等同器械

在临床评价计划（CEP）中，若计划通过与一个或多个已合法上市的医疗器械（即“等同器械”）进行比对，并利用其临床数据来支持待评价器械的安全性和性能，则必须设立一个专门的章节来严谨、详尽地论证这种“等同性”。本章节的核心任务是依据法规要求（如欧盟MDR法规第61条第3款及附件XIV A部分第3节，并参考MDCG 2020-5等指南文件），清晰、系统地证明待评价器械与所选定等同器械在临床、技术和生物学特性方面不存在任何具有临床显著性的差异。

等同器械的选择标准

在开始详细的比较之前，首先必须阐明选择特定器械作为等同器械的理由和标准。选择的等同器械应为已在欧盟市场合法销售（通常带有CE标志）的产品。其选择不应仅基于表面相似，而必须能够承受在以下三个关键维度上进行的细致比较：

1. 临床等同性： 器械需用于相同的临床状况（包括相似的疾病状态和严重程度）、相同的预期目的（包括相似的治疗或诊断效果）、相似的目标人群（包括年龄、解剖结构、健康状况等方面的考量）、以及相似的使用部位和应用方法。
2. 技术等同性： 器械需采用相似的设计和技术规格（例如，相似的工作原理、关键性能参数、部署方法、以及与待评价器械类似的关键部件的材料和设计）、在相似的使用条件下使用，并具有相似的软件算法（如适用）。
3. 生物学等同性： 器械需采用与人体组织接触的相同材料或高度相似的材料，且这些材料与人体的接触性质和时长也应相似。

系统性地论证等同性

等同性的论证是一个系统化、细致的对比过程，非简单罗列。需要在CEP中概述这一过程，并计划在临床评价报告（CER）中完整呈现详细的对比数据和分析。

核心环节是进行逐项的特性比较。需要将待评价器械与每一个选定的等同器械，就所有相关的临床、技术和生物学特性进行并列比较。常通过表格形式清晰展示各项特征在不同器械间的具体表现，对比应覆盖的范围广泛，例如：

• 临床特性方面： 详细对比预期用途的每一个细节、适应症的范围、目标患者群体的精确定义、目标疾病或状况的特性、器械在体内的具体使用部位，乃至禁忌症、警告和注意事项的表述差异等。
• 技术特性方面： 深入剖析设计特点（如：特定的几何形状、能量输出参数、软件版本等）、作用机制或工作原理的异同、关键性能规格（如尺寸范围、机械强度、输送系统的兼容性等）、灭菌方法及无菌屏障系统、以及是否为一次性使用等。
• 生物学特性方面： 明确列出所有与人体直接或间接接触的材料成分，评估这些材料的生物相容性数据，并比较与人体组织的接触方式和预期接触时长。

差异的识别与分析

在进行细致的逐项比较时，几乎不可避免地会发现待评价器械与等同器械之间存在某些差异。必须明确识别出所差异。

一旦识别出差异，需要对每一项差异进行深入的科学分析和论证，以证明这些差异不会对器械的安全性和/或临床性能产生具有临床显著性的负面影响。这种分析需要：

• 清晰描述差异的性质和程度。
• 基于科学原理、工程评估、标准要求、已发表文献或特定的临床前研究（如台架测试、动物实验）来解释为何该差异不会导致临床结果（如有效性、并发症发生率、操作便捷性等）的不同。
• 如果差异涉及材料，需评估其生物相容性、化学性质、物理性质等方面的潜在影响。
• 如果差异涉及设计或性能规格，需评估其对器械在预期临床场景下按预期运行的能力的影响。

在CEP中规划和呈现等同性论证

在临床评价计划（CEP）的本章节中，需要清晰地阐述进行等同性论证的计划和方法学。

应首先明确声明计划与哪些特定的、已合法上市的器械进行等同性论证，并简述选择这些器械的主要理由。

接着，概述将如何进行临床、技术和生物学特性的详细比较。可以提及计划采用的比较参数的范围。重点在于说明将如何系统地识别差异，并对这些差异的临床显著性进行评估和论证。

CEP应指明支持等同性论证所需的数据来源。这可能包括：

• 制造商内部已完成的或计划中的临床前研究（如台架测试、模拟使用测试、动物研究等，特别是那些直接头对头比较待评价器械与等同器械性能的测试）。
• 对已发表科学文献的系统检索和分析，以获取关于等同器械特性、性能、安全性以及某些技术或材料差异临床影响的信息。
• 对相关国际标准和指南的遵循情况。
• 对等同器械的上市后监测数据、不良事件报告、临床研究数据（如有）的计划性检索和分析。

本章节应为后续临床评价报告（CER）中如何利用已证实的等同性来支持待评价器械的临床安全性和性能，设定一个清晰的路径。例如，说明在CER中将如何整合和评价来自等同器械的临床数据。

等同性的论证是监管机构审查的重点之一。整个过程必须透明、严谨、科学，并充分符合相关的法规指南（如MDCG 2020-5）的要求。任何宣称的等同性都必须有充分的证据支持，且对差异的分析必须具有说服力。

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Within the Clinical Evaluation Plan (CEP), if the strategy involves comparing the device under evaluation with one or more legally marketed medical devices (i.e., “equivalent devices”) and leveraging their clinical data to support the safety and performance claims of the new device, a dedicated chapter is essential to rigorously and comprehensively substantiate this “equivalence.” The core task of this chapter is to clearly and systematically demonstrate, in accordance with regulatory requirements (such as EU MDR Article 61(3) and Annex XIV Part A Section 3, with reference to guidance documents like MDCG 2020-5), that no clinically significant differences exist between the device under evaluation and the chosen equivalent device(s) in terms of their clinical, technical, and biological characteristics.

Selection Criteria for Equivalent Devices

Before embarking on a detailed comparison, it is imperative to first articulate the rationale and criteria for selecting specific devices as equivalent. The chosen equivalent device(s) should be products legally marketed in the EU (typically bearing a CE mark). Their selection should not be based merely on superficial similarity but must withstand meticulous comparison across three key dimensions:

1. Clinical Equivalence: The devices must be used for the same clinical condition (including similar disease state and severity), for the same intended purpose (including similar therapeutic or diagnostic effects), in similar target populations (considering aspects like age, anatomy, health status), and at similar sites of use and with similar application methods.
2. Technical Equivalence: The devices must utilize similar designs and technical specifications (e.g., similar operating principles, key performance parameters, deployment methods, and materials and designs of critical components analogous to the device under evaluation), be used under similar conditions of use, and possess similar software algorithms (if applicable).
3. Biological Equivalence: The devices must use the same or highly similar materials in contact with human tissues, and the nature and duration of this contact with the body must also be similar.

Systematically Demonstrating Equivalence

The demonstration of equivalence is a systematic and highly detailed comparative process, not a simple listing. You need to outline this process in the CEP, with the plan to present the full detailed comparative data and analysis in the Clinical Evaluation Report (CER).

The core activity is a feature-by-feature comparison. This means juxtaposing the device under evaluation with each selected equivalent device across all relevant clinical, technical, and biological characteristics. This comparison should be extensive, covering areas such as:

• Clinical Characteristics: A detailed comparison of every aspect of the intended use, the scope of indications, precise definitions of target patient populations, characteristics of the target disease or condition, specific anatomical sites of use, and even differences in the wording of contraindications, warnings, and precautions.
• Technical Characteristics: An in-depth analysis of design features (e.g., specific geometric shapes, energy output parameters, software versions, etc.), similarities and differences in the mechanism of action or operating principle, key performance specifications (such as dimensional ranges, mechanical strength, delivery system compatibility), sterilization methods and sterile barrier systems, and whether they are designated for single use.
• Biological Characteristics: A clear listing of all material components that come into direct or indirect contact with the human body, an assessment of the biocompatibility data for these materials, and a comparison of the mode and intended duration of contact with human tissues.

Identification and Analysis of Differences

When conducting a meticulous feature-by-feature comparison, it is almost inevitable that some differences will be found between the device under evaluation and the equivalent device(s). All such differences must be transparently identified.

Once differences are identified, an in-depth scientific analysis and justification for each difference to prove that it does not have a clinically significant negative impact on the safety and/or clinical performance of the device must be conducted. Such an analysis requires:

• A clear description of the nature and extent of the difference.
• An explanation, based on scientific principles, engineering assessments, standard requirements, published literature, or specific preclinical studies (such as bench testing, animal studies) of why this difference will not lead to different clinical outcomes (e.g., in efficacy, complication rates, ease of use).
• If the difference involves materials, an assessment of potential impacts on biocompatibility, chemical properties, physical properties, etc.
• If the difference involves design or performance specifications, an assessment of its impact on the device’s ability to perform as intended in the anticipated clinical scenario.

Planning and Presenting the Equivalence Argument in the CEP

In this chapter of the Clinical Evaluation Plan (CEP), you need to clearly articulate the plan and methodology for demonstrating equivalence.

It should begin by explicitly stating which specific, legally marketed device(s) are intended for the equivalence demonstration and briefly outline the primary reasons for their selection.

Next, provide an overview of how the detailed comparison of clinical, technical, and biological characteristics will be conducted. You can mention the planned scope of comparative parameters. The emphasis should be on describing how differences will be systematically identified, and how their clinical significance will be assessed and justified.

The CEP should indicate the data sources required to support the equivalence demonstration. This may include:

• Manufacturer’s internal completed or planned preclinical studies (e.g., bench tests, simulated use tests, animal studies, especially those directly comparing the performance of the device under evaluation against the equivalent device(s)).
• Systematic retrieval and analysis of published scientific literature to obtain information on the characteristics, performance, and safety of the equivalent device(s), as well as the clinical impact of certain technical or material differences.
• Adherence to relevant international standards and guidelines.
• Planned retrieval and analysis of post-market surveillance data, adverse event reports, and clinical study data for the equivalent device(s) (if available).

This chapter should set a clear path for how the demonstrated equivalence will be used in the subsequent Clinical Evaluation Report (CER) to support the clinical safety and performance of the device under evaluation. For example, it should state how clinical data from the equivalent device(s) will be integrated and appraised in the CER.

Tthe demonstration of equivalence is a key area of scrutiny by regulatory authorities. The entire process must be transparent, rigorous, scientific, and fully compliant with relevant regulatory guidance (such as MDCG 2020-5). Any claim of equivalence must be substantiated by robust evidence, and the analysis of differences must be convincing.