Standard Operating Procedure for Environmental Monitoring During Purification in Biosimilar Manufacturing

Department	Biosimilars
SOP No.	SOP/BS/196/2025
Supersedes	SOP/BS/196/2022
Page No.	Page 1 of 10
Issue Date	04/05/2025
Effective Date	06/05/2025
Review Date	04/05/2026

1. Purpose

To establish a comprehensive and GMP-compliant procedure for environmental monitoring (EM) during the purification processes in biosimilar manufacturing to detect microbial and particulate contamination in controlled areas.

2. Scope

This SOP applies to viable and non-viable monitoring activities carried out in Grade B and C areas where biosimilar purification activities are conducted, including chromatography, filtration, and hold steps.

3. Responsibilities

• Microbiology/EM Analyst: Perform sampling, incubation, and data recording for all EM parameters.
• Production: Support coordination during operation-based sampling and report any abnormal conditions.
• QA: Review EM data, approve trend reports, and take decisions in case of alert/action level excursions.

4. Accountability

The Head of Microbiology is accountable for implementation and evaluation of the EM program to ensure environmental control during downstream biosimilar processing.

5. Procedure

5.1 EM Sampling Plan

1. Define EM plan based on risk assessment of purification activities and classified areas.
2. Include sampling points for:
   • Airborne viable count (settle plates and active air sampling)
   • Non-viable particulate monitoring (0.5 µm and 5.0 µm)
   • Surface monitoring (contact plates/swabs)
   • Personnel monitoring (gloves, gown)
3. Frequency: Daily (critical steps), weekly (routine), and per batch (process monitoring).

5.2 Viable Monitoring

1. Expose settle plates for 4 hours at critical sites such as chromatography skids, filtration units.
2. Use portable active air sampler calibrated for 1,000 L of air; position near operator workstation and process area.
3. Perform contact plate sampling on cleaned surfaces post-operation (Annexure-1).
4. Incubation conditions:
   • 30–35°C for 3–5 days
   • 20–25°C for 5–7 days

5.3 Non-Viable Monitoring

1. Use calibrated particle counter during operations to monitor 0.5 µm and 5.0 µm particles.
2. Monitor during filtration, bulk transfer, and other critical open operations.
3. Log particle count results in Annexure-2. Ensure compliance with ISO Class 7/8 limits as applicable.

5.4 Personnel Monitoring

1. Collect fingertip and gown surface samples from operators at end of operation.
2. Record results and compare with limits:
   • Fingertip: ≤ 10 cfu/glove
   • Gown surface: ≤ 5 cfu/plate
3. Deviations must be investigated (Annexure-3).

5.5 Alert and Action Limits

1. Establish limits based on area classification and historical trending.
2. If alert limit is breached: monitor additional samples and initiate alert notification.
3. If action limit is breached: quarantine product, initiate deviation/CAPA, and investigate root cause.

5.6 Trend Analysis and Reporting

1. Monthly EM trend reports to be prepared and reviewed by QA and Microbiology.
2. Identify upward trends, repeat observations, and seasonal variation.
3. Submit to QA for periodic review and regulatory compliance.

6. Abbreviations

• EM: Environmental Monitoring
• cfu: Colony Forming Unit
• QA: Quality Assurance
• CAPA: Corrective and Preventive Action

7. Documents

1. Surface Monitoring Log – Annexure-1
2. Non-Viable Particulate Log – Annexure-2
3. EM Deviation Report – Annexure-3

8. References

• EU GMP Annex 1 – Manufacture of Sterile Medicinal Products
• ISO 14644 – Cleanroom Classification Standards
• WHO TRS 961 – GMP for Biologics

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Surface Monitoring Log

Date	Location	Plate ID	cfu Count	Operator
04/05/2025	Chromatography Skid	SP-145	2	Ajay Verma

Annexure-2: Non-Viable Particulate Log

Date	Location	0.5 µm Count	5.0 µm Count	Operator
04/05/2025	Buffer Transfer Point	2,120	80	Sunita Reddy

Annexure-3: EM Deviation Report

Date	Location	Parameter	Observation	CAPA	QA Reviewed
03/05/2025	Grade C Filtration Zone	Settle Plate	14 cfu	Repeat cleaning, enhanced monitoring	Dr. Neha Rao

Revision History:

Revision Date	Revision No.	Details	Reason	Approved By
04/05/2025	2.0	Added trend analysis section and alert/action handling protocols	Regulatory Enhancement