updated to reflect name change to CHemical RISk calculator

color_module/static/COU.html

@@ -8,11 +8,11 @@
 </head>
 
 <header>
-   <h1 style="text-align:center"><font color="#0070C0">C</font>olor <font color="#0070C0">H</font>azard and <font color="#0070C0">RIS</font>k calculator (CHRIS) </h1>
+   <h1 style="text-align:center"><font color="#0070C0">CH</font>emical <font color="#0070C0">RIS</font>k calculator (CHRIS) - Color additives</h1>
 </header>
 <h2 id="context-of-use-cou">Context of Use (COU)</h2>
-<p>The Color Hazard and RISk calculator (CHRIS) is (proposed to be) qualified to conduct screening level risk assessments to aid in the biocompatibility evaluation of polymeric medical device components that contain color additives (CAs)<a href="#fn1" class="footnote-ref" id="fnref1" role="doc-noteref"><sup>1</sup></a>. These assessments can assist device manufacturers by providing instantaneous feedback on whether the presence of CAs or other additives and impurities associated with CAs in a device would require additional justification and/or testing to demonstrate acceptable biological risk. The output of CHRIS is a conservative margin of safety (MOS = toxicological safety limit ÷ exposure dose) value for a CA (and associated additives and impurities) contained within a polymeric medical device component. Based on the MOS value, the calculator determines if further assessment of one or more biocompatibility endpoints is necessary for the CA and/or associated impurities.</p>
-<p>Because CHRIS only addresses CAs, a favorable outcome by CHRIS does not imply acceptable biological risk for the final finished form of a medical device. CHRIS is also not intended to establish device classification or identify biocompatibility requirements. However, in addition to providing guidance to device manufacturers on acceptable levels of CA in a particular device, CHRIS can potentially be used to:</p>
+<p>The CHRIS - Color additives module is (proposed to be) qualified to conduct screening level risk assessments to aid in the biocompatibility evaluation of polymeric medical device components that contain color additives (CAs)<a href="#fn1" class="footnote-ref" id="fnref1" role="doc-noteref"><sup>1</sup></a>. These assessments can assist device manufacturers by providing instantaneous feedback on whether the presence of CAs or other additives and impurities associated with CAs in a device would require additional justification and/or testing to demonstrate acceptable biological risk. The output is a conservative margin of safety (MOS = toxicological safety limit ÷ exposure dose) value for a CA (and associated additives and impurities) contained within a polymeric medical device component. Based on the MOS value, the calculator determines if further assessment of one or more biocompatibility endpoints is necessary for the CA and/or associated impurities.</p>
+<p>Because the CHRIS - color additive module only addresses CAs, a favorable outcome does not imply acceptable biological risk for the final finished form of a medical device. CHRIS is also not intended to establish device classification or identify biocompatibility requirements. However, in addition to providing guidance to device manufacturers on acceptable levels of CA in a particular device, the tool can potentially be used to:</p>
 <ul>
 <li>reduce the amount of biocompatibility testing needed following a supplier or manufacturing changes related to only the presence of the CA in the device;</li>
 <li>obviate the need for additional biocompatibility testing when existing biocompatibility testing is inconclusive with respect to a CA. For example, when biocompatibility extracts are colored, yet pass the testing (note that the presence of colored extracts may give rise to additional concerns unrelated to the color additive);</li>
@@ -32,14 +32,14 @@
 <li>Ultramarine blue - CAS #57455-37-5</li>
 <li>Pigment Yellow 138 - CAS # 30125-47-4</li>
 </ul>
-<p>CHRIS provides clinically relevant, yet still conservative, exposure dose estimates using a physics-based transport model for polymeric systems where transport data are available to support the use of the model. The model applies worst-case boundary conditions for release of a substance from the polymer matrix and is based on four (4) primary assumptions:</p>
+<p>The CHRIS - Color additives module provides clinically relevant, yet still conservative, exposure dose estimates using a physics-based transport model for polymeric systems where transport data are available to support the use of the model. The model applies worst-case boundary conditions for release of a substance from the polymer matrix and is based on four (4) primary assumptions:</p>
 <ol type="1">
 <li>The polymer does not swell or degrade in-vivo, nor does the presence of CA impact the integrity of the polymer.</li>
 <li>The total amount of CA is present in dilute concentrations (&lt;= 2 % m/v) within the colored component.</li>
 <li>The CA is homogeneously distributed throughout the polymer.</li>
 <li>The smallest dimension of the colored device component is much greater than the size of any color additive particles that may be present (&lt;= 50x).</li>
 </ol>
-<p>While these assumptions are typically valid for color additive containing device components, users of CHRIS must confirm conformance to the underlying assumptions or provide supporting justification to ensure compliance for a given system. Further, CHRIS only enables system specific exposure estimates for nineteen (19) polymeric systems that are generally biostable (non-swelling and non-degrading) and contain less than 2 % m/v of a given CA. These polymers are listed below. To estimate CA release based on the model, the diffusion coefficient of the CA in the polymer matrix must be specified. For the nineteen (19) listed polymeric systems, a worst-case (upper bound) diffusion coefficient, as a function of additive molecular weight, has been established based on data from the literature. For polymer matrices that are not included in this list, CHRIS assigns an ultra-conservative diffusion coefficient that assumes the polymer has the properties of water. Note that the worst-case diffusion coefficient is only defined over a molecular weight range of 100 to 1100 g/mol. Therefore, for substances with a molecular weight &gt; 1100 g/mol, the value of the diffusion coefficient assuming a molecular weight of 1100 g/mol can be used as a conservative value; for substances with a molecular weight &lt; 100 g/mol, CHRIS currently cannot be used to estimate exposure.</p>
+<p>While these assumptions are typically valid for color additive containing device components, users of the tool must confirm conformance to the underlying assumptions or provide supporting justification to ensure compliance for a given system. Further, CHRIS only enables system specific exposure estimates for nineteen (19) polymeric systems that are generally biostable (non-swelling and non-degrading) and contain less than 2 % m/v of a given CA. These polymers are listed below. To estimate CA release based on the model, the diffusion coefficient of the CA in the polymer matrix must be specified. For the nineteen (19) listed polymeric systems, a worst-case (upper bound) diffusion coefficient, as a function of additive molecular weight, has been established based on data from the literature. For polymer matrices that are not included in this list, CHRIS assigns an ultra-conservative diffusion coefficient that assumes the polymer has the properties of water. Note that the worst-case diffusion coefficient is only defined over a molecular weight range of 100 to 1100 g/mol. Therefore, for substances with a molecular weight &gt; 1100 g/mol, the value of the diffusion coefficient assuming a molecular weight of 1100 g/mol can be used as a conservative value; for substances with a molecular weight &lt; 100 g/mol, CHRIS currently cannot be used to estimate exposure.</p>
 <ul>
 <li>Silicone</li>
 <li>Polyethylene (density &lt;= 0.94 g/cm<sup>3</sup>)</li>

color_module/static/COU.md

@@ -9,21 +9,21 @@
 </head>
 
 <header>
-   <h1 style="text-align:center"><font color="#0070C0">C</font>olor <font color="#0070C0">H</font>azard and <font color="#0070C0">RIS</font>k calculator (CHRIS) </h1>
+   <h1 style="text-align:center"><font color="#0070C0">CH</font>emical <font color="#0070C0">RIS</font>k calculator (CHRIS) - Color additives</h1>
 </header>
 ```
 
 ## Context of Use (COU)
 
-The Color Hazard and RISk calculator (CHRIS) is (proposed to be) qualified to conduct screening level risk assessments 
+The CHRIS - Color additives module is (proposed to be) qualified to conduct screening level risk assessments 
 to aid in the biocompatibility evaluation of polymeric medical device components that contain color additives (CAs)[^1]. These assessments can assist device manufacturers by providing instantaneous feedback on whether the presence of CAs or 
 other additives and impurities associated with CAs in a device would require additional justification and/or testing to 
-demonstrate acceptable biological risk.  The output of CHRIS is a conservative margin of safety (MOS = toxicological 
+demonstrate acceptable biological risk.  The output is a conservative margin of safety (MOS = toxicological 
 safety limit &#247; exposure dose) value for a CA (and associated additives and impurities) contained within a polymeric 
 medical device component.  Based on the MOS value, the calculator determines if further assessment of one or more 
 biocompatibility endpoints is necessary for the CA and/or associated impurities.
 
-Because CHRIS only addresses CAs, a favorable outcome by CHRIS does not imply acceptable biological risk for the final finished form of a medical device.  CHRIS is also not intended to establish device classification or identify biocompatibility requirements.  However, in addition to providing guidance to device manufacturers on acceptable levels of CA in a particular device, CHRIS can potentially be used to:
+Because the CHRIS - color additive module only addresses CAs, a favorable outcome does not imply acceptable biological risk for the final finished form of a medical device.  CHRIS is also not intended to establish device classification or identify biocompatibility requirements.  However, in addition to providing guidance to device manufacturers on acceptable levels of CA in a particular device, the tool can potentially be used to:
 
 * reduce the amount of biocompatibility testing needed following a supplier or manufacturing changes related to only the presence of the CA in the device;
 * obviate the need for additional biocompatibility testing when existing biocompatibility testing is inconclusive with respect to a CA. For example, when biocompatibility extracts are colored, yet pass the testing (note that the presence of colored extracts may give rise to additional concerns unrelated to the color additive);
@@ -43,14 +43,14 @@ In the absence of adequate toxicological and exposure data for a CA (or associat
 * Ultramarine blue - CAS #57455-37-5
 * Pigment Yellow 138 - CAS # 30125-47-4
 
-CHRIS provides clinically relevant, yet still conservative, exposure dose estimates using a physics-based transport model for polymeric systems where transport data are available to support the use of the model.  The model applies worst-case boundary conditions for release of a substance from the polymer matrix and is based on four (4) primary assumptions:
+The CHRIS - Color additives module provides clinically relevant, yet still conservative, exposure dose estimates using a physics-based transport model for polymeric systems where transport data are available to support the use of the model.  The model applies worst-case boundary conditions for release of a substance from the polymer matrix and is based on four (4) primary assumptions:
 
 1. The polymer does not swell or degrade in-vivo, nor does the presence of CA impact the integrity of the polymer.
 1. The total amount of CA is present in dilute concentrations (<= 2 % m/v) within the colored component.
 1. The CA is homogeneously distributed throughout the polymer.
 1. The smallest dimension of the colored device component is much greater than the size of any color additive particles that may be present (<= 50x).
 
-While these assumptions are typically valid for color additive containing device components, users of CHRIS must confirm conformance to the underlying assumptions or provide supporting justification to ensure compliance for a given system.  Further, CHRIS only enables system specific exposure estimates for nineteen (19) polymeric systems that are generally biostable (non-swelling and non-degrading) and contain less than 2 % m/v of a given CA.  These polymers are listed below.  To estimate CA release based on the model, the diffusion coefficient of the CA in the polymer matrix must be specified.  For the nineteen (19) listed polymeric systems, a worst-case (upper bound) diffusion coefficient, as a function of additive molecular weight, has been established based on data from the literature.  For polymer matrices that are not included in this list, CHRIS assigns an ultra-conservative diffusion coefficient that assumes the polymer has the properties of water.  Note that the worst-case diffusion coefficient is only defined over a molecular weight range of 100 to 1100 g/mol.  Therefore, for substances with a molecular weight > 1100 g/mol, the value of the diffusion coefficient assuming a molecular weight of 1100 g/mol can be used as a conservative value; for substances with a molecular weight < 100 g/mol, CHRIS currently cannot be used to estimate exposure.
+While these assumptions are typically valid for color additive containing device components, users of the tool must confirm conformance to the underlying assumptions or provide supporting justification to ensure compliance for a given system.  Further, CHRIS only enables system specific exposure estimates for nineteen (19) polymeric systems that are generally biostable (non-swelling and non-degrading) and contain less than 2 % m/v of a given CA.  These polymers are listed below.  To estimate CA release based on the model, the diffusion coefficient of the CA in the polymer matrix must be specified.  For the nineteen (19) listed polymeric systems, a worst-case (upper bound) diffusion coefficient, as a function of additive molecular weight, has been established based on data from the literature.  For polymer matrices that are not included in this list, CHRIS assigns an ultra-conservative diffusion coefficient that assumes the polymer has the properties of water.  Note that the worst-case diffusion coefficient is only defined over a molecular weight range of 100 to 1100 g/mol.  Therefore, for substances with a molecular weight > 1100 g/mol, the value of the diffusion coefficient assuming a molecular weight of 1100 g/mol can be used as a conservative value; for substances with a molecular weight < 100 g/mol, CHRIS currently cannot be used to estimate exposure.
 
 * Silicone
 * Polyethylene (density <= 0.94 g/cm<sup>3</sup>)

color_module/static/Changelog.html

@@ -1,15 +0,0 @@
-<!DOCTYPE html>
-<html lang="en">
-<head>
-    <title>CHRIS-COU</title>
-    <link rel="stylesheet" href="styles.css">
-    <meta charset="UTF-8">
-    
-</head>
-
-<header>
-   <h1 style="text-align:center"><font color="#0070C0">C</font>olor <font color="#0070C0">H</font>azard and <font color="#0070C0">RIS</font>k calculator (CHRIS) </h1>
-</header>
-<h2 id="change-log">Change Log</h2>
-<h3 id="version-1.0---2022-08-23">Version 1.0 - 2022-08-23</h3>
-<p>Original release</p>

color_module/static/FAQ.html

@@ -7,7 +7,7 @@
 </head>
 
 <header>
-   <h1 style="text-align:center"><font color="#0070C0">C</font>olor <font color="#0070C0">H</font>azard and <font color="#0070C0">RIS</font>k calculator (CHRIS) </h1>
+   <h1 style="text-align:center"><font color="#0070C0">CH</font>emical <font color="#0070C0">RIS</font>k calculator (CHRIS) - Color additives</h1>
 </header>
 <h2 id="frequently-asked-questions">Frequently asked questions</h2>
 <h3 id="what-is-the-primary-purpose-of-chris">What is the primary purpose of CHRIS?</h3>

color_module/static/FAQ.md

@@ -8,7 +8,7 @@
 </head>
 
 <header>
-   <h1 style="text-align:center"><font color="#0070C0">C</font>olor <font color="#0070C0">H</font>azard and <font color="#0070C0">RIS</font>k calculator (CHRIS) </h1>
+   <h1 style="text-align:center"><font color="#0070C0">CH</font>emical <font color="#0070C0">RIS</font>k calculator (CHRIS) - Color additives</h1>
 </header>
 ```
 

color_module/static/README.html

@@ -7,10 +7,10 @@
 </head>
 
 <header>
-   <h1 style="text-align:center"><font color="#0070C0">C</font>olor <font color="#0070C0">H</font>azard and <font color="#0070C0">RIS</font>k calculator (CHRIS) </h1>
+   <h1 style="text-align:center"><font color="#0070C0">CH</font>emical <font color="#0070C0">RIS</font>k calculator (CHRIS) - Color additives</h1>
 </header>
 <h2 id="overview">Overview</h2>
-<p>The Color Hazard and RISk calculator (CHRIS) is a tool under development within the Center for Devices and Radiological Health (CDRH) at the Food and Drug Administration (FDA). The tool enables the user to perform rapid, screening level toxicological risk assessments of color additives and additives and impurities associated with the color additive that might be released from a polymer medical device component. CHRIS applies a model that computes an exposure estimate and compares the result to a tolerable exposure (TE) or threshold of toxicological concern (TTC) value. The tool assists the user in determining (a) whether the toxicological risk of a color additive associated substance should be further assessed and/or (b) the potential impact of the substance on device biocompatibility.</p>
+<p>The CHRIS - Color additives module is a tool under development within the Center for Devices and Radiological Health (CDRH) at the Food and Drug Administration (FDA). The tool enables the user to perform rapid, screening level toxicological risk assessments of color additives and additives and impurities associated with the color additive that might be released from a polymer medical device component. CHRIS applies a model that computes an exposure estimate and compares the result to a tolerable exposure (TE) or threshold of toxicological concern (TTC) value. The tool assists the user in determining (a) whether the toxicological risk of a color additive associated substance should be further assessed and/or (b) the potential impact of the substance on device biocompatibility.</p>
 <h2 id="important-considerations">Important considerations</h2>
 <ol type="1">
 <li><p>CHRIS assists in screening the potential risk of a color additive associated substance in a polymer medical device component. Because color additives and concentrates may contain multiple distinct substances, e.g. impurities and carrier resins, CHRIS can be used to evaluate each substance present in the component individually.</p></li>

color_module/static/README.md

@@ -8,13 +8,13 @@
 </head>
 
 <header>
-   <h1 style="text-align:center"><font color="#0070C0">C</font>olor <font color="#0070C0">H</font>azard and <font color="#0070C0">RIS</font>k calculator (CHRIS) </h1>
+   <h1 style="text-align:center"><font color="#0070C0">CH</font>emical <font color="#0070C0">RIS</font>k calculator (CHRIS) - Color additives</h1>
 </header>
 ```
 
 ## Overview
 
-The Color Hazard and RISk calculator (CHRIS) is a tool under development within the Center for Devices and Radiological Health (CDRH) at the Food and Drug Administration (FDA). The tool enables the user to perform rapid, screening level toxicological risk assessments of color additives and additives and impurities associated with the color additive that might be released from a polymer medical device component. CHRIS applies a model that computes an exposure estimate and compares the result to a tolerable exposure (TE) or threshold of toxicological concern (TTC) value. The tool assists the user in determining (a) whether the toxicological risk of a color additive associated substance should be further assessed and/or (b) the potential impact of the substance on device biocompatibility.
+The CHRIS - Color additives module is a tool under development within the Center for Devices and Radiological Health (CDRH) at the Food and Drug Administration (FDA). The tool enables the user to perform rapid, screening level toxicological risk assessments of color additives and additives and impurities associated with the color additive that might be released from a polymer medical device component. CHRIS applies a model that computes an exposure estimate and compares the result to a tolerable exposure (TE) or threshold of toxicological concern (TTC) value. The tool assists the user in determining (a) whether the toxicological risk of a color additive associated substance should be further assessed and/or (b) the potential impact of the substance on device biocompatibility.
 
 ## Important considerations
 

color_module/static/md2html.sh

@@ -3,4 +3,3 @@
 pandoc FAQ.md > FAQ.html
 pandoc README.md > README.html
 pandoc COU.md > COU.html
-pandoc Changelog.md > Changelog.html

color_module/templates/index.html

@@ -15,10 +15,9 @@
   <h1 style="text-align:center"><font color="#0070C0">CH</font>emical <font color="#0070C0">RIS</font>k calculator (CHRIS) - Color additives </h1>
 </header>
 
-<p> For details on how to use CHRIS, please read the <a href="{{url_for('.static', filename='README.html')}}"> instructions.</a> and
+<p> For details on how to use the CHRIS color additive module, please read the <a href="{{url_for('.static', filename='README.html')}}"> instructions</a> and
   <a href="{{url_for('.static', filename='COU.html')}}"> context of use (COU)</a>, which includes limitations of use. Answers to frequently asked questions can be
-  found <a href="{{url_for('.static', filename='FAQ.html')}}"> here</a>.  For a history of updates, please see the
-  <a href="{{url_for('.static', filename='Changelog.html')}}"> changelog</a>. </p>
+  found <a href="{{url_for('.static', filename='FAQ.html')}}"> here</a>. </p>
 
 <body>
 

color_module/templates/report.html

@@ -16,7 +16,7 @@
 
 <body>
 
-<p> The following report was generated using CHRIS v.1.0 on 
+<p> The following report was generated using CHRIS v.1.1 on
 <script> document.write(new Date().toLocaleDateString()); </script>.
 </p>
 

{color_module/static → static}/Changelog.md

@@ -9,11 +9,17 @@
 </head>
 
 <header>
-   <h1 style="text-align:center"><font color="#0070C0">C</font>olor <font color="#0070C0">H</font>azard and <font color="#0070C0">RIS</font>k calculator (CHRIS) </h1>
+   <h1 style="text-align:center"><font color="#0070C0">CH</font>emical <font color="#0070C0">RIS</font>k calculator (CHRIS) </h1>
 </header>
 ```
 ## Change Log
 
+### Version 1.1 - 2022-09-26
+
+* Renamed "Color Hazard RISk calculator" to "CHemical RISk calculator"
+* Color additive tool is now "CHemical RISk calculator - Color additives"
+* Added landing page
+
 ### Version 1.0 - 2022-08-23
 
-Original release
+* Original release

static/md2html.sh

@@ -0,0 +1,3 @@
+#!/bin/bash
+
+pandoc Changelog.md > Changelog.html

templates/main.html

@@ -8,9 +8,11 @@
 
 </head>
 
+<!--
 <img src="{{ url_for('static',filename='images/FDAlogo.png') }}" style="float: left;" height="100"/>
 <img src="{{ url_for('static',filename='images/FDAgraphic.png') }}" style="float: right;"  height="100"/>
 <br clear="all" />
+-->
 
 <header>
   <h1 style="text-align:center">CHRIS: <font color="#0070C0">CH</font>emical <font color="#0070C0">RIS</font>k calculator</h1>
@@ -19,14 +21,16 @@
 <body>
 
 <p>
-The CHemical RISk calculator (CHRIS) is a collection of MDDT-qualified modules to facilitate the use of physics-based models to estimate exposure
-as part of toxicological risk assessment (TRA) of medical device polymers.
+The CHemical RISk calculator (CHRIS) is a collection of modules to facilitate the use of physics-based models to estimate exposure
+as part of toxicological risk assessment (TRA) of medical device polymers.  For a history of updates, please see the
+  <a href="{{url_for('static', filename='Changelog.html')}}"> changelog</a>.
  </p>
-
+<!--
 <p>
 Note: Currently, there is only one MDDT-qualified module available.  However, there is a development version that includes additional modules
     and functionality, which are not yet formally qualified for regulatory use, available <a href="https://chrisdev-osel.pythonanywhere.com">here</a>.
  </p>
+-->
 
 <h2>Modules</h2>