During the preclinical state of device testing, one measurement regulatory officials are looking at is the activated clotting time (ACT) of the animal model., whichThis is measured periodically while an invasive device is inserted in its vasculature, to monitor clotting time before and afterand the anti-coagulant has been administered.
Of course, when any foreign device is interacting with blood vessels in this fashion, one dangerous outcome is clotting, or a thrombus formation in the vein. This is the reason it’s important to control the coagulating conditions with the right dosing of anticoagulant.
Those who are familiar with using an invasive device in a clinical setting will be familiar with how ACT levels are monitored with a simple blood test. Because ACT levels are easily managed, managing a spike or a decrease needs only a simple, fast-acting remedy to get the patient to their target ACT range.
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Why ACT levels present challenges in preclinical studies
In medical device testing, the FDA places more emphasis on ACT levels than one might be accustomed to seeing in a clinical setting.
“The FDA wants to know how these devices behave because in many circumstances, they’re worried about any potential clot forming on these devices,” says Dr. Mark Smith, Emeritus Cchief Sscientific Oofficer of American Preclinical Services (APS). “How this new device behaves in a preclinical model predicts how it’s going to behave in a clinic.”
A spike in the ACT reading can raise a flag to regulators that the study wasn’t well designed, or it may raise other questions about the study and its results. When regulators are scrutinizing the data, that sets up obstacles in the approval process.
That’s why APS has developed careful procedures for administering and monitoring the anticoagulants, so ACT levels remain within the target endpoints while the medical device is inserted in the animal model’s vasculature. It’s just a prime example of why well-designed procedures are critical to a successful preclinical study that meets all the requirements of regulators.
Developing the right protocols for ACT values during premedical testing
In light of regulatory focus on ACT values during the preclinical phase of medical device testing, APS developed robust protocols.
- Studies, experiments, internal documentation, and animal training provided the data set to lay the foundation for the protocols.
- From this data, APS developed reference documents and reference guidelines to instruct the surgical staff. These processes are also tailored for species and animal weights so a specific dose of anticoagulant is administered as a loading dose and an infusion dose.
- APS also developed protocols for monitoring ACT levels in the animal, and administering additional anticoagulants or reversamoval as needed.
As a result of these processes, APS has achieved higher fidelity of ACT values so that that area fulfills the regulatory expectations of the agencies evaluating the studies, Smith says. “We have fewer instances where we’re being asked about ACT by the clients and by the regulatory agency.”
[Learn more about what to expect with your APS preclinical program]
ACT values aligning with what regulatory reviewers are looking for in a successful trial is one way APS can help you get your promising new device closer to market. Contact us to learn more.