<p class="MsoBodyText" style="mso-layout-grid-align: none; text-autospace: none;"><span lang="EN-GB" style="mso-bidi-font-size: 12.0pt;">This document specifies the process and requirements for the toxicological risk assessment of medical device constituents. The methods and criteria used to assess whether exposure to a constituent is without appreciable harm are also specified. The toxicological risk assessment can be part of the biological evaluation of the final product, as described in <span class="stdpublisher"><span style="color: black; mso-color-alt: windowtext;">ISO</span></span> <span class="stddocNumber"><span style="color: black; mso-color-alt: windowtext;">10993</span></span>-<span class="stddocPartNumber"><span style="color: black; mso-color-alt: windowtext;">1</span></span>.</span></p>
<p class="MsoBodyText" style="mso-layout-grid-align: none; text-autospace: none;"><span lang="EN-GB" style="mso-bidi-font-size: 12.0pt;">The process described in this document applies to chemical characterization information obtained in line with <span class="stdpublisher"><span style="color: black; mso-color-alt: windowtext;">ISO</span></span> <span class="stddocNumber"><span style="color: black; mso-color-alt: windowtext;">10993</span></span>-<span class="stddocPartNumber"><span style="color: black; mso-color-alt: windowtext;">18</span></span>. When a toxicological risk assessment of either the compositional information or analytical chemistry data (e.g. extractable data or leachable data) are required to determine whether the toxicological risks related to the constituents are negligible or tolerable.</span></p>
<p class="MsoBodyText" style="mso-layout-grid-align: none; text-autospace: none;"><span lang="EN-GB" style="mso-bidi-font-size: 12.0pt;">The process described in this document is not intended to apply to circumstances where the toxicological risk has been estimated by other means, such as:</span></p>
<p class="ListContinue1" style="tab-stops: 19.85pt 39.7pt 59.55pt 79.4pt 99.25pt 119.05pt 138.9pt 158.75pt 178.6pt 7.0cm; mso-layout-grid-align: none; text-autospace: none;"><span lang="EN-GB" style="mso-bidi-font-size: 12.0pt;">—<span style="mso-tab-count: 1;"> </span>constituents, excluding cohort of concern or excluded chemicals, that are present in or extracted from a medical device at an amount representative of patient exposure below a relevant, toxicologically-based reporting threshold (see applicable requirements in <span class="stdpublisher"><span style="color: black; mso-color-alt: windowtext;">ISO</span></span> <span class="stddocNumber"><span style="color: black; mso-color-alt: windowtext;">10993</span></span>-<span class="stddocPartNumber"><span style="color: black; mso-color-alt: windowtext;">18</span></span>:</span><span class="stdyear"><span lang="EN-GB" style="color: black; mso-color-alt: windowtext;">2020</span></span><span lang="EN-GB" style="mso-bidi-font-size: 12.0pt;">, <span class="stdsection"><span style="color: black; mso-color-alt: windowtext;">Annex E</span></span> and <span class="stdpublisher"><span style="color: black; mso-color-alt: windowtext;">ISO</span></span>/<span class="stddocumentType"><span style="color: black; mso-color-alt: windowtext;">TS</span></span> <span class="stddocNumber"><span style="color: black; mso-color-alt: windowtext;">21726</span></span>);</span></p>
<p class="ListContinue1" style="tab-stops: 19.85pt 39.7pt 59.55pt 79.4pt 99.25pt 119.05pt 138.9pt 158.75pt 178.6pt 7.0cm; mso-layout-grid-align: none; text-autospace: none;"><span lang="EN-GB" style="mso-bidi-font-size: 12.0pt;">—<span style="mso-tab-count: 1;"> </span>a new or changed medical device for which chemical or biological equivalence has been established with an existing biocompatible or clinically established medical device (see applicable requirements in <span class="stdpublisher"><span style="color: black; mso-color-alt: windowtext;">ISO</span></span> <span class="stddocNumber"><span style="color: black; mso-color-alt: windowtext;">10993</span></span>-<span class="stddocPartNumber"><span style="color: black; mso-color-alt: windowtext;">18</span></span>:</span><span class="stdyear"><span lang="EN-GB" style="color: black; mso-color-alt: windowtext;">2020</span></span><span lang="EN-GB" style="mso-bidi-font-size: 12.0pt;">, <span class="stdsection"><span style="color: black; mso-color-alt: windowtext;">Annex C</span></span>).</span></p>
<p class="MsoBodyText" style="mso-layout-grid-align: none; text-autospace: none;"><span lang="EN-GB" style="mso-bidi-font-size: 12.0pt;">The process described in this document is also not applicable to:</span></p>
<p class="ListContinue1" style="tab-stops: 19.85pt 39.7pt 59.55pt 79.4pt 99.25pt 119.05pt 138.9pt 158.75pt 178.6pt 7.0cm; mso-layout-grid-align: none; text-autospace: none;"><span lang="EN-GB" style="mso-bidi-font-size: 12.0pt;">—<span style="mso-tab-count: 1;"> </span>medical device constituents that do not contact the body (e.g. in vitro diagnostics);</span></p>
<p class="ListContinue1" style="tab-stops: 19.85pt 39.7pt 59.55pt 79.4pt 99.25pt 119.05pt 138.9pt 158.75pt 178.6pt 7.0cm; mso-layout-grid-align: none; text-autospace: none;"><span lang="EN-GB" style="mso-bidi-font-size: 12.0pt;">—<span style="mso-tab-count: 1;"> </span>biological risks associated with physical interactions of the medical device with the body (i.e. application of mechanical forces, energy or surface morphology, etc.), provided that the chemical exposure is not changed;</span></p>
<p class="ListContinue1" style="tab-stops: 19.85pt 39.7pt 59.55pt 79.4pt 99.25pt 119.05pt 138.9pt 158.75pt 178.6pt 7.0cm; mso-layout-grid-align: none; text-autospace: none;"><span lang="EN-GB" style="mso-bidi-font-size: 12.0pt;">—<span style="mso-tab-count: 1;"> </span>active pharmaceutical ingredients of device-drug combination products or biologic components of device-biologic combination products as additional regulatory considerations can apply;</span></p>
<p class="ListContinue1" style="tab-stops: 19.85pt 39.7pt 59.55pt 79.4pt 99.25pt 119.05pt 138.9pt 158.75pt 178.6pt 7.0cm; mso-layout-grid-align: none; text-autospace: none;"><span lang="EN-GB" style="mso-bidi-font-size: 12.0pt;">—<span style="mso-tab-count: 1;"> </span>exposure to a particular constituent that arises from sources other than the device, such as food, water or air.</span></p>
Registration number (WIID)
75323
Scope
<p class="MsoBodyText" style="mso-layout-grid-align: none; text-autospace: none;"><span lang="EN-GB" style="mso-bidi-font-size: 12.0pt;">This document specifies the process and requirements for the toxicological risk assessment of medical device constituents. The methods and criteria used to assess whether exposure to a constituent is without appreciable harm are also specified. The toxicological risk assessment can be part of the biological evaluation of the final product, as described in <span class="stdpublisher"><span style="color: black; mso-color-alt: windowtext;">ISO</span></span> <span class="stddocNumber"><span style="color: black; mso-color-alt: windowtext;">10993</span></span>-<span class="stddocPartNumber"><span style="color: black; mso-color-alt: windowtext;">1</span></span>.</span></p>
<p class="MsoBodyText" style="mso-layout-grid-align: none; text-autospace: none;"><span lang="EN-GB" style="mso-bidi-font-size: 12.0pt;">The process described in this document applies to chemical characterization information obtained in line with <span class="stdpublisher"><span style="color: black; mso-color-alt: windowtext;">ISO</span></span> <span class="stddocNumber"><span style="color: black; mso-color-alt: windowtext;">10993</span></span>-<span class="stddocPartNumber"><span style="color: black; mso-color-alt: windowtext;">18</span></span>. When a toxicological risk assessment of either the compositional information or analytical chemistry data (e.g. extractable data or leachable data) are required to determine whether the toxicological risks related to the constituents are negligible or tolerable.</span></p>
<p class="MsoBodyText" style="mso-layout-grid-align: none; text-autospace: none;"><span lang="EN-GB" style="mso-bidi-font-size: 12.0pt;">The process described in this document is not intended to apply to circumstances where the toxicological risk has been estimated by other means, such as:</span></p>
<p class="ListContinue1" style="tab-stops: 19.85pt 39.7pt 59.55pt 79.4pt 99.25pt 119.05pt 138.9pt 158.75pt 178.6pt 7.0cm; mso-layout-grid-align: none; text-autospace: none;"><span lang="EN-GB" style="mso-bidi-font-size: 12.0pt;">—<span style="mso-tab-count: 1;"> </span>constituents, excluding cohort of concern or excluded chemicals, that are present in or extracted from a medical device at an amount representative of patient exposure below a relevant, toxicologically-based reporting threshold (see applicable requirements in <span class="stdpublisher"><span style="color: black; mso-color-alt: windowtext;">ISO</span></span> <span class="stddocNumber"><span style="color: black; mso-color-alt: windowtext;">10993</span></span>-<span class="stddocPartNumber"><span style="color: black; mso-color-alt: windowtext;">18</span></span>:</span><span class="stdyear"><span lang="EN-GB" style="color: black; mso-color-alt: windowtext;">2020</span></span><span lang="EN-GB" style="mso-bidi-font-size: 12.0pt;">, <span class="stdsection"><span style="color: black; mso-color-alt: windowtext;">Annex E</span></span> and <span class="stdpublisher"><span style="color: black; mso-color-alt: windowtext;">ISO</span></span>/<span class="stddocumentType"><span style="color: black; mso-color-alt: windowtext;">TS</span></span> <span class="stddocNumber"><span style="color: black; mso-color-alt: windowtext;">21726</span></span>);</span></p>
<p class="ListContinue1" style="tab-stops: 19.85pt 39.7pt 59.55pt 79.4pt 99.25pt 119.05pt 138.9pt 158.75pt 178.6pt 7.0cm; mso-layout-grid-align: none; text-autospace: none;"><span lang="EN-GB" style="mso-bidi-font-size: 12.0pt;">—<span style="mso-tab-count: 1;"> </span>a new or changed medical device for which chemical or biological equivalence has been established with an existing biocompatible or clinically established medical device (see applicable requirements in <span class="stdpublisher"><span style="color: black; mso-color-alt: windowtext;">ISO</span></span> <span class="stddocNumber"><span style="color: black; mso-color-alt: windowtext;">10993</span></span>-<span class="stddocPartNumber"><span style="color: black; mso-color-alt: windowtext;">18</span></span>:</span><span class="stdyear"><span lang="EN-GB" style="color: black; mso-color-alt: windowtext;">2020</span></span><span lang="EN-GB" style="mso-bidi-font-size: 12.0pt;">, <span class="stdsection"><span style="color: black; mso-color-alt: windowtext;">Annex C</span></span>).</span></p>
<p class="MsoBodyText" style="mso-layout-grid-align: none; text-autospace: none;"><span lang="EN-GB" style="mso-bidi-font-size: 12.0pt;">The process described in this document is also not applicable to:</span></p>
<p class="ListContinue1" style="tab-stops: 19.85pt 39.7pt 59.55pt 79.4pt 99.25pt 119.05pt 138.9pt 158.75pt 178.6pt 7.0cm; mso-layout-grid-align: none; text-autospace: none;"><span lang="EN-GB" style="mso-bidi-font-size: 12.0pt;">—<span style="mso-tab-count: 1;"> </span>medical device constituents that do not contact the body (e.g. in vitro diagnostics);</span></p>
<p class="ListContinue1" style="tab-stops: 19.85pt 39.7pt 59.55pt 79.4pt 99.25pt 119.05pt 138.9pt 158.75pt 178.6pt 7.0cm; mso-layout-grid-align: none; text-autospace: none;"><span lang="EN-GB" style="mso-bidi-font-size: 12.0pt;">—<span style="mso-tab-count: 1;"> </span>biological risks associated with physical interactions of the medical device with the body (i.e. application of mechanical forces, energy or surface morphology, etc.), provided that the chemical exposure is not changed;</span></p>
<p class="ListContinue1" style="tab-stops: 19.85pt 39.7pt 59.55pt 79.4pt 99.25pt 119.05pt 138.9pt 158.75pt 178.6pt 7.0cm; mso-layout-grid-align: none; text-autospace: none;"><span lang="EN-GB" style="mso-bidi-font-size: 12.0pt;">—<span style="mso-tab-count: 1;"> </span>active pharmaceutical ingredients of device-drug combination products or biologic components of device-biologic combination products as additional regulatory considerations can apply;</span></p>
<p class="ListContinue1" style="tab-stops: 19.85pt 39.7pt 59.55pt 79.4pt 99.25pt 119.05pt 138.9pt 158.75pt 178.6pt 7.0cm; mso-layout-grid-align: none; text-autospace: none;"><span lang="EN-GB" style="mso-bidi-font-size: 12.0pt;">—<span style="mso-tab-count: 1;"> </span>exposure to a particular constituent that arises from sources other than the device, such as food, water or air.</span></p>
