The Food and Drug Administration (FDA) has developed a guidance document dedicated to the benefit-risk factors to be considered when determining substantial equivalence in premarket notifications (510(k)) with different technological characteristics. The document is intended to provide additional clarifications and recommendations for industry representatives and other parties involved in operations with medical devices.

 It is important to mention that due to its legal nature, the document does not introduce any regulatory requirements to be followed but describes the suggested approach. An alternative approach could also be applied, providing that such an approach complies with the relevant legislation and is approved by the regulating authority in advance. The present guidance constitutes a final version of the document initially issued earlier in July 2014. 

Regulatory Background 

According to the general rule, when submitting a premarket notification submission (510(k)), the medical device manufacturer shall demonstrate that the medical device in question is “substantially equivalent” (SE) to another medical device already approved and placed on the market. 

The present document is intended to describe in detail the particular approach to be applied to demonstrate such equivalence. The Agency additionally emphasizes that the guidance does not affect the review process or standards. It was initially developed by the FDA to improve the predictability of the review process and make it more transparent. The document describes the approach to be applied when evaluating the benefit-risk profile of a new medical device in comparison to an existing one – the predicate device. 

However, it is stated that it is not necessary for the benefit-risk profile of the medical device in question to be identical to the existing device in order for the substantial equivalence concept to be applicable. The present guidance describes the cases when the benefit-risk profiles of medical devices are different and outlines the approach to be applied. 

In particular, the Agency has developed the present guidance to address the cases when:

1. The risks associated with the new device are higher, or

2. The benefits associated with the new device are lower. 

According to the document, should any of the situations mentioned above occur, both risks and benefits should be compared separately in order to evaluate the substantial equivalence of a new medical device.

Statutory Standard for Substantial Equivalence

As was mentioned before, an interested party submitting the 510(k) premarket notification submission shall demonstrate that the new medical device subject to review is substantially equivalent to the existing medical device already placed on the market. The same rule applies in the case of modification to the existing medical device, providing that such modification requires a new 510(k) premarket notification submission. 

According to the document, the concept of a substantial equivalence means that the medical device in question has the same intended use as the predicate device and:

  •  Has the same technological characteristics as the predicate device, or
  • Has different technological characteristics, but the information submitted shows that the device is substantially equivalent to the predicate device. Submitted information includes appropriate clinical or scientific data if deemed necessary by the Secretary or a person accredited under section 523, that demonstrates that the device is as safe and effective as a legally marketed device and does not raise different questions of safety and effectiveness than the predicate device. 

Hence, in order to determine whether the medical device in question constitutes a substantial equivalent to the existing one, the Agency starts with the intended purpose of the device. Later the FDA shall evaluate the technological characteristics in order to determine whether they are the same for both devices subject to review or not. During this process, the regulating authorities also evaluate whether the new medical device is as safe and effective as the one already placed on the market. 

The document also provides additional clarifications with regard to the term “different technological characteristics” used in the context of the evaluation of substantial equivalence. According to the applicable regulation, this refers to the significant changes in the design of the medical device, the materials it is comprised of, the source of energy used, or other important features of the new device that differ significantly from the ones of the predicate device. 

The Agency states that if it identifies significant differences in technological characteristics of the medical devices subject to review, and if these differences result in additional questions related to the safety and effectiveness of a new medical device, the latter would be found as not significantly equivalent. At the same time, if the differences identified do not result in the aforementioned questions, such differences would be rigorously evaluated by the FDA in order to assess their actual impact on the safety and effectiveness of a new medical device. The same approach will be applied in case of modification to the FDA-cleared device. 

In accordance with the applicable legislation, each time determining the safety and effectiveness of a medical device, the Agency is weighing any probable benefit to health from the use of the device against any probable risk of injury or illness from such use, as well as any other important factors to be considered. The FDA also states that the approach described in the present document is in line with the applicable regulatory requirements for the 510(k) Program in general. 


Performance Data Evaluation 

As it is stated in the present FDA guidance, an interested party may submit the performance data in order to demonstrate that the new medical device is as safe and effective as the one already placed on the market. The particular scope of information to be submitted depends on the medical device itself. The necessary scientific evidence could be generated from both non-clinical and clinical performance data. The aforementioned data would be subject to review by the FDA in the course of the premarket review process. 

According to the document, non-clinical testing covers such aspects as:

  • Product safety,
  • Reliability, 
  • Characterization,
  • Human factors,
  • Usability,
  • Mechanical testing under simulated conditions,
  • Animal studies,
  • Cell-based studies, and 
  • Computer simulation. 

The aforementioned testing should be conducted in order to evaluate various characteristics of a medical device. 

The Agency also mentions that clinical data is not usually included in 510(k) premarket notification submission in order to demonstrate substantial equivalence. At the same time, in certain cases, the scientific evidence related to the device could include the data deriving from randomized clinical trials. 

In Summary, the present FDA guidance describes in detail the aspects associated with the evaluation of the benefit-risk profile of medical devices in the context of substantial equivalence. The document outlines the approach to be applied in case if the risks and benefits associated with the new medical device and the existing one are different.

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