MATERIAL EQUIVALENCE
Résumé
As part of the evaluation of the biocompatibility of a medical device, one of the first steps in the process is the chemical characterization of the materials, described by standard ISO 10993-18. The information collected constitutes a basis for the characterization of the dangers, it is therefore important to carry it out on a device and materials as representative as possible of the one which will be placed on the market and which will actually be in contact with patients. However, in the field, economic and technical conditions sometimes give rise to changes in references for different reasons: shortages of materials, selection of a more efficient material, change of manufacturing aid, etc.
So how can we show that the battery of tests carried out is still applicable despite these changes? How to avoid having to rerun tests that have already been carried out?
In what context is material equivalence relevant?
The chemical characterization of materials is described by standard ISO 10993-18. It is a crucial step in the biological evaluation process which involves the physical and chemical identification of the constituent materials of the medical device as first intention, and which most of the time continues with a study of extractables and/or releasables from these materials in the laboratory. The information collected constitutes a basis for hazard characterization, and subsequently makes it possible to determine the relevant biological assessment tests. It is therefore important to carry it out on a device and materials that are as representative as possible of that which will be placed on the market and which will actually be in contact with patients. In the event that any change occurs, it is therefore necessary to ensure that the previously established assessment is still applicable following these modifications.
In the field, manufacturers face economic and technical conditions which sometimes give rise to changes in references for different reasons:
- Material shortages: These force the manufacturer to turn to an alternative supplier, which appears to be identical to the base material
- Selection of a more efficient material: the manufacturer finds a material supplier with more attractive properties, quality or even a price
- Change of manufacturing adjuvant, cleaning product or any other “additional” product.
Why is there a need to make a material equivalence?
Material equivalence is used to justify questions such as:
- Despite this change in material, can we still consider that the device is not a skin irritant?
- Despite this change in processing aid, is the validation of the cleaning process still applicable to the device?
In the case where equivalence can be established (eg. there are sufficient data and arguments in favor of equivalence), the process then allows us to avoid having to rerun the tests in question: this therefore makes it possible to save time and money.
How to achieve material equivalence?
In order to provide convincing justification, it is not enough to show that the composition of the material is the same: a more in-depth and more specific analysis will make it possible to avoid non-conformities as much as possible during audits.
For example, in the case of a change of material for another material which appears identical in terms of composition, it is also necessary to ensure that this second material is equivalent in terms of impurities and other traces of compounds not intentionally added. . In fact, supplier A and supplier B do not necessarily have the same manufacturing process, which could lead to differences in compounds which will potentially be in contact with patients.
In the same way, in the event of a change to a manufacturing adjuvant, the objective will be to demonstrate that the new adjuvant will not provide new potentially toxic molecules.
Equivalence must be demonstrated for each test that one wishes to retain, using appropriate arguments.
Where to find relevant data?
The information necessary to justify an equivalence can come from two main sources:
- Technical documentation from the material manufacturer
The manufacturer of the raw material may have any given type available: biocompatibility tests, chemical characterizations, etc. All of this data is relevant and will reinforce the scientific veracity of the equivalence. For example, if the manufacturer performed a skin irritation test on the "replacement" material and the device was found to be non-irritating with the old material, it is reasonable to assume that the change in material will not affect not skin irritation results.
- Scientific literature
Over the years, numerous toxicology data on various substances have been generated and are accessible in the databases of institutions relating to various sectors (pharmaceutical, food, cosmetics, etc.). This data can also be used to demonstrate the equivalence of a material. For example, if an adjuvant is added in the manufacturing process, it is possible, on the basis of reliable experimental tests found in these databases, to show that this new adjuvant is not irritating to the skin and that its addition will not affect the skin irritation results previously obtained.
What information should be collected?
In order to best establish equivalence, here is the main and necessary information to collect:
- Precise composition
The precise composition in percentage by mass of each substance present in the material must be available. Also the chemical identity of each of these substances must be known (CAS number and/or chemical formula). This information will allow the new material to be compared to the old in terms of composition.
- Impurities and contaminants
Impurities, traces and possible contaminants in the material must be available: in fact, these elements can have a significant impact on the possible toxicity of the product.
- Toxicological profiles
It is interesting to generate a toxicological profile for each of the substances making up the material: thanks to this, the dangers intrinsic to each substance will be characterized and can be weighed in favor or against equivalence. All local toxicity data (skin and eye irritation, sensitization), severe toxicity (genotoxicity, carcinogenicity, reproductive and developmental toxicity) and systemic toxicity (for acute to chronic exposures) are recorded.
Some concrete examples
- Change of material
My device contains plastic A. My current supplier of plastic A is out of stock: I therefore turn to supplier B. To ensure that this change will not have an impact on the biocompatibility tests carried out with plastic A, I get:
- The composition and chemical identity of plastic B
- Data on impurities and contaminants in plastic B.
If the composition, impurities and contaminants of plastic B are identical to those of plastic A, then equivalence can be established.
- Added a cleaning step involving detergent
I choose to add a cleaning step when manufacturing my device. This cleaning step involves a detergent composed of an identified chemical substance. In order to show that my skin irritation test carried out without this new cleaning step is still valid, I carry out the toxicological profile of the substance. The data available in the animal literature show an absence of irritant effect and the test in question is reliable. It is reasonable to assume that this new detergent will not affect skin irritation results.
What to do when data is not available?
However, sometimes it is not possible to collect this data for various reasons: the supplier does not have it or does not want to transmit it, the composition is not well defined, no data is available in the literature, etc.
In this case, before rerunning all the tests, it may be interesting to carry out a new study of extractables/leachables following the same protocol as previously. It will then be necessary to compare the results of the two extractable studies, and try to show that this change in material or process did not affect the chemical characterization of the device.
Author: Manon Averseng
For more information, do not hesitate to contact Manon Averseng, toxicology and ecotoxicology manager or Grégory Voisin, président & toxicologue en chef – Toxi Map.
