The new article covers regulatory matters related to non-clinical animal testing and alternatives thereto, as well as clinical performance testing and the approach to be applied when determining whether it is reasonably needed to collect additional data.

The Food and Drug Administration (FDA or the Agency), the US regulating authority in the sphere of healthcare products, has published a draft guidance document dedicated to orthopedic non-spinal bone plates, screws, and washers in the context of 510(k) premarket notification submissions.

Once finalized, the guidance will provide an overview of the applicable regulatory requirements, as well as additional clarifications and recommendations to be taken into consideration by medical device manufacturers and other parties involved in order to ensure compliance therewith.

At the same time, provisions of the guidance are non-binding in their legal nature, and they are not 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 applicable legislation and has been agreed upon with the authority in advance.

The scope of the guidance covers, inter alia, aspects related to non-clinical animal and clinical performance testing.

Regulatory Background

As a general rule, non-clinical animal studies are not required for bone plates and screws. At the same time, this type of testing could still be necessary in certain cases, namely:

  • Indications for use dissimilar from legally marketed devices of the same type;
  • New technology, i.e., technology different from that used in legally marketed devices of the same type (e.g., dynamic or flexible fixation systems that differ in stiffness or strength from other predicates), yet does not raise different questions of safety or effectiveness; or
  • Cases where engineering and/or animal testing raise issues that warrant further evaluation with clinical evidence. 

The authority also encourages the wider use of the Q-Submissions Program, which allows medical device manufacturers to request additional feedback and comments from the authority before submitting the initial application. In this particular case, the program could be used to discuss safety concerns related to the animal study protocol.

The authority also mentions that the Good Laboratory Practice (GLP) regulation should be followed when conducting animal studies intended to assess the safety of the product. Apart from that, the Q-Submission framework could be used to discuss the application of another non-animal testing method that the manufacturer believes is appropriate for the specific case.

The authority would review such a request and determine whether the use of an alternative method could be a proper replacement for animal testing in terms of the evidence to be generated. In this respect, the authority refers to a separate guidance document dedicated to the Q-Submission Program for further guidance on specific steps to be taken and aspects to be considered. 

Specific Aspects

As further explained by the authority, any alternatives suggested by the manufacturer should be supported by a proper scientific rationale. It should also be taken into account that the authority considers the products covered by the scope of the present guidance to be significant risk devices subject to the respective regulatory requirements and level of regulatory scrutiny. In this respect, the parties responsible for medical devices and clinical studies associated therewith should take into account provisions of a separate guidance document dedicated to significant risk and nonsignificant risk medical device studies published by the authority 

The authority also mentions that, under the general rule, the data from clinical investigations taking place in foreign countries could be accepted, subject to compliance with the respective provisions of the applicable regulations and ensuring the necessary conditions are met. In this respect, the authority refers to a guidance document titled “Acceptance of Clinical Data to Support Medical Device Applications and Submission: Frequently Asked Questions”. 

According to the guidance, in some cases, “real-world data” (RWD) may be used to support the expansion of indications, changes in surgical technique, or changes in design/prominence for a device for which 510(k) clearance has already been obtained. As explained by the authority, the need for real-world data to be collected will be determined on a case-by-case basis depending on the numerous factors related to the product in question, its intended use, and the risks associated therewith. In particular, if the product in question is currently in use in the course of normal medical practice, an Investigational Device Exemption would not be required. In this respect, the authority refers to a separate guidance document dedicated to the matter named “Use of Real-World Evidence to Support Regulatory Decision-Making for Medical Devices”. 

In summary, the present FDA draft guidance addresses aspects related to non-clinical animal and clinical performance testing to be conducted in order to collect additional data supporting the claims made by the medical device manufacturer when applying for marketing approval. The document explains the approach to be applied, should the manufacturer decide to apply alternative methods instead of animal non-clinical testing – according to the guidance, the use of such methods should be properly justified. The guidance also describes the approach to be applied when determining whether a clinical investigation is required to collect additional data for evidence supporting the claims.

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