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Biological evaluation of medical devices, the change has come

 

The key message from REGULATION (EU) 2017/745 OF THE EUROPEAN PARLIAMENT

 

“Devices shall be designed, manufactured and packaged to minimise the risk posed by contaminants and residues to patients, included packaging, transport, storage and use of the devices […] Devices shall be designed and manufactured in such a way that they can be used safely with the materials and substances, with which they enter into contact during their intended use […] Devices shall be designed and manufactured in such a way as to reduce as far as possible the risks posed by substances or particles, including wear debris, degradation products and processing residues, that may be released from the device.”

REGULATION (EU) 2017/745 OF THE EUROPEAN PARLIAMENT

 

Significance

The amount of contaminants, debris, residues and degration product that can be released from a medical device after manufacturing and till the end of shelf life are of concern in term of patient safety. That’s why the physico-chemical characterisation of medical devices comes into force in the medical device regulation 2017/745 as a part of general safety and performance requirements and has to be documented in the technical documentation, product verification and validation as well as in pre-clinical and clinical data. 

 

Past approach

The biocompatibility of medical device has been done primarily through animal testing, such as irritation, sensitization, acute systemic toxicity... by following the biological evaluation test matrix according to category, kind of contact and contact duration. This approach cannot be conducted any more.

 

New approach

“The principles of replacement, reduction and refinement in the area of animal experimentation […] should be observed”

 

REGULATION (EU) 2017/745 OF THE EUROPEAN PARLIAMENT
Directive 2010/63/EU of the European Parliament and of the Council 

 

The recent review of ISO 10993-1 standard deeply questions priorities: chemical and physical characterization have to be performed prior to evaluate if further in vivo tests are necessary. Additionally, the chemical characterization has to be documented in the Technical documentation, product verification and validation, as a part of clinical/pre-clinical data. The product stability has to be insured during its shelf life.

 

Make it possible

According to the material characterization identified through eg MSDS, CoA and provided by the material manufacturer a test strategy can be defined together with the medical device manufacturer. At Medistri sensitive analytical equipments are used through validated analytical methods allowing to

 

  • extract (simulated or exhaustive extraction, simulated or exaggerated use, suitable extraction vehicles, suitable extraction duration)

  • analyse and quantify inorganic compounds, organic polar/ apolar volatile organic compounds (VOC),semi-volatile organic compounds (SVOC), non –volatile organic compounds. Non-specific approach (THC, TOC, cytotoxicity tests) can also be initially proposed (process development)

  • identify and deliver consistent qualitative and quantitative data on extractable/leachable substances thank to profiling and comparison to powerful databases and/or internal standardisation(types and amounts of chemicals that may migrate from a device to a patient during use and potential toxicities can be predicted). 

 

We recommend to perform the chemical characterization on the final product and after the shelf-life. Please consider the transport simulation during the shelf-life definition.

 

Commonly: 

  • ICP-MS for inorganic substances, 
  • GC-MS/HS-GC-MS for VOC/SVOC 
  • if required HPLC-MS for NVOC

 

Alternatively?

Faster and cheaper than a chemical characterization: Cytotoxicity tests to assess any corrosive/irritant/toxic to cell properties as well as a non-specific evaluation on extracts of (total polar) organic carbon (TOC) and (total apolar) hydrocarbon (THC) are suitable for the evaluation of organic residues during design development, process qualification and validation but does not replace the chemical characterization required for the final product.

 

What does Material Characterization means?

Material characterization = identifying all the components constituting a final product. An exhaustive list of data has to be gathered from material manufacturers to target on the chemical tests to be performed. The material characterization is a part of the technical documentation and gathering data from the initial manufacturer of the material is the best way to characterize it. In general the data provided by the material manufacturer is sufficient to assess the material characterization. If a lack of information is detected or in case of quality control, Medistri can also initiate a material characterization by (non exhaustive) XRF, FTIR, XPS.

 

The material characterization (material itself) is not a chemical characterization (material extract).