 2°C/60% RH ± 5% RH)
- Accelerated storage conditions (e.g., 40°C ± 2°C/75% RH ± 5% RH)
- Intermediate storage conditions (if applicable, e.g., 30°C ± 2°C/65% RH ± 5% RH)
4.3.2 Establish the time points for sampling, such as 0, 3, 6, 9, 12, 18, and 24 months for long-term studies, and additional time points for accelerated studies.
4.4 Conducting the Stability Tests
4.4.1 Store samples under the defined conditions, monitoring temperature and humidity to ensure compliance with the set parameters.
4.4.2 At each specified time point, remove samples and conduct stability-indicating tests, including physical, chemical, microbiological, and functional tests, as applicable.
4.4.3 Record all results meticulously in stability data sheets, ensuring accuracy and traceability of data.
4.5 Data Analysis and Documentation
4.5.1 Review the stability data to identify any trends, deviations, or out-of-specification (OOS) results.
4.5.2 Investigate any OOS results, document findings, and implement corrective actions as necessary.
4.5.3 Compile a stability report that includes a summary of the study design, results, conclusions, and recommended shelf life and storage conditions for the drug substance.
4.6 Quality Assurance Review and Approval
4.6.1 Submit the stability report and all associated data to the QA Team for review.
4.6.2 QA Team to verify the completeness, accuracy, and compliance of the stability study with US FDA guidelines.
4.6.3 Address any discrepancies or required changes identified by the QA Team and finalize the report for approval.
5) Abbreviations, if any
US FDA: United States Food and Drug Administration
QA: Quality Assurance
OOS: Out-of-Specification
6) Documents, if any
Stability protocol, stability data sheets, stability testing records, stability report, submission package to the US FDA.
7) Reference, if any
US FDA Guidance for Industry: Stability Testing of New Drug Substances and Products.
8) SOP Version
Version 1.0