Document ID: FDA-2007-D-0207-0007
Agency: fda
Document Type: Supporting & Related Material
Title: 
Posted Date: 2008-06-26T04:00Z

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<SPAN STYLE="color:#000000;position:absolute;left:94.10pt;top:74.00pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 48.00pt">Guidance for Industry</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:126.65pt;top:183.30pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 24.00pt">Microbiological Considerations for</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:91.60pt;top:210.90pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 24.00pt">Antimicrobial Food Additive Submissions</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:230.70pt;top:295.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><i><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">Additional copies are available from:</FONT></FONT></i></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:245.45pt;top:306.90pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><i><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">Office of Food Additive Safety</FONT></FONT></i></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:231.55pt;top:318.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><i><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">Division of Petition Review HFS-265</FONT></FONT></i></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:214.85pt;top:329.85pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><i><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">Center for Food Safety and Applied Nutrition</FONT></FONT></i></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:243.60pt;top:341.40pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><i><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">Food and Drug Administration</FONT></FONT></i></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:248.95pt;top:352.85pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><i><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">51</FONT></FONT></i></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:258.95pt;top:352.85pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><i><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">0</FONT></FONT></i></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:263.95pt;top:352.85pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><i><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">0</FONT></FONT></i></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:271.45pt;top:352.85pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><i><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">Paint Branch Parkway</FONT></FONT></i></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:254.15pt;top:364.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><i><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">College Park, MD 20740</FONT></FONT></i></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:266.65pt;top:375.90pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><i><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">(Tel) 301-436-1226</FONT></FONT></i></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:225.95pt;top:387.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><i><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt"><a href="http://www.cfsan.fda.gov/guidance.html">http://www.cfsan.fda</a></FONT></FONT><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">.</FONT></FONT><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt"><a href="http://www.cfsan.fda.gov/guidance.html">gov</a></FONT></FONT><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">/</FONT></FONT><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt"><a href="http://www.cfsan.fda.gov/guidance.html">gu</a></FONT></FONT><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">i</FONT></FONT><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt"><a href="http://www.cfsan.fda.gov/guidance.html">dance.h</a></FONT></FONT><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">t</FONT><FONT COLOR="000000"></FONT><FONT STYLE="font-size: 10.02pt"><a href="http://www.cfsan.fda.gov/guidance.html">ml</a></FONT></i><FONT STYLE="font-size: 10.02pt"></FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:433.40pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">You may submit written or electronic comments regarding this guidance at any time.  Submit</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:447.20pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">written comments on the guidance to the Division of Dockets Management (HFA-305), Food</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:461.00pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.  Submit</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:474.80pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">electronic comments to </FONT></FONT><u><FONT COLOR="0000ff"><FONT STYLE="font-size: 12.00pt"><a href="http://www.regulations.gov">http://www.regulations.gov</a></FONT></FONT></u><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:183.00pt;top:571.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">U.S. Department of Health and Human Services</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:226.15pt;top:585.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Food and Drug Administration</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:188.65pt;top:599.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Center for Food Safety and Applied Nutrition</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:280.15pt;top:612.95pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">June 2008</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="position:absolute;left:71.76pt;top:792.00pt"> </SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:252.70pt;top:878.45pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 13.98pt">Table of Contents</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:910.50pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">I.</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:910.50pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Introduction</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:936.30pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">II.</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:936.30pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Questions and Answers</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:961.95pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">A.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:144.00pt;top:961.95pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">What is and is not a food additive?</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:987.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">B.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:144.00pt;top:987.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">What is an antimicrobial food additive?</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:1013.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">C.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:144.00pt;top:1013.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">What is FDA’s regulatory authority with respect to antimicrobial food additives?</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:1039.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">D.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:144.00pt;top:1039.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">What is FDA’s regulatory authority with respect to requesting microbiological</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:144.00pt;top:1053.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">data?</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:1078.90pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">E.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:144.00pt;top:1078.90pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">How do I get my antimicrobial food additive approved?</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:1104.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">F.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:144.00pt;top:1104.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Why does FDA require that data on the intended effect of an antimicrobial food</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:144.00pt;top:1118.50pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">additive be included as part of the submission seeking approval of the additive?</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:1146.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">G.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:144.00pt;top:1146.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">What types of data and other information should be included to demonstrate that</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:144.00pt;top:1159.90pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">the use of an antimicrobial food additive achieves its intended physical or other</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:144.00pt;top:1173.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">technical effect?</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:1199.50pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">H.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:144.00pt;top:1199.50pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">How should a study be designed to demonstrate the antimicrobial food additive’s</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:144.00pt;top:1213.30pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">effect?</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:1239.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">I.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:144.00pt;top:1239.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Are there unique circumstances that should be taken into consideration when</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:144.00pt;top:1252.90pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">designing a study to show that an antimicrobial food additive achieves its</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:144.00pt;top:1266.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">intended effect?</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:1292.50pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">J.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:144.00pt;top:1292.50pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Does FDA recommend any specific experimental methods?</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:1318.30pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">K.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:144.00pt;top:1318.30pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">What is FDA’s performance standard for a new antimicrobial food additive?</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:1344.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">L.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:144.00pt;top:1344.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">What information may be helpful to provide to FDA to demonstrate the intended</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:144.00pt;top:1357.90pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">technical effect of a source of radiation as an antimicrobial treatment for food?</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:1383.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">M.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:144.00pt;top:1383.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">What additional safety information may be helpful to provide to FDA if my</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:144.00pt;top:1397.50pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">antimicrobial food additive is derived from a microorganism?</FONT></FONT></FONT></SPAN>
<span style="color:#000000;background-color:#ffffff;position:absolute;left:0.00pt;top:792.00pt;z-index:-1;"><img style="width:612pt;height:792pt;" src="outputfile1388387824.htm_files\outputfile1388387824_background1.png"></span>
<SPAN STYLE="position:absolute;left:71.76pt;top:1584.00pt"> </SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:205.25pt;top:1620.45pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><i><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Contains Nonbinding Recommendations</FONT></FONT></i></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:303.00pt;top:2326.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">1</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:226.45pt;top:1668.05pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 16.02pt">Guidance for Industry</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:380.30pt;top:1665.45pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 10.50pt">1</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:186.40pt;top:1698.45pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 16.02pt">Microbiological Considerations for</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:163.10pt;top:1716.80pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 16.02pt">Antimicrobial Food Additive Submissions</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1759.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">This guidance represents the Food and Drug Administration's (FDA's) current thinking on this</FONT></FONT></FONT></SPAN>
<SPAN STYLE="position:absolute;font-size:0;left:65pt;top:1757pt;width: 1pt;height: 1pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:65pt;top:1757pt;width: 1pt;height: 1pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:66pt;top:1757pt;width:478pt;height: 1pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:545pt;top:1757pt;width: 1pt;height: 1pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:545pt;top:1757pt;width: 1pt;height: 1pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:65pt;top:1758pt;width: 1pt;height:14pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:545pt;top:1758pt;width: 1pt;height:14pt;background-color:#000000;"></SPAN><SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1773.30pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">topic.  It does not create or confer any rights for or on any person and does not operate to bind</FONT></FONT></FONT></SPAN>
<SPAN STYLE="position:absolute;font-size:0;left:65pt;top:1772pt;width: 1pt;height:13pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:545pt;top:1772pt;width: 1pt;height:13pt;background-color:#000000;"></SPAN><SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1787.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">FDA or the public.  You can use an alternative approach if the approach satisfies the</FONT></FONT></FONT></SPAN>
<SPAN STYLE="position:absolute;font-size:0;left:65pt;top:1786pt;width: 1pt;height:13pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:545pt;top:1786pt;width: 1pt;height:13pt;background-color:#000000;"></SPAN><SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1800.90pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">requirements of the applicable statutes and regulations.  If you want to discuss an alternative</FONT></FONT></FONT></SPAN>
<SPAN STYLE="position:absolute;font-size:0;left:65pt;top:1800pt;width: 1pt;height:13pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:545pt;top:1800pt;width: 1pt;height:13pt;background-color:#000000;"></SPAN><SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1814.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">approach, contact the FDA staff responsible for implementing this guidance.  If you cannot</FONT></FONT></FONT></SPAN>
<SPAN STYLE="position:absolute;font-size:0;left:65pt;top:1814pt;width: 1pt;height:13pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:545pt;top:1814pt;width: 1pt;height:13pt;background-color:#000000;"></SPAN><SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1828.50pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">identify the appropriate FDA staff, call the appropriate telephone number listed on the title page</FONT></FONT></FONT></SPAN>
<SPAN STYLE="position:absolute;font-size:0;left:65pt;top:1828pt;width: 1pt;height:13pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:545pt;top:1828pt;width: 1pt;height:13pt;background-color:#000000;"></SPAN><SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1842.45pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">of this guidance.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="position:absolute;font-size:0;left:65pt;top:1856pt;width: 1pt;height: 1pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:65pt;top:1856pt;width: 1pt;height: 1pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:66pt;top:1856pt;width:478pt;height: 1pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:545pt;top:1856pt;width: 1pt;height: 1pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:545pt;top:1856pt;width: 1pt;height: 1pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:65pt;top:1841pt;width: 1pt;height:14pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:545pt;top:1841pt;width: 1pt;height:14pt;background-color:#000000;"></SPAN><SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1880.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">I.</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:1880.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Introduction</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1908.20pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">The Food and Drug Administration (FDA) is responsible for prescribing the conditions of safe</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1922.00pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">use of food additives under section 409 of the Federal Food, Drug, and Cosmetic Act (the Act).</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1935.80pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">To evaluate the safety of food additives and determine their conditions of safe use, the agency</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1949.60pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">uses the food additive petition (FAP) process and the food contact notification (FCN) process.  In</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1963.40pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">addition, FDA may, upon request, exempt from regulation as a food additive those substances</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1977.20pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">used in food-contact articles (also known as food contact substances) that migrate into food at</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1991.00pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">levels that are below the threshold of regulation (TOR).  This guidance is directed at questions</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2004.80pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">regarding microbiological data requirements for FAPs, FCNs, and TOR requests that are unique</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2018.60pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">to the use of antimicrobial food additives and food contact substances.  This guidance will assist</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2032.40pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">petitioners and notifiers in designing studies to determine whether an antimicrobial food additive</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2046.20pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">achieves its intended technical effect.  Also, this guidance discusses microbiological data that</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2060.00pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">may be necessary to demonstrate that an antimicrobial agent will be safe for the intended use.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2079.80pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">This guidance applies to all FAPs, FCNs and TOR requests where the food additive is intended</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2093.60pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">to control microbes in or on food. This includes sources of radiation for treating food.  However,</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2107.40pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">it is important to note that the U.S. Department of Agriculture (USDA) Food Safety and</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2121.20pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Inspection Service (FSIS) is responsible for determining the suitability of food additives in meat</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2135.00pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">and poultry products; according to FSIS, “suitability relates to the effectiveness of the substance</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2148.80pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">in performing the intended technical purpose of use, at the lowest level necessary, and the</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2162.60pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">assurance that the conditions of use will not result in an adulterated product or one that misleads</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2176.40pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">consumers.”</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:131.65pt;top:2174.50pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 7.98pt">2</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:141.65pt;top:2176.40pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">FSIS derives its authority to regulate the suitability of food additives in meat and</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2190.20pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">poultry from the Federal Meat Inspection Act (FMIA) and the Poultry Products Inspection Act</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2204.00pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">(PPIA), respectively.  FDA and FSIS currently have a Memorandum of Understanding (MOU)</FONT></FONT></FONT></SPAN>
<SPAN STYLE="position:absolute;font-size:0;left:72pt;top:2229pt;width:144pt;height: 1pt;background-color:#000000;"></SPAN><SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2233.95pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 6.48pt">1</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:77.75pt;top:2235.30pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">This guidance has been prepared by the Office of Food Additive Safety in the Center for Food Safety and Applied</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2246.80pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">Nutrition at the U.S. Food and Drug Administration.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2256.90pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 6.48pt">2</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:77.75pt;top:2258.25pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><i><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">Guidance on the Procedures for Joint Food Safety and Inspection Service (FSIS) and Food and Drug</FONT></FONT></i></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2269.80pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><i><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">Administration (FDA), Approval of Ingredients and Sources of Radiation Used in the Production of Meat and</FONT></FONT></i></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2281.30pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><i><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">Poultry Products, U.S. Department of Agriculture, Docket No. 00-022N, E. coli O157:H7 Contamination of Beef</FONT></FONT></i></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2292.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">Products.</FONT></FONT></FONT></SPAN>
<span style="color:#000000;background-color:#ffffff;position:absolute;left:0.00pt;top:1584.00pt;z-index:-1;"><img style="width:612pt;height:792pt;" src="outputfile1388387824.htm_files\outputfile1388387824_background2.png"></span>
<SPAN STYLE="position:absolute;left:71.76pt;top:2376.00pt"> </SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:206.75pt;top:2412.45pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><i><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Contains Nonbinding Recommendations</FONT></FONT></i></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:285.00pt;top:3118.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">2</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2448.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">regarding each agency's responsibilities in the evaluation and approval of food ingredients and</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2462.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">sources of radiation used in the production of meat and poultry products</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2475.95pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">(</FONT></FONT><u><FONT COLOR="0000ff"><FONT STYLE="font-size: 12.00pt"><a href="http://www.fsis.usda.gov/OPPDE/larc/ingredients/mou.htm">http://www.fsis.usda.gov/OPPDE/larc/ingredients/mou.htm</a></FONT></FONT></u><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">).  In accordance with this MOU,</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2489.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">FDA will collaborate with FSIS on any antimicrobial food additive submission to FDA involving</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2503.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">meat or poultry.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2523.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Given the complexity and variety of antimicrobial products and the diverse conditions of use, no</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2537.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">single document can anticipate and address all microbiological issues.  Therefore, this guidance</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2550.95pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">is intended to answer common questions associated with microbiological data requirements for</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2564.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">FAPs, FCNs, or TOR requests for antimicrobial food additives so that meaningful and sufficient</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2578.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">data are provided with each submission.  It is intended to assist developers of antimicrobial</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2592.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">agents for use in or on food in providing evidence to support their intended uses.  FDA</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2606.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">recommends that petitioners and notifiers discuss with the agency any proposed studies prior to</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2619.95pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">their initiation to ensure that these studies will address FDA’s safety concerns.  In addition, FDA</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2633.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">recommends that submitters meet with the agency prior to the submission of a petition or</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2647.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">notification to prevent an expenditure of resources on activities that may not provide adequate</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2661.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">data.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2681.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">FDA's guidance documents, including this guidance, do not establish legally enforceable</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2694.95pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">responsibilities.  Instead, guidances describe the Agency's current thinking on a topic and should</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2708.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">be viewed only as recommendations, unless specific regulatory or statutory requirements are</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2722.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">cited.  The use of the word should in Agency guidances means that something is suggested or</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2736.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">recommended, but not required.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2776.05pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">II.</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:2776.05pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Questions and Answers</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2795.85pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">A.</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:2795.85pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><u><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">What is and is not a food additive?</FONT></FONT></u></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2815.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">The term “food additive” is defined in section 201(s) of the Act.  The first part of that section</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2829.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">states that a food additive is any substance the intended use of which results or may reasonably</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2843.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">be expected to result, directly or indirectly, in its becoming a component or otherwise affecting</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2856.90pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">the characteristics of any food including any substance intended for use in packing, packaging,</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2870.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">producing, manufacturing, processing, preparing, treating, transporting, or holding food; and</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2884.50pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">including any source of radiation intended for any such use.  Section 201(s) goes on to expressly</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2898.30pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">exempt from the definition of food additive certain categories of substances, including</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2912.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">substances that are "generally recognized as safe" or "GRAS" for the intended use.  A partial list</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2925.90pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">of substances recognized by FDA as GRAS may be found in 21 CFR Part 182, and a list of</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2939.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">substances affirmed by FDA as GRAS appears in 21 CFR Part 184.  These lists may include</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2953.50pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">substances which are GRAS for use as antimicrobial agents.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="position:absolute;left:71.76pt;top:3168.00pt"> </SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:205.25pt;top:3204.45pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><i><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Contains Nonbinding Recommendations</FONT></FONT></i></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:303.00pt;top:3910.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">3</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3271.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">"Pesticide chemicals," as defined at section 201(q) of the Act, are exempt from the definition of a</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3285.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">food additive.  Pesticide chemicals and pesticide chemical residues in or on food must conform</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3299.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">to a tolerance, or an exemption from tolerance, established by the Environmental Protection</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3312.95pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Agency (EPA) under section 408 of the Act.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3332.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">For the complete definition of a food additive and the exemptions, see section 201(s) of the Act</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3346.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">(</FONT></FONT><u><FONT COLOR="0000ff"><FONT STYLE="font-size: 12.00pt"><a href="http://www.fda.gov/opacom/laws/fdcact/fdctoc.htm">http://www.fda.gov/opacom/laws/fdcact/fdctoc.htm</a></FONT></FONT></u><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">).</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3386.25pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">B.</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:3386.25pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><u><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">What is an antimicrobial food additive?</FONT></FONT></u></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3405.95pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">The term “antimicrobial food additive,” as used in this guidance, refers to a substance or a source</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3419.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">of radiation that meets the food additive definition and is used to control microorganisms such as</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3433.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">bacteria, viruses, fungi, protozoa, or other microorganisms in or on food or food contact articles.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3473.25pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">C.</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:3473.25pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><u><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">What is FDA’s regulatory authority with respect to antimicrobial food additives?</FONT></FONT></u></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3492.95pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">FDA is the primary Federal agency responsible for ensuring the safety of food additives.  Under</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3506.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">section 409 of the Act, all food additives are subject to review and approval by FDA before they</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3520.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">can be marketed in the United States.  This guidance applies to FAP, FCN, and TOR</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3534.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">submissions.  Food additives that are intended to have a technical effect in food are authorized</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3548.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">through the petition process prescribed in section 409 of the Act. The standard that FDA applies</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3561.95pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">to determine whether the intended use of a food additive is safe is reasonable certainty of no</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3575.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">harm (see 21 CFR 170.3(i)).  For food additives demonstrated to FDA to be safe under the</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3589.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">intended conditions of use, FDA will issue a regulation that specifies the conditions of safe use.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3603.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">The food additive regulations are codified in 21 CFR parts 172-180 and may be obtained from</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3617.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">the Internet by going to </FONT></FONT><u><FONT COLOR="0000ff"><FONT STYLE="font-size: 12.00pt"><a href="http://www.gpoaccess.gov/cfr/index.html">http://www.gpoaccess.gov/cfr/index.html </a></FONT></FONT></u><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">and searching the current</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3630.90pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">edition of the CFR.  Part 172 lists food additives for direct addition to food, part 173 lists food</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3644.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">additives used during food processing, and parts 174-178 list food additives used in food</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3658.50pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">packaging and other food contact articles.  Approved sources of radiation for inspecting and</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3672.30pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">treating food are listed in 21 CFR part 179.  Food additives permitted in food or in contact with</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3686.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">food on an interim basis pending additional study are listed in 21 CFR part 180.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3705.90pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Food additives that are intended for use as a component of materials used in manufacturing,</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3719.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">packing, packaging, transporting, or holding food, if such uses are not intended to have any</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3733.50pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">technical effect in food, are considered food contact substances (see section 409(h)(6) of the</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3747.30pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Act).  As a result of the FDA Modernization Act of 1997, the primary method for authorizing</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3761.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">new uses of food contact substances is the FCN process (see section 409(h) of the Act).  In the</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3774.90pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">case of a food contact substance, FDA will allow a notification for the subject food contact</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3788.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">substance to become effective prescribing the conditions under which a food additive may be</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3802.50pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">safely used.  The standard used to establish the safety of a food contact substance is the same as</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3816.30pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">that for any other food additive (i.e., reasonable certainty of no harm).  More information on this</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3830.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">process is available at </FONT></FONT><u><FONT COLOR="0000ff"><FONT STYLE="font-size: 12.00pt"><a href="http://www.cfsan.fda.gov/~dms/opa-notf.html">http://www.cfsan.fda.gov/~dms/opa-notf.html</a></FONT></FONT></u><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="position:absolute;left:71.76pt;top:3960.00pt"> </SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:205.25pt;top:3996.45pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><i><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Contains Nonbinding Recommendations</FONT></FONT></i></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:303.00pt;top:4702.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">4</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:4063.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">A current inventory of effective notifications for food contact substances is found at</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:4077.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><u><FONT COLOR="0000ff"><FONT STYLE="font-size: 12.00pt"><a href="http://www.cfsan.fda.gov/~dms/opa-fcn.html">http://www.cfsan.fda.gov/~dms/opa-fcn.html</a></FONT></FONT></u><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:4097.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">In addition, under 21 CFR 170.39, FDA may, upon request, exempt from regulation as a food</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:4110.95pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">additive food contact substances that become a component of food at levels below the threshold</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:4124.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">of regulation.  Such a request is commonly referred to as a threshold of regulation (TOR)</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:4138.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">submission.  More information on the TOR submission process is available at</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:4152.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><u><FONT COLOR="0000ff"><FONT STYLE="font-size: 12.00pt"><a href="http://www.cfsan.fda.gov/~dms/">http://www.cfsan.fda.gov/~dms/</a></FONT></FONT><FONT COLOR="0000ff"><FONT STYLE="font-size: 12.00pt"> torguid.html</FONT></FONT></u><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">.  A current inventory of TOR exemptions issued</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:4166.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">by FDA is available at </FONT></FONT><u><FONT COLOR="0000ff"><FONT STYLE="font-size: 12.00pt"><a href="http://www.cfsan.fda.gov/~dms/opa-torx.html">http://www.cfsan.fda.gov/~dms/opa-torx.html</a></FONT></FONT></u><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">.  The data requirements for</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:4179.95pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">a TOR submission are the same as those for a FAP or FCN and the safety standard that FDA</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:4193.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">applies is the same.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:4213.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">For a detailed discussion of FDA’s regulatory authority over antimicrobial food additives, see</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:4227.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">FDA’s Guidance to Industry entitled Antimicrobial Food Additives – Guidance</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:4241.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">(</FONT></FONT><u><FONT COLOR="0000ff"><FONT STYLE="font-size: 12.00pt"><a href="http://www.cfsan.fda.gov/~dms/opa-antg.html">http://www.cfsan.fda.gov/~dms/opa-antg.html</a></FONT></FONT></u><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">).  It is important to note that, depending on the</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:4254.95pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">proposed use, an antimicrobial food additive may also be a pesticide under the Federal</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:4268.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Insecticide, Fungicide, and Rodenticide Act (FIFRA).  As such, it may be subject to registration</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:4282.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">as a pesticide by the EPA as well as regulation as a food additive.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:4322.25pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">D.</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.05pt;top:4322.25pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><u><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">What is FDA’s regulatory authority with respect to requesting microbiological data?</FONT></FONT></u></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:4341.95pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Microbiological data may need to address certain issues raised by the findings that FDA makes</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:4355.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">under section 409 of the Act.  Several are described below.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:90.00pt;top:4375.10pt;z-index:3;"><FONT FACE ="Symbol" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">x</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:4376.45pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Under section 409(c)(3)(B) of the Act, a food additive regulation will not be established</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:4390.20pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">if an evaluation of the data “shows that the proposed use of the food additive would</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:4404.00pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">promote deception of the consumer in violation of [the] Act or would otherwise result in</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:4417.80pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">adulteration or in misbranding of food within the meaning of the Act.”  Here, the</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:4431.60pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">microbiological data may be used to demonstrate that an antimicrobial agent does not</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:4445.40pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">promote consumer deception, such as making a food product appear to be fresher or of</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:4459.20pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">greater value than it actually is.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:90.00pt;top:4478.55pt;z-index:3;"><FONT FACE ="Symbol" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">x</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:4479.90pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Under section 409(c)(4) of the Act, if “a tolerance limitation is required in order to assure</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:4493.60pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">that the proposed use of an additive will be safe, the Secretary shall not fix such a</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:4507.40pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">tolerance limitation at a level higher than he finds reasonably required to accomplish the</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:4521.20pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">physical or other technical effect for which such additive is intended; and, shall not</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:4535.00pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">establish a regulation for such proposed use if he finds upon a fair evaluation of the data</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:4548.80pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">before him that such data do not establish that such use would accomplish the intended</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:4562.60pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">physical or other technical effect.”  When a tolerance limitation is required, the</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:4576.40pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">microbiological data may be used to demonstrate that an antimicrobial agent achieves its</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:4590.20pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">intended technical effect and that the maximum permitted use level is not higher than</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:4604.00pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">what is reasonably required to achieve this effect.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="position:absolute;left:71.76pt;top:4752.00pt"> </SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:205.25pt;top:4788.45pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><i><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Contains Nonbinding Recommendations</FONT></FONT></i></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:303.00pt;top:5494.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">5</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:90.00pt;top:4855.10pt;z-index:3;"><FONT FACE ="Symbol" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">x</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:4856.45pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Microbiological data may be needed to supplement the safety assessment of the</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:4870.20pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">antimicrobial food additive under section 409(c)(3)(A) of the Act, which states that</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:4884.00pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">“…[n]o such regulation shall issue if a fair evaluation of the data before the Secretary</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:4897.80pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">fails to establish that the proposed use of the food additive, under the conditions of use to</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:4911.60pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">be specified in the regulation, will be safe…”  Cases where microbiological data may be</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:4925.40pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">used to supplement the safety assessment are described in Items I, L, and M below.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:4965.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">E.</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.05pt;top:4965.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><u><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">How do I get my antimicrobial food additive approved?</FONT></FONT></u></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:4984.80pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Antimicrobial food additives are regulated through the FAP process, the FCN process, or the</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:4998.60pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">TOR exemption process.  Section 409(b) of the Act sets forth the statutory requirements for data</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:5012.40pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">in an FAP to establish the safety of a food additive; section 409(h) sets forth the requirements for</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:5026.20pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">notification of a food contact substance; and 21 CFR 170.39 sets forth the requirements for a</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:5040.00pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">TOR submission.  A more detailed description of the information to be submitted in an FAP and</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:5053.80pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">the proper format are specified in 21 CFR 171.1; information requirements for a food contact</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:5067.60pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">notification are found in 21 CFR170.101.  Guidance documents from the FDA detailing the</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:5081.40pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">procedures for preparing and submitting an FAP, FCN, or TOR submission can be found on the</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:5095.20pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Internet at </FONT></FONT><u><FONT COLOR="0000ff"><FONT STYLE="font-size: 12.00pt"><a href="http://www.cfsan.fda.gov/~lrd/foodadd.html">http://www.cfsan.fda.gov/~lrd/foodadd.html</a></FONT></FONT></u><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:5115.00pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">It is important to note that there are some antimicrobial additives for which the proposed use</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:5128.80pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">makes them both a food additive and drug (e.g., a no-rinse hand sanitizer used by food handlers).</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:5142.60pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">In this case, the product will have to comply with the requirements of the Act applicable to both</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:5156.40pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">food additives and drug products.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:5196.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">F.</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:5196.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><u><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Why does FDA require that data on the intended effect of an antimicrobial food</FONT></FONT></u></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:5209.90pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><u><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">additive be included as part of the submission seeking approval of the additive?</FONT></FONT></u></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:5229.60pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Section 409(b)(2)(C) of the Act requires that a petition for a food additive contain all relevant</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:5243.40pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">data bearing on the physical or other technical effect such additive is intended to produce, and</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:5257.20pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">the quantity of such additive required to produce such effect.  Therefore, data on the intended</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:5271.00pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">effect are required in a petition for an antimicrobial food additive.  Furthermore, if FDA</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:5284.80pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">determines that a tolerance is needed to ensure that the petitioned use of an antimicrobial food</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:5298.60pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">additive will be safe, intended effect data will be used to ensure that the tolerance is set at a level</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:5312.40pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">no higher than what is reasonably required to achieve the intended physical or other technical</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:5326.20pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">effect.  In addition, if a tolerance is necessary and data do not establish that the petitioned use</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:5340.00pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">will accomplish the intended physical or other technical effect, FDA is not authorized to</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:5353.80pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">establish a regulation for that use (section 409(c)(4) of the Act).</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:5373.60pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">For antimicrobial food additives used on meat or poultry, FDA and FSIS have separate</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:5387.40pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">regulatory responsibilities which must be satisfied before the additive may be legally marketed.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:5401.20pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">For these cases, intended effect data will be needed to satisfy the requirements of both FDA and</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:5415.00pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">FSIS.  Under the Federal Meat Inspection Act (FMIA) and the Poultry Products Inspection Act</FONT></FONT></FONT></SPAN>
<SPAN STYLE="position:absolute;left:71.76pt;top:5544.00pt"> </SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:205.25pt;top:5580.45pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><i><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Contains Nonbinding Recommendations</FONT></FONT></i></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:303.00pt;top:6286.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">6</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:5627.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">(PPIA), FSIS has authority over suitability of food ingredients and sources of radiation used in</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:5641.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">meat and poultry processing plants.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:5661.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">In accordance with the procedures described in the MOU between FDA and FSIS (see</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:5675.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><u><FONT COLOR="0000ff"><FONT STYLE="font-size: 12.00pt"><a href="http://www.cfsan.fda.gov/~dms/opa-fsis.html">http://www.cfsan.fda.gov/~dms/opa-fsis.html</a></FONT></FONT></u><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">) requests for approval to use food ingredients and</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:5688.95pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">sources of radiation in the production of meat and poultry products are evaluated simultaneously</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:5702.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">for safety by FDA and for suitability by FSIS.  Prior to submission, petitioners and notifiers may</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:5716.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">wish to consult with FSIS independently; however, FDA believes joint consultations with FDA</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:5730.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">and FSIS facilitate the petition and notification processes.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:5770.05pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">G.</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:5770.05pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><u><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">What types of data and other information should be included to demonstrate that</FONT></FONT></u></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:5783.85pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><u><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">the use of an antimicrobial food additive achieves its intended physical or other technical</FONT></FONT></u></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:5797.65pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><u><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">effect?</FONT></FONT></u></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:5817.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">To demonstrate that an antimicrobial agent achieves its intended technical effect and that the</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:5831.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">proposed use level is the minimum level necessary to accomplish the intended technical effect,</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:5844.95pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">the following information is recommended at a minimum:</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:90.00pt;top:5864.30pt;z-index:3;"><FONT FACE ="Symbol" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">x</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:5865.65pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">The chemical identity or biological identity of the antimicrobial agent, which ever is</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:5879.40pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">appropriate;</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:90.00pt;top:5898.75pt;z-index:3;"><FONT FACE ="Symbol" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">x</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:5900.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">A detailed description of intended antimicrobial effect and identification of any</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:5913.80pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">individual or groups of targeted microbes, if appropriate;</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:90.00pt;top:5933.15pt;z-index:3;"><FONT FACE ="Symbol" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">x</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:5934.50pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">A description of the conditions of use and any limitations on conditions of use, e.g.:</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:126.00pt;top:5955.00pt;z-index:3;"><FONT FACE ="Courier New" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">o</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:144.00pt;top:5954.30pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">types of foods;</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:126.00pt;top:5974.80pt;z-index:3;"><FONT FACE ="Courier New" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">o</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:144.00pt;top:5974.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">proposed use level or range;</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:126.00pt;top:5994.60pt;z-index:3;"><FONT FACE ="Courier New" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">o</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:144.00pt;top:5993.90pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">temperature range of use;</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:126.00pt;top:6014.40pt;z-index:3;"><FONT FACE ="Courier New" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">o</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:144.00pt;top:6013.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">method of application, such as spraying, dipping or fumigating, when applicable;</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:126.00pt;top:6034.20pt;z-index:3;"><FONT FACE ="Courier New" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">o</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:144.00pt;top:6033.50pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">post-processing steps (e.g., potable water rinse, cooking by the consumer);</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:90.00pt;top:6052.85pt;z-index:3;"><FONT FACE ="Symbol" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">x</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:6054.20pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Antimicrobial effect data, including full reports of the efficacy studies;</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:90.00pt;top:6073.50pt;z-index:3;"><FONT FACE ="Symbol" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">x</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:6074.85pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Directions, recommendations, and suggestions regarding the proposed use, as well as a</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:6088.60pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">sample of the label proposed for the food additive and any labeling that will be required</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:6102.40pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">on the finished food as a result of the use of the food additive; and</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:90.00pt;top:6121.75pt;z-index:3;"><FONT FACE ="Symbol" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">x</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:6123.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">For a petition, proposed wording for establishing or amending a food additive regulation</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:6136.85pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">is recommended.  This draft regulation helps FDA understand the petitioner’s intent and</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:6150.65pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">may help the petitioner understand the issues that need to be addressed.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="position:absolute;left:71.76pt;top:6336.00pt"> </SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:205.25pt;top:6372.45pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><i><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Contains Nonbinding Recommendations</FONT></FONT></i></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:303.00pt;top:7078.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">7</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:6419.85pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">H.</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:6419.85pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><u><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">How should a study be designed to demonstrate the antimicrobial food additive’s</FONT></FONT></u></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:6433.65pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><u><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">effect?</FONT></FONT></u></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:6453.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">FDA recommends that any study carried out to support the intended technical effect of an</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:6467.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">antimicrobial food additive should be designed to generate data that directly supports any</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:6480.95pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">particular effect(s) specified.  For example, if the intended technical effect is extending shelf life,</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:6494.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">the study should generate data which measure shelf life; or if the intended technical effect is the</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:6508.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">control of specific organisms, the study should generate data which directly enumerate those</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:6522.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">organisms.  FDA recommends that any of the subject studies reflect the following characteristics,</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:6536.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">to the extent practical:</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:90.00pt;top:6555.50pt;z-index:3;"><FONT FACE ="Symbol" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">x</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:6556.85pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">The study is conducted in a manner that simulates, to the extent feasible, the intended</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:6570.60pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">conditions of use of the antimicrobial food additive;</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:90.00pt;top:6589.95pt;z-index:3;"><FONT FACE ="Symbol" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">x</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:6591.30pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">The study is conducted using samples of the relevant medium (e.g., food, process water,</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:6605.00pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">food packaging) treated under the proposed conditions of use, and the study includes</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:6618.80pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">appropriate controls;</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:90.00pt;top:6638.15pt;z-index:3;"><FONT FACE ="Symbol" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">x</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:6639.50pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">The study focuses on pertinent organisms that the antimicrobial food additive is intended</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:6653.30pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">to target, especially those associated with a given medium (e.g., Salmonellas and</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:6667.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><i><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Campylobacter jejuni for poultry, E. coli for beef, Vibrio spp. for seafood, Salmonellas</FONT></FONT></i></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:6680.90pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">for juices, etc.);</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:90.00pt;top:6700.25pt;z-index:3;"><FONT FACE ="Symbol" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">x</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:6701.60pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Where appropriate, a study uses a direct method for enumeration of microorganisms such</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:6715.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">as plate counting or visual microscopic counts, as opposed to measuring biomass, and</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:6729.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">evaluates the reduction (or suppression) of microorganisms affected by the treatment;</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:90.00pt;top:6748.50pt;z-index:3;"><FONT FACE ="Symbol" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">x</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:6749.85pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Enumeration methods capture damaged or stressed microbial cells that survive the</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:6763.60pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">antimicrobial treatment;</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:90.00pt;top:6782.95pt;z-index:3;"><FONT FACE ="Symbol" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">x</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:6784.30pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">The study includes collection and analysis of replicate samples for each data point with a</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:6798.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">description of the variability of the data; and</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:90.00pt;top:6817.45pt;z-index:3;"><FONT FACE ="Symbol" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">x</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:6818.80pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">When appropriate, the study includes an analysis of the data such as a comparison of the</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:6832.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">treatment and control.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:6852.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">A petition or notification will not be treated differently simply because an alternative approach</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:6866.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">was chosen.  FDA invites submitters to consult with the agency in designing experimental</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:6879.95pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">protocols and recommends that submitters provide their experimental protocol to the agency for</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:6893.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">comment prior to the initiation of any study.  It is the agency’s experience that these</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:6907.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">consultations lead to consensus between the agency and the submitter prior to experimentation</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:6921.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">being conducted.  FDA believes these consultations result in studies that are more likely to</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:6935.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">address the agency’s concerns which leads to a more efficient regulatory process and a faster</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:6948.95pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">time to market for the proposed food additive.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="position:absolute;left:71.76pt;top:7128.00pt"> </SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:205.25pt;top:7164.45pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><i><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Contains Nonbinding Recommendations</FONT></FONT></i></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:303.00pt;top:7870.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">8</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:7211.85pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">I.</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:7211.85pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><u><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Are there unique circumstances that should be taken into consideration wh</FONT></FONT></u><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">en</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:7225.65pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><u><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">designing a study to show that an antimicrobial food additive achieves its intended effect?</FONT></FONT></u></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:7245.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">There are a number of unique circumstances that might be considered when designing a study to</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:7259.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">show an antimicrobial food additive's effect.  Several are described below.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:90.00pt;top:7278.50pt;z-index:3;"><FONT FACE ="Symbol" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">x</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:7279.85pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">A study should consider the typical organisms expected to be observed under the</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:7293.60pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">conditions under which they would be present.  For example, the commonly consumed</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:7307.40pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">portions of beef, lamb, pork, and poultry are generally considered uncontaminated with</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:7321.20pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">pathogens prior to slaughter.  Contamination with enteric pathogens may occur as a result</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:7335.00pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">of improper slaughtering techniques and subsequent processing.  Therefore, we believe</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:7348.80pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">that enteric pathogens are the likely organisms of concern for meat and poultry, and they</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:7362.60pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">should be the subject of any intended effect studies.  (NOTE: We recommend that FSIS</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:7376.40pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">be consulted regarding the design of any study where the intended use includes the</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:7390.20pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">treatment of meat and poultry.)</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:90.00pt;top:7409.55pt;z-index:3;"><FONT FACE ="Symbol" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">x</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:7410.90pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Seafood, fruits and vegetables may have indigenous pathogens present at harvest, or</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:7424.60pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">(different) pathogens may be introduced during harvest or processing.  We recommend</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:7438.40pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">that petitioners/notifiers consider whether their additive is equally effective against</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:7452.20pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">indigenous and introduced microorganisms.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:90.00pt;top:7471.55pt;z-index:3;"><FONT FACE ="Symbol" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">x</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:7472.90pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Experimental design should consider and address whether the use of the antimicrobial</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:7486.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">agent may result in unintended consequences.  For example, an antimicrobial agent may</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:7500.50pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">change the microbiological profile of food such that it suppresses one group of</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:7514.30pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">pathogenic microorganisms while allowing others to proliferate, thereby creating a</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:7528.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">potential health problem.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:90.00pt;top:7547.45pt;z-index:3;"><FONT FACE ="Symbol" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">x</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:7548.80pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Organoleptic changes affected by spoilage organisms are indicators that consumers may</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:7562.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">use to gauge the freshness of meat and poultry, seafood, and produce, and indirectly, their</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:7576.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">safety.  As such, an antimicrobial agent that preferentially eliminates spoilage organisms</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:7590.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">over pathogens might allow the pathogens to proliferate while suppressing spoilage</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:7603.95pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">organisms and their effects.  Under such conditions, a consumer’s senses may not reliably</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:7617.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">discern spoiled and contaminated products, and the use of an antimicrobial agent under</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:7631.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">those conditions might not be safe.  We recommend submitters provide data on the</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:7645.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">effects of their agent on specific pathogens as well as general (spoilage) populations for</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:7659.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">comparison; typically, aerobic plate counts are sufficient to characterize general</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:7672.95pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">populations.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:7712.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">J.</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:7712.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><u><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Does FDA recommend any specific experimental methods?</FONT></FONT></u></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:7732.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">FDA recognizes it is impractical to design a standard experimental protocol that addresses all</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:7746.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">relevant safety issues for every antimicrobial agent.  However, there are a number of resources</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:7759.95pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">specific to microbiological methods that the agency recommends.  FDA publishes an online</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:7773.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">version of its Bacteriological Analytical Manual (</FONT></FONT><u><FONT COLOR="0000ff"><FONT STYLE="font-size: 12.00pt"><a href="http://www.cfsan.fda.gov/~ebam/bam-">http://www.cfsan.fda.gov/~ebam/bam-</a></FONT></FONT></u></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:7787.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><u><FONT COLOR="0000ff"><FONT STYLE="font-size: 12.00pt">toc.html</FONT></FONT></u><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">) which presents useful laboratory procedures for microbiological analyses of foods and</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:7801.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">cosmetics.  Furthermore, FDA maintains a website with numerous links to related resources on</FONT></FONT></FONT></SPAN>
<SPAN STYLE="position:absolute;left:71.76pt;top:7920.00pt"> </SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:205.25pt;top:7956.45pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><i><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Contains Nonbinding Recommendations</FONT></FONT></i></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:303.00pt;top:8662.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">9</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8003.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">microbiological methods (</FONT></FONT><u><FONT COLOR="0000ff"><FONT STYLE="font-size: 12.00pt"><a href="http://www.cfsan.fda.gov/~comm/microbio.html">http://www.cfsan.fda.gov/~comm/microbio.html</a></FONT></FONT></u><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">).  Also, FSIS</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8017.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">maintains a laboratory guidebook of current protocols for analytical tests required by FSIS in its</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8031.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">regulatory activities on meat, poultry and egg products</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8045.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">(</FONT></FONT><u><FONT COLOR="0000ff"><FONT STYLE="font-size: 12.00pt"><a href="http://www.fsis.usda.gov/Science/Microbiological_Lab_Guidebook/">http://www.fsis.usda.gov/Science/Microbiological_Lab_Guidebook/</a></FONT></FONT></u><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">); these test procedures may</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8058.95pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">be useful in the experimental design of technical effect studies.  However, a petition or</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8072.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">notification will not be treated differently simply because an alternative study design was chosen.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8112.45pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">K.</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:8112.45pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><u><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">What is FDA’s performance standard for a new antimicrobial food additive?</FONT></FONT></u></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8132.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">A performance standard defines the minimal level of reduction of microorganisms from the use</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8145.95pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">of the antimicrobial food additive (e.g., a 5-log reduction in the number of microbe(s) targeted).</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8159.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Given the variability in the intended technical effect of antimicrobial food additives and types of</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8173.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">food treated, FDA does not have a single performance standard for antimicrobial food additives.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8187.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">However, to prove that an additive achieves its intended technical effect as an antimicrobial</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8201.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">agent, data from an efficacy study should demonstrate that, at a minimum, there is a measurable</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8214.95pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">difference between the treated samples and a negative control (e.g., the treatment absent the</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8228.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">active agent).  Such a demonstration may be achieved through statistical analysis, graphical</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8242.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">comparison, or another equivalent method.  In those particular cases where the intended</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8256.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">technical effect specifies the use of the additive as part of a process where a performance</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8270.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">standard has been established by regulation (e.g., Juice HAACP (21 CFR 120.24)) or regulatory</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8283.95pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">guidance (e.g., FSIS guidance on control of Listeria monocytogenes), FDA may consider that</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8297.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">performance standard when regulating the additive.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8337.45pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">L.</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:8337.45pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><u><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">What information may be helpful to provide to FDA to demonstrate the intended</FONT></FONT></u></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8351.20pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><u><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">technical effect of a source of radiation as an antimicrobial treatment for food?</FONT></FONT></u></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8370.90pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">A source of radiation used to treat food is included in the food additive definition (section 201(s)</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8384.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">of the Act).  Furthermore, section 402(a)(7) of the Act states that a food is adulterated if it has</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8398.50pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">been subjected to radiation, unless the use of the regulation was in conformity with a regulation</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8412.30pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">or exemption under section 409 of the Act.  Because a source of radiation used to treat food does</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8426.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">not meet the definition of a food contact substance in that it has a technical effect in the food, it</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8439.90pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">is regulated through the FAP process under section 409 rather than the FCN process or the TOR</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8453.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">exemption process.  In addition to information typically submitted in an FAP, a petition for the</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8467.50pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">use of a source of radiation as an antimicrobial treatment for food should include information</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8481.30pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">related to technical effect, such as:</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8501.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">1.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:8501.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Information describing the microbiological profile of targeted foods (occurrence and</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8514.90pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">levels of pathogenic and non-pathogenic microorganisms); and</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8534.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">2.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:8534.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Information describing the effects of the proposed irradiation on microorganisms in or on</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8548.50pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">the targeted food, including growth patterns of surviving microorganisms compared with food</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8562.30pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">that has not been irradiated.  For example, Clostridium botulinum is of particular concern as a</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8576.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">potential microorganism surviving irradiation.  Therefore, it may be necessary to consider</FONT></FONT></FONT></SPAN>
<SPAN STYLE="position:absolute;left:71.76pt;top:8712.00pt"> </SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:205.25pt;top:8748.45pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><i><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Contains Nonbinding Recommendations</FONT></FONT></i></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:300.00pt;top:9454.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">10</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8795.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">whether C. botulinum is able to proliferate to a greater extent in food treated by irradiation than</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8809.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">in untreated food because of a reduced number of competing spoilage organisms.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8843.25pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">M.</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:8843.25pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><u><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">What additional safety information may be helpful to provide to FDA if my</FONT></FONT></u></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8857.05pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><u><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">antimicrobial food additive is derived from a microorganism?</FONT></FONT></u></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8876.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">If an antimicrobial food additive is derived from a microorganism, FDA recommends that the</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8890.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">following additional information be provided, at a minimum:</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8910.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">1.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:8910.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">The biological identity of the specific isolate of microorganism to be used for production.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8924.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">If the strain has been genetically manipulated, a description of how the strain was derived,</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8937.95pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">including information about any strain contributing genetic material to the production strain</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8951.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">should be included with the submission;</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8971.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">2.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:8971.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">A description of the procedures used to maintain the cultural purity and genetic stability</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8985.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">of the production microorganism. Details of procedures employed to assure strain purity and</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:8999.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">integrity should be included with the submission;</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:9018.95pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">3.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:9018.95pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">A description of the quality control procedures used during production, the procedures</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:9032.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">for assurance of cultural purity, and the procedures to be followed if contamination is observed</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:9046.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">in the starter (pure) cultures or during production;</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:9066.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">4.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:9066.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">A description of the methods used to verify the absence of clinically relevant antibiotics.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:9080.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">The production microorganism should not produce clinically relevant antibiotics in preparations</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:9093.95pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">of the antimicrobial food additive;</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:9121.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">5.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:9121.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Information that demonstrates that the production strain is not infectious or toxicogenic,</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:9135.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">and that no toxin is present at toxicologically significant levels in the preparation for use in food,</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:9149.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">if it is necessary to employ a toxicogenic strain; and</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:9174.40pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">6.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:9174.40pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">A description of the methods employed and relevant quality control procedures followed</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:9188.20pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">to ensure that no viable cells of the production strain are found in the product when those cells</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:9202.00pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">represent a safety concern.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:9221.80pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">FDA understands that there may be newly developed antimicrobial products for which some of</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:9235.60pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">these recommendations may not be valid.  A petition or notification will not be treated</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:9249.40pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">differently simply because safety information other than that recommended here was provided.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:9263.20pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">We will consider the sufficiency of the safety information provided with antimicrobial product</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:9277.00pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">petitions on a case-by-case basis.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="position:absolute;left:71.76pt;top:9504.00pt"> </SPAN>
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