manufacturing area for intravenous, intramuscular, subcutaneous, and other parenteral dosage forms in sterile injectable facilities.

3. Responsibilities

• Manufacturing Operator: Execute solution preparation activities as per batch manufacturing record.
• Production Supervisor: Supervise and verify all steps during solution preparation.
• QA Officer: Perform in-process checks and review records.

4. Accountability

The Head – Production shall be accountable for implementation and compliance of this SOP.

5. Procedure

5.1 Pre-Operation Checks

1. Verify cleanliness status of the preparation room, equipment (vessels, transfer lines), and entry logs.
2. Ensure availability and calibration status of instruments such as pH meter, thermometer, and conductivity meter.
3. Review previous batch reconciliation and clearance documentation from QA.

5.2 Material Verification

1. Collect dispensed raw materials and excipients along with CoA, label, and dispensing log.
2. Verify material identity, quantity, status label, and batch number before charging.
3. Record in Annexure-1: Material Verification Sheet.

5.3 Charging Procedure

1. Start recirculation of WFI to sanitize the solution preparation vessel.
2. Add pre-measured quantity of WFI into the preparation vessel and adjust temperature if required.
3. Charge active and excipient materials one by one under LAF using a closed transfer system.
4. For temperature-sensitive APIs, ensure controlled cooling during charging.

5.4 Mixing and Dissolution

1. Start mechanical agitation at defined RPM as per BMR.
2. Continue agitation until complete dissolution or dispersion.
3. Check for visual clarity, pH, and specific gravity as required.
4. Record readings in Annexure-2: In-Process Check Log.

5.5 pH and Volume Adjustment

1. Measure pH using a calibrated pH meter; adjust with 0.1N acid or alkali as per specification.
2. Make up the final volume using WFI under mixing conditions.
3. Confirm batch yield calculation and reconciliation.

5.6 Filtration

1. Use pre-sterilized 0.22 µm filter cartridges for final solution filtration.
2. Maintain sterile conditions throughout the filtration process.
3. Record filter integrity test results before and after filtration in Annexure-3.

5.7 Post-Filtration Sampling

1. Draw samples for QC testing (Assay, pH, Sterility, Endotoxin).
2. Send sample along with sample request form and fill in Annexure-4: Sampling Record.

5.8 Documentation and Line Clearance

1. Fill solution preparation log with details including time, batch no., temperature, operator initials.
2. Submit completed batch record to QA for review and line clearance.

6. Abbreviations

• SOP: Standard Operating Procedure
• BMR: Batch Manufacturing Record
• WFI: Water for Injection
• LAF: Laminar Air Flow
• API: Active Pharmaceutical Ingredient

7. Documents

1. Material Verification Sheet – Annexure-1
2. In-Process Check Log – Annexure-2
3. Filter Integrity Test Log – Annexure-3
4. Sampling Record – Annexure-4

8. References

• EU GMP Annex 1 – Manufacture of Sterile Medicinal Products
• WHO TRS 986 – Sterile Pharmaceutical Production
• ICH Q8 – Pharmaceutical Development

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation	Manufacturing Executive	QA Executive	Head QA
Department	Production	Quality Assurance	Quality Assurance

11. Annexures

Annexure-1: Material Verification Sheet

Material	Qty	Batch No.	Status	Checked By
Sodium Chloride	50 g	SC2401	Approved	Meena Patil

Annexure-2: In-Process Check Log

Parameter	Specification	Observed	Time	Initials
pH	4.5 – 5.5	5.1	10:30	AK

Annexure-3: Filter Integrity Test Log

Date	Filter ID	Bubble Point	Status	Checked By
18/06/2025	FLTR1025	54 psi	Pass	Sunil Rao

Annexure-4: Sampling Record

Sample Type	Quantity	Container No.	Sent By	Time
Assay + pH	25 ml	S-10	Deepa Sharma	11:15

Revision History

Revision Date	Revision No.	Details	Reason	Approved By
05/04/2022	1.0	Initial Release	New SOP	QA Head
18/06/2025	2.0	Filter test and in-process checks enhanced	Annual Review	QA Head