Jul 08, 2022 | 3 min read
Christopher Doyle is the director of IBC Services at WCG and works with research sites, sponsors, and clinical research organizations to ensure HGT clinical trials are conducted safely and in accordance with relevant regulations. Prior to joining WCG, Christopher was a research fellow at the Albert Einstein College of Medicine in Bronx, NY, where he explored mechanisms of antibody activity against bacterial pathogens. He received his PhD in molecular genetics and microbiology from Stony Brook University in Stony Brook, NY.
Today, there are at least 700 active clinical trials in the United States testing products that contain or consist of recombinant or synthetic DNA or RNA. Many trials testing such human gene transfer (HGT) products are subject to unique rules outlined by the National Institutes of Health (NIH) that can present operational challenges for investigators and institutional staff. One of the most noteworthy requirements for clinical trial research subject to these guidelines is that an institutional biosafety committee (IBC) must review and approve the study at each trial site before participants can be dosed at that site.
IBCs are responsible for ensuring the safety of site staff, the work environment, and the general public. As part of each review, IBCs conduct a risk assessment focused on two broad areas: the investigational product and the trial site. In their review of the product, IBCs examine (among other things) its ability to replicate, be shed, and cause disease. In their review of the trial site, IBCs review facilities and safety equipment, product handling and emergency response plans, and staff training.
I have served on hundreds of IBCs that oversee HGT clinical trial research at hospitals and clinics around the world. Across the thousands of reviews those IBCs have conducted, many of the most significant site-level concerns have been related to the improper use of sterile compounding equipment: biosafety cabinets (BSCs), compounding aseptic isolators (CAI), compounding aseptic containment isolators (CACIs), and laminar airflow workstations (LAFWs).
This finding is not surprising, as all four types of equipment are commonly used to provide sterile work environments in laboratories and pharmacies and are often referred to interchangeably as “hoods.” In reality, however, their abilities to protect personnel from hazardous products vary considerably (see table):
- LAFWs are the simplest of the four. They blow filtered air over the work surface and exhaust it directly at the user without further filtration. These units provide good product protection but no personnel protection, so they should only be used with non-hazardous products.
- BSCs (Class II or Class III) are similar in that they blow HEPA-filtered air over the work surface, but this “dirty” air is filtered again before being exhausted into the room (or a building’s HVAC system, depending on the specific type of BSC). These units provide excellent product and personnel protection andcan be used with hazardous and non-hazardous products alike.
- CAIs and CACIs are both glovebox isolators that are nearly identical in terms of construction and appearance. They both blow filtered air over the work surface and all exhausted air is also filtered. The difference between the two comes down to air pressure: air is positively pressurized in CAIs and negatively pressurized in CACIs. This means that for a CAI, even the slightest breach in containment (like a glove tear or seam leak) will compromise personnel protection, as air would be exhausted without filtration. Because of this, CAIs should only be used with non-hazardous products. In contrast, a containment breach in a CACI will maintain personnel protection but not product protection, as unfiltered room air would be drawn into the unit.
|Sterile Compounding Equipment Commonly Used in Laboratories & Research Pharmacies|
|Exhaust||Room or ducted||Room or ducted||Room or ducted||Room|
|Certification standards||NSF/ANSI 49||CAG-002-2006||CAG-002-2006||IEST-RP-CC-022.3|
|Suitable for biohazards||Yes||Yes||No||No|
|*Breach in containment will lead to leakage of contaminated air.|
Some IBCs may assess the risk of certain products, like mRNA-based vaccines, to be sufficiently low that they can be manipulated without specialized equipment. For higher-risk products, like oncolytic viruses or live engineered bacteria, IBCs may require the use of a BSC or CACI. Understanding the differences between these “hoods” will go a long way to ensuring staff safety, and when research requires IBC approval, smooth study startup.