Standard Operating Procedure for Long-Term Storage Stability of Analyte in BA/BE Studies
| Department | BA-BE Studies |
|---|---|
| SOP No. | SOP/BA-BE/176/2025 |
| Supersedes | SOP/BA-BE/176/2022 |
| Page No. | Page 1 of 9 |
| Issue Date | 17/04/2025 |
| Effective Date | 20/04/2025 |
| Review Date | 17/04/2026 |
1. Purpose
To define the process for assessing the long-term stability of analytes in plasma samples stored at -20°C and/or -70°C over extended periods as part of bioavailability/bioequivalence (BA/BE) studies.
2. Scope
This SOP applies to the bioanalytical laboratory performing method validation and sample analysis for BA/BE studies, specifically evaluating analyte stability in plasma samples stored for long durations.
3.
Responsibilities
- Analyst: Prepares and stores QC samples and performs analysis after designated storage periods.
- Reviewer: Evaluates stability data and ensures compliance with acceptance criteria.
- QA Officer: Verifies documentation and ensures SOP and regulatory guideline adherence.
4. Accountability
The Bioanalytical Lab Manager is accountable for ensuring long-term storage stability is evaluated, documented, and incorporated in validation reports or regulatory submissions as required.
5. Procedure
5.1 Sample Preparation and Storage
- Prepare at least six replicates of LQC and HQC samples from the same plasma lot used during validation.
- Label vials with the following:
- Study code
- Analyte
- QC level
- Date of preparation
- Designated stability time point
- Store samples in deep freezers at -20°C or -70°C as defined in the method validation protocol.
- Record entries in Annexure-1: Long-Term Storage Sample Log.
5.2 Time Points and Duration
- Commonly assessed durations include 30, 60, 90, 180, and 365 days.
- Retrieve and analyze stability samples at specified intervals.
- Do not allow samples to undergo freeze-thaw cycles before analysis.
5.3 Sample Analysis
- Analyze stability samples alongside fresh calibration standards and system suitability samples.
- Use validated LC-MS/MS methods to quantify analyte concentration.
- Document and process raw data in accordance with method SOP.
5.4 Acceptance Criteria
- Mean measured concentrations for LQC and HQC must be within ±15% of nominal values.
- %CV should be ≤15% for replicate values at each QC level.
- Document results in Annexure-2: Long-Term Stability Summary.
5.5 Reporting and Documentation
- Prepare a report containing:
- Raw data printouts
- System suitability results
- QC charts
- Acceptance conclusions
- Submit to QA for review and approval before finalizing the validation/study report.
6. Abbreviations
- BA/BE: Bioavailability/Bioequivalence
- LQC: Low Quality Control
- HQC: High Quality Control
- %CV: Percent Coefficient of Variation
- QA: Quality Assurance
7. Documents
- Long-Term Storage Sample Log – Annexure-1
- Long-Term Stability Summary – Annexure-2
8. References
- ICH M10: Bioanalytical Method Validation
- US FDA Guidance for Industry: Bioanalytical Method Validation (2022)
- Method Validation Protocol
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: Long-Term Storage Sample Log
| Sample ID | QC Level | Storage Temp | Prep Date | Target Analysis Date | Stored By |
|---|---|---|---|---|---|
| BE176-LTS-01 | LQC | -70°C | 17/04/2025 | 17/10/2025 | Rajesh Kumar |
Annexure-2: Long-Term Stability Summary
| QC Level | Nominal (ng/mL) | Mean Measured | %CV | % Difference | Status |
|---|---|---|---|---|---|
| HQC | 1500.0 | 1486.0 | 3.8 | -0.9% | Accepted |
| LQC | 20.0 | 19.4 | 4.5 | -3.0% | Accepted |
Revision History:
| Revision Date | Revision No. | Details | Reason | Approved By |
|---|---|---|---|---|
| 01/01/2022 | 1.0 | Initial version | New SOP | QA Head |
| 17/04/2025 | 2.0 | Clarified time points, annexures, and regulatory references | Annual Review | QA Head |