Should You Level Up Your BSL??

July 3, 2024 by Cody Grasswick

Ensuring the right manufacturing approach

As therapeutics developers are aware, key factors for drug development are making sure that the backing organism utilized is safe, quick to reproduce, and efficient. Non-pathogenic E. Coli and a variety of yeasts dominate the market for these reasons. But with our fast-growing biological pharmaceutical market, one question for proposed treatments that is sometimes overlooked is: at what Biological Safety Level (BSL) should we be producing?

Let’s briefly explore this concept of Biological Safety Levels. There are four levels of BSL (I – IV), with containment requirements increasing from level I to IV, with levels III and IV being out of scope for biological therapies due to safety concerns. Therefore, most organizations work to develop a platform suitable for BSL I needs, involving no additional containment (other than good laboratory practices) and defined/known organisms that are highly unlikely to cause disease to the user, i.e. non-pathogenic E. coli.

Due to the implied safety of these organisms (low risk of disease), many manufacturers take for granted the ability to industrialize and scale-up a manufacturing plant utilizing a BSL I containment strategy. But that isn’t always the case.

BSL II requires some additional containment regarding air handling and proper procedures during open processes to ensure operator safety. These organisms represent a moderate risk of being able to cause disease but are still opportunistic and not of the degree of concern such as found in BSL III and IV levels. Examples include equine encephalitis viruses and HIV, as well as Staphylococcus aureus (staph infections).

Why should I choose one over the other?
What does this all mean in manufacturing and why is this important? Though many gene therapy developers and manufacturers strive to develop a platform suitable for a BSL I level containment strategy, there may be future benefits to medicine that require a step up to a BSL II containment strategy.

An initial example would be self-amplifying RNA (saRNA) treatments that have shown great promise in the scientific peer reviewed world, as mentioned by Aldevron CSO Venkata Indurthi in a previous blog post. As the potential for greater efficacy and safety for patients is explored, the question around regulations and proper control for the manufacture of these biologics always come into question.

It is likely that proper control for initial drug development may often stay within the realm of BSL I due to the level of separation from the end user. However, it’s important to stay on the cutting edge of innovation, designing and building lab spaces that can support either BSL I or II levels of containment strategy so that those levels are easily and quickly available for client usage.

• Have questions on this topic? Contact Cody Grasswick
• Learn more about Biosafety Levels
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