Medical Devices Regulation

Medical Devices Regulation

1. Medical Devices Biocompatibility report

Biocompatibility report

The ISO 10993-1: 2018 standard defines biocompatibility as the “ability of a medical device or material to perform with an appropriate host response in a specific application”.

Based on information provided by you (the manufacturer), Tox by Design will identify the potential risks from a biocompatibility perspective which can include:

  • chemical toxicity
  • unacceptable biological response to physical characteristics of the device, and
  • aspects of manufacturing and processing that could alter the physicochemical characteristics of the device

Once the risks have been identified, SOCOSUR should assess what information is already available regarding those risks and identify the knowledge gaps that remain. Considering the potential biological impact, a plan should be developed to address the knowledge gaps either by biocompatibility testing or other evaluations that appropriately address the risks.

The interpretation of the overall biocompatibility evaluation will be considered in the appropriate benefit-risk context.

ISO 10993-1:2018

Biological evaluation of medical devices — Part 1: Evaluation and testing within a risk management process specifies

  • general principles governing the biological evaluation within a risk management process;
  • general categorization based on the nature and duration of their contact with the body;
  • evaluation of existing relevant data from all sources;
  • identification of gaps in the available data set on the basis of a risk analysis;
  • identification of additional data sets necessary
  • assessment of the biological safety

Is your product eligible?

It concerns materials and medical devices that are expected to have direct or indirect contact with:

  • patient's body during intended use;
  • user's body, if the medical device is intended for protection

It concerns all types of medical devices including active, non-active, implantable and non-implantable medical devices.

Why should you do an assessment of biological hazards?

To prevent risks due to: 

  • changes to the medical device over time or
  • to breakage of your medical device or its components which can lead the patient to be exposed to new or novel materials.

This assessment excludes hazards related to bacteria, moulds, yeasts, viruses, transmissible spongiform encephalopathy (TSE) agents and other pathogens.

Biological Evaluation Report (BER) is designed to meet the requirements outline in ISO 10993-1:2018 clause 7 “Expert assessors who have the necessary knowledge and experience shall determine and document”.

(Use of International Standard ISO 10993-1, "Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process" Guidance for Industry and Food and Drug Administration Staff by FDA on September 4th, 2020). 

2. Toxicological Assessment of Impurities

According to ICH M7 / ICH Q3B, these guidelines discuss the methodology behind risk evaluation of impurities. 

ICH M7: Guidance, Assessment and Control of DNA Reactive (mutagenic) impurities in Pharmaceuticals to limit potential
ICH Q3B: Impurities in new drug products



Proposed action for control

(details in ICH M7 (R1) Section 7 and 8)

1Known mutagenic carcinogensControl at or below compound-specific acceptable limit
2Known mutagens with unknown carcinogenic potential (bacterial mutagenicity positive*, no rodent carcinogenicity data)Control at or below acceptable limits (appropriate TTC)
3Alerting structure, unrelated to the structure of the drug substance; no mutagenicity data

Control at or below acceptable limits (appropriate TTC) or conduct bacterial mutagenicity assay;

If non-mutagenic => Class 5

If mutagenic => Class 2

4Alerting structure, same alert in drug substance or compounds related to the drug substance (e.g., process intermediates) which have been tested and are non-mutagenicTreat as non-mutagenic impurity
5No structural alerts, or alerting structure with sufficient data to demonstrate lack of mutagenicity or carcinogenicityTreat as non-mutagenic impurity


3. Clinical Evaluation report

According to MEDDEV 2.7.1 Rev4, Guidelines on Medical Devices, Clinical Evaluation: A guide for manufacturers and notified bodies under directives 93/42/EEC and 90/385/EEC

Clinical evaluation is a responsibility of the manufacturer and the clinical evaluation report is an element of the technical documentation of a medical device.

Usually, it is first performed during the development of a medical device in order to identify data that need to be generated for market access

Clinical evaluation is mandatory for your initial CE-marking and you have to actively update it thereafter.

Conformity to the Essential Requirements can only be assumed when the following items are aligned with each other:

  • the information materials supplied by the manufacturer (the labelling, instructions for use, available promotional materials, including accompanying documents foreseen by the manufacturer)
  • the clinical evaluation (the device description used for the clinical evaluation, other contents of the clinical evaluation report)
  • the available clinical data (such as results of Clinical Investigations, publications, PMS studies, etc.).

When do you need to undertake a clinical evaluation?

  1. Clinical evaluation undertaken for the development of a medical device
  2. Clinical evaluation for initial CE-marking
  3. Updating the clinical evaluation

Tox by Design clinical evaluation report will summarise and draw all relevant clinical data documented or referenced in other parts of the technical documentation.

Tox by Design clinical evaluation report and the relevant clinical data constitute the clinical evidence for conformity assessment.


4. Extractables and Leachables in Medical Devices

With respect to extractables and leachables testing, there are two ways to get into contact with an extractable/leachable from a medical device:

  • Product in a medical device which contains the leachable and thus, the leachable is administered through the medical device usage (ie: infusion pumps, syringes…).
  • Medical devices which generate leachables when they are in direct contact with the tissue (ie: bandages, contact lens, prosthesis…).

In all cases, the compatibility between the material and the product/tissue and its safety for the patient must be guaranteed.

For the first scenario, extractable testing required is mostly the same as for extractable/leachables testing of packaging material or plastic material used during manufacturing.


You can check Tox by Design methodology for Medical Devices Risk Assessments, signed by an European Registered Toxicologist expert here.

In the event you are performing this exercise for innovative compounds GMP scale up manufacturing, please be noted Tox by Design is duly accredited for the French Research Tax Credit CIR

Feel free to contact us using this email link to receive a quotation for Tox Medical Devices procedure used on your manufacturing line.