Animal Study Mishaps: How to Prevent Mistakes
Animal studies are an important aspect of any medical device product development program. Animal studies provide data and evidence needed for development and regulatory submission. It can illustrate the performance and efficacy of the device in a live biological system. The study can also provide evidence on the safety of the device, demonstrate proof of principle early in the product development process and show the living being’s response to the product. It also can be a major investor milestone.
There are two types of animal studies: Good Laboratory Practice (GLP) and Non-Good Laboratory Practice (Non-GLP). GLP animal study follows 21 CFR Part 58 standards thereby these animal studies must follow the approved protocol exactly. The protocol will be developed in collaboration between the lab, quality, and the client. Any protocol deviations will be recorded and inspected by a quality team. All equipment needs to be qualified and calibrated. Due to the complexity of these studies, they are more expensive. Animal studies can also be “Non-GLP”. These studies do not need to follow 21 CFR part 28 standards. The protocol can be changed during the execution and can be more experimental. Typically, teams start with several non-GLP studies before conducting a GLP study. Any data needed for a regulatory submission must be done in a GLP study.
Animal studies follow a specific process. A protocol needs to be developed including determining the type of animal to be used, how to emulate the situation needed for the device, the number of devices needed to test, and the number of animal subjects. The study needs to be scheduled with a lab and the correct personnel will need to be coordinated to be on site including the lab technicians, anesthesiologists, surgeon, engineers etc. The equipment and product that is needed for the animal study needs to be thoroughly tested by the client and shipped to the lab. The study will be conducted, data and pictures will be collected. A report will be written following the study summarizing the results.
There are different stages of the product development process that can be conducted for an animal study. The most common stages are at the beginning of the product development during the initial concept generation as well as at the end of product development during the verification and validation stage. Testing early in development is helpful to perfect the performance of the product and initial safety. The animal study testing in the verification and validation stage will show the safety and efficiency of the product.
Animal studies can be critical for finalizing the product development stages and submitting for market clearance with a regulatory body. Animal studies can be tricky to successfully conduct and execute, being it can be hard to recover from a mistake. These studies are not only expensive but also difficult to reschedule. There are plenty of mishaps that can occur during an animal study but most importantly, ways to avoid them.
Animal Study Mishaps
An example animal study mishap happened during a GLP animal study with pigs. The product was being tested on three pigs in one day, which was an extremely tight timeline. A saline drip was required to be turned on at a specific rate and during specific times. The specific rate was supposed to be 3 mL/min; however, halfway through the second animal subject, it was discovered that the rate was at 3mL/hour not per minute. Being extremely diligent to double and triple check every setting can help to mitigate mishaps like this. Also assigning multiple people to conduct the final checks would be beneficial to the success of the study. Due to the discovery of the incorrect flow rate, additional testing needed to be done on the subject in an attempt to get enough data so the GLP study could remain valid. It resulted in the study needing additional review and approval from the quality team as well as the Institutional Animal Care and Use Committee. This resulted in the testing duration of the study increasing by an additional 3 hours as well as pushing the physical limits of the test subject.
Things happen. In an instant, something can occur that provides insight into the product being tested, or into the procedure or protocol but then the event is over. In testing a new form of endoscope, a flash was seen briefly on the display screen. Fortunately, a multi-view video recording was in process. Such multi-view capability combines a view of the operator (i.e., the doctor), the operating site of the patient, the fluoroscope screen and vital signs monitor simultaneously in one video recording. Note that the cameras and video mixing equipment to accomplish this is not very expensive, and the potential to capture, analyze and correct problems based on the recordings is extremely valuable. In this case the attempted articulation of the endoscope tip while in a particular part of the animal anatomy had placed too much stress on the control wire and snapped a fiber-optic illumination conduit. The design was adjusted to prevent this possibility in future product builds.
So how do you avoid these mishaps that can complicate and/or end an animal study early? The simple answer is preparation, precision and diligence. Let’s dive a little deeper.
When preparing for the animal study, it is essential to plan to test equipment and your device beforehand as well as have extra product in case a failure occurs. For one animal study that was conducted, we brought 10 products for an early-stage product development animal study where only one was needed, and all 10 were used.
In addition to more product, create data sheets beforehand of all manual data that needs to be collected during the animal study. This requires great attention to detail and thoroughness to determine all these data points prior to starting the study. This will keep the team organized, ensure all data is collected and ideally minimize errors from occurring.
Along with the lab staff, plan on bringing at least 2-3 staff members to ensure the animal study goes smoothly. A study manager should be the lead to ensure the protocol steps are conducted correctly, and that all data and details are collected. An engineering team member should mainly be responsible for the data collection. And a third team member, engineer or quality, should be there for any support where needed. Now obviously, if the product is complicated or the animal study is complicated, more people may be needed during the animal study.
Lastly, if possible, having an in-person meeting with the animal lab team prior to the study can help to ensure everyone is on the same page. The same goes for setting up and checking all the equipment the prior evening to prepare for a smooth study. We have found this helpful with complicated studies where many people are needed to participate in the study.
During the animal study, plan on videotaping the entire animal study so tape can be reviewed if needed, especially if timing is important in the study. The videotaping should be on the animal and a data acquisition system (if used), or any other critical equipment needed using a multi-view video mixer as described in the example above.
In addition, it is important to double, and triple check every piece of equipment, equipment settings, product setup and settings throughout the entire study. Being diligent and continuously checking set points and data points can prevent and catch mistakes early.
Animal studies are critical for product development and must be conducted with great attention to detail and significant preparation. Performance of product and proof of concept can be proven and later illustrate the safety of the product. Animal studies can be difficult to perform flawlessly but not impossible. Mishaps happen, so it is recommended that several non-GLP animal studies should be conducted prior to a GLP study. Mishaps can be reduced through preparation, diligence during the animal study, recording the data through data sheets, data acquisition systems and videotaping. Animal studies are expensive and hard to reschedule, so it’s important to be as prepared as possible in advance. Reviewing, rehearsing, and being fully prepared can make the difference between a failed or successful animal study.