Standard Operating Procedure for Real-Time Yield Monitoring During Reactions in API Manufacturing
| Department | API Manufacturing |
|---|---|
| SOP No. | SOP/API/090/2025 |
| Supersedes | SOP/API/090/2022 |
| Page No. | Page 1 of 10 |
| Issue Date | 13/04/2025 |
| Effective Date | 15/04/2025 |
| Review Date | 13/04/2026 |
1. Purpose
To define the procedure for real-time yield monitoring during chemical reactions in the manufacturing of Active Pharmaceutical Ingredients (APIs) in order to assess process efficiency, trigger corrective actions, and support in-process control.
2. Scope
This SOP applies to all chemical synthesis processes in API manufacturing where reaction progress and intermediate product yields are calculated in real time for monitoring and optimization.
3. Responsibilities
- Production Chemist: Monitor reaction time and record in-process yield data.
- QC Analyst: Analyze samples for yield determination (e.g., by HPLC, gravimetric, titrimetric methods).
- QA Officer: Review records and ensure results are documented as per GMP.
4. Accountability
The Production Head is accountable for implementation. QA Head is responsible for compliance review and deviation handling.
5. Procedure
5.1 Yield Monitoring Plan
- Define yield checkpoints in the Batch Manufacturing Record (BMR) based on reaction stages (e.g., after 30%, 60%, and 100% theoretical conversion).
- Use validated methods for quantitative analysis, e.g., HPLC assay, LOD correction, or titration.
5.2 Sampling
- Collect ~2–5 mL (or as required) of reaction mass in clean, dry containers at defined time points.
- Label sample with Batch No., Reaction Stage, Date, Time, and Initials.
- Deliver sample immediately to QC; store under controlled conditions if delayed.
5.3 Analytical Testing
- Perform testing to quantify desired product concentration.
- Document result as concentration (% w/w or % area) or mass obtained per volume sampled.
5.4 Yield Calculation
- Calculate yield as per formula:
% Yield = (Actual Amount of Product / Theoretical Amount) × 100 - Use molecular weights and stoichiometry as defined in the MFR.
- Adjust for dilution factors, LOD (moisture), or assay correction if applicable.
5.5 Trending and Response
- Plot yield data on control charts for trend evaluation.
- If yield is outside target range (e.g., ±5% of expected), inform QA and investigate root cause.
- Delay or abort next stage if yield is critically low or shows unexpected decline.
5.6 Documentation
- Record all yields, calculations, and time stamps in the Reaction Yield Log (Annexure-1).
- Attach corresponding QC report or test printouts.
- Review and sign by Production Supervisor and QA Reviewer.
6. Abbreviations
- SOP: Standard Operating Procedure
- API: Active Pharmaceutical Ingredient
- QC: Quality Control
- QA: Quality Assurance
- BMR: Batch Manufacturing Record
- LOD: Loss on Drying
7. Documents
- Reaction Yield Log (Annexure-1)
- Batch Manufacturing Record
- Analytical Test Reports
8. References
- ICH Q8 – Pharmaceutical Development
- 21 CFR Part 211 – US FDA GMP
- WHO TRS 986 – GMP for APIs
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: Reaction Yield Log
| Date | Batch No. | Stage | Sample Time | Yield (%) | Performed By | Remarks |
|---|---|---|---|---|---|---|
| 13/04/2025 | API-20250413 | 60% Conversion | 14:20 | 62.3 | Within expected |
Revision History:
| Revision Date | Revision No. | Details | Reason | Approved By |
|---|---|---|---|---|
| 01/01/2022 | 1.0 | Initial SOP Release | New Process Implementation | QA Head |
| 13/04/2025 | 2.0 | Added real-time trending and control chart instruction | Audit Compliance | QA Head |