It was my first day of work and I was in a room with a table full of pig tissue. The sight and smell of raw tissue brought me back to my college anatomy class. Back then, seeing an animal opened up on a table for the first time was shocking, but I realized the key was to focus on WHY we were using the animal.
Clinical Research Associate I
Live animal models, animal tissue, and parts of animals have been used for centuries for education and testing to advance medical treatment. Learning from an animal can be essential to understand how it can be translated to the human body.
In the medical device field, we cannot use a device with significant risk in a human being without testing in a lab environment or animal model.
Animal models are the closest models we currently have that can mimic the complex anatomy and physiology of a human being. We learn from them to understand device safety and performance.
Early prototyping and designing for medical devices include many iterations, where designers want feedback as soon as possible with every change. This feedback can be received through avenues other than animal studies, such as bench testing using synthetic tissues or 3D models that mimic the human anatomy in the laboratory. Sometimes, it is as simple as asking an expert in the field.
The goal is to use a minimum number of animals to generate valid scientific data to demonstrate safety and function. We must consider the ethical principles of replacement, reduction, and refinement.
We must also ask ourselves:
After exhausting all potential in vitro avenues, many medical devices will require an animal study. Before starting a study, a protocol must be submitted to the institution or laboratory’s Institutional Animal Care and Use Committee (IACUC) for approval. The committee is mandated by Federal law (Animal Welfare Act) to ensure animals used in research, testing, or teaching will be humanely and ethically treated. The protocol must give a detailed description of the proposed use of the animals in the study.
There are rules and regulations in place to protect animals. However, it is still the job of an engineer, researcher, teacher, and scientist to think about what goes into a study protocol so that an animal is not misused.
An animal study for medical devices can be conducted during the prototyping phase to collect feedback before a clinical investigation or FDA submission. It can be performed anytime between Phase 0 (Prototyping) and Phase 3 (Verification/Validation).
As a Product Development Engineer, my initial months at Biotex were spent testing out devices in pig tissue and testing iterations of the device in live pigs during Phase 0 of the project.
The IACUC protocol was broad enough for us to try different prototypes. These initial studies do not need extensive documentation and oversight by quality assurance unless the data is submitted to the FDA for regulatory evaluation and premarket approval. In other words, they do not need to comply with FDA regulations 21 CFR 58 Good Laboratory Practices (GLP).
GLP provides stricter regulations for animal studies, while non-GLP only needs to be IACUC compliant. GLP studies are designed to promote the development of quality test data and provide tools and methodologies to ensure data is consistent, reproducible, and reliable.
Below are the differences between non-GLP vs GLP:
Most GLP studies are conducted at an external GLP-specific testing facility due to the number of trained personnel and regulations required for the study to be GLP.
The testing facility is responsible for:
The study director is responsible for the technical conduct, study, interpretation, analysis, documentation, and reporting of results. Giving the final statement on whether or not the study complied with GLP principles is also the study director’s responsibility.
The IACUC and the study director will approve the written protocol before starting the study. The protocol will indicate the objectives and all methods for conducting the study.
The protocol will include:
The quality assurance unit ensures the study is GLP-compliant, FDA-regulated, and safe. It also audits the testing facility management, which includes the facilities, equipment, personnel, methods, practices, records, and controls to confirm conformance with GLP regulations.
The testing facility shall record what happened during the study per the protocol. These records can be qualitative or quantitative. Once the study is complete, the data shall be compiled into a report which will include:
Of course, we all know that testing on animals before humans is a safer alternative, but there are pros and cons to conducting these studies.
Pros
Cons
We can mitigate these cons by thinking about how the study should be conducted, implementing it in the protocol, and going through all the options for design testing before beginning animal studies. Our job as engineers is to think about what goes into a protocol so that the animal is not misused.
At Biotex, we sometimes work with clients who drive and execute these studies. We, as engineers, should be the ones to think about whether we can build a bench model or reduce the number of animals through the study design and remind clients that every design iteration does not require an animal study.
The first project I worked on was the vaginal stent, and one of our initial goals was to assess device retention in the vaginal canal. However, it quickly became apparent that the pig model was not an ideal match for female human anatomy.
Since pigs urinate through the same orifice where the vaginal stent was being inserted, it was inevitable that the stent would be expelled every time the pig urinated. To combat this anatomical difference and in an attempt to get better animal study results, the vaginal stent design was adapted to align with the pig anatomy.
Given the anatomical differences, how can a device design tailored for the pig demonstrate retention in a human? Well, it would be difficult to translate that data. Recognizing that this was a low-risk device, we concluded that conducting a clinical study would be a more effective approach.
In any animal study we conduct, whether for feasibility or safety, we need to prove the device can work in humans. We have to ask whether the animal data we receive is representative of what we would see in humans.
Not only do we have to make sure the animal data we receive is transferrable, but we also have to ensure the animal model we choose is anatomically and physiologically able to show these results.
As we plan our animal studies, we need to consider how it could impact a future clinical investigation or the lives of the patients receiving these devices. As engineers, researchers, teachers, and scientists, we are responsible for treating the animals used for studies with utmost care and using them only if it is the best option before clinical investigations in humans.
We test in animals so we can provide better treatment options to patients.
At Biotex, we pride ourselves on building and sustaining relationships with institutions and personnel involved in helping plan and execute animal studies. We have conducted studies in the medical center, including BCM and THI, and have branched out to Texas A&M and UTMB.
Selecting an appropriate location and establishing a strong connection with the chosen site are pivotal steps when initiating an animal study. We prioritize local sites to enhance accessibility for our clients and have a list of sites and contacts for conducting animal studies in the area. Building relationships with local sites also fosters collaboration with local researchers, institutions, and stakeholders leading to valuable partnerships, shared resources, and a collaborative approach to medical device design work.
Early engagement in discussions regarding Institutional Animal Care and Use Committee (IACUC) submission dates, the availability of equipment and suppliers, and budget considerations is crucial. Additionally, it is imperative to verify with the site what specific equipment and supplies required for the study are available at the site, such as sutures, imaging tools, and more. Clients have certain dates or time periods they want to run studies so we have to ensure we give them accurate timelines about how long it would take to begin a study.
Project Managers and Product Development Engineers are usually the main points of contact for beginning/executing a study at Biotex. The protocol must be approved by team members and any physicians and veterinarians involved with the study before IACUC submission.
We involve everyone in the project team (Executives, Project Managers, Product Development Engineers, Mechanical Engineers, Design Engineers, etc.) on the day of study. There is something about seeing the device in use and in person vs just the testing you do on the bench model. You always learn something new because it is a live environment.
Ready to test your medical device prototypes? Need help starting a non-GLP or GLP study?
Biotex can help you conduct an animal study from start to finish, including contacting study locations, animal model selection, protocol and report writing, and data collection.
Contact our team today for more information.
Anishaa is a Clinical Research Associate and Project Manager at Biotex, Inc. She has worked at Biotex for almost six years in product development engineering and the medical device industry for over eight years. Her professional experience includes animal studies, working in various hospital/clinical settings, early-stage device development, and clinical investigation start-up/close-out.
