The new article highlights the aspects related to the risk assessment to be duly performed by a medical device manufacturer in order to identify new risks arising in connection to modifications suggested.

The Food and Drug Administration (FDA or the Agency), the US regulating authority in the sphere of healthcare products, has published a guidance document dedicated to the replacement reagent and instrument family policy for in vitro diagnostic (IVD) medical devices allowed for marketing and use in the country. The guidance is intended to provide additional clarifications regarding the existing regulatory framework, as well as recommendations to be considered by medical device manufacturers and other parties involved in order to ensure compliance thereto. At the same time, provisions of the guidance are non-binding in their legal nature, nor are intended to introduce new rules or impose new obligations. Moreover, the authority explicitly states that an alternative approach could be applied, provided such an approach is in line with the underlying legislation and has been agreed with the authority in advance.

Risk-Based Assessment: Key Points

Under the general rule, the manufacturer of an assay is responsible for conducting a risk-based assessment for any modified test system. As further explained by the FDA, the risk-based assessment should address analytical and clinical performance, indications for use, and any other factors that could affect the risk profile of the IVD; when the risk-based assessment indicates that the performance of the modified test system could significantly change relative to the performance characteristics of the cleared test system, including performance claims in the labeling, a new 510(k) is likely required. Thus, in the course of such an assessment, a medical device manufacturer should identify the risks and changes thereto. In this respect, the authority refers to a separate guidance document dedicated to changes to existing medical devices and 510(k) submissions associated thereto in the part of determining whether the new submission is required. 

According to the guidance, changes to test system performance characteristics (e.g., precision, linearity or recovery, interference, assay traceability, detection limits, bias, or scatter observed in method comparison) from those indicated in the labeling for the cleared test system could have the potential to be significant and change the clinical performance of the device. As further explained by the authority, significant changes are that ones that could impact significantly the interpretation of test results provided by the system of the subsequent decision-making process. For instance, should the changes be expected to impact the intended use population due to the performance changes, such changes would most likely require a new submission for marketing approval. 

It is also stated that when conducting a risk-based assessment as described herein, medical device manufacturers should consider the instructions for use accompanying the initial device, as well as the clinical and performance needs associated thereto. Apart from that, they should also take into consideration susceptibility to change in the specific assay technology. For instance, special attention will be required in case of changes related to modifications to reaction conditions. As it was mentioned before, should the changes be considered significant, a new 510(k) submission would most probably be required in order to demonstrate compliance of a modified product with the applicable safety and performance requirements. 

The authority also mentions that in performing the risk-based assessment of the changed test system, manufacturers should consider whether a modification could cause possible effects that would lead a risk-based assessment to identify new risks or significantly modify existing risks that could significantly affect the safety or effectiveness of the device and thus a submission of a new 510(k) would likely be required. 

In accordance with the recommendations provided by the authority, should no new risks be identified by a medical device manufacturer in the course of a risk assessment described herein, additional testing will anyway be required in order to verify the initial assessment.

POC Test Systems: Specific Aspects

The document also pays additional attention to POC test systems and specific aspects associated thereto due to their intended use and use environment. First of all, the authority mentions that in most cases these systems are not intended to be used with additional instruments (i.e., are not considered open), while the policy described herein applies only to open ones. At the same time, in certain cases, its provisions could still apply, provided the assay and instrument are manufactured by the same manufacturer as the original ones, with the additional instruments being closely related family members. The authority additionally emphasizes that the recommendations provided in the guidance document on changes to existing medical devices should also be followed. Furthermore, it is stated that neither of the documents is exhaustive in terms of aspects that are specific to POC test systems, so the authority encourages medical device manufacturers to get in touch and request case-specific advice in advance, before submitting an application or taking any other action. 

To illustrate the applicable approach, the authority provides an example of a change to the exterior of an instrument – according to the document, such a change will not be considered significant, as long as it does not affect reaction conditions or usability of the device in question. 

Apart from the above, the authority mentions that POC test systems may present a higher likelihood of pre-analytical and use error than non-POC test systems, challenges related to the types of multi-tasking common to the POC environment, and challenges due to varying environmental conditions (e.g., temperature, movement, or vibrations). Hence, the risk assessment to be performed by a medical device manufacturer with respect to a POC test system should cover, inter alia, the aspects related to the risk of the impact of changes in user workflow.

In summary, the present FDA guidance provides an overview of the regulatory requirements to be followed with respect to a risk assessment to be performed in order to assess the impact planned modifications could have on the safety and effectiveness of a medical device. The document highlights the key points to be considered by a medical device manufacturer and explains the approach to be applied.

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