solution preparation, filtration, filling, lyophilization, sealing, and packaging stages where critical observations are required.

3. Responsibilities

• Production Operator: To make real-time entries of observed parameters and any events during processing.
• Shift Supervisor: To verify entries and review for any anomalies or missing data.
• Quality Assurance (QA): To audit and evaluate documentation accuracy and integrity.

4. Accountability

Head of Manufacturing shall be accountable for ensuring adherence to this SOP and timely review of all in-process observation records.

5. Procedure

5.1 Documentation Standards

1. All entries must be made using a permanent blue or black ball pen.
2. Entries must be made at the time of activity (contemporaneous).
3. Do not leave blank spaces. Cross out unused lines with a single stroke and initial.
4. Corrections must follow ALCOA+ principles:
   • Draw a single line through the incorrect entry.
   • Write the correct entry above or next to it.
   • Initial, date, and provide justification.
5. Use standard templates as mentioned in Annexure-1 and Annexure-2.

5.2 Types of Observations to be Recorded

1. Visual Observations:
   • Clarity of solution
   • Presence of particulate matter
   • Foaming, color changes, crystallization
2. Process Observations:
   • Pressure differentials
   • Fill volume and weight variations
   • Sealing parameters (temperature, vacuum levels)
3. Environmental Conditions:
   • Temperature and RH inside filling zone
   • Grade-A area monitoring status

5.3 Real-Time Recording

1. Observations shall be noted in the In-Process Observation Log (Annexure-1) during each stage.
2. Wherever automated data is collected (e.g., SCADA), manual confirmation or annotations shall be made.
3. Entries must reflect:
   • Batch number
   • Stage of processing
   • Time of observation
   • Operator initials

5.4 Handling Abnormal Observations

1. Any out-of-trend (OOT) or unusual observation must be immediately reported to the supervisor.
2. Supervisor to evaluate and escalate to QA, if needed.
3. Deviations must be documented in the Observation Deviation Form (Annexure-2).
4. Follow SOP for deviation handling if required.

5.5 Review and Control

1. All observation logs to be reviewed by QA within 24 hours of batch completion.
2. QA shall ensure completeness, legibility, and data integrity.
3. Logs to be archived in Batch Production Record (BPR) file.

5.6 Data Integrity Guidelines

1. All data must be Attributable, Legible, Contemporaneous, Original, and Accurate (ALCOA).
2. Avoid use of correction fluid or overwriting.
3. Sign and date each entry with full name or employee code.

6. Abbreviations

• SOP: Standard Operating Procedure
• BPR: Batch Production Record
• OOT: Out-of-Trend
• QA: Quality Assurance
• ALCOA: Attributable, Legible, Contemporaneous, Original, Accurate

7. Documents

1. In-Process Observation Log – Annexure-1
2. Observation Deviation Form – Annexure-2

8. References

• WHO TRS 1019 Annex 4 – GMP for sterile products
• MHRA GxP Data Integrity Guidance
• ICH Q7 – Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients

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: In-Process Observation Log

Date	Batch No.	Stage	Observation	Time	Initials
24/06/2025	BN-239A	Filling	No foam observed, clear solution	10:30 AM	SK

Annexure-2: Observation Deviation Form

Date	Batch No.	Stage	Description of Deviation	Immediate Action	QA Reviewed
23/06/2025	BN-238C	Solution Prep	Particulate matter observed in solution	Solution filtered again	Yes

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
01/02/2022	1.0	Initial Release	New SOP	QA Head
24/06/2025	2.0	Updated format and annexures	Annual Review	QA Head