The new article highlights the key points related to the clinical evidence for heart valve replacements using a prosthetic valve.

The Therapeutic Good Administration (TGA), an Australian regulating authority in the sphere of healthcare products, has published a guidance document dedicated to the clinical evidence for different types of medical devices. The document provides additional clarifications regarding the existing regulatory framework, as well as recommendations to be considered to ensure compliance thereto. However, provisions of the guidance are non-binding, nor are intended to introduce new rules or impose new obligations, and could be subject to changes, should such changes be reasonably necessary to reflect corresponding changes to the underlying regulations. The scope of the guidance covers, inter alia, the aspects related to the clinical evidence for heart valve replacements using a prosthetic valve conducted to address the native valvular disease or to replace a prosthetic valve in case of its malfunctions. 


Recommendations in Brief

First of all, the document provides a summary of recommendations to be considered by medical device manufacturers and other parties involved to ensure compliance with the applicable regulatory requirements. 

According to the document, prosthetic heart valves are complex medical devices that are currently made of either synthetic material (mechanical valves) or biological tissues (bioprosthesis), or a combination of both and inserted via open surgery or percutaneously. The existing regulatory framework requires medical device manufacturers to provide clinical evidence substantiating the claims made concerning their safety and performance. It is important to mention that such evidence should cover the aspects related to both devices themselves and accessories associated thereto – i.e., the one’s intent ended to deliver the device. 

Concerning clinical investigation data, the authority outlines the following key points: 

  • The clinical trials intended to collect additional clinical data should be designed by the highest practical NHMRC level of evidence, while the scope of such a trial should duly address all the important matters in terms of the safety and effectiveness of the product in question.
  • The term of a trial should be determined depending on the period of the follow-up, which should be at least one year for the minimum number of patients. 
  • The evaluation of the devices in question should be based on the Objective Performance Criteria (OPC) as set forth by the applicable standard (ISO 5840) with the following reporting periods: (i) within 30 days post-implantation, (ii) after 30 days post-implantation, and (iii) one year. 

The authority also mentions that the pre-clinical and clinical data used by the manufacturer should be consistent with the intended purposes of the medical device in question and the way it should operate. Apart from this, the authority expects medical device manufacturers to provide details regarding biocompatibility. 

In certain cases, clinical data from comparable devices will be admissible, however, it should be accompanied by the appropriate justification provided by the clinical expert, referring to a substantial equivalence between both products described. 

In case a comprehensive literature review is used to collect additional data substantiating the claims, it is necessary to provide all the details allowing to replicate the search, e.g., the search strategy, inclusion/exclusion criteria, as well as the approach applied to conduct the analysis. 

Apart from the above, the authority also expects medical device manufacturers to provide a duly documented risk analysis and management system based on all the elements described herein (the clinical investigation data, literature review, and post-market clinical experience). In this respect, the authority mentions that all clinical risks identified in the clinical data should be reflected in the risk assessment documentation; these risks should be appropriately rated and quantified and ideally be presented as risk matrices, before assigning risk reduction activities such as statements in the IFU and training materials to reduce residual risk. 

The manufacturers are also expected to provide information regarding the clinical context in which the clinical data was initially collected, which should also be consistent with the indications for use. 

The document also covers the aspects related to the compilation of clinical evidence. In this respect, the authority mentions that the clinical data related to prosthetic heart valve products should be evaluated by a competent clinical expert. Furthermore, the said expert should also endorse the CER to demonstrate that the evidence provided is sufficient in terms of the applicable Essential Principles for Safety and Effectiveness. It is also stated that the CV of an expert involved should be submitted. 

Terms and Definitions 

The authority also provides the definitions to be applied when determining the scope of medical devices covered by the scope of the guidance. In particular, the document outlines the types of prosthetic heart valve products subject to recommendations provided therein and highlights the key points to be considered concerning specific risks associated thereto. According to the guidance, there are three main types of prosthetic heart valves: mechanical, biological, and valves that combine mechanical and biological components (using hybrid valve technology). The authority further describes in detail the characteristics of the abovementioned device types. As explained by the TGA, the main designs of mechanical (synthetic) valves include:

  • The caged ball valve, 
  • The tilting disc (single leaflet) valve, and 
  • The bileaflet valve. 

In summary, the present TGA guidance provides an overview of the existing regulatory framework for prosthetic heart valve products. By the virtue of the document, the authority describes the main considerations related to clinical evidence for such products in terms of the scope of clinical data the authority expects to be provided when applying for marketing approval. 



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