The new article describes in detail the regulatory approach to be applied when determining the particular type of submission to be filed concerning the changes in question.
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 modifications to devices subject to premarket approval (PMA). In particular, the document describes the aspects related to the PMA supplement decision-making process. The document is intended to provide additional clarifications regarding the applicable regulatory requirements, as well as recommendations to be followed by medical device manufacturers to ensure compliance thereto. At the same time, provisions of the guidance are non-binding and are not intended to introduce new rules or impose new obligations the parties involved should fulfill. Moreover, the authority explicitly states that an alternative approach could be applied, provided such an approach is in line with existing legislation and has been agreed with the authority in advance.
Submission Type Determination: Key Points
First of all, the authority states that the determination of the submission type should be based on the data related to the changes, as well as the need in demonstrating that the new (modified) product meets the applicable regulatory requirements in terms of safety and effectiveness. To assist medical device manufacturers and other parties involved in making such determination, the authority describes in detail different types of PMA submissions including, inter alia, traditional PMA, a panel-track supplement, a 180-day supplement, a real-time supplement, a Special PMA Supplement – Changes Being Effected, 30-day notice, and manufacturing site change supplement). The authority also highlights the key points to be considered concerning each type of submission, outline the scope of supporting data the authority expects to receive, and also the criteria the FDA will use when determining the admissibility of specific submission. The authority also provides examples of the modifications to medical devices corresponding to each of the submission types described in the document to demonstrate the way the approach described in the guidance should be applied. In particular, the FDA indicates the changes to the device, the expected impact of such changes on the safety and effectiveness of the device, and also the scope of data to be submitted by the party responsible for a medical device to demonstrate compliance with the respective requirements. However, the authority acknowledges that real-world situations could be more complex than the ones described in the examples. Thus, the authority encourages medical device manufacturers to get in touch with the FDA and request additional clarifications to ensure the proper determination of the supplement type. The document provides a step-by-step description of the process to be followed by a medical device manufacturer when determining the appropriate submission type.
According to the guidance, a traditional PMA (not a supplement) should be submitted in case the changes made result in a new device. This means that the procedure of obtaining a premarket approval will start from the very beginning. This happens in cases when the difference between the initial device and the modified one is so significant that the preclinical data related to the initial device is no longer applicable for the modified one, and could not be used to support the claims made by the manufacturer. The above matter determines the approach to be applied – the manufacturer shall, first of all, assess whether the existing preclinical data could be used for a modified one. If new clinical and preclinical testing is required to demonstrate that the modified medical device meets the applicable safety and performance requirements, the entire new PMA should be submitted. To illustrate the situation described hereinabove, the document provides several examples of the changes potentially resulting in a traditional PMA being required. This includes, inter alia, the cases when the modified device has new indications for use or new clinical effects; or – in the case of in vitro diagnostic medical devices – modified analyte and indication/patient population or significant modification of technology the device is based on. In all the above mentioned cases, new preclinical and clinical data will be required to demonstrate compliance with the applicable regulatory requirements in terms of safety and effectiveness – hence, a traditional PMA will be required. This constitutes an entirely new submission, so the modified medical device will undergo the entire registration process as a new product. As explained by the FDA, the changes to the indications for use are significant enough to result in the new data required to assess the product and its compliance with the requirements it should meet.
Concerning the above mentioned, the authority provides the following clarifications:
- In case the difference in the indications for use results in differences in the clinical outcomes, new clinical data will be necessary to ensure the proper risk assessment;
- In case the changes to the design result in changes to the performance of a medical device, the aspects related to safety and effectiveness should be reassessed as well, hence, new preclinical testing will be required, and new clinical data is to be collected;
- If the manufacturer makes changes to the analyte used for an in vitro diagnostic medical device and also changes the intended use population, additional data would be required to assess the performance of a modified device;
- The same approach in case of changes to the technology the product is based on, if this impacts the clinical performance characteristics of the device in question.
In summary, the present FDA guidance highlights the key points to be considered by medical device manufacturers when determining the particular submission type depending on the nature of changes and their impact on the safety and effectiveness of the device. The document describes in detail the situations when the entirely new (traditional) PMA will be required.
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