Standard Operating Procedure (SOP) for Active Pharmaceutical Ingredient (API) Manufacturing Proces 【 Part -2 】

5.2 Process Flow Diagram (English)

Starting Materials (QC Verified) → Charging/Feed Preparation → Chemical Synthesis (Controlled Temp/Pressure/Time) → Quenching (Quenching Agent Added) → Phase Separation (Organic Phase Retained) → Crude Product Isolation (Filtration/Centrifugation) → Purification (Distillation/Extraction/Recrystallization, QC Purity Test) → Drying (Vacuum/Fluid Bed, Moisture Test) → Milling & Sizing (Particle Size Test) → Final QC Testing (Comprehensive Inspection) → Qualified API → Bulk Packaging & Storage

6. Safety Requirements

Operators must wear personal protective equipment (PPE) during operation, including gloves, goggles, protective clothing, and gas masks (if using toxic or corrosive materials).

Strictly abide by the safety operation regulations of chemical reactions, especially for exothermic reactions, to prevent overheating, pressure buildup and other dangerous situations.

All solvents, catalysts and other chemicals must be stored in dedicated containers, labeled clearly, and stored separately according to their properties (such as flammable, corrosive, toxic).

The operation site must be equipped with fire-fighting equipment, emergency washing facilities and first-aid supplies, and operators must be familiar with their use methods.

In case of abnormal situations (such as leakage, fire, explosion), immediately stop the operation, evacuate personnel, and report to the supervisor and safety department in a timely manner.

7. Record Requirements

All operation steps, process parameters, sampling results, QC test results and abnormal situations must be recorded accurately, completely and timely in the API Manufacturing Record Form.

Records must be filled in with black or blue ink, and any modification must be signed by the modifier and indicate the modification date; no erasure or alteration is allowed.

Manufacturing records must be reviewed by the manufacturing supervisor, and archived for at least 5 years after the expiration date of the API batch.

8. Annex

Annex 1: Supplementary Process for Sterile API

After Step 5 (Purification), the purified API is transferred to a clean area (class A/B) for sterile processing.

Dissolution: Dissolve the purified API in a sterile solvent (meets injection grade standard) under sterile conditions, stir until completely dissolved.

Sterile Filtration: Filter the dissolved solution through a sterile filter (pore size: 0.22μm) to remove microorganisms and particles.

Aseptic Crystallization: Transfer the sterile filtrate to an aseptic crystallization vessel, cool slowly to induce crystallization under aseptic conditions.

Freeze-Drying/Spray-Drying: Dry the aseptic crystal mixture by freeze-drying (temperature: -40 to -50℃, pressure: ≤0.01MPa) or spray-drying (inlet temperature: 120-140℃, outlet temperature: 60-80℃) under sterile conditions.

Sterile API Packaging: Package the dried sterile API in sterile, sealed packaging containers under class A clean conditions, label clearly, and store in a sterile storage room.

9. Revision History

Approved by: ________________________ Date: ________________________

Distributed to: Manufacturing Department, QC Department, Technical Department