Safety and Efficacy Cardiovascular Device Testing Models

Cardiovascular devices include different types of implantable products aiming to treat and/or prevent diseases of the heart itself or diseases of the cardiovascular system (arterial or venous occlusion, thrombus management, aneurysms, etc.). Cardiovascular devices can be implanted either surgically by a cardiac or vascular surgeon or percutaneously via trans-catheter approach performed by an interventional cardiologist or radiologist.

The main types of cardiovascular devices can be regrouped within the following categories:

  • Coronary and Peripheral Interventions:
    • Drug-eluting stents (DES)
    • Drug-coated balloons (DCB)
    • Bioresorbable scaffolds (metallic and polymeric)
    • Venous endovascular devices
    • Atherectomy and aspiration systems
    • Embolic protection systems
    • Diagnostic probes and implants
  • Structural Heart Interventions:
    • TAVI (Trans-aortic valve implantation)
    • Mitral and Tricuspid valve repair/replacement
    • Closure devices (LAA, PFO)

    Charles River is well versed in the preclinical assessment of medical devices that treat or cure structural heart defects. Such devices typically target the anatomical structures such as heart valves or conduits between chambers of the heart. Learn more about structural heart studies

  • Electrophysiology and Heart Failure Therapies:
    • Pacemakers
    • Defibrillators
    • Ablation devices
    • Reperfusion devices
    • Myocardial regeneration (cell therapy, drugs)

Considering the greater degree of risk cardiovascular devices pose to patients, their testing is subject to rigorous oversight by regulators globally.


Cardiovascular Models for Medical Devices Product Sheet

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Key Considerations for the Selection of Your Cardiovascular Medical Device Partner

Every cardiovascular device implant or combination product is unique and requires customized study plans.

  • Our multidisciplinary team of cardiovascular device testing experts combine their deep understanding of efficacy, safety, performance, and regulatory guidelines to develop an appropriate cardiovascular device testing strategy adapted to the particulars of your cardiovascular device.
  • Our specialty cardiovascular device testing program customizes protocols to your device with the guidance of dedicated study directors, boarded veterinary cardiologists, human-boarded cardiologists, and boarded veterinary pathologists familiar with preclinical cardiovascular studies.

This unique combination of regulatory expertise and comprehensive portfolio of services allows us to create a tailored plan to carry you from the earliest stages of study design to GLP assessments so you can get to market faster.

Our comprehensive portfolio of cardiac medical device services includes:

  • Imaging modalities and diverse histological endpoints that are quantitatively assessed using manual and software-guided automated histomorphometry.
  • Dedicated veterinary pathologists who can perform a full histopathological analysis and create resulting quantitative reports.
  • Specialized models can help accelerate the development of your cardiovascular devices and therapies.

Cardiac Medical Device Services

  • Coronary and Peripheral Studies

    Coronary and peripheral studies and cardiovascular device testing.Multiple sites feature purpose-built surgical and interventional suites to support your cardiovascular device testing needs. Our facilities include four catheterization labs staffed by highly trained professionals, fluoroscopy (digital angiography), intravascular ultrasound (IVUS), optical coherence tomography (OCT), fluoroscopy, echocardiography, image analysis software (for quantitative artery analysis), digital radiography, micro-computed tomography and clinical CT, and magnetic resonance imaging (MRI).

    Our interventional cardiology experts routinely perform coronary and peripheral interventions with a wide variety of cardiovascular devices like drug-eluting stents (DES), drug-coated balloons (DCB), bioresorbable scaffolds, venous endovascular devices, diagnostic probes, and more.

    Coronary and peripheral studies publications:

  • Structural and Cardiac Research

    Structural and cardiac medical devices testing at Charles River.Structural cardiac disease is a rapidly advancing area of cardiovascular device development. Using our interventional suites, we can conduct cardiovascular device implantation studies on several types of sophisticated cardiac devices such as aortic valve (TAVI) and mitral valve (TMVI) replacements (with transapical or transseptal approaches), tricuspid valve, and closure devices (LAA, PFO).

    Our continued investment in advanced instrumentation and modalities helps to best support tomorrow’s needs of cardiovascular device testing. Current on-site technologies include magnetic resonance imaging (MRI) (Siemens 1.5 Tesla MAGNETOM Sonata™), a hybrid surgical room with computer tomography (CT) scanner (SOMATON Sensation 16, Siemens) and intracardiac echography (Siemens ACUSON) to achieve appropriate sizing pre-implantation, monitor delivery, and evaluate migration and cardiovascular device performance.

    Structural and cardiac research publications:

  • Electrophysiology Studies

    Electrophysiology medical device testing at Charles River.Using electrophysiology (EP) study equipment like EP-Tracer, Cardiotek, and a Biosense Webster Stockert system, we perform electrophysiology studies in a variety of large animal models. We can conduct ablation, intracardiac electrical pathway, pacemaker, cardiac defibrillator and arrhythmia, and neurostimulation studies for your cardiovascular device testing needs.

  • Ischemia Reperfusion Model

    We routinely work with challenging myocardial infarction models as part of our cardiovascular device testing portfolio. In the past three years alone, we have conducted more than 16 GLP and/or non-GLP studies in over 500 animals to evaluate diverse treatment modalities, including cell therapies, RNA-based treatments, and local drug delivery. Our surgeons and interventionalists are skilled in both surgical and endovascular approaches for cardiovascular device testing and can evaluate LVEF, LVEDV, LVESV, wall motion and wall thickening (both regional and global), infarct size, infarct percentage, area at risk, and edema.

Charles River offers complete support for your Cardiovascular work, from design and proof of concept, to GLP-compliant studies tailored to your specific needs.

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Frequently Asked Questions (FAQs) about Cardiovascular Device Testing

  • What is a cardiac or vascular medical device?

    Cardiovascular devices are comprised of different types of implantable products aiming to treat and/or prevent diseases of the heart itself (e.g., valve dysfunction, arrhythmia, heart failure, etc.) or diseases of the cardiovascular system (arterial or venous occlusion, thrombus management, aneurysms, etc.). Those devices can be implanted either surgically by a cardiac or vascular surgeon or percutaneously via a trans-catheter approach performed by an interventional cardiologist or radiologist.

    The main types of devices can be regrouped within the following categories:

    • Coronary and Peripheral Interventions:
      • Drug-eluting stents (DES)
      • Drug-coated balloons (DCB)
      • Bioresorbable scaffolds (metallic and polymeric)
      • Venous endovascular devices
      • Atherectomy and aspiration systems
      • Embolic protection systems
      • Diagnostic probes and implants
    • Structural Heart Interventions:
      • TAVI (Trans-aortic valve implantation)
      • Mitral and Tricuspid valve repair/replacement
      • Closure devices (LAA, PFO)
    • Electrophysiology and Heart Failure Therapies:
      • Pacemakers
      • Defibrillators
      • Ablation devices
      • Reperfusion devices
      • Myocardial regeneration (cell therapy, drugs)
  • How can a CRO who specializes in cardiovascular device testing improve my preclinical medical device study plan?

    Considering the greater degree of risk that they pose to patients, cardiovascular devices are subject to significant oversight by medical device regulators globally.

    Every cardiovascular implant or combination product is different, and there is no “one-size-fits-all” study plan. Having seen a vast array of cardiovascular device types in development, our multidisciplinary team of experts use their deep understanding of efficacy, safety, performance, and regulatory guidelines to develop an appropriate testing strategy adapted to the particularities of your cardiovascular device.

    A CRO must demonstrate flexibility in evolving the study design as needed and support the sponsor in its quest for a study design that will meet regulator’s expectations (i.e., proposing to sponsors to engage into a protocol writing to be reviewed in a pre-submission meeting with the authorities). Our specialty study program tailors the study to your cardiovascular device under the expert guidance of experienced study directors, a boarded veterinary cardiologist, a human-boarded cardiologist, and boarded veterinary pathologists familiar with preclinical cardiovascular studies.

    This unique combination of expertise and comprehensive portfolio of services allows us to create a tailored plan to carry you from the earliest stages of study design to GLP assessments, so you can get to market faster.

  • Can I use the data obtained in a coronary study with my cardiovascular device to support a regulatory submission for a peripheral vascular disease indication?

    According to the FDA, data in coronary studies cannot be used directly to submit for peripheral indications.

    Preclinical studies will assess cardiovascular device safety, their performance when used in a living animal, and the biologic response that a living system may mount towards the device. Any medical device needs to be tested in a relevant clinical site and since peripheral and coronary vessels are located in different parts of the body, the data obtained from a coronary study would not be acceptable to support a peripheral vascular indication.

    If the study is well-planned, it is possible to integrate, in the same preclinical study, the assessment of a medical device for both coronary and peripheral vascular disease indications. Coronary studies can be submitted in support as supplemental data, but peripheral studies will be necessary in the submission.

    For example, cardiovascular devices can cause mechanical or biologic stresses when used in the vasculature. If the device is used in, or tracked through, the coronary or peripheral vasculature, the FDA recommends to identify key biologic response variables at regional sites, at locations adjacent to the implant site, and along all paths to and from the point of implantation to assess the impact of the device on the vasculature.

  • We are developing a bioresorbable vascular scaffold. What should be the longest time point to consider in a safety animal safety study?

    According to ISO 10993-6, before starting an animal study with degradable materials, it is recommended to assess degradation information using in vitro testing by real-time or accelerated degradation studies or in certain circumstances by mathematical modelling. For absorbable materials, a pilot study in rodents may be considered to determine the expected rate of degradation before embarking on studies involving larger animals.

    The objective of the preclinical safety study is to characterize the evolution of the tissue response after implantation of a cardiovascular device, including final degradation of the material.

    The test period will depend in part on the degradation rate and the estimated degradation time of the test product at a clinically relevant implantation site. Study duration should extend up to or beyond the point of complete absorption. Study intervals should span a significant portion of the degradation time frame for the implant, and shall include, as a minimum, the following time points:

    • Early time frame (where there is no or minimal degradation) should be used to assess the early tissue response.
    • Mid time frame (when degradation is taking place) should be guided by the degradation profile of the specific absorbable material. The target interval should allow assessment of histological response when the tissue response is expected to be most pronounced (e.g., substantial structural disruption and/or fragmentation of the device is most likely to occur). Implants with longer-term degradation profiles may require multiple assessment time points, with intervals targeted in accordance with the expected pattern of degradation. When a cardiac device with multiple materials with differing absorption rates is implanted, implant intervals reflecting the degradation profile of those components should be included.
    • Late time frame (when the cardiac implant is essentially absorbed) is targeted to observe when minimal amounts of the absorbable component remain at the implant site.

    Gross and microscopic evaluation after complete implant absorption is highly desirable. In the absence of complete absorption, the overall data collected should be sufficient to allow characterization of the local effects after implantation if:

    • the affected tissue’s response, structure, and function have achieved an acceptable steady-state condition, and
    • the absorbable material and/or its degradation products are in a state of limited visually identifiable presence.

    In vivo degradation can occur over a long period of time, sometimes more than a year. Additional animals to extend the observation period (intervals “to-be-determined” group) can be beneficial if the implant has not been completely absorbed within the expected investigational time period and cannot be observed microscopically.

    In those situations when the material is not fully absorbed within the late time frame, an appropriate scientific justification can be included for ending the study, and the estimated percentage of remaining absorbable material should be reported.