The new article describes in detail specific aspects to be considered for clinical evidence to be submitted for patient-matched medical devices. 

The Therapeutic Goods Administration (TGA), an Australian regulatory agency in the sphere of healthcare products, has published a guidance document dedicated to clinical evidence for medical devices. In particular, the document outlines the scope of clinical data and information the authority expects to receive from a party applying for marketing approval for a medical device intended to be marketed and used in the country. The guidance provides additional clarifications regarding the applicable regulatory requirements, as well as recommendations to be taken into consideration to ensure compliance thereto. At the same time, provisions of the guidance are non-binding, and could be subject to changes, should it be reasonably necessary to reflect the respective changes to the underlying legislation. The present revision of the guidance provides device-specific recommendations related to patient-matched medical devices, as they were missing in previous versions. 

The authority provides an overview of the general regulatory requirements related to patient-matched devices and also highlights the key points to be taken into consideration due to the specifics of such products, and the way they are designed, manufactured, and intended to be used. 


Generalizability of Devices Within the Design Envelope 

As it was mentioned in the previous article, the authority pays special attention to the concept of a design envelope, which stands for a set of technical requirements and specifications the patient-matched device should comply with to meet the needs of a specific patient. Apart from this, the authority further explains the approach to be applied when assessing the clinical data deriving from the use of patient-matched devices. In particular, it is stated that an expert should be engaged to determine whether such data could be used to assess the safety and performance of all the devices based on the same design envelope. This assessment should cover, inter alia, the analysis of the impact that could potentially be caused by certain differences that exist due to the specific nature of such products. The said expert should provide comments regarding the risks arising in worst-case and common-use scenarios using the approach below:

  • Worst-case scenario(s): identified devices with the highest risk features within the design envelope (more than one may exist for patient-matched medical devices within a specified design envelope);
  • Common-use scenario(s): identified devices within the design envelope with the most frequently used design parameters; when defining common-use scenario(s), it may be useful to consider anthropometric differences (e.g., sex, age, ethnicity), as common-use scenario(s) may vary between sub-populations. 

Hence, when using clinical data to substantiate the claims and statements regarding the safety and effectiveness of a patient-matched medical device made by the manufacturer, it is important to ensure it is representative of the devices it is used for. In certain cases, it makes sense to use different data sets for each scenario, while in case the same data is used, the appropriate justification should be provided. 


Substantial Equivalence 

Another important aspect addressed in the guidance relates to substantial equivalence – an approach when the manufacturer demonstrates compliance with the applicable safety- and performance-related requirements by demonstrating substantial equivalence to a similar medical device already placed on the market. The said approach allows reducing significantly the regulatory burden for all the parties involved, however, its applicability depends significantly on the actual similarity of the products in question in terms of clinical, technical, and biological characteristics, as well as the manufacturing process. In this respect, the manufacturer should analyze the differences and assess the way they may potentially impact the safety and/or effectiveness of a new device. The authority additionally emphasizes that in case claims of substantial equivalence are made with a device that is either a non-PMD or has a different design envelope, there should be a reasoned argument provided as to why the clinical evidence for the claimed equivalent device can be applied to the entire design envelope (or if this is not claimed, what subset of the design envelope the data is relevant to). In this situation, worst-case and common-use scenarios should be considered as well. 

The TGA further states that the above approach could be only one of the elements of the overall strategy for use of clinical evidence, as anyway direct clinical evidence is needed to address the device-specific risks, and also to make sure the changes would not adversely affect the safety and effectiveness of the device. 


Clinical Investigation 

The scope of the guidance also covers the aspects related to clinical investigation and the way it should be designed to ensure the accuracy and reliability of the results. In this respect, the authority mentions that a key challenge in the design of clinical investigation for PMDs is that the PMD device intervention will be heterogeneous with regards to several of its parameters (compared to non-PMD studies where features such as materials, structure, and dimensions are either constant or subject to minor variations). Hence, it is important to ensure the comparability of subjects. 

However, even in the light of the above complications that could potentially affect the reliability of the study results, the authority finds it more appropriate to conduct a clinical investigation to collect additional clinical data rather than apply for marketing approval without having sufficient data in place. Moreover, in the case of high-risk medical devices, or the ones for which there is no sufficient clinical data, an additional investigation is a must. 

In summary, the present TGA guidance describes in detail the approach to be applied by medical device manufacturers when determining the scope of clinical evidence required to support the application for marketing approval. The document also pays attention to the specific aspects to be considered to ensure the accuracy and reliability of such data. 


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