The assessment of local tissue effects after implantation according to ISO 10993-6:2016 is essential to evaluate the interactions of medical devices having direct contact with human tissues during clinical use.
From a regulatory point of view, ISO 10993-6:2016 provides general requirements for evaluating the local tissue effects after implantation of biomaterials intended for use in medical devices mainly in subcutaneous tissue, muscle, bone or brain tissue.
This guideline describes biological evaluation in general terms and requires testing strategies that mirror the medical device’s intended clinical use without giving detailed test procedures.
The first phase is to define, for a specific medical device, implantation study design recommendations that meet applicable standard requirements (i.e., ISO 10993-1:2018, ISO 10993-6:2016 and ISO 10993-12:2021), along with justifications for the customised test design recommendations to determine the most ethical and cost-effective, but scientifically relevant and regulatory compliant study.
Subsequently, the definition of recommendations for the design of the implantation study prior to the drafting of the study plan and its implementation in animals is of crucial importance.
This helps refine testing conditions and save time for further discussions with the testing laboratories in charge of the in vivo testing. In addition, it also facilitates exchanges with competent authorities for in vivo studies, to ensure acceptance of the study design.
Indeed, care should be taken regarding the choice of:animal species selected and number of animals involved, implantation site (tissue), implantation periods (e.g., short-term, long-term), number of samples (i.e., implantation sites) to analyse, sample preparation and evaluation parameters (clinical follow-up, sample collection, microscopic/histological assessment). The choice of control(s) is also crucial. The selection of a relevant predicate (i.e., marketed medical device whose clinical acceptability and biocompatibility characteristics have been established) should be considered (if available).
The predicate device is similar to the medical device under evaluation in design, composition and intended clinical use.
Eurofins Medical Device Services can support manufacturers in planning a local tissue effects evaluation, both in terms of study design recommendations and in vivo testing, in accordance with ISO 10993-6:2016.