Standard Operating Procedure for Mixing Time Validation in Elixir Manufacturing
| Department | Elixir Department |
|---|---|
| SOP No. | SOP/ELX/095/2025 |
| Supersedes | SOP/ELX/095/2022 |
| Page No. | Page 1 of 8 |
| Issue Date | 11/04/2025 |
| Effective Date | 15/04/2025 |
| Review Date | 11/04/2026 |
1. Purpose
To establish a validated and scientifically justified procedure for determining and confirming the optimal mixing time required to achieve homogeneous elixir formulations during manufacturing.
2. Scope
This SOP applies to validation activities for establishing, reviewing, and revalidating mixing times for all elixir products in the Elixir Department during development, scale-up, or post-change control.
3. Responsibilities
- Formulation Scientist / R&D:
- Design mixing validation protocol based on product characteristics.
- Determine sampling points and acceptance criteria.
- Production Supervisor:
- Ensure execution of validation batches as per protocol.
- Record data during mixing trials and control parameters.
- QA Officer:
- Review and approve protocol and report.
- Ensure compliance to validation master plan (VMP).
4. Accountability
The Head of Quality Assurance is accountable for ensuring that mixing time validation is performed according to regulatory guidelines, documented, and revalidated as needed.
5. Procedure
5.1
Preparation of Validation Protocol
- Prepare a protocol detailing:
- Product name, batch size, equipment used
- Mixing time intervals (e.g., 10, 20, 30, 40 minutes)
- Sampling points (top, middle, bottom)
- Parameters to test: pH, assay, viscosity, color, clarity
- Acceptance criteria: RSD ≤ 5%, homogeneity within ±3%
- Obtain protocol approval from QA before execution.
5.2 Execution of Validation Batches
- Manufacture three consecutive batches as per approved manufacturing process.
- At each pre-defined time interval, collect samples from different depths.
- Analyze each sample in QC laboratory for defined parameters.
- Document observations in the Mixing Time Validation Log (Annexure-1).
5.3 Evaluation of Results
- Compare results for each time point to check when consistent homogeneity is achieved.
- Select the mixing time where all results meet acceptance criteria for all three batches.
- Ensure no further improvement in results is seen beyond that point.
5.4 Finalization and Documentation
- Summarize validation results and finalize optimal mixing time.
- Document final mixing time in the Master Formula Record (MFR).
- Attach protocol, results, and approval page in the Validation Summary Report.
5.5 Revalidation Criteria
- Change in batch size (±10% or more)
- Change in mixing equipment or tank geometry
- Product formulation change
- Failure in product homogeneity during routine batch
6. Abbreviations
- SOP: Standard Operating Procedure
- QA: Quality Assurance
- QC: Quality Control
- MFR: Master Formula Record
- VMP: Validation Master Plan
- RSD: Relative Standard Deviation
7. Documents
- Mixing Time Validation Log (Annexure-1)
- Mixing Time Validation Protocol and Report
- Master Formula Record (MFR)
8. References
- ICH Q8 – Pharmaceutical Development
- WHO TRS 1019 – GMP Validation Guidelines
- 21 CFR Part 211.110 – Sampling and Testing of In-Process Materials
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: Mixing Time Validation Log
| Batch No. | Time Interval (min) | Top | Middle | Bottom | RSD (%) | Result |
|---|---|---|---|---|---|---|
| ELX-1034 | 20 | 98.2% | 97.9% | 98.1% | 0.15 | Pass |
| ELX-1034 | 30 | 98.0% | 97.8% | 97.9% | 0.10 | Pass |
Revision History:
| Revision Date | Revision No. | Revision Details | Reason for Revision | Approved By |
|---|---|---|---|---|
| 01/01/2024 | 1.0 | Initial SOP Release | New SOP | QA Head |
| 11/04/2025 | 2.0 | Added revalidation triggers and RSD thresholds | Process Standardization | QA Head |