WHAT IS?
The preclinical evaluation of a medical device is an analysis and collection of documentary evidence to demonstrate, through sufficient scientific evidence, its preclinical safety and efficacy.
The scientific evidence on which the preclinical evaluation of a medical device must be based can be gathered by systematically reviewing existing scientific preclinical literature or generated by performing preclinical tests (in silico, in vitro, ex vivo and in vivo) on the device in scope.
WHAT IS IT FOR?
Preclinical evaluation aims to verify and prove the safety of a medical device, in terms of biocompatibility and toxicological risk, and its preclinical performance and efficacy, including the definition of the mechanism of action by which the device achieves its intended use.
In addition, the preclinical evaluation allows the manufacturer to demonstrate that its medical device complies with and meets the general safety and performance requirements relating to design and manufacture (Annex I, Chapter II of Regulation 2017/745).
WHERE TO START FROM?
Having established what the preclinical evaluation of a device is and what it is for, let us try to understand where the manufacturer must start to proceed.
Preclinical safety assessment
The preclinical safety assessment or biological evaluation, regardless of the type and risk class of the medical device, must start from its categorization. Medical devices shall be categorized according to the nature and duration of body contact. Clearly, these characteristics are established according to the intended use.
Based on this categorization, the manufacturer shall establish the endpoints to be addressed in a biological risk assessment. The correlation between device categorization and the endpoints can be found in the ISO 10993-1.
Once the biological safety endpoints to be addressed have been defined, the manufacturer may use data from the scientific literature, where available, or data obtained from laboratory tests to confirm the biological safety of his medical device.
Finally, the manufacturer shall verify the medical device biological safety throughout its entire life cycle, and therefore from the design and development phases, to those of manufacture, storage, transport and use.
For further information: Preclinical evaluation of a medical device. Focus on Substance-based devices
Assessment of preclinical efficacy
According to Article 2(1) of the MDR, a medical device does not achieve its principal intended action by pharmacological, immunological or metabolic (FIM) means, in or on the human body, but which may be assisted in its function by such means.
This means that the main mechanism of action of a medical device must be based on physical, mechanical or chemical means, e.g. physical barrier action with the creation of a protective film, lubrication, heat transfer, ultrasound, etc.
In order to proceed with the medical device preclinical efficacy evaluation and with the demonstration of its mechanism of action, it is useful to start by considering its intended use, posology (where applicable), the site of application, and the clinical condition to be treated. At this point, the product characteristics responsible for its preclinical efficacy, performance and mechanism of action shall be analysed.
For example, in the case of substance-based medical devices, the starting point for the assessment of pre-clinical efficacy is the characterisation of their qualitative and quantitative formulation, assigning a specific function to each of the individual ingredients. Indeed, the device’s mechanism of action and preclinical efficacy depend on the type and quantity of each ingredient.
The function of each ingredient shall be demonstrated by literature screening, if available, or in vitro tests.
Finally, the manufacturer shall demonstrate the mechanism of action and preclinical efficacy of the medical device in its entirety, considering possible synergies of action between two or more ingredients. If literature data are not sufficient, in vitro tests shall be performed.
The tests that can be conducted either demonstrate the mechanism of action and efficacy, such as a barrier efficacy test, or exclude FIM-type activity, such as a test to verify the absence of anti-inflammatory properties.
For further information: The preclinical characterization of the formulation of a substance-based medical device: a case report
In the case of preclinical efficacy evaluation, no technical reference standard is available. However, there is a wide range of in vitro tests and cellular models that can be used for the design and execution of ad hoc tests, able of reproduce the medical device conditions of use and the designated target area, resulting in robust and representative outcomes.
PRINEOS, a Strategic Consulting Company for Medical Devices and Pharma, bases its customers' satisfaction on the high quality of the services provided. Conducting a precise and comprehensive preclinical evaluation is of fundamental importance; therefore, PRINEOS assist and supports Manufacturers in drafting the documents and defining the most effective approach to demonstrate the safety and the preclinical efficacy of medical devices.