Standard Operating Procedure for Process Yield Calculation and Documentation in API Manufacturing
| Department | API Manufacturing |
|---|---|
| SOP No. | SOP/API/030/2025 |
| Supersedes | SOP/API/030/2022 |
| 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 a standardized and GMP-compliant procedure for calculating and documenting process yields at every critical stage of Active Pharmaceutical Ingredient (API) manufacturing, ensuring transparency, traceability, and data integrity.
2. Scope
This SOP applies to all yield calculations performed from raw material input to final API output in the manufacturing of APIs, including intermediate, crude, purified, and dried stages.
3. Responsibilities
- Production Chemist: Perform calculations and record yields at each processing stage.
- QA Personnel: Review and verify the accuracy and completeness of documentation.
- Production Supervisor: Ensure reconciliation of material usage and identification of yield variations.
4. Accountability
The Production Head is accountable for accurate yield documentation, while QA Head is responsible for reviewing yield trends and identifying deviations or trends.
5. Procedure
5.1 Definitions
- Theoretical Yield: The calculated amount of expected product based on stoichiometry and input quantity.
- Actual Yield: The quantity of product actually obtained at any process stage.
- % Yield: (Actual Yield ÷ Theoretical Yield) × 100
- Cumulative Yield: Yield calculated by combining multiple process stages.
5.2 Yield Calculation Steps
- Calculate Theoretical Yield:
- Based on the limiting raw material used and the molecular weight ratio.
- Record in “Theoretical Yield Calculation Sheet” (Annexure-1).
- Determine Actual Yield:
- Weigh product after each critical step: reaction, filtration, crystallization, drying.
- Use calibrated balance and record in BMR.
- Calculate % Yield:
- Use standard formula: % Yield = (Actual / Theoretical) × 100
- Record losses:
- Identify and document losses during transfer, hold-up, evaporation, and filtration (Annexure-2).
5.3 Documentation and Review
- Record yield calculations and observations at each stage in the BMR.
- Transfer all yield data into the “Process Yield Summary Sheet” (Annexure-3).
- QA to review all entries and compare against standard yield range (SYR) for trend analysis.
- For yield outside standard range, initiate deviation and perform investigation.
6. Abbreviations
- SOP: Standard Operating Procedure
- API: Active Pharmaceutical Ingredient
- BMR: Batch Manufacturing Record
- SYR: Standard Yield Range
7. Documents
- Theoretical Yield Calculation Sheet (Annexure-1)
- Yield Loss Identification Log (Annexure-2)
- Process Yield Summary Sheet (Annexure-3)
8. References
- ICH Q7 – GMP for Active Pharmaceutical Ingredients
- 21 CFR Part 211 – Subpart J: Records and Reports
- Internal Yield Calculation 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: Theoretical Yield Calculation Sheet
| Batch No. | Raw Material Used (kg) | Molecular Weight Ratio | Theoretical Yield (kg) | Calculated By |
|---|---|---|---|---|
| API-202504 | 85.0 | 1.15 | 97.75 |
Annexure-2: Yield Loss Identification Log
| Stage | Type of Loss | Estimated Loss (kg) | Reason | Action Taken |
|---|---|---|---|---|
| Filtration | Hold-up | 1.2 | Residue in filter cloth | Optimized washing |
Annexure-3: Process Yield Summary Sheet
| Stage | Yield (kg) | Theoretical Yield (kg) | % Yield | Within SYR (Y/N) |
|---|---|---|---|---|
| Crude API | 92.4 | 97.75 | 94.5% | Y |
| Purified API | 89.8 | 97.75 | 91.8% | Y |
Revision History:
| Revision Date | Revision No. | Details | Reason | Approved By |
|---|---|---|---|---|
| 01/01/2022 | 1.0 | Initial Version | New SOP Implementation | QA Head |
| 13/04/2025 | 2.0 | Enhanced format and annexures added | Audit and Quality Review | QA Head |