conditions under GMP guidelines.

2. Scope

This SOP applies to all sterile injectable manufacturing processes involving critical process parameters (CPPs) such as temperature, pressure, fill volume, mixing speed, and filter flow rate that may require adjustment based on real-time monitoring and feedback systems.

3. Responsibilities

• Manufacturing Operators: Monitor critical parameters continuously and report any drift or deviation immediately.
• Production Supervisor: Assess process trends, authorize and execute minor real-time adjustments as per pre-approved ranges.
• Quality Assurance (QA): Review and approve any deviation or adjustment outside validated ranges. Ensure proper documentation.
• Engineering/Maintenance: Investigate equipment-related causes and assist in technical resolution if adjustments are linked to machinery behavior.

4. Accountability

The Production Head is accountable for ensuring that real-time process adjustments are compliant with the validated ranges and documented per GMP and quality requirements.

5. Procedure

5.1 Definition of Real-Time Adjustment

1. A real-time process adjustment is a controlled change in process conditions made during batch execution in response to monitored trends or feedback signals to avoid a process deviation or failure.

5.2 Pre-Defined Adjustment Ranges

1. Each process parameter must have a validated acceptable operating range defined in the Batch Manufacturing Record (BMR) or Master Formula Record (MFR).
2. Operators shall not exceed the lower or upper bound of validated ranges without QA review and deviation initiation.

5.3 Monitoring Systems

1. Install sensors and automated systems for real-time tracking of parameters like:
   • Temperature (e.g., during solution preparation or sterilization)
   • Pressure (e.g., in filtration lines)
   • Flow rates (e.g., during filtration or filling)
   • Fill volumes (e.g., vial filling line)
2. Operators must verify readings at defined intervals and ensure logs are maintained.

5.4 Execution of Adjustments

1. Operator identifies trend drift approaching a critical limit and informs the supervisor.
2. Supervisor verifies the trend and evaluates the need for adjustment within allowed ranges.
3. Adjustment is made (e.g., reducing stirring speed from 120 RPM to 110 RPM to stabilize temperature).
4. Adjustment must be documented in the Process Adjustment Log (Annexure-1).
5. QA must verify the final parameter and counter-sign the adjustment entry.

5.5 Documentation

1. Details of each adjustment must include:
   • Date and Time
   • Batch Number
   • Parameter Adjusted
   • Before and After Value
   • Reason for Adjustment
   • Approval Signature
2. Update associated records like BMR, SCADA logs, or PLC trend reports if applicable.

5.6 Evaluation of Impact

1. QA shall assess the adjustment post-batch completion to determine:
   • If product quality was maintained
   • If similar trends exist in historical batches
   • If CAPA is required to revise process controls or retrain staff

5.7 Non-Compliant Adjustments

1. If an adjustment is found outside validated ranges, treat it as a deviation and initiate a deviation report immediately.
2. Product impact assessment must be conducted and decision made regarding reprocessing, hold, or rejection.

6. Abbreviations

• SOP: Standard Operating Procedure
• CPP: Critical Process Parameter
• QA: Quality Assurance
• RPM: Revolutions Per Minute
• BMR: Batch Manufacturing Record
• SCADA: Supervisory Control and Data Acquisition

7. Documents

1. Process Adjustment Log – Annexure-1
2. SCADA or PLC Report Printouts – Annexure-2

8. References

• ICH Q8 – Pharmaceutical Development
• ICH Q10 – Pharmaceutical Quality System
• WHO Technical Report Series on GMP

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: Process Adjustment Log

Date	Batch No.	Parameter	Before	After	Reason	Operator	QA Verified By
22/06/2025	INJ/167/2025	Mixing Speed	120 RPM	110 RPM	Foaming observed	Ravi Mehta	Sunita Reddy

Annexure-2: SCADA Printout Sample

Timestamp	Parameter	Value	Comment
22/06/2025 10:45	Temperature	25.6°C	Stable
22/06/2025 11:00	Mixing Speed	110 RPM	Adjusted due to foaming

Revision History

Revision Date	Revision No.	Details	Reason	Approved By
01/08/2022	1.0	Initial Release	New SOP	QA Head
24/06/2025	2.0	Integrated real-time SCADA/PLC documentation	Process improvement	QA Head