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

1. Calculate Theoretical Yield:
   • Based on the limiting raw material used and the molecular weight ratio.
   • Record in “Theoretical Yield Calculation Sheet” (Annexure-1).
2. Determine Actual Yield:
   • Weigh product after each critical step: reaction, filtration, crystallization, drying.
   • Use calibrated balance and record in BMR.
3. Calculate % Yield:
   • Use standard formula: % Yield = (Actual / Theoretical) × 100
4. Record losses:
   • Identify and document losses during transfer, hold-up, evaporation, and filtration (Annexure-2).

5.3 Documentation and Review

1. Record yield calculations and observations at each stage in the BMR.
2. Transfer all yield data into the “Process Yield Summary Sheet” (Annexure-3).
3. QA to review all entries and compare against standard yield range (SYR) for trend analysis.
4. 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

1. Theoretical Yield Calculation Sheet (Annexure-1)
2. Yield Loss Identification Log (Annexure-2)
3. 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