Standard Operating Procedure for System Suitability Test (SST) Before Bioanalysis in BA/BE Studies
| Department | BA-BE Studies |
|---|---|
| SOP No. | SOP/BA-BE/162/2025 |
| Supersedes | SOP/BA-BE/162/2022 |
| 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 procedure for performing System Suitability Tests (SST) prior to initiating sample analysis on LC-MS/MS systems to ensure that the bioanalytical method is performing acceptably for BA/BE studies.
2. Scope
This SOP is applicable to all analysts and scientific staff involved in operating LC-MS/MS instrumentation for quantitative bioanalysis of plasma samples in BA/BE studies.
3.
Responsibilities
- Analyst: Performs SST and evaluates results based on predefined acceptance criteria.
- QA Reviewer: Reviews SST data and logs prior to bioanalytical batch release.
- Lab Supervisor: Approves continuation of analysis based on successful SST performance.
4. Accountability
The Head of the Bioanalytical Department is accountable for ensuring that SSTs are executed as per validated protocols and documented before bioanalytical sample analysis begins.
5. Procedure
5.1 Pre-Requisites
- Ensure LC-MS/MS instrument setup and calibration is complete as per SOP/BA-BE/161/2025.
- Verify that mobile phases and column are equilibrated.
- Prepare and label system suitability solutions (SSS) per validated method SOP.
5.2 Injection and Evaluation
- Inject the SSS at the beginning of the sequence using the same injection parameters defined in the bioanalytical method.
- Evaluate the following system performance criteria:
- Retention time (RT) within ±2% of validated value.
- Signal-to-noise (S/N) ratio ≥ 10 at LLOQ.
- Peak shape: Symmetry factor between 0.8 to 1.5.
- Resolution between analyte and IS > 2 (if applicable).
- Area reproducibility: RSD for 5 replicate injections < 5%.
5.3 System Suitability Logs
- Record all SST parameters in Annexure-1: SST Summary Log.
- Include chromatograms, peak integration results, and calculations.
5.4 Deviation Handling
- If any parameter fails the acceptance criteria:
- Do not proceed with sample analysis.
- Investigate cause: mobile phase composition, column issues, or instrument error.
- Repeat SST after corrective action.
- Document deviations in Annexure-2: SST Deviation Log.
5.5 Re-Qualification
- If three consecutive SST failures occur:
- Requalify LC-MS/MS system.
- Notify QA and pause all active sequences.
5.6 Approval to Proceed
- Only after SST pass results are reviewed and signed by the Lab Supervisor and QA personnel may the analyst initiate injection of study samples.
6. Abbreviations
- BA/BE: Bioavailability/Bioequivalence
- SST: System Suitability Test
- SSS: System Suitability Solution
- RSD: Relative Standard Deviation
- RT: Retention Time
- IS: Internal Standard
7. Documents
- SST Summary Log – Annexure-1
- SST Deviation Log – Annexure-2
8. References
- ICH M10: Bioanalytical Method Validation
- FDA and EMA Bioanalytical Method Guidance
- Internal Bioanalytical Method SOPs
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: SST Summary Log
| Date | Instrument ID | Analyte | RT | Peak Area | S/N Ratio | RSD (%) | Result |
|---|---|---|---|---|---|---|---|
| 17/04/2025 | LCMS-004 | Metoprolol | 2.35 | 83546 | 28 | 2.1 | Pass |
Annexure-2: SST Deviation Log
| Date | Run ID | Parameter Failed | Cause | Corrective Action | Reviewed By |
|---|---|---|---|---|---|
| 17/04/2025 | SST-BE-22 | RT Shift | Column Pressure Fluctuation | Column Flushed | Sunita Reddy |
Revision History:
| Revision Date | Revision No. | Details | Reason | Approved By |
|---|---|---|---|---|
| 01/01/2022 | 1.0 | Initial release | New SOP | QA Head |
| 17/04/2025 | 2.0 | Added S/N criteria and RSD thresholds | Regulatory Review | QA Head |