Recent Developments in ISO 10993: An Overview of Updates and Changes

# Introduction

At the IME East event held in New York, Thor S. Rollins, Vice President and Global Market Segment Leader for Medical Devices at Nelson Laboratories, undertook the role of hosting a session titled "Significant Revisions to ISO 10993-1: Current Developments in the Primary Biocompatibility Standard" during which he delved into the recent modifications to the standard and explored potential global acceptance of these changes. Prior to the session, MD+DI engaged in a discussion with Rollins to gain insights into the historical context of the standard, specific testing procedures such as extractables studies employed in the process, and Nelson Laboratories' role in assisting clients in comprehending the nuanced aspects of ISO 10993.

As we delve into the present suggested alterations and revisions to ISO 10993, it might be pertinent to provide a brief historical context. How did the original version of ISO 10993, formulated for the purpose of biocompatibility assessment of medical devices, differ in its inception? Additionally, was it introduced as a replacement for any preexisting evaluation methodologies?

ISO 10993 comprises a series of standards that offer direction for the assessment of the biological compatibility of medical devices. Initially introduced in 1995, this framework superseded the outdated biological testing methodology outlined in the United States Pharmacopeia (USP). The inaugural iteration of ISO 10993 encompassed a checklist of assessments mandated for manufacturers to undertake in order to ascertain the safety of their devices. These evaluations encompassed aspects like cytotoxicity, sensitization, and irritation. In 2018, a revision was made to ISO 10993 to advocate for a risk-based methodology in lieu of a mere checkbox approach. This strategic shift aimed to enable manufacturers to concentrate on the specific endpoints of relevance for their particular device, thereby curbing unnecessary testing and potentially streamlining assessment processes in terms of efficiency and cost-effectiveness. This revised approach also placed greater importance on comprehending the influence of materials and processing, either through research or chemical analysis.

# 2018 transformations introduction

A notable modification involved the incorporation of a biocompatibility assessment strategy, delineating the necessary tests for a given device alongside the reasoning for test selection. This adaptation empowers manufacturers to customize evaluations according to device specifics and pertinent endpoints, deviating from a rigid test protocol. Furthermore, the revised standard offered fresh directives for executing and deciphering biological endpoints, encompassing areas like genotoxicity and carcinogenicity. The industry response was varied; naturally, the transition towards streamlined and cost-efficient evaluations was welcomed. However, any departure from standardized checkbox testing necessitated a higher level of proficiency and alignment with regulatory authorities. This introduced an element of uncertainty and an increased reliance on expertise.

The transition to a risk-oriented approach was prompted by recognizing that numerous tests within the original iteration of ISO 10993 were inapplicable or superfluous for certain devices. Through concentrating on the precise biological endpoints of interest, manufacturers gained the ability to conduct more precise assessments, thereby enhancing the overall safety evaluation of their devices.

The necessity of conducting extractables testing within the ISO 10993 protocol is contingent upon the composition of the device and its potential interactions with the human body. Should a device incorporate materials prone to leaching or interacting with the body, an extractables investigation becomes essential to evaluate potential patient risks. Nevertheless, not all devices mandate extractables testing, as this verdict is rendered on a per-case evaluation. The primary factor guiding this decision is the duration of contact with the body: devices with short-term contact usually elude extractables evaluations, whereas those with prolonged interaction typically necessitate such assessments.

# Proposed Revisions to ISO 10993

At present, ISO 10993 is in the process of undergoing numerous revisions, with anticipated modifications slated for release by the end of 2023. Among the contemplated alterations are fresh instructions on executing in vitro assays and enhancements to pertinent biological endpoints. Furthermore, a conclusive draft of 10993-17 has been issued, while ongoing efforts are focused on 10993-1, -3, -5, and -18. However, there has been certain resistance from the industry, notably concerning the suggested amendments to the carcinogenicity endpoint and the rigorous solvent extractions involved in extractable studies.