FDA Insights: The ISO Standard for Endovascular Grafts
A new standard will help to advance and globalize the evaluation of endovascular grafts.
The views and opinions in this article are those of the authors and do not necessarily reflect those of the US FDA, the US Department of Health and Human Services, or the Public Health Service.
Identifying the appropriate preclinical and clinical evaluation of endovascular grafts has been a challenge since the inception of this novel technology. To date, the evaluation plan for each device has been established by the manufacturer, with little guidance available for development. As such, there has been little consistency among manufacturers and difficulty in optimizing the testing. No direct comparison of data for different devices has been possible. Improvements in testing have been made in isolation and therefore have not been communicated or applied broadly. In an effort to advance and globalize the evaluation of endovascular grafts, an international standard was developed and has been published.
Q: What is the endovascular graft standard?
A: There is a wide variety of information that can be included in an international standard. A standard may be specific to a type of device, such as endovascular grafts, or can have a broader scope, as does the standard for evaluating biocompatibility, which is applicable to all medical devices. The standard may include specific performance criteria, that is, set acceptable limits for tests that are described, or may be less definitive, identifying which tests to conduct without mandating the acceptance criteria. The endovascular graft standard was written in accordance with the latter framework, given the extreme variability in the devices under the scope of the standard (eg, aorto-uniiliac, unibody, modular, fully supported, “active fixation,”) and a lack of knowledge regarding the values necessary to ensure adequate clinical performance.
The official title of the endovascular graft standard, published early this spring, is ISO 25539-1: 2003 Cardiovascular implants–Endovascular devices–Part 1: Endovascular prostheses. It is identified as Part 1, with future parts to include standards for vascular stents and vena cava filters. The standard is applicable to endovascular grafts used to treat arterial aneurysms, arterial stenoses, and other vascular abnormalities. Delivery systems are addressed by the standard if they comprise an integral component of the deployment of the graft. Procedures and devices used prior to the introduction of the endovascular system (eg, balloon angioplasty devices) are excluded from the scope of the standard.
Q: Who wrote the standard?
A: ISO (the International Organization of Standardization) is a worldwide federation of national standards bodies. Technical committees established under ISO are responsible for writing the standards. The Vascular Prostheses Working Group of ISO was in charge of the endovascular graft standard. In order to garner the necessary expertise for drafting the standard, an international ad hoc committee was formed that consisted of approximately 25 volunteers from clinical practice, industry, regulatory bodies, academia, and testing facilities. A wide range of disciplines encompassing the diverse community involved in the design, development, testing, manufacture, use, and regulation of endovascular grafts, such as endovascular clinicians, engineers, scientists, and regulatory personnel, formed the committee.
Q: What was the process for developing the standard?
A: In 1997, the committee began writing the rationale for the requirements that would be included in the standard. This was done by first identifying the individual design goals (ie, functional attributes) needed for adequate clinical performance. The committee then recognized the problems that could occur if each individual design goal was not achieved. The associated complications or failures that could be observed with clinical use were then outlined. This information formed the basis for recommendations regarding the testing needed to evaluate each aspect of an endovascular graft design. The results from this exercise were published in an ISO Technical Specification (ISO TS 15539:2000–Cardiovascular implants–Endovascular prostheses).
The technical specification was then used as the template for the standard. Each attribute was listed with its associated potential problems and reportable clinical events, followed by a list of the bench tests that could be done to evaluate the particular device characteristic. For example, there must be an ?ability to access? the intended implantation site. Access may not be achieved if there is a size mismatch between the introducer and delivery system, which could potentially result in vessel injury. Therefore, testing or characterization must include dimensional verification, component dimensional compatibility, and device profile measurements in an effort to minimize the potential for access-related problems. Other sections of the standard, such as guidance in the design of animal and clinical studies, were also written by the committee and incorporated in the standard.
Once a draft standard was completed, it was widely distributed by national standards bodies in the member countries of ISO for review and comment. After adjudication of the comments, the revised draft was sent out so the countries could vote on whether it should be published. Now that it has been published, access to the standard is available through the ISO or, in the US, through the Association for the Advancement of Medical Instrumentation.
Given the amount of time that it would take to write test methods for the standard, the ad hoc committee separately undertook the task of writing these methods concurrently with the development of the standard. Approximately 35 test methods were identified, drafted, and refined by the ad hoc committee. These methods are not intended to be normative; that is, in order to conform to the standard, the methods do not need to be followed. Deviation from the methods, however, would need to be reported and justified. Intensive committee review and editing are still being undertaken in order to gain consensus and to optimize each test method. When the test methods are completed, the published standard will be amended to include them in the form of an Annex, possibly in early 2004.
Q: What is the standard used for?
A: In the US, the standard serves as a tool in preparing investigational device exemption (IDE) applications and premarket approval (PMA) applications. It can be used by the sponsor to ensure that their submission will contain all of the information needed to allow for an evaluation of their device. Use of the standard is not associated with a change in the regulation of endovascular grafts. In the US, claiming conformance to the standard is not sufficient to address the regulatory requirements because performance criteria are not incorporated in the standard and it is intentionally nonprescriptive to allow for its application to various device designs. Similarly, use of the standard is not mandatory; however, a sponsor would be expected to identify any tests not completed and any deviations from the test methods once published, with a rationale for the deviations from the standard in all new IDEs and PMAs. From a device-evaluation standpoint, the standard is only applicable in the IDE and PMA approval processes; that is, there is no mechanism to retrospectively apply it to PMA-approved devices. Conversely, a sponsor with a previously approved IDE would need to consider the standard in preparing a PMA.
For device modifications, the fundamental concept of the standard, that is, identifying the appropriate and necessary testing by first recognizing the design attributes, is helpful in devising the testing plan needed to evaluate the change. The attributes that could be affected by the device modification should be identified, with the applicable testing. This mechanism helps to refine the testing strategy, minimizing the conduct of unnecessary testing, and ensuring full consideration of the potential impact of the change.
In the European Union (EU), standards are used by manufacturers to address regulatory requirements by including the information required by the standard in the design dossier for the device. For endovascular grafts, manufacturers will likely be expected to follow the ISO standard. There is an interesting twist to the use of standards for endovascular grafts in the EU, however, because the entity responsible for publishing standards for the EU will soon publish their own standard that covers endovascular grafts. This standard has a broader scope, covering endovascular grafts, stents, and vena cava filters. If both standards are available, manufacturers may choose either standard for reference.
Establishing the criteria for the appropriate evaluation of endovascular grafts is and will continue to be a significant challenge. Publication of the standard will begin the incremental harmonization of the testing for these devices, with publication of the test methods being the next significant milestone in this process. Modification and improvement of the standard will be necessary as the technology evolves, the stresses imposed by the implantation environment are better understood, and the testing is refined.
Dorothy B. Abel, is the Convener of the ISO Vascular Prostheses Working Group; a Regulatory Review Scientist with the US FDA Center for Devices and Radiologic Health in Rockville, Maryland; she is also a regular columnist for Endovascular Today. Ms. Abel may be reached at (301) 443-8262, ext. 165; firstname.lastname@example.org.
Louis J. Smith, BSE, is an Associate of W.L. Gore and Associates, and the Project Leader for the development of test methods for the standard. Mr. Smith may be reached at (928) 864-3785; email@example.com.