Standard Operating Procedure for Periodic Equipment Cleaning Schedule in Biosimilar Manufacturing

Department	Biosimilars
SOP No.	SOP/BS/120/2025
Supersedes	SOP/BS/120/2022
Page No.	Page 1 of 11
Issue Date	04/05/2025
Effective Date	06/05/2025
Review Date	04/05/2026

1. Purpose

To define a standardized approach for scheduling and executing periodic cleaning of equipment used in biosimilar upstream manufacturing, ensuring control of contamination, compliance with GMP, and maintenance of validated equipment conditions.

2. Scope

This SOP applies to cleaning schedules for all critical equipment such as bioreactors, seed vessels, tubing assemblies, mixing tanks, sensors, and support equipment used in the upstream biosimilar area.

3. Responsibilities

• Operators: Perform cleaning activities and complete logbook entries.
• Maintenance: Support equipment readiness and availability.
• QA: Verify cleaning compliance and review cleaning records.

4. Accountability

The Head of Production is accountable for ensuring all upstream equipment is cleaned according to an approved schedule and maintained in a validated state.

5. Procedure

5.1 Cleaning Frequency Classification

1. Classify equipment into cleaning frequency categories:
   • Category A – Daily: Sampling ports, feed lines, exterior surfaces.
   • Category B – Weekly: Agitators, inlet/outlet nozzles, connectors.
   • Category C – Monthly: Complete disassembly and deep cleaning of bioreactors, holding tanks.

5.2 Scheduling and Calendar Maintenance

1. Create a monthly equipment cleaning calendar in coordination with batch plans (Annexure-1).
2. Label all scheduled activities with equipment ID, frequency, and responsible personnel.
3. QA to review and approve the calendar at the beginning of each month.

5.3 Execution of Cleaning

1. Follow approved equipment-specific cleaning SOPs (cross-referenced in Annexure-2).
2. Use validated cleaning agents only (e.g., 1% non-ionic detergent, 70% IPA).
3. Record:
   • Cleaning start and end time
   • Operator initials
   • Visual inspection results

5.4 Cleaning Verification

1. Perform post-cleaning visual inspection and swab sample collection (if required).
2. Log observations in the Equipment Cleaning Log (Annexure-3).
3. Report deviations immediately using standard deviation management SOP.

5.5 Missed or Delayed Cleaning

1. If cleaning is delayed due to operational issues:
   • Document the reason
   • Reschedule cleaning with QA approval
   • Ensure cleaning is performed before next batch use

6. Abbreviations

• IPA: Isopropyl Alcohol
• QA: Quality Assurance
• SOP: Standard Operating Procedure

7. Documents

1. Monthly Equipment Cleaning Calendar – Annexure-1
2. List of Equipment-Specific Cleaning SOPs – Annexure-2
3. Equipment Cleaning Log – Annexure-3

8. References

• WHO TRS 1019 – GMP for Biological Products
• EU GMP Annex 15 – Qualification and Validation

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Monthly Equipment Cleaning Calendar

Date	Equipment ID	Category	Assigned To	Status
05/05/2025	BR-200L	C	Ajay Verma	Scheduled

Annexure-2: List of Equipment-Specific Cleaning SOPs

Equipment	SOP No.	Title
Bioreactor 200L	SOP/BS/015/2025	CIP and SIP Procedure

Annexure-3: Equipment Cleaning Log

Date	Equipment ID	Cleaning Agent	Performed By	Visual Check	QA Review
04/05/2025	MT-150	70% IPA	Sunita Reddy	OK	Approved

Revision History:

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
04/05/2025	2.0	Added monthly calendar requirement and cleaning verification logs	Process streamlining