Medical Plastic Data Service Magazine

 

A TECHNO-ECONOMIC NEWS MAGAZINE FOR MEDICAL PLASTICS AND PHARMACEUTICAL INDUSTRY

Our 30th Year of Publication
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Quality

Importance Of Biocompatibility For Medical Polymers

And Regulatory Requirements

 

Biocompatibility testing is a decision that is taken based on the available information on a medical device, which is documented in the BEP. When adequate information is already existing to support the biocompatibility of the device, further testing is not recommended. One of the major information required here is the chemical/material composition of the device. In case of polymers, data on the characteristics such as the levels of residual monomers, oligomers, surface composition, residual catalysts/initiators, additives. Process residues, traces, impurities and chemical structure are useful in determining any potential hazards. ISO 10993-18:2020 (Biological evaluation of medical devices — Part 18: Chemical characterization of medical device materials within a risk management process) suggests that the compositional details of polymers should be obtained from the supplier of the material and or published literature. In the absence of any such data, these data shall be obtained through chemical analysis.

If the chemical analysis reveals absence of any hazardous extractables or if the levels of extractables are below the Analytical Evaluation Threshold (AET), no further toxicological risk assessment may be required. AET is the threshold below which it is not needed to identify, quantify or report leachables or extractables, for potential toxicological assessment. Therefore, a substance that is present at a concentration below the AET is established as having an acceptable toxicological risk without further assessment. When the levels of the extractables are above the AET, a toxicological risk assessment is performed to evaluate safe levels, which when exceeded would trigger biocompatibility testing. Given the effects that manufacturing, and processing may have on a polymer as incorporated into the final finished medical device, use of material standards may not be sufficient to identify biocompatibility risks for devices made from polymers. ISO 10993-1 emphasizes that all biocompatibility tests be conducted on a final finished device or representative devices that have exactly the same composition as the final finished device and have gone through the same manufacturing, packaging and sterilization process as the final finished device.

In a case where a biocompatibility testing is required, the test selection is based on the site of contact and duration of contact of the device as described in ISO 10993-1-2018.

The rigor of testing depends on the invasiveness of the device. While a thermometer, which is a surface device contacting intact for less than 24 h will have to be tested for cytotoxicity, sensitization and skin irritation, a pacemaker may require, in addition to these three tests, testing for systemic toxicity, genotoxicity and local effects after implantation. Polymeric devices that contact blood directly or indirectly may require testing for hemocompatibility as outlined in ISO 10993-4:2017
(Biological evaluation of medical devices — Part 4: Selection of tests for interactions with blood). An intravenous catheter requires testing for indirect hemolysis. A
polymeric implant placed in the heart would require additional endpoints to determine any thrombogenic property.

The use of vertical standards is another important thing to be considered when selecting tests for certain polymeric medical devices. For example, intra ocular lenses
(IOLs) have to be tested based on the requirements outlined in ISO 11979-5:2020 (Ophthalmic implants — Intraocular lenses — Part 5: Biocompatibility).

With respect to selecting solvents for extraction, great care should be taken for testing polymers. According to ISO 10993- 12:2021 (Biological evaluation of medical
devices — Part 12: Sample preparation and reference materials), extraction solvents should be selected to optimize compatibility with the device materials and provide
information on the types of chemicals that are likely to be extracted in clinical use. Solvents that swell the polymer, cause the polymer to degrade or dissolve, or interfere with detection of chemicals should be used with caution.

Devices containing degradable /absorbable polymers, e.g. absorbable sutures made of polyglycolic acid/poly caprolactone, may also require testing for degradation as described in ISO 10993-6 (Biological evaluation of medical devices — Part 6: Tests for local effects after implantation). This is because polymeric, metallic, or ceramic materials that are intended to be absorbed in vivo will release soluble components or degradation products. If the release rate of a material is sufficiently rapid, elevated concentrations of one or more of the released products could alter the pH and/or osmolality of an in vitro test system. Since the in vivo condition provides the combined presence of perfusion and carbonate equilibria, when evaluating intentionally absorbable materials it is possible that adjustment of the pH and/or osmolality of an in vitro test system will be necessary to maintain physiologically relevant conditions – thereby allowing evaluation for other causation and provided a scientific justification for the adjustments and the effect on the in vitro test system, as performed without pH or osmolality adjustment, is documented within the report. Results from both the standard assay and adjusted assay should be compared, as modifications can mask important considerations.

Once the physical, chemical and biocompatibility data are available, the BER is documented by a toxicologist. The conclusion that the polymeric device is safe comes with the collection, review, identification of gaps, testing and critical review of test reports. Clinical data are very useful to support the biological evaluation of a device. Documentation of biological safety of the device is a continuous process and needs to be updated throughout the life cycle of a device.

When medical polymers produce the desired favourable tissue response and clinically meaningful performance, they are considered biocompatible. The goal of employing biocompatible polymers is to improve healing functions while avoiding harmful, negative physiological, allergy, or toxic effects.

 
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