intraosseous injection manufacturing at the sterile injectable manufacturing unit, including formulation, filtration, aseptic filling, in-process checks, and documentation.

3. Responsibilities

• Manufacturing Executive: Responsible for executing manufacturing operations as per BMR.
• Quality Assurance Executive: Ensures compliance and batch record verification.
• Engineering Team: Responsible for equipment calibration and maintenance.
• Microbiology: Monitors environmental parameters and sterility controls.

4. Accountability

The Head of Manufacturing is accountable for overall compliance, documentation, and review of manufacturing operations related to intraosseous injection batches.

5. Procedure

5.1 Pre-Manufacturing Preparation

1. Ensure the designated cleanroom is cleaned, disinfected, and documented.
2. Verify availability of raw materials, packaging materials, and utilities.
3. Confirm equipment calibration and cleaning logs are complete and within validity.

5.2 Solution Preparation

1. Transfer raw materials to manufacturing through dynamic pass box.
2. Dissolve API and excipients in WFI inside a jacketed SS316L vessel equipped with stirrer.
3. Maintain defined temperature and stirring rate to ensure homogenous mixture.
4. Adjust pH if required and filter the solution through pre-filter (5 µm).

5.3 Sterile Filtration

1. Filter the solution using sterile 0.22 µm membrane filter into a sterile filling vessel.
2. Perform integrity testing (Bubble Point Test) pre and post filtration. Record in Annexure-2.
3. Use sterile, single-use tubing systems or autoclaved connections to maintain sterility.

5.4 Aseptic Filling and Sealing

1. Transfer sterile solution to aseptic filling area under Grade A conditions in LAF.
2. Fill the IO solution into sterile containers/vials as per validated filling volume.
3. Seal the vials with pre-sterilized rubber stoppers and aluminum seals.
4. Visually inspect filled units for integrity, clarity, and absence of particulate matter (Annexure-3).

5.5 In-Process Quality Control

1. Monitor and record temperature, differential pressure, and relative humidity.
2. Perform in-process checks every 30 minutes for fill volume, clarity, sealing, and particulate matter.
3. Document observations in Annexure-4: In-Process Quality Log.

5.6 Post-Manufacturing Activities

1. Transfer vials to designated quarantine area with proper labeling.
2. Clean all equipment as per SOP and record in equipment cleaning log.
3. Submit BMR to QA for review and batch disposition.

6. Abbreviations

• IO: Intraosseous
• WFI: Water for Injection
• BMR: Batch Manufacturing Record
• QA: Quality Assurance
• LAF: Laminar Air Flow

7. Documents

1. Formulation Log – Annexure-1
2. Filter Integrity Test Report – Annexure-2
3. Visual Inspection Report – Annexure-3
4. In-Process Quality Control Log – Annexure-4

8. References

• ICH Q8: Pharmaceutical Development
• WHO TRS No. 961: Annex 6
• Schedule M (India): Good Manufacturing Practices

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name	Priya Natarajan	Rakesh Jadhav	Dr. Neha Menon
Designation	Production Executive	QA Executive	Head QA
Department	Manufacturing	Quality Assurance	Quality Assurance

11. Annexures

Annexure-1: Formulation Log

Date	Batch No.	Temp (°C)	pH	Operator
17/06/2025	IO/0625/01	22	6.5	Rajesh Kumar

Annexure-2: Filter Integrity Test Report

Filter ID	Type	Pre-Test	Post-Test	Status
FT-005	0.22 µm	Pass	Pass	Accepted

Annexure-3: Visual Inspection Report

Unit No.	Clarity	Particles	Seal Integrity	Status
IO-0543	Clear	Absent	Intact	Pass

Annexure-4: In-Process Quality Control Log

Time	Volume (mL)	Clarity	Remarks	Checked By
11:00 AM	2.0	Clear	Compliant	Sunita Reddy

Revision History

Revision Date	Revision No.	Details	Reason	Approved By
05/01/2022	1.0	Initial Issue	New SOP	QA Head
18/06/2025	2.0	Procedure and annexures updated	Periodic Review	QA Head