In January 2021, a new member, namely ISO 10993-23, of the ISO 10993 family was released. But what created the need for the introduction of this standard in the series of ISO 10993 standards? The purpose was to facilitate a comprehensive examination of a medical device’s irritation capacity. Since the standard’s release, there has been a lot of confusion about it in the medical device industry. Let’s take a look at what are the common questions to which companies are seeking answers:

Is this standard irrelevant to only certain types of Medical Devices?

It is noted that no medical device is exempt from this standard as it is applicable to all devices regardless of the nature and duration of contact. 

Which standard is considered as the grandfather of ISO 10993-23:2021?

This new standard has emerged from the previously released ISO 10993-10:2010 Biological Evaluation of Medical Devices – Part 10: Tests for irritation and skin sensitization, which already contains information about the estimation of potential irritants in medical devices. Therefore, now there are two standards for the evaluation of skin irritation associated with the use of medical devices.

What are the advantages of adopting the ISO 10993-23:2021 standard?

• Defined approach for conducting skin irritation study

The ISO 10993-23:2021 presents a defined approach for conducting a study on the evaluation of potential irritants in a medical device. The approach defined in the standard is as follows:

1. Material characterization of all the constituents used in manufacturing a medical device is performed as per ISO 10993-18. This shall also include characterization of additives used for building the device.
2. An exhaustive review of the literature is performed to evaluate the physical and chemical properties of the materials used in manufacturing the medical device.
3. It is recommended to conduct in-vitro testing if applicable.
4. It is recommended to conduct in-vivo testing only when the In-vitro testing is not viable.
5. It is then suggested to perform the non-invasive clinical studies if the irritancy potential has not been evaluated from the above-mentioned steps or tests.

• Focus on Animal Welfare

No doubt the ISO 10993-10 standard already talks about giving priority to in-vitro testing so that the animals are not required in the study, however, there were no defined protocols and methods for performing an in-vitro study for skin irritation. The ISO 10993-23:2021 version comes with a detailed explanation of the in-vitro test methods that utilize Reconstructed human Epidermis (RhE) models which are cultured human-derived epidermal keratinocytes. Further, the RhE models have the potential to detect the chemicals which are extracted from polymeric materials used in the manufacture of a variety of medical devices including hip implants.

In summary, this subpart of the ISO 10993 follows the “3R” approach while considering animal studies i.e Replacement, Reduction and Refinement. However, it must be kept in mind that the animal studies can be replaced by in-vitro RhE testing only by employing suitable validation methods.

Can RhE in-vitro testing replace in-vivo testing in the future?

The in-vitro RhE testing is validated and can replace the in-vivo rabbit test for irritation by skin exposure and intracutaneous administration. In general, if the devices are made for intact skin, in vitro testing is the need of the hour. 

Which all devices are in harmony with the in-vitro testing?

Implants and Externally communicating Devices.

What are the advantages of in-vitro testing from a manufacturer’s standpoint?

From a manufacturer’s perspective, the in-vitro tests can give quick results when compared to the in-vivo testing since the rabbit skin is less responsive to an irritant. In addition, there is a drastic decrease in the cost incurred for conducting tests since animal transportation and housing costs take up a ton of money.

Is the ISO 10993-23 standard recognized by the worldwide Regulatory Jurisdictions?

It is noted that the US FDA had included the 2021 version of ISO 10993-23 under the List of Consensus Standards dated June 7, 2021. Further, the European Union (EU) has also included this standard under the list of Harmonized Standards applicable for MDR 2017/745 dated July 19, 2021. Talking about other jurisdictions, TGA (Australia) already accepts the ISO 10993 series of standards for biological evaluation and Japan has also included the in-vitro testing in its PMDA regulation.

Nevertheless, it is clearly mentioned in the standard that the regulators shall accept both positive and negative controls, however, it is recommended that manufacturers contact the Notified Bodies first before applying the in-vitro RhE testing approach mentioned in ISO 10993-23:2021 standard. 

Under what conditions, a potentially irritant material shall not be tested on human subjects?

1. The materials are carcinogenic or present a toxicity hazard.
2. The material can lead to respiratory sensitization.
3. The material has proven to be corrosive in previous tests.
4. The materials present a genotoxic or reproductive hazard.

Concerned about performing Gap Analysis and how to comply with the new standard?

Don’t Worry! Elexes team is here to help you. Our dedicated team has years of experience performing the gap analysis for any newly released version of medical device standards. Please contact us via email jennifer@elexes.com or call +1 650-503-6615 for further details.

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