The new article highlights the aspects related to the documenting requirements, as well as to the concept of an instrument family and the way it should be applied in the context of using an assay with an instrument from a different family.

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 to be marketed and used in the country. The approach described in the guidance is intended to expand the availability of medical devices addressing the needs of healthcare professionals and patients. It is important to mention that guidance documents issued by FDA are non-binding in their legal nature, nor are intended to introduce new rules or impose new obligations, but rather to provide additional clarifications regarding the existing regulatory framework, as well as recommendations to be taken into consideration by medical device manufacturers and other parties involved in order to ensure compliance thereto. Moreover, the authority explicitly states that an alternative approach could be applied, provided such an approach is in line with the existing legislation and has been agreed with the authority in advance.

Replacement Reagent Policy: Documentation

The guidance describes in detail the approach to be applied in the context of the reagent replacement. This includes, inter alia, the matters related to documentation to be submitted by the parties responsible for medical devices.

In accordance with the applicable legislation, among other requirements, FDA’s quality system regulation (QS regulation) requires manufacturers of finished devices to review and approve changes to device design and production (21 CFR 820.30 and 820.70) and to document changes and approvals in the device master record (21 CFR 820.181). The authority further explains that the documentation in question should be dated and signed by the responsible individual(s); while the medical device manufacturer should duly keep the relevant records and make them available to the authority upon request. It is also important to mention that documentation should include a comparison between the old and new assay-instrument combination, risk-based assessment, detailed protocols, acceptance criteria, and results. Should the medical device manufacturer determine that some of the abovementioned aspects are not applicable, the appropriate justification should be duly documented as well.

Instrument Family Policy

The scope of the guidance also covers the aspects related to the Instrument Family Policy – the one that applies to modifications made to an instrument by its original manufacturer, to produce a new version of the instrument (i.e., a new instrument family member). Under the general rule, all the instruments within an instrument family are the same in terms of hardware and software components. For the purpose of guidance, an instrument family stands for a group of one or more instruments produced by, or for, the same manufacturer, having the same general architecture, design, tolerance limits, and capabilities, such as detection methods, signal range, and intensity, and reaction conditions. At the same time, an instrument family could cover similar instruments with certain changes and improvements, however, all covered by the same classification rule and product code. At the same time, if decided by the manufacturer, separate design history files could be used for each of the instruments included in a family instead of having a single design history file covering them all. Irrespective of the approach applied, the information to be covered by the design history file should demonstrate that each instrument can be considered an instrument family member (as defined above), rather than an instrument that is not an instrument family member. 

As further explained by the FDA, the medical device manufacturer would also have to conduct the appropriate testing in order to validate the actual performance of a new product and confirm its compliance with any and all applicable regulatory requirements, as well as product specifications applicable to the respective instrument family. The documentation demonstrating compliance with the above should be duly kept by the manufacturer and provided to the authority upon request. The scope of information should cover the details of similarities and differences in terms of technologies used. 

When deciding on the application of an assay to a different instrument family, an assay manufacturer should first determine whether a new 510(k) is needed due to the significance of the impact this will have on the actual performance. In order to be eligible for placement on the market without a new application being submitted, the new combination should be similar to the existing ones in terms of performance. 

For instance, in certain cases, it could be determined that the application of an assay to a different instrument family will not require a new set of tests to be conducted in addition to the ones carried out when initially applying for marketing approval. The document provides an example of changes related to post-analytic data storage – such changes will not require new testing to be conducted as they are not expected to impact the actual performance of the device. In order for such an assessment to be precise and reliable, in-depth knowledge of the specific instrument family is required since the risk-based approach is to be applied when making the final determination. The authority also mentions that in case an instrument family in question is comprised of multiple instruments, the ones that are most relevant should be used for comparison.

In summary, the present FDA guidance describes the documentation the authority expects to be collected and maintained with respect to the changes, as well as the approach to be applied when applying an assay to a different instrument family. With regard to the latter, the document highlights the key points to be taken into consideration by medical device manufacturers in order to ensure the proper performance and effectiveness of the products allowed for marketing and use.

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