Before a drug even reaches the clinical trial stage, preclinical studies indicate early results that move the development process forward. But, if the animals that are part of the preclinical research are not cared for in a consistent way, results can be misleading and a clinical trial could be set up to fail.
Ensuring consistent animal health is a vital part of preclinical research and can be challenging for lab managers. Especially when working with immuno-compromised mice, the risk of infection is high.
Not every health scare presents itself in an obvious way
“Some mouse pathogens you can’t even tell are affecting the mice, but they can change their systems,” explains Adrienne Edgell of SoBran BioScience, an expert in preclinical toxicology that offers on-site support and contract research services. “It could affect their ability to grow or respond to treatment, or affect their lifespan. It could compromise study results in the long run.”
With subjects housed in close proximity to each other, any change in condition could affect multiple studies being conducted in the same lab. Colonies are expensive and hold vital information; researchers can’t simply start over. Labs need to be proactive in preventing and detecting disease and have procedures in place to stop any outbreak quickly and keep it from spreading.
How the pathogens get in
Pathogens that cause disease can be brought into the lab environment by people handling the studies, transferred via clothing or skin.
The Guide for the Care and Use of Laboratory Animals sets industry standards for humane animal care and use in research. However, there are no definitive requirements for sterile operating procedures used by researchers and lab staff.
“It’s all facility-specific,” says Edgell. “There are no set rules for personal protective devices or health checks. It’s all in what kind of animals are in the lab and what the veterinarians and researchers think is adequate for their type of research.”
Regular testing can pick up pathogens, particularly preliminary chain reaction (PCR) tests that use comparison samples of tissues, rather than a typical blood test. But most labs may not conduct tests like these more than once per year due to expense. What’s more, labs that handle molecular tests such as these have proprietary methodologies and may in fact offer conflicting test results, making the lab manager’s job even more difficult in detecting and protecting against outbreaks.
Edgell says that researchers need to be more proactive in defending against any kind of outbreak among their research subjects that could affect study results.
Changing behavior to protect animal health
If a lab is large enough, it is possible to design operating procedures in which staff will always enter rooms from one door and exit from another, so they cannot backtrack and contaminate a clear area. Not every lab is large enough for that kind of process, but using separate rooms for at-risk subjects, holding regular training on hood use, and enforcing the use of personal protective equipment can go a long way toward preventing pathogens from finding their way into studies.
Step one, Edgell says, is a careful review of the sources for research subjects. For example, if mouse colonies are imported from overseas, standards of care may not be the same as in the United States. It’s important to create special procedures to manage imported colonies, and prevent any mingling with domestic sources while working with sources to set the same standards.
At SoBran’s contract research facility in the science and technology park at Johns Hopkins, all subjects are handled in a highly sterile environment. Staff use personal protective equipment (PPE) such as coveralls, hair covers, masks, gloves, and shoe coverings whenever they enter the facility.
Immune compromised mice have an even higher level of protection. They are handled with tongs, rather than gloved hands. The tongs are placed in a dissecting solution after each use, rotated out and then decontaminated again before use.
Animals coming from overseas or from non-commercial or new vendors are housed in a separate quarantine room. Staff use double PPE when entering this area, and go into that room last in the day so they do not bring any pathogen back into the main lab.
Processes like these require ongoing staff training and constant vigilance, says Edgell. But, they are essential to ensuring preclinical results are consistent and replicable, eventually leading to drugs that are proven safe and effective for humans.