Document ID: FDA-2008-N-0474-0005
Agency: fda
Document Type: Supporting & Related Material
Title: 
Posted Date: 2008-09-15T04:00Z

<!DOCTYPE HTML PUBLIC "-//-//W3C//DTD HTML 3.2//EN">
<HTML>
<HEAD>
<META name="generator" content="PDFCreactiveX HTML Export">
<META name="creation-date" content="15/09/2008 09:55:14 ">
<TITLE></TITLE>
<SCRIPT LANGUAGE="JavaScript1.2"> var agt=navigator.userAgent.toLowerCase();if ( (parseInt(navigator.appVersion)>=4) &&(agt.indexOf('mozilla')!=-1) && (agt.indexOf('spoofer')==-1)&& (agt.indexOf('compatible') == -1) ){msie = false;} else if ( (parseInt(navigator.appVersion)>=4) &&(agt.indexOf('msie') != -1) ) {msie = true;	} page=0;</SCRIPT>
</HEAD>
<BODY bgcolor="#ffffff" text="#000000" topmargin=0 leftmargin=0 marginheight=0 marginwidth=0 >
<SPAN STYLE="color:#000000;background-color:#ffffff;position:absolute;left:76.80pt;top:59.60pt;z-index:2;"><IMG WIDTH=172 HEIGHT=72 style="width:136pt;height:66pt;" SRC="outputfile-734207331.htm_files\outputfile-734207331_p0.jpg"></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:225.05pt;top:67.45pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 18.00pt">Time and Extent Application (TEA)</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:223.85pt;top:88.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 18.00pt">Review for Ecamsule (Mexoryl SX)</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:461.20pt;top:86.00pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 11.52pt">®</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:200.75pt;top:150.80pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 13.98pt">Office of Nonprescription Products</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:96.70pt;top:167.80pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 13.98pt">Center for Drug Evaluation and Research</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:332.30pt;top:166.15pt;z-index:3;"><FONT FACE ="Symbol" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 13.98pt">•</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:342.15pt;top:167.80pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 13.98pt">Food and Drug Administration</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:231.55pt;top:184.90pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 13.98pt">Silver Spring</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:309.35pt;top:183.25pt;z-index:3;"><FONT FACE ="Symbol" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 13.98pt">•</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:319.20pt;top:184.90pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 13.98pt">MD 20993</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:244.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">CONDITION</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:306.90pt;top:244.60pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Ecamsule (Mexoryl</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:401.95pt;top:242.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 7.98pt">®</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:411.00pt;top:244.60pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">SX), 10%</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:272.30pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">PHARMACOLOGICAL CLASS</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:306.90pt;top:272.20pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Sunscreen</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:299.90pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">MONOGRAPH</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:308.70pt;top:299.80pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">OTC Sunscreen Drug Products (21 CFR part</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:308.70pt;top:313.60pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">352)</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:341.30pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">APPLICANT</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:308.70pt;top:341.20pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">L’Oreal USA Products, Inc.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:308.70pt;top:355.00pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">30 Terminal Avenue</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:308.70pt;top:368.80pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Clark, NJ  07066</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:396.50pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">SUBMISSION DATE</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:308.70pt;top:396.40pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">September 18, 2007</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:424.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">REVIEW DATE</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:308.70pt;top:424.00pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">September 25, 2007</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:451.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">REVIEWER</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:308.70pt;top:451.60pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Michael Chasey</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:479.30pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">TEAM LEADER</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:308.70pt;top:479.20pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Matthew R. Holman, Ph.D.</FONT></FONT></FONT></SPAN>
<span style="color:#000000;background-color:#ffffff;position:absolute;left:0.00pt;top:0.00pt;z-index:-1;"><img style="width:612pt;height:792pt;" src="outputfile-734207331.htm_files\outputfile-734207331_background0.png"></span>
<SPAN STYLE="position:absolute;left:71.76pt;top:792.00pt"> </SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:838.65pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><u><FONT COLOR="000000"><FONT STYLE="font-size: 10.98pt">TEA</FONT></FONT></u></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:226.30pt;top:837.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><u><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Ecamsule (Mexoryl</FONT></FONT></u></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:321.35pt;top:835.80pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 7.98pt">®</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:330.40pt;top:837.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><u><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">SX)</FONT></FONT></u></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:534.45pt;top:838.65pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 10.98pt">2</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:864.45pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">BACKGROUND</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:905.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">The applicant requests addition of ecamsule (Mexoryl</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:331.30pt;top:903.80pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 7.98pt">®</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:340.40pt;top:905.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">SX) in combination with any other active</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:926.45pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">ingredients listed in 21 CFR 352.10 to the sunscreen monograph (21 CFR part 352).  The</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:947.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">applicant requests that the maximal concentration of this ingredient be 10 percent.  The applicant</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:967.85pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">does not request any other changes (</FONT></FONT><FONT COLOR="000000"><i><FONT STYLE="font-size: 12.00pt">e.g.</FONT></i><FONT STYLE="font-size: 12.00pt">, labeling or testing) to the sunscreen monograph other</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:988.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">than addition of ecamsule.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1030.05pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">REVIEWER’S COMMENTS</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1071.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">The applicant provides basic information about ecamsule, including a detailed chemical</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1092.05pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">description as required in 21 CFR 330.14(c)(1)(i), as well as a detailed description of the method</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1112.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">of synthesis and purification.  Ecamsule is not included in the U.S. Pharmacopeia-National</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1133.45pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Formulary (USP-NF), but the applicant indicates that, a submission was made to the USP on</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1154.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">February 23, 2006, and that the draft is currently undergoing review.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1195.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">The applicant indicates that ecamsule is or has been marketed in 55 countries.  Of these</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1216.25pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">countries, ecamsule has been marketed for at least five continuous years in 48 of them.  The</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1236.90pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">applicant has designated Canada, United Kingdom (including Ireland), France, Italy, and Spain</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1257.60pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">as “selected countries,” in accordance with 21 CFR 330.14(c)(4).  Ecamsule has been marketed</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1278.30pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">for over 12 years in each of the “selected countries.”</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1319.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">As indicated in 21 CFR 330.14(b)(2), extent of marketing is determined by the extent to which</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1340.40pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">sales meets the requirements outlined in 21 CFR 330.14(c)(2)(ii), (c)(2)(iii), and (c)(2)(iv).</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1361.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">These paragraphs collectively address the adequacy of the markets and marketing to reveal</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1381.80pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">“infrequent but serious ADEs” (adverse drug events) that may occur in the U.S. population if</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1402.50pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">FDA finds the condition generally recognized as safe and effective (67 FR 3060 at 3065).</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1443.90pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">As specified in 21 CFR 330.14(c)(2)(ii), the applicant provides the “cumulative total number of</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1464.60pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">dosage units . . . sold for each dosage form of the condition.”  In this case, the applicant reports</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1485.30pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">that almost 472 million units of sunscreen products containing ecamsule in combination with</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1506.00pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">other European Community approved UV filters have been sold in Europe and globally.  The</FONT></FONT></FONT></SPAN>
<SPAN STYLE="position:absolute;left:71.76pt;top:1584.00pt"> </SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1630.65pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><u><FONT COLOR="000000"><FONT STYLE="font-size: 10.98pt">TEA</FONT></FONT></u></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:226.30pt;top:1629.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><u><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Ecamsule (Mexoryl</FONT></FONT></u></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:321.35pt;top:1627.80pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 7.98pt">®</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:330.40pt;top:1629.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><u><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">SX)</FONT></FONT></u></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:534.45pt;top:1630.65pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 10.98pt">3</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1656.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">applicant estimates that France, Italy, Spain, United Kingdom (including Ireland), and Germany</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1677.05pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">market approximately 75 percent of all ecamsule-containing products.  Four of those countries</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1697.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">are included in the applicant’s five “selected countries.”</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1739.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Table 1.  Estimated sales of ecamsule in sunscreen drug products in “selected countries” (1993-</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1759.85pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">2006)</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:226.00pt;top:1781.00pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Continent</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:337.90pt;top:1781.00pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Dosage Units Sold</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:352.45pt;top:1801.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">(in Millions)</FONT></FONT></FONT></SPAN>
<SPAN STYLE="position:absolute;font-size:0;left:172pt;top:1780pt;width: 1pt;height: 1pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:172pt;top:1780pt;width:266pt;height: 1pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:438pt;top:1780pt;width: 1pt;height: 1pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:172pt;top:1780pt;width: 1pt;height:41pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:326pt;top:1780pt;width: 1pt;height:41pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:438pt;top:1780pt;width: 1pt;height:41pt;background-color:#000000;"></SPAN><SPAN STYLE="color:#000000;position:absolute;left:178.20pt;top:1822.90pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">North America (2 countries)</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:372.40pt;top:1822.90pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">20.1</FONT></FONT></FONT></SPAN>
<SPAN STYLE="position:absolute;font-size:0;left:172pt;top:1822pt;width:266pt;height: 1pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:172pt;top:1822pt;width: 1pt;height:20pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:326pt;top:1822pt;width: 1pt;height:20pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:438pt;top:1822pt;width: 1pt;height:20pt;background-color:#000000;"></SPAN><SPAN STYLE="color:#000000;position:absolute;left:178.20pt;top:1844.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Central/South America (9</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:178.20pt;top:1864.80pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">countries)</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:349.60pt;top:1844.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Sales data not</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:359.30pt;top:1857.90pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">submitted</FONT></FONT></FONT></SPAN>
<SPAN STYLE="position:absolute;font-size:0;left:172pt;top:1843pt;width:266pt;height: 1pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:172pt;top:1843pt;width: 1pt;height:41pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:326pt;top:1843pt;width: 1pt;height:41pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:438pt;top:1843pt;width: 1pt;height:41pt;background-color:#000000;"></SPAN><SPAN STYLE="color:#000000;position:absolute;left:178.20pt;top:1886.00pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Europe (26 countries)</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:369.40pt;top:1886.00pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">451.9</FONT></FONT></FONT></SPAN>
<SPAN STYLE="position:absolute;font-size:0;left:172pt;top:1885pt;width:266pt;height: 1pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:172pt;top:1885pt;width: 1pt;height:20pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:326pt;top:1885pt;width: 1pt;height:20pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:438pt;top:1885pt;width: 1pt;height:20pt;background-color:#000000;"></SPAN><SPAN STYLE="color:#000000;position:absolute;left:178.20pt;top:1907.20pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Asia (11 countries)</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:349.65pt;top:1907.20pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Sales data not</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:359.30pt;top:1921.00pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">submitted</FONT></FONT></FONT></SPAN>
<SPAN STYLE="position:absolute;font-size:0;left:172pt;top:1906pt;width:266pt;height: 1pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:172pt;top:1906pt;width: 1pt;height:27pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:326pt;top:1906pt;width: 1pt;height:27pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:438pt;top:1906pt;width: 1pt;height:27pt;background-color:#000000;"></SPAN><SPAN STYLE="color:#000000;position:absolute;left:178.20pt;top:1935.30pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Africa (5 countries)</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:349.65pt;top:1935.30pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Sales data not</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:359.30pt;top:1949.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">submitted</FONT></FONT></FONT></SPAN>
<SPAN STYLE="position:absolute;font-size:0;left:172pt;top:1934pt;width:266pt;height: 1pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:172pt;top:1934pt;width: 1pt;height:27pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:326pt;top:1934pt;width: 1pt;height:27pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:438pt;top:1934pt;width: 1pt;height:27pt;background-color:#000000;"></SPAN><SPAN STYLE="color:#000000;position:absolute;left:178.20pt;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">Australia (1 country)</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:349.60pt;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">Sales data not</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:359.30pt;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">submitted</FONT></FONT></FONT></SPAN>
<SPAN STYLE="position:absolute;font-size:0;left:172pt;top:1962pt;width:266pt;height: 1pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:172pt;top:1963pt;width: 1pt;height:27pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:326pt;top:1963pt;width: 1pt;height:27pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:438pt;top:1963pt;width: 1pt;height:27pt;background-color:#000000;"></SPAN><SPAN STYLE="color:#000000;position:absolute;left:236.05pt;top:1991.60pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Total 472.0</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="position:absolute;font-size:0;left:172pt;top:1990pt;width:266pt;height: 1pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:172pt;top:1991pt;width: 1pt;height:21pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:172pt;top:2011pt;width:153pt;height: 1pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:326pt;top:1991pt;width: 1pt;height:21pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:326pt;top:2011pt;width:112pt;height: 1pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:438pt;top:1991pt;width: 1pt;height:21pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:438pt;top:2011pt;width: 1pt;height: 1pt;background-color:#000000;"></SPAN><SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2033.40pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">The applicant submitted information on hundreds of labels of sunscreen products containing</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2054.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">ecamsule in combination with other sunscreen active ingredients.  The products include</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2074.80pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">combinations with eight currently monograph sunscreen active ingredients in addition to three</FONT></FONT></FONT></SPAN>
<SPAN STYLE="position:absolute;font-size:0;left:225pt;top:2082pt;width: 9pt;height: 1pt;background-color:#000000;"></SPAN><SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2095.50pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">active ingredients being considered under separate TEAs.  No labeling was submitted in which</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2116.20pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">ecamsule was the sole active ingredient.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2157.60pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">The applicant reports that there have been 24,676 spontaneous adverse event reports from the</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2178.30pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">approximately 472 million units of ecamsule-containing product formulations sold.  This is an</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2199.00pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">incidence rate of 0.0052 percent.  They report that this incidence rate is on the order of that</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2219.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">reported for avobenzone, which has reported incidence rate of 0.0067 percent (61 FR 48645 at</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2240.40pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">48650).  The applicant did not supply any specific information on the types of adverse events</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2261.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">associated with ecamsule-containing products, specifically serious adverse events.  However,</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2281.80pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">there is information on serious adverse events in new drug applications (NDAs) for ecamsule-</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2302.50pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">containing products.  There is no data available in the NDAs that would prevent a GRAS</FONT></FONT></FONT></SPAN>
<SPAN STYLE="position:absolute;left:71.76pt;top:2376.00pt"> </SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2422.65pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><u><FONT COLOR="000000"><FONT STYLE="font-size: 10.98pt">TEA</FONT></FONT></u></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:226.30pt;top:2421.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><u><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Ecamsule (Mexoryl</FONT></FONT></u></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:321.35pt;top:2419.80pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 7.98pt">®</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:330.40pt;top:2421.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><u><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">SX)</FONT></FONT></u></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:534.45pt;top:2422.65pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 10.98pt">4</FONT></FONT></b></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">determination for ecamsule-containing products. All five of the applicant’s “selected countries”</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2469.05pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">are listed in Section 802(b)(1)(A) of the Federal Food, Drug, and Cosmetic Act (the Act).</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">Inclusion in this section of the Act has been interpreted to indicate that the regulatory systems in</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2510.45pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">these countries are of comparable sophistication to that in the United States (64 FR 71062 at</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2531.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">71068).</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2572.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">The applicant provides specific demographic information about the population in each of the 5</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2593.25pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">selected countries in tab 5 of the TEA.  This information complies with 21 CFR 330.14(c)(2)(iii),</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2613.95pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">which requires a description of population demographics “to ensure that the condition’s use(s)</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2634.65pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">can be reasonably extrapolated to the U.S. population.”  The demographics of the 5 selected</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2655.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">countries represent a diverse population of persons that seems to reflect the diversity of the U.S.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2676.05pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">population.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2717.45pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">The applicant provides an explanation of the “use pattern,” as required by</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2738.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">21 CFR 330.14(c)(2)(iv).  Use pattern is defined as how often the product is used (according to</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2758.85pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">the label) and for how long.  The applicant notes that the route of administration is</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2779.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">topical/dermal in a sunscreen formulation for OTC use.  Dosage forms of the final sunscreen</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2800.25pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">formulation containing ecamsule will be the typical dosage forms for sunscreen products,</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2820.90pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">including, but not limited to, lotions, creams, sticks, sprays, etc.  The applicant explains that the</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2841.60pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">directions for use will depend upon the final formulation and will comply with standard</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2862.30pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">monograph language (21 CFR 352.60).  Additionally, the applicant would like to include under</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2883.00pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">the “Uses” statement in Drug Facts:</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:90.00pt;top:2923.90pt;z-index:3;"><FONT FACE ="Symbol" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">•</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:2925.30pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">“helps provide protection from UVA rays (short and long wavelengths)”</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2966.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">The applicant argues that this statement is currently approved for use in the United States on</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2987.40pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">ecamsule-containing sunscreen product labeling in NDAs 21-501, 21-502, and 21-471.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3028.90pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">RECOMMENDATION</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3070.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">I recommend that ecamsule (Mexoryl</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:252.65pt;top:3068.20pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 7.98pt">®</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:261.70pt;top:3070.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">SX), 10 percent or less, be considered eligible for review</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3090.80pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">as an active ingredient, both alone and in combination with GRASE sunscreen active ingredients,</FONT></FONT></FONT></SPAN>
<SPAN STYLE="position:absolute;left:71.76pt;top:3168.00pt"> </SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3214.65pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><u><FONT COLOR="000000"><FONT STYLE="font-size: 10.98pt">TEA</FONT></FONT></u></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:226.30pt;top:3213.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><u><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Ecamsule (Mexoryl</FONT></FONT></u></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:321.35pt;top:3211.80pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 7.98pt">®</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:330.40pt;top:3213.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><u><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">SX)</FONT></FONT></u></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:534.45pt;top:3214.65pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 10.98pt">5</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3240.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">in the OTC sunscreen drug product monograph (21 CFR part 352).  To be considered eligible for</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3261.05pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">review under the TEA process, a product must meet the criteria of marketing for a material time</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3281.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">and to a material extent as set forth in 21 CFR 330.14(b)(2).  Ecamsule meets the requirement for</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3302.45pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">the material time criteria because ecamsule-containing sunscreen products have been marketed</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3323.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">directly to consumers for over five continuous years in 48 countries.  In addition, ecamsule meets</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3343.85pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">the criteria for marketing to a material extent because it has been marketed in 55 countries with</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3364.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">an estimated 472 million dosage units of sunscreen products containing ecamsule sold.</FONT></FONT></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">In addition to the labeling prescribed by the sunscreen monograph, the applicant would like the</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3426.65pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">additional claim “helps provide protection from UVA rays (short and long wavelengths).”  This</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3447.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">claim is currently approved in NDAs containing ecamsule.  On August 27, 2007, we published a</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3468.05pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">proposed rulemaking (PR) that addresses, amongst other things, UVA labeling for sunscreen</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3488.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">products (72 FR 49070).  The labeling proposed by the applicant is similar in nature to the</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3509.45pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">labeling proposed in the 2007 PR.  Therefore, the applicants claim may be appropriate for OTC</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3530.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">sunscreen products containing ecamsule.  A final determination will be made during review of</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3550.85pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">submitted safety and efficacy data.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="position:absolute;left:71.76pt;top:3960.00pt"> </SPAN>
</BODY>
</HTML>