Standard Operating Procedure for System Suitability Testing in HPLC for API Manufacturing
| Department | API Manufacturing |
|---|---|
| SOP No. | SOP/API/124/2025 |
| Supersedes | SOP/API/124/2022 |
| Page No. | Page 1 of 8 |
| Issue Date | 13/04/2025 |
| Effective Date | 15/04/2025 |
| Review Date | 13/04/2026 |
1. Purpose
To establish a standard procedure for performing system suitability testing (SST) in HPLC analysis before initiating sample analysis of API raw materials, intermediates, or finished products to verify the performance of the chromatographic system.
2. Scope
This SOP applies to all QC analysts and instruments used for HPLC-based analysis in the Quality Control (QC) laboratory involved
in the testing of APIs at various manufacturing stages.
3. Responsibilities
- QC Analyst: Perform SST as per method and document results in SST logbook.
- QC Reviewer: Verify system suitability parameters before approving batch analysis.
- QA Officer: Audit SST compliance during data review and batch release.
4. Accountability
The Head – QC is accountable for ensuring that no analysis is initiated unless the HPLC system meets the system suitability criteria as per approved analytical method or pharmacopeial monograph.
5. Procedure
5.1 General Guidelines
- System suitability must be run at the start of each sequence or analysis session.
- Prepare the system suitability solution or standard as per the method (STP or pharmacopoeia).
- Ensure column, detector, pump, and autosampler are stabilized.
5.2 SST Parameters
- System suitability parameters include but are not limited to:
- Retention time (Rt): Must be consistent (±2%)
- Theoretical plates (N): Indicates column efficiency
- Tailing factor (T): Should be ≤2.0 unless specified
- Resolution (Rs): Between critical peaks must be ≥2.0
- % RSD: For replicate injections should be within acceptance criteria (usually NMT 2.0%)
5.3 SST Execution
- Inject the standard solution as per method (minimum 5 injections unless specified).
- Record the chromatographic data and calculate system suitability parameters.
- Compare the observed values with the criteria defined in the STP or monograph.
- Document results in the SST Record Sheet (Annexure-1).
5.4 Acceptance and Continuation
- If SST passes:
- Proceed with sample analysis.
- Ensure no major instrument changes are made post-SST.
- If SST fails:
- Do not proceed with sample analysis.
- Investigate cause (e.g., column issue, mobile phase prep, instrument error).
- Rectify and re-perform SST.
5.5 Frequency
- Perform SST:
- Before each analytical run
- After major instrument maintenance
- After column change or mobile phase change
6. Abbreviations
- HPLC: High-Performance Liquid Chromatography
- SST: System Suitability Testing
- Rt: Retention Time
- N: Number of Theoretical Plates
- Rs: Resolution
- RSD: Relative Standard Deviation
- QA: Quality Assurance
- QC: Quality Control
7. Documents
- System Suitability Test Record Sheet (Annexure-1)
- Instrument Usage Logbook
- Analytical Method or STP
8. References
- USP <621> – Chromatography
- ICH Q2 (R1) – Validation of Analytical Procedures
- 21 CFR Part 211 – US FDA GMP Guidelines
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: System Suitability Test Record Sheet
| Date | Instrument ID | Column ID | Parameter | Observed Value | Limit | Pass/Fail |
|---|---|---|---|---|---|---|
| 13/04/2025 | HPLC-02 | C18-0923 | %RSD | 1.2% | NMT 2.0% | Pass |
| 13/04/2025 | HPLC-02 | C18-0923 | Resolution | 3.2 | NLT 2.0 | Pass |
Revision History:
| Revision Date | Revision No. | Details | Reason | Approved By |
|---|---|---|---|---|
| 01/01/2022 | 1.0 | Initial Release | New SOP | QA Head |
| 13/04/2025 | 2.0 | Added specific SST parameters and log format | Audit Feedback | QA Head |