A strategy for downgrading a BL2 manufacturing process to a BL1

3 October 2023
Advanced Therapy Medicinal Products
Rachel Hodges
Senior Global Change Facilitator

The biopharmaceutical industry is expanding exponentially, with a focus on getting cell and gene therapy products to market as quickly and safely as possible for the benefit of patients. One of the main impediments can be timelines around facility build, fit-out, and various certifications. If some operations are deemed acceptable to be performed in a Biosafety Level 1 (BL1) environment, it may allow retrofitting of existing facilities to facilitate quicker manufacturing timelines.

This new paper, EHS Biosafety Risk Assessment for a Theoretical Model of a Gene Therapy Process Transfer from R&D to Large-Scale Manufacturing, authored by a global consortium of environmental health and safety and biosafety experts and members of BioPhorum, can help make this possible.

Published in the Journal of Applied Biosafety, it gives you a strategy by which a manufacturing process with a Biosafety Level 2 (BL2) designation can be considered for downgrading to BL1. The principles of the downgrading process are based on the robust contamination controls in clinical and commercial manufacturing that typically are not part of R&D processes. These strict requirements and the application of cGMP principles provide a framework by which processes can be suitably managed and controlled to mitigate biohazard risk, specifically for cell lines that may be contaminated with human pathogenic viral agents.

We demonstrate how a risk assessment guide can be used to define the risk profile of a theoretical process with a human cell line intended for clinical/commercial application. Based on the risk assessment, key BL2 elements were identified as suitable for downgrading, including facility containment controls, emergency spill response plans, and storage and shipping requirements. The paper provides a theoretical example of such a risk assessment.

The risk assessment guide contains sections ranging from process materials and employee personal protective equipment, to waste management and emergency response. An accompanying Biosafety risk assessment template for manufacturing and processing of biological materials can be downloaded from the BioPhorum website and used to assess and mitigate biosafety risk for human-derived cell lines susceptible to adventitious agents.

Biosafety risk assessment template for manufacturing and processing of biological materials

276.85 KB · 188 downloads

We have used a risk assessment guide to show how cGMP complements and augments biosafety containment. We provide justification for downgrading from BL2 to BL1 for selected processes.

The changes from BL2 to BL1 containment can make a significant difference in enabling biopharmaceutical companies to deliver lifesaving or life-altering medicines quickly to the populations in need. Downgrading to BL1 would provide significant advantages for facility design, footprint, operations, cost savings, biosafety risk control, and more. In addition, downgrading to BL1 would also offer shared manufacturing access for processes of similar design but with different risk classifications. While hypothetical, the scenario is representative of a realistic and relevant example commonly found in the field of biologics manufacturing.

This paper is a development from a previous article, Environmental Health and Biosafety Risk Assessment Guidance for Commercial-Scale Cell and Gene Therapy Manufacturing, published in the Journal of Applied Biosafety, and the associated guide is available from the BioPhorum website. For more information, contact Rachel Hodges, Senior Global Change Facilitator, at

A unique safety data sheet for cell and gene therapies

Advanced Therapy Medicinal Products

Advanced Therapy Medicinal Products support the quest for better and faster development of cell, gene and RNA therapies​ through connecting therapy developers, contract manufacturing, and testing organizations to gain an understanding and respond to the challenges faced by the advanced therapeutics industry.

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