The new article describes in detail the matters related to the evaluation of substantial equivalence under the 510(k) premarket notification framework. In particular, the article describes the aspects related to predicate devices – similar medical devices already placed on the market.
As it was mentioned before, medical device manufacturers may refer to the substantial equivalence of their products to similar medical devices already placed on the market and allowed for use in the US to demonstrate compliance with the applicable regulatory requirements. Such an approach significantly reduces the regulatory burden imposed on medical device manufacturers and accelerates the process of placing new medical devices on the market while ensuring their safety and effectiveness. According to the applicable legislation, a predicate device is the one that is already placed on the market and is:
- Not subject to the PMA framework; or
- Has been reclassified from Class III to Class II or I; or
- Has been found SE [substantially equivalent] through the 510(k) process.
The authority further explains that to follow this approach, it would be sufficient to indicate at least one predicate device, while multiple medical devices could be identified as well. However, the Agency recommends making references to only one device to simplify the procedures and streamline the process. Should the manufacturer decide to make references to multiple predicate devices, it would be necessary to indicate the primary predicate which is the one that is the most similar to the medical device in question.
According to the applicable legislation, for a new device to be considered substantially equivalent to a predicate device, the new device must have the same intended use as the predicate device and the same technological characteristics or different technological characteristics that do not raise different questions of safety and effectiveness than the predicate device. The Agency states that when making references to predicates, medical device manufacturers are not allowed to “split predicate” – make references related to the intended use to one predicate, and references related to the technology – to another one since it is important to ensure that all the points are addressed about the same predicate. At the same time, the authority may also consider references to additional devices as suggested by the applicant, should it be reasonably necessary.
The document further describes in detail the approach to be applied in case the manufacturer will decide to make references to multiple predicate devices when demonstrating substantial equivalence. The guidance also provides some examples of the ways such an approach could be applied. The authority explicitly states that even in the case of multiple predicates used, each feature or characteristic should meet at least one of the predicates.
The cases described in the examples provided by the FDA include, inter alia, the following ones:
- A single medical device is to be marketed for multiple uses, hence, references are made to multiple predicate devices having different intended use and indications for use.
- The indications for use for the predicate devices are different, however, they are falling within the scope of the general intended use. In such a case, the new device is found substantially equivalent to the predicate devices because it has the same intended use and the new device’s technological characteristics are similar to the cited predicates.
Previous experience should be always considered when placing new products on the market under the 510(k) premarket notification framework. In this regard, the document distinguishes “predicate devices” and “reference devices”. The latter stands for medical devices already placed on the market, which could be used to support scientific methodology or standard reference values. At the same time, the authority explicitly states that reference devices should not be considered predicate devices. Hence, medical device manufacturers should not use them when demonstrating substantial equivalence for the 510(k) framework. Moreover, the Agency will evaluate the applicability of reference devices on a case-by-case basis. For instance, it is stated that if a selected reference device is used in an anatomical location or for a physiological purpose that is considerably different than that of the new device, its utility as a reference device may be limited. Should the manufacturer decide to use a reference device, the appropriate justification should be duly provided. This approach is further described in several examples provided in the guidance.
Lack of Predicate Device
The document also describes the approach to be applied in case there is no similar device already placed on the market, which could potentially be used to establish a substantial equivalence and demonstrate compliance with the applicable regulatory requirements. As explained by the FDA, if a predicate device with the same intended use cannot be identified, or if the new device’s different technological characteristics raise different questions of safety or effectiveness, a manufacturer may submit a De Novo request, either after receipt of an NSE letter or directly requesting classification through the De Novo process. Depending on the risks associated with the device in question, a PMA framework could be applicable.
Identification and Documentation of the Predicate(s)
As it was mentioned before, the manufacturer making references to predicate devices should indicate the primary predicate device, even though the references to multiple predicate devices are allowed. Thus, the substantial equivalence would be determined about the primary predicate device. This would be also considered when assessing documentation submitted by the applicant. In case of making references to multiple predicates, the manufacturer should identify each of them and justify the approach applied. The number of predicates should be reasonable due to the specific nature of medical devices subject to review.
In summary, the present FDA guidance describes the approach to be applied by medical device manufacturers when making references to similar medical devices already placed on the market to establish substantial equivalence and demonstrate compliance with the applicable regulatory requirements. The document highlights the most important aspects to be taken into consideration and also provides additional clarifications regarding some specific matters, such as making references to multiple predicates.
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