Standard Operating Procedure for Risk Assessment in Genetic Engineering for Biosimilar Development

Department	Biosimilars
SOP No.	SOP/BS/039/2025
Supersedes	SOP/BS/039/2022
Page No.	Page 1 of 12
Issue Date	04/05/2025
Effective Date	06/05/2025
Review Date	04/05/2026

1. Purpose

To establish a systematic procedure for risk assessment associated with genetic engineering operations during biosimilar development, including evaluation of biological hazards, vector-host systems, gene inserts, and containment strategies in accordance with applicable biosafety and regulatory guidelines.

2. Scope

This SOP applies to all genetic engineering activities conducted in the biosimilars R&D laboratories, including transfection, vector design, GMO handling, and gene expression studies involving recombinant DNA technologies.

3. Responsibilities

• Principal Investigator: Initiates risk assessment, classifies genetic work, and obtains IBSC approval.
• Biosafety Officer: Reviews and verifies risk control measures; maintains risk logs and approvals.
• QA Personnel: Audits compliance with risk assessment SOP and maintains documentation.

4. Accountability

The R&D Head is accountable for ensuring all genetic engineering activities are reviewed for risk prior to execution, and proper containment, PPE, and documentation are in place.

5. Procedure

5.1 Risk Categorization of Genetic Work

1. Identify the biological material used:
   • Host organism (e.g., CHO, E. coli, HEK293)
   • Donor DNA (e.g., antibody, cytokine)
   • Vector type (plasmid, viral)
2. Classify the experiment under:
   • Category I: Minimal risk
   • Category II: Moderate risk requiring IBSC approval
   • Category III: High-risk requiring RCGM review
3. Document classification using the Genetic Work Risk Log (Annexure-1).

5.2 Hazard Identification

1. Evaluate potential risks including:
   • Allergenicity or toxicity of gene product
   • Resistance marker (e.g., antibiotic resistance)
   • Pathogenic potential of host-vector system

5.3 Containment and Control Measures

1. For Category I/II experiments, implement:
   • BSL-2 containment
   • Work inside biosafety cabinet
   • Autoclaving of waste
2. Prepare SOPs for PPE, disinfection, and transport of GMOs.
3. Use containment checklist (Annexure-2) before beginning work.

5.4 Approval Process

1. Submit Genetic Engineering Risk Assessment Form (Annexure-3) to IBSC.
2. Await written clearance before initiating experiments.

5.5 Training and Awareness

1. All personnel involved in genetic engineering must:
   • Complete biosafety training annually
   • Sign awareness and compliance statement (Annexure-4)

6. Abbreviations

• IBSC: Institutional Biosafety Committee
• RCGM: Review Committee on Genetic Manipulation
• GMO: Genetically Modified Organism
• BSL-2: Biosafety Level 2

7. Documents

1. Genetic Work Risk Log (Annexure-1)
2. Containment Compliance Checklist (Annexure-2)
3. Genetic Engineering Risk Assessment Form (Annexure-3)
4. Personnel Biosafety Declaration (Annexure-4)

8. References

• Rules 1989 under EPA for GMO regulation in India
• NIH Guidelines for Recombinant DNA Molecules
• WHO Biosafety Manual (4th Edition)

9. SOP Version

Version: 2.0

10. Approval Section

	Prepared By	Checked By	Approved By
Signature
Date
Name
Designation
Department

11. Annexures

Annexure-1: Genetic Work Risk Log

Date	Experiment ID	Host	Vector	Gene Insert	Category	Risk Status
03/05/2025	GE-039-01	CHO	pcDNA3.1	mAb Gene	II	Moderate

Annexure-2: Containment Compliance Checklist

Item	Checked	Remarks
BSL-2 Facility Available	Yes	Certified
Autoclave Available	Yes	On-site
Spill Kit Ready	Yes	Inside Lab

Annexure-3: Genetic Engineering Risk Assessment Form

Experiment Title	CHO Cell Line Engineering
Principal Investigator	Dr. Sunita Reddy
Gene Product	Monoclonal Antibody
Vector	pcDNA3.1
Host Cell	CHO-K1
Risk Category	II
Containment	BSL-2

Annexure-4: Personnel Biosafety Declaration

Name	Department	Training Completed On	Signature
Ajay Verma	CLD	01/03/2025

Revision History:

Revision Date	Revision No.	Revision Details	Reason for Revision	Approved By
04/05/2025	2.0	Added NIH and WHO references and updated Annexures	Process alignment with biosafety standards