Standard Operating Procedure for Charging of Materials into Reactor in API Manufacturing
| Department | API Manufacturing |
|---|---|
| SOP No. | SOP/API/021/2025 |
| Supersedes | SOP/API/021/2022 |
| Page No. | Page 1 of 11 |
| Issue Date | 13/04/2025 |
| Effective Date | 15/04/2025 |
| Review Date | 13/04/2026 |
1. Purpose
To establish a standardized procedure for charging raw materials into reactors in a controlled, safe, and sequential manner to ensure process consistency, personnel safety, and compliance with cGMP requirements.
2. Scope
This SOP applies to all operations involving the transfer of raw materials (solids and liquids) into reactors used in active pharmaceutical ingredient (API) manufacturing processes.
3. Responsibilities
- Production Operator: Execute material charging as per batch manufacturing record (BMR).
- Shift Supervisor: Supervise the operation, ensure sequence and quantities are followed.
- QA Personnel: Verify material identity, line clearance, and witness initial and final charges as per protocol.
4. Accountability
The Production Manager and QA Head are jointly accountable for ensuring that the reactor charging process is performed as per defined procedures and recorded accurately.
5. Procedure
5.1 Pre-Charging Preparations
- Review the approved BMR for batch-specific instructions including sequence and charge rates.
- Verify reactor status: cleaning, equipment ID, and readiness using equipment logbook and “Line Clearance Checklist” (Annexure-1).
- Confirm that all materials are approved, weighed, labeled correctly, and staged near the reactor area.
- Ensure availability of required PPE, nitrogen (if inert atmosphere is required), and calibrated load cells or balances.
5.2 Line Clearance
- QA to perform line clearance of reactor and surrounding area.
- Record line clearance details in the “Line Clearance Checklist.”
- Ensure that all previous batch labels, materials, and residues are removed.
5.3 Charging Process
- Switch ON the reactor agitator (if specified in BMR) prior to charging.
- Use vacuum transfer, gravity feeding, or manual scooping as permitted.
- Charge materials in the exact sequence mentioned in BMR. Do not deviate.
- For liquids, use flow meters or graduated vessels for quantity confirmation.
- For solids, ensure complete transfer by rinsing containers with suitable solvents (if permitted) and charge rinses too.
- Record start time, end time, and operator signature for each material charged.
5.4 Inert Atmosphere Charging (if applicable)
- Flush reactor headspace with nitrogen before and after charging each sensitive component.
- Use pressure gauge and purge log to verify nitrogen pressure inside reactor jacket.
5.5 Post-Charging Activities
- Re-weigh empty containers to confirm complete material transfer.
- Update raw material consumption in ERP system or manual log (Annexure-2).
- Send empty containers to washing area and update the “Container Usage Log.”
- Clean the surrounding floor and working area.
6. Abbreviations
- SOP: Standard Operating Procedure
- QA: Quality Assurance
- BMR: Batch Manufacturing Record
- PPE: Personal Protective Equipment
7. Documents
- Line Clearance Checklist (Annexure-1)
- Material Charging Log (Annexure-2)
- Container Usage Log (Annexure-3)
8. References
- ICH Q7 – GMP Guidelines for Active Pharmaceutical Ingredients
- 21 CFR Part 211.101 – Written procedures for production and process control
- WHO GMP Guidelines for Pharmaceutical Production
9. SOP Version
Version: 2.0
10. Approval Section
| Prepared By | Checked By | Approved By | |
|---|---|---|---|
| Signature | |||
| Date | |||
| Name | |||
| Designation | |||
| Department |
11. Annexures
Annexure-1: Line Clearance Checklist
| Date | Reactor ID | Checked By | Observations | Status |
|---|---|---|---|---|
| 13/04/2025 | R-102 | Clean, ready | Cleared |
Annexure-2: Material Charging Log
| Date | Material Name | Batch No. | Charged Qty | Start Time | End Time | Charged By |
|---|---|---|---|---|---|---|
| 13/04/2025 | Acetic Anhydride | AA202504 | 50 L | 10:05 | 10:15 |
Annexure-3: Container Usage Log
| Date | Container ID | Material | Washed | Sent By | Remarks |
|---|---|---|---|---|---|
| 13/04/2025 | CT-56 | Acetic Anhydride | No | To be cleaned |
Revision History:
| Revision Date | Revision No. | Revision Details | Reason for Revision | Approved By |
|---|---|---|---|---|
| 01/01/2022 | 1.0 | Initial Release | New SOP | QA Head |
| 13/04/2025 | 2.0 | Incorporated Nitrogen Purging and Log Templates | Process Enhancement | QA Head |