MD: the role of pre-clinical data in technical documentation (MDR & ISO 13485 :2016)

Medical devices shall achieve the performance intended by their manufacturer and shall be designed and manufactured in such a way that, during normal conditions of use, they are suitable for their intended purpose.

Pre-clinical data allow to document regulatory and normative requirements of medical devices, such as:

• Regulation (EU) 2017/745 “MDR”
• Annex I: General Safety and Performance Requirements (GSPRs)
• ISO 13485 :2016 (Medical devices — Quality management systems — Requirements for regulatory purposes)
  • Chapter 7.3.6 – Design and development verification
  • Chapter 7.3.7 – Design and development validation

 Pre-clinical evaluation allows to demonstrate that:

• The design and development outputs have met the design and development input requirements,
• The device meets the requirements for the specified application or intended use,
• The device is compliant to the GSPRs,
• The device characteristics are maintained during its lifetime.

Clinical/pre-clinical data: what’s the difference(s)?

Pre-clinical data are the intrinsic properties of the device that enable it to achieve the manufacturer’s intended use. 

These data result from the evaluation of the technical and functional characteristics of the device, and may be mechanical, physical, chemical, electrical etc.

Clinical data are resulting in part from clinical investigation and from the review of the medical and scientific literature of the device and similar products.

Clinical data documents the clinical evidence that the device is safe and achieves the intended clinical benefit(s), when used as intended by the manufacturer. In other words, they are used to demonstrate the clinical performance of the device referred to in Article 32 of MDR.

Where do the pre-clinical data originate from?

Pre-clinical data can be derived from test results, use simulations, animal testing and literature evaluations that are applicable to the device. 

These data document the characteristic of the device claimed by the manufacturer, such as:

• Performance and safety,
• Mechanical properties,
• Biocompatibility,
• Tolerance and toxicity,
• Electrical safety and electromagnetic compatibility (EMC), if applicable
• Software verification and validation, if applicable,
• Compatibility and interoperability with other device(s), if applicable,
• Devices incorporating medicinal and/or biological materials, if applicable,
• Sterilization validation and reprocessing of reusable surgical instruments, if applicable,
• Stability (lifetime and shelf life),
• Validation of packaging and transport.

What information are included in the pre-clinical data?

Pre-clinical data are an integral part of the technical documentation (Annex II, Chapter 6 – Product verification and validation) as part of an assessment of compliance with MDR.

For a given test, the information expected by a Notified Body may include:

• The applied standard or the associated state of art reference,
• The demonstrated characteristic (intrinsic property of the medical device),
• The acceptance criteria of the test,
• The method used,
• The laboratory and its certification, if applicable,
• Justification of the “worst-case” choice and the sample size,
• The results obtained and the conclusion regarding the acceptance criteria.

At what stages of the MD life cycle does the demonstration of pre-clinical data apply?

The evaluation of pre-clinical data demonstrates that device characteristics are maintained over its lifetime, from design output to disposal.

The demonstration of maintenance of characteristics allows to justify the shelf life (through stability studies) and the device lifetime.

In addition, for a device that can be reused n-times, the characteristics must be maintained at each reprocessing, until the n^th use.

In general, it is important to ensure that at each step of the device’s lifetime, the characteristics claimed by the manufacturer are maintained, in particular, after cleaning/sterilization (if applicable), storage, transport and until the end of the device’s lifetime.

How to keep the technical documentation up to date?

The compliance review of the mechanical, physical, chemical, electrical, etc. evaluation of the device must be carried out regularly taking into consideration:

• The evolution of the state of art,
• The update of a standard, a common specification or a regulatory text,
• The change of facilities/equipment,
• An evolution of the performances claimed by the manufacturer,
• For tests performed several years ago, the relevance of the validity of the results.

Why seek Efor support?

• As part of the constitution/compliance of technical documentation with regard to MDR and ISO 13485:2016 requirements, EFOR-CVO supports you in the implementation/compliance of DHF and pre-clinical data, taking into consideration the recommendations of Notified Bodies and its experience feedback (for example: Summary of Product Verification & Validation).
• For “Legacy devices”: EFOR-CVO supports manufacturers in performing a Gap Analysis of the test results already performed in order to evaluate the relevance of these tests and propose a  test plan, if necessary.
• For new devices: EFOR-CVO assists manufacturers in identifying the tests to be performed according to the characteristics claimed.
• Our technical experts also advise on more specific subjects such as:
  • Strategic and operational regulatory and quality support, in platform mode or within your teams.
  • Technical support: clinical investigations and evaluations, Design History File (DHF), usability engineering (IEC 62366), biocompatibility (ISO 10993), ADME reports*, qualification, validation, software (IEC 62304), electromedical (IEC 60601-1),…

[1]ADME: absorption/distribution/metabolism/excretion. Report required for MDs containing substances (Rule 21).