Clinical and Biological Evaluation of Medical Devices
According to MDD 93/42/EEC Annex I “Essential Requirements” clause 6a and Annex X, a clinical evaluation must be performed to demonstrate that unexpected side effects do not constitute an unacceptable risk when weighed against a medical device’s intended performance.
According to MDD Annex X, “As a general rule, confirmation of conformity ….. and the evaluation of the side-effects and of the acceptability of the benefit/risk ratio …. must be based on clinical data.”
MEDDEV 2.7/1 rev4 and clinical evaluation
The new European guideline MEDDEV 2.7/1 rev4 (June 2016) provides a description for clinical data generated and held by the manufacturer (section 8.1) or detected by literature search (Appendix A4).
The major difference from the former version of the MEDDEV is that now the number of the “equivalent devices” is limited to one instead of an unlimited number. Also, the revision of the clinical evaluation must be reviewed and determined each year for high-risk medical devices and two to five years for other medical devices depending on their risk potential.
Based on all summarized data, a decision can be made as to whether these clinical data are sufficient to show the acceptability of a device’s benefit/risk profile. If clinical data is deemed not significant to show the clinical property regarding the device’s intended use, indications, contraindications and side-effects, then at a minimum, a post market follow up study (PMCF) must be performed to investigate long-term effects that the available clinical data does not sufficiently describe.
If the clinical data, held by the manufacturer as well as found during literature search, are not applicable for the medical device under consideration because there is no identifiable equivalent device or the device is novel or innovative, a clinical trial in accordance with ISO 14155 must be performed.
According to the MDD 93/42/EEC Annex I “Essential requirements” Clause 7 and EU Member State regulations, every medical device manufacturer has to demonstrate that their devices will not cause potential biological risks. This applies to medical devices that have direct or indirect contact with the human body. The standard EN ISO 10993-1 “Evaluation and testing within a risk management process” and the US FDA Guidance “Use of International Standard ISO 10993-1, Biological evaluation of medical devices – Part 1: Evaluation and testing within a risk management process (June 2016)” give a pathway to achieve this requirements within a risk management process, as part of the overall evaluation and development of each device.
To avoid unwelcome surprises with the final product to be used for the biological investigations, the material selection should begin during the development process. The selection of material(s) to be used in device manufacture and its biocompatibility evaluation should initially take into account the likelihood of direct or indirect tissue contact, and any available information about the materials of manufacture, for example, chemical formulation for each component material, including adhesives, known and suspected impurities, and constituents associated with processing. The device in its final finished form as well as possible leachable chemicals or degradation products should be considered for their relevance to the overall biocompatibility evaluation of the device.
The manufacturer should use materials that are well-known to be appropriate for the intended use and assumed to be biocompatible. Depending on the material, the manufacturing process and the intended use, some of the required investigations can be met through literature search and animal testing can be limited.