The present article describes in detail the way the least burdensome approach should be applied. In particular, it explains the ideas behind the concept of the minimum information necessary.
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 least burdensome approach. The document outlines the key concept and principles related to the least burdensome provisions introduced to facilitate the regulatory procedures and reduce the unneeded regulatory burden medical device manufacturers and other parties involved in operations with medical devices could face. The guidance is non-binding in its legal nature and is not intended to introduce new rules or impose new obligations, but rather to provide additional clarifications regarding the existing regulatory requirements, as well as recommendations to be followed 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 current legislation and has been agreed with the authority in advance.
Less Burdensome Sources of Clinical Data
Under the general rule, the safety and effectiveness of a medical device intended to be marketed and used in the US should be confirmed by the respective scientific data. As further explained by the authority, it bases its safety and effectiveness determinations on several factors, including, among others, intended use, conditions of use, probable benefits weighed against any probable risks, and the reliability of the device. It is also stated that the evidence to be provided depends on the specifics of the medical device in question and the way it is intended to be used, as well as the experience and information related to its use. Thus, alternative sources of clinical data could be taken into consideration as well. Such sources can include, inter alia, the data collected outside the US, results of literature review, real-world evidence (RWE), and also the case histories, provided they are duly documented. The above mentioned sources could be used in the context of demonstrating safety, the effectiveness of a medical device, and compliance with the applicable regulatory requirements. At the same time, the authority additionally emphasizes that isolated case reports, random experience, reports lacking sufficient details to permit scientific evaluation, and unsubstantiated opinions are not regarded as valid scientific evidence (even though such information could be taken into consideration when assessing the safety- and effectiveness-related matters in case there are concerns associated thereto).
Use of Nonclinical Data
According to the guidance, nonclinical data states for the one collected in the course of medical device development and may include, inter alia, the use of benchtop models, nonclinical literature, use of tissue phantoms, or computer modeling and simulations based on recognized standards. In certain cases, such nonclinical data could be of importance and used instead or together with the clinical data. As further explained by the FDA, nonclinical data could be used as the initial source of information about the safety and performance of the medical device in question, while clinical data is to be requested to address specific aspects that could not be evaluated using nonclinical data only.
When reviewing applications for marketing approval, the authority often identifies the need for additional information to be able to decide on whether the product in question should be allowed for marketing and use in the country or not. In such cases, the authority will require the applicant to provide additional descriptive information and nonclinical or clinical performance data. When sending these requests, the authority will follow the least burdensome approach by ensuring that the information and data requested are reasonably necessary to complete the review. According to the Deficiencies Guidance, in these requests, the authority should:
- Acknowledge information submitted;
- Explain why it is not adequate to address the issue;
- Explain the relevance of the request to the marketing submission decision; and
- Explicitly request information.
Such an approach should be applied, inter alia, concerning 510(k) submissions. When reviewing such submissions, the authority should assess the information provided first. Usually, clinical data is to be requested in cases when descriptive information and nonclinical data provided to the FDA are not sufficient to assess all the important matters related to the safety and effectiveness of a medical device subject to review. In this respect, the authority also refers to the guidance document The 510(k) Program: Evaluating Substantial Equivalence in Premarket Notifications.
Acceptance of Alternative Approaches
As it was mentioned before, alternative approaches could be also considered, provided their application is reasonable in terms of reduction of the regulatory burden while ensuring all the important safety- and performance-related aspects are duly addressed.
For instance, such an approach is often applied in case of a premarket review of a novel medical device – in this case, both the authority and the applicant should be flexible in determining the approaches to be applied. For example, they may agree to use justifications instead of additional data.
The document further explains the way the least burdensome approach could be applied in terms of biocompatibility-related matters.
Another application of alternative approaches relates to labeling. Under the general rule, when applying for marketing approval, the interested party (the applicant) should provide the samples of labeling to be used for the device when placed on the market including the indications for use (IFU). The least burdensome approach provides that if a labeling statement or proposed IFU is not supported by the submitted evidence and would otherwise result in an adverse decision, such as a not substantially equivalent determination for a 510(k), FDA staff and industry should discuss both (1) a labeling statement or an IFU, if any, that can be supported by the information submitted to FDA, and (2) the minimum information that would support the sought-after labeling statement or IFU.
In summary, the present FDA guidance describes the way the least burdensome approach could be applied concerning information and data used to substantiate the claims made by the medical device manufacturer and demonstrate compliance with the applicable regulatory requirements. The document provides additional clarifications regarding the use of various sources of data and explains the way the regulatory burden associated thereto could be reduced while ensuring the safety and effectiveness of medical devices.
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