Document ID: FDA-2007-D-0306-0004
Agency: fda
Document Type: Supporting & Related Material
Title: 
Posted Date: 2009-01-12T05:00Z

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<span style="color:#000000;background-color:#ffffff;position:absolute;left:0.00pt;top:0.00pt;z-index:-1;"><img style="width:652pt;height:918pt;" src="outputfile-273907952.htm_files\outputfile-273907952_background0.png"></span>
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<SPAN STYLE="color:#000000;position:absolute;left:75.30pt;top:992.00pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 48.00pt">Guidance for Industry</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:77.75pt;top:1069.30pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 25.98pt">Q4B Evaluation and Recommendation of</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:104.10pt;top:1099.25pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 25.98pt">Pharmacopoeial Texts for Use in the</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:234.10pt;top:1129.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 25.98pt">ICH Regions</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:260.10pt;top:1184.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 25.98pt">Annex 3</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:106.30pt;top:1214.20pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 25.98pt">Test for Particulate Contamination:</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:99.85pt;top:1244.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 25.98pt">Subvisible Particles General Chapter</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:228.40pt;top:1298.45pt;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:225.65pt;top:1321.50pt;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 Training and Communication</FONT></FONT></i></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:244.70pt;top:1332.95pt;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 Drug Information</FONT></FONT></i></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:219.40pt;top:1344.45pt;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 Drug Evaluation and Research</FONT></FONT></i></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:241.30pt;top:1355.90pt;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:247.60pt;top:1367.45pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><i><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">1</FONT></FONT></i></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:252.65pt;top:1367.45pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><i><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">090</FONT></FONT></i></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:267.70pt;top:1367.45pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><i><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">3 New Hampshire Ave.</FONT></FONT></i></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:261.35pt;top:1378.95pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><i><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">Bldg. 51, Room 2201</FONT></FONT></i></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:240.55pt;top:1390.40pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><i><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">Silver Spring, MD 20993-0002</FONT></FONT></i></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:264.40pt;top:1401.95pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><i><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">(Tel) 301-796-3400</FONT></FONT></i></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:215.70pt;top:1413.45pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><i><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt"></FONT></FONT></i><i><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt"><a href="http://www.fda.gov/cder/guidance/index.htm">http://www.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.fda.gov/cder/guidance/index.htm">gov/cder/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.fda.gov/cder/guidance/index.htm">dance/index.h</a></FONT></FONT><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">t</FONT></FONT><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt"><a href="http://www.fda.gov/cder/guidance/index.htm">m</a></FONT></FONT><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt"></FONT></FONT></i></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:301.50pt;top:1434.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><i><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">or</FONT></FONT></i></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:224.40pt;top:1454.85pt;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 Communication, Training and</FONT></FONT></i></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:231.65pt;top:1466.30pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><i><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">Manufacturers Assistance, HFM-40</FONT></FONT></i></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:211.10pt;top:1477.85pt;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 Biologics Evaluation and Research</FONT></FONT></i></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:242.65pt;top:1489.35pt;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:206.95pt;top:1500.80pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><i><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">1401 Rockville Pike, Rockville, MD 20852-1448</FONT></FONT></i></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:224.45pt;top:1512.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><i><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt"></FONT></FONT></i><i><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt"><a href="http://www.fda.gov/cber/guidelines.htm.">http://www.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.fda.gov/cber/guidelines.htm.">gov/cber/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.fda.gov/cber/guidelines.htm.">delines.htm.</a></FONT></FONT><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt"></FONT></FONT></i></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:183.00pt;top:1540.20pt;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:1554.00pt;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:176.05pt;top:1567.80pt;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 Drug Evaluation and Research (CDER)</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:166.70pt;top:1581.60pt;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 Biologics Evaluation and Research (CBER)</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:271.15pt;top:1609.20pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">January 2009</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:294.65pt;top:1623.00pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">ICH</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="position:absolute;left:71.76pt;top:1710.00pt"> </SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:304.30pt;top:2457.20pt;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:241.30pt;top:1782.45pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">TABLE OF CONTENTS</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1837.65pt;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:1837.65pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">INTRODUCTION (1)....................................................................................................... 1</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1857.45pt;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:1857.45pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Q4B OUTCOME (2)......................................................................................................... 2</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:84.25pt;top:1877.30pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 10.98pt">A.</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:1877.30pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 10.98pt">Analytical Procedures (2.1)...........................................................................................................2</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:84.25pt;top:1896.25pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 10.98pt">B.</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:1896.25pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 10.98pt">Acceptance Criteria (2.2)...............................................................................................................2</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1915.20pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">III.</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:1915.20pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">TIMING OF ANNEX IMPLEMENTATION (3) .......................................................... 2</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:1935.00pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">IV.</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:1935.00pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">CONSIDERATIONS FOR IMPLEMENTATION (4).................................................. 2</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:84.25pt;top:1954.85pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 10.98pt">A.</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:1954.85pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 10.98pt">General Consideration (4.1)..........................................................................................................2</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:84.25pt;top:1973.85pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 10.98pt">B.</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:1973.85pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 10.98pt">FDA Consideration (4.2) ...............................................................................................................2</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:84.25pt;top:1992.80pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 10.98pt">C.</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:1992.80pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 10.98pt">EU Consideration (4.3) ..................................................................................................................3</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:84.25pt;top:2011.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 10.98pt">D.</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:2011.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 10.98pt">MHLW Consideration (4.4)..........................................................................................................3</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2030.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">V.</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:2030.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">REFERENCES USED FOR THE Q4B EVALUATION (5) ........................................ 3</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2050.50pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">ATTACHMMENT........................................................................................................................ 4</FONT></FONT></b></FONT></SPAN>
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<SPAN STYLE="color:#000000;position:absolute;left:205.25pt;top:2538.45pt;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:303.50pt;top:3244.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">1</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:226.45pt;top:2574.65pt;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:2572.05pt;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:87.30pt;top:2593.05pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 16.02pt">Q4B Evaluation and Recommendation of Pharmacopoeial Texts</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:213.80pt;top:2611.40pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 16.02pt">for Use in the ICH Regions</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:277.75pt;top:2643.65pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 16.02pt">Annex 3</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:112.20pt;top:2662.05pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 16.02pt">Test for Particulate Contamination:  Subvisible Particles</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:248.00pt;top:2680.40pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 16.02pt">General Chapter</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="position:absolute;font-size:0;left:60pt;top:2712pt;width: 1pt;height: 5pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:60pt;top:2712pt;width: 5pt;height: 1pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:65pt;top:2717pt;width: 1pt;height: 1pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:65pt;top:2717pt;width: 1pt;height: 1pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:66pt;top:2712pt;width:478pt;height: 1pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:66pt;top:2717pt;width:478pt;height: 1pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:550pt;top:2712pt;width: 1pt;height: 5pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:545pt;top:2712pt;width: 5pt;height: 1pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:545pt;top:2717pt;width: 1pt;height: 1pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:545pt;top:2717pt;width: 1pt;height: 1pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:60pt;top:2717pt;width: 1pt;height:13pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:65pt;top:2717pt;width: 1pt;height:13pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:550pt;top:2717pt;width: 1pt;height:13pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:545pt;top:2717pt;width: 1pt;height:13pt;background-color:#000000;"></SPAN><SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2732.00pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 10.98pt">This guidance represents the Food and Drug Administration's (FDA's) current thinking on this topic.  It</FONT></FONT></FONT></SPAN>
<SPAN STYLE="position:absolute;font-size:0;left:60pt;top:2731pt;width: 1pt;height:12pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:65pt;top:2731pt;width: 1pt;height:12pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:550pt;top:2731pt;width: 1pt;height:12pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:545pt;top:2731pt;width: 1pt;height:12pt;background-color:#000000;"></SPAN><SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2744.65pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 10.98pt">does not create or confer any rights for or on any person and does not operate to bind FDA or the public.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="position:absolute;font-size:0;left:60pt;top:2744pt;width: 1pt;height:12pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:65pt;top:2744pt;width: 1pt;height:12pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:550pt;top:2744pt;width: 1pt;height:12pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:545pt;top:2744pt;width: 1pt;height:12pt;background-color:#000000;"></SPAN><SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2757.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 10.98pt">You can use an alternative approach if the approach satisfies the requirements of the applicable statutes</FONT></FONT></FONT></SPAN>
<SPAN STYLE="position:absolute;font-size:0;left:60pt;top:2756pt;width: 1pt;height:12pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:65pt;top:2756pt;width: 1pt;height:12pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:550pt;top:2756pt;width: 1pt;height:12pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:545pt;top:2756pt;width: 1pt;height:12pt;background-color:#000000;"></SPAN><SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2770.00pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 10.98pt">and regulations.  If you want to discuss an alternative approach, contact the FDA staff responsible for</FONT></FONT></FONT></SPAN>
<SPAN STYLE="position:absolute;font-size:0;left:60pt;top:2769pt;width: 1pt;height:12pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:65pt;top:2769pt;width: 1pt;height:12pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:550pt;top:2769pt;width: 1pt;height:12pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:545pt;top:2769pt;width: 1pt;height:12pt;background-color:#000000;"></SPAN><SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2782.65pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 10.98pt">implementing this guidance.  If you cannot identify the appropriate FDA staff, call the appropriate</FONT></FONT></FONT></SPAN>
<SPAN STYLE="position:absolute;font-size:0;left:60pt;top:2782pt;width: 1pt;height:12pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:65pt;top:2782pt;width: 1pt;height:12pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:550pt;top:2782pt;width: 1pt;height:12pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:545pt;top:2782pt;width: 1pt;height:12pt;background-color:#000000;"></SPAN><SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2795.25pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 10.98pt">number listed on the title page of this guidance.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="position:absolute;font-size:0;left:60pt;top:2794pt;width: 1pt;height:12pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:65pt;top:2794pt;width: 1pt;height:12pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:550pt;top:2794pt;width: 1pt;height:12pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:545pt;top:2794pt;width: 1pt;height:12pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:60pt;top:2821pt;width: 1pt;height: 5pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:60pt;top:2826pt;width: 5pt;height: 1pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:65pt;top:2821pt;width: 1pt;height: 1pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:65pt;top:2821pt;width: 1pt;height: 1pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:66pt;top:2826pt;width:478pt;height: 1pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:66pt;top:2821pt;width:478pt;height: 1pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:550pt;top:2821pt;width: 1pt;height: 5pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:545pt;top:2826pt;width: 5pt;height: 1pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:545pt;top:2821pt;width: 1pt;height: 1pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:545pt;top:2821pt;width: 1pt;height: 1pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:60pt;top:2807pt;width: 1pt;height:13pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:65pt;top:2807pt;width: 1pt;height:13pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:550pt;top:2807pt;width: 1pt;height:13pt;background-color:#000000;"></SPAN><SPAN STYLE="position:absolute;font-size:0;left:545pt;top:2807pt;width: 1pt;height:13pt;background-color:#000000;"></SPAN><SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2869.05pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">I. INTRODUCTION (1)</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:221.00pt;top:2867.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 7.98pt">2</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2896.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">This annex is one in a series of guidance documents that describe the evaluations and</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2910.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">recommendations by the Q4B Expert Working Group (EWG) of selected pharmacopoeial texts</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2924.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">to facilitate their recognition by regulatory authorities for use as interchangeable in the ICH</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2937.95pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">regions. Implementation of the Q4B annexes is intended to avoid redundant testing by industry.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2951.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">For general information on the Q4B process, the reader is referred to the core guidance </FONT></FONT><i><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Q4B</FONT></FONT></i></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2965.50pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><i><FONT STYLE="font-size: 12.00pt">Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions</FONT></i><FONT STYLE="font-size: 12.00pt">.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:492.65pt;top:2963.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 7.98pt">3</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:2993.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">This annex is the result of the Q4B process for the Test for Particulate Contamination: Subvisible</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3006.90pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Particles General Chapter.  The proposed texts were submitted by the Pharmacopoeial</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3020.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Discussion Group (PDG).</FONT></FONT></FONT></SPAN>
<SPAN STYLE="position:absolute;font-size:0;left:72pt;top:3059pt;width:144pt;height: 1pt;background-color:#000000;"></SPAN><SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3063.50pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 7.98pt">1</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:79.00pt;top:3067.25pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">This guidance was developed within the Expert Working Group (Quality) of the International Conference on</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3079.20pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) and has been</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3090.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">subject to consultation by the regulatory parties, in accordance with the ICH process. This document has been</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3102.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">endorsed by the ICH Steering Committee at </FONT></FONT><FONT COLOR="000000"><i><FONT STYLE="font-size: 10.02pt">Step 4 </FONT></i><FONT STYLE="font-size: 10.02pt">of the ICH process, June 2008.  At </FONT></FONT><FONT COLOR="000000"><i><FONT STYLE="font-size: 10.02pt">Step 4 </FONT></i><FONT STYLE="font-size: 10.02pt">of the process, the final</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3113.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">draft is recommended for adoption to the regulatory bodies of the European Union, Japan, and the United States</FONT><FONT STYLE="font-size: 12.00pt">.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3138.15pt;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:3139.50pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">Arabic numbers reflect the organizational breakdown of the document endorsed by the ICH Steering Committee at</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3151.00pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">Step 4 of the ICH process, June 2008.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3172.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 7.98pt">3</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:78.95pt;top:3175.85pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">We update guidances periodically.  To make sure you have the most recent version of a guidance, check the CDER</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3187.80pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">guidance page at </FONT></FONT><u><FONT COLOR="0000ff"><FONT STYLE="font-size: 10.02pt"><a href="http://www.fda.gov/cder/guidance/index.htm">http://www.fda.gov/cder/guidance/index</a></FONT></FONT><FONT COLOR="0000ff"><FONT STYLE="font-size: 10.02pt">.</FONT></FONT><FONT COLOR="0000ff"><FONT STYLE="font-size: 10.02pt"><a href="http://www.fda.gov/cder/guidance/index.htm">h</a></FONT></FONT><FONT COLOR="0000ff"><FONT STYLE="font-size: 10.02pt">t</FONT></FONT><FONT COLOR="0000ff"><FONT STYLE="font-size: 10.02pt"><a href="http://www.fda.gov/cder/guidance/index.htm">m </a></FONT></FONT></u><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">or the CBER guidance page at</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3199.30pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><u><FONT COLOR="0000ff"><FONT STYLE="font-size: 10.02pt"><a href="http://www.fda.gov/cber/guidelines.htm">http://www.fda.gov</a></FONT></FONT><FONT COLOR="0000ff"><FONT STYLE="font-size: 10.02pt">/</FONT></FONT><FONT COLOR="0000ff"><FONT STYLE="font-size: 10.02pt"><a href="http://www.fda.gov/cber/guidelines.htm">cber/gu</a></FONT></FONT><FONT COLOR="0000ff"><FONT STYLE="font-size: 10.02pt">i</FONT></FONT><FONT COLOR="0000ff"><FONT STYLE="font-size: 10.02pt"><a href="http://www.fda.gov/cber/guidelines.htm">delines.htm</a></FONT></FONT></u><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">..</FONT></FONT></FONT></SPAN>
<span style="color:#000000;background-color:#ffffff;position:absolute;left:0.00pt;top:2502.00pt;z-index:-1;"><img style="width:612pt;height:792pt;" src="outputfile-273907952.htm_files\outputfile-273907952_background3.png"></span>
<SPAN STYLE="position:absolute;left:71.76pt;top:3294.00pt"> </SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:205.25pt;top:3330.45pt;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:303.50pt;top:4036.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">2</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3366.35pt;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 documents, including this guidance, do not establish legally enforceable</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3380.15pt;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:3393.95pt;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:3407.75pt;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 </FONT></FONT><FONT COLOR="000000"><i><FONT STYLE="font-size: 12.00pt">should </FONT></i><FONT STYLE="font-size: 12.00pt">in Agency guidances means that something is suggested or</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3421.55pt;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:3463.05pt;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:3463.05pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Q4B OUTCOME (2)</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:3490.65pt;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:144.00pt;top:3490.65pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Analytical Procedures (2.1)</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3518.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">The ICH Steering Committee, based on the evaluation by the Q4B Expert Working Group</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3531.95pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">(EWG), recommends that the official pharmacopoeial texts, Ph. Eur. 2.9.19. Particulate</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3545.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Contamination: Sub-visible Particles, JP 6.07 Insoluble Particulate Matter Test for Injections,</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3559.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">and USP <788> Particulate Matter in Injections, can be used as interchangeable in the ICH</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3573.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">regions subject to the following condition:</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:3600.60pt;z-index:3;"><FONT FACE ="Symbol" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 10.98pt">•</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:126.00pt;top:3600.95pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><b><FONT STYLE="font-size: 12.00pt">Condition (2.1.1): </FONT></b><FONT STYLE="font-size: 12.00pt">Instrument calibration and system suitability measurements should</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:126.00pt;top:3614.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">follow regional good manufacturing practice (GMP) requirements.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:3642.45pt;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:144.00pt;top:3642.45pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Acceptance Criteria (2.2)</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3669.95pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Except for nominal 100-milliliter (mL) parenteral products, the acceptance criteria are</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3683.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">interchangeable.  At the 100-mL nominal volume, the criteria specified in JP are more stringent</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3697.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">than those in the Ph. Eur. and the USP pharmacopoeias; therefore, the criteria are not</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3711.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">interchangeable in all three regions at that volume.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3752.80pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">III.</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:107.95pt;top:3752.80pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">TIMING OF ANNEX IMPLEMENTATION (3)</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3780.30pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">When this annex has been implemented (incorporated into the regulatory process at ICH Step 5)</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3794.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">in a region, it can be used in that region.  Timing might differ for each region.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3835.60pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">IV.</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:3835.60pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">CONSIDERATIONS FOR IMPLEMENTATION (4)</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:3863.20pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">A. General Consideration (4.1)</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3890.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">When sponsors or manufacturers change their existing methods to the implemented Q4B-</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3904.50pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">evaluated pharmacopoeial texts that are referenced in section II.A (2.1) of this annex, any change</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3918.30pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">notification, variation, and/or prior approval procedures should be handled in accordance with</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:3932.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">established regional regulatory mechanisms pertaining to compendial changes.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:3959.80pt;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:144.05pt;top:3959.80pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">FDA Consideration (4.2)</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="position:absolute;left:71.76pt;top:4086.00pt"> </SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:205.25pt;top:4122.45pt;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:303.50pt;top:4828.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">3</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:4158.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Based on the recommendation above, and with reference to the conditions set forth in this annex,</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:4172.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">the pharmacopoeial texts referenced in section II.A (2.1) of this annex can be considered</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:4185.95pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">interchangeable.  However, FDA might request that a company demonstrate that the chosen</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:4199.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">method is acceptable and suitable for a specific material or product, irrespective of the origin of</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">the method.  For nominal 100-mL parenteral products, the FDA considers testing criteria from all</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">three pharmacopoeias as interchangeable.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:4255.05pt;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:144.00pt;top:4255.05pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">EU Consideration (4.3)</FONT></FONT></b></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">For the European Union, the monographs of the Ph. Eur. have mandatory applicability.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:4296.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Regulatory authorities can accept the reference in a marketing authorization application, renewal</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:4310.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">or variation application citing the use of the corresponding text from another pharmacopoeia as</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:4323.95pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">referenced in section II.A (2.1), in accordance with the conditions set out in this annex, as</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:4337.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">fulfilling the requirements for compliance with the Ph. Eur. Chapter, Particulate Contamination:</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:4351.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Sub-visible Particles: 2.9.19., on the basis of the declaration of interchangeability made above.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:4365.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">For nominal 100-mL parenteral products, the EU considers testing criteria from all three</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:4379.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">pharmacopoeias as interchangeable.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:4406.85pt;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:144.05pt;top:4406.85pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">MHLW Consideration (4.4)</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:4434.35pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">The pharmacopoeial texts referenced in section II.A (2.1) of this annex can be used as</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:4448.15pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">interchangeable in accordance with the conditions set out in this annex.  Details of</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:4461.95pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">implementation requirements will be provided in the notification by MHLW when this annex is</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:4475.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">implemented.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:72.00pt;top:4517.20pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">V.</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:108.00pt;top:4517.20pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">REFERENCES USED FOR THE Q4B EVALUATION (5)</FONT></FONT></b></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:103.50pt;top:4544.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><b><FONT STYLE="font-size: 12.00pt">A. (5.1</FONT></b><FONT STYLE="font-size: 12.00pt">)  The PDG Stage 5B sign-off document:  </FONT></FONT><FONT COLOR="000000"><i><FONT STYLE="font-size: 12.00pt">Japanese Pharmacopoeial Forum</FONT></i><FONT STYLE="font-size: 12.00pt">,</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:126.00pt;top:4558.50pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Volume 13, Number 3 (August 2004).</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:103.50pt;top:4586.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><b><FONT STYLE="font-size: 12.00pt">B. (5.2) </FONT></b><FONT STYLE="font-size: 12.00pt">The pharmacopoeial references for Particulate Matter for this annex are:</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:130.50pt;top:4613.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><i><FONT STYLE="font-size: 12.00pt">1. (5.2.1) European Pharmacopoeia </FONT></i><FONT STYLE="font-size: 12.00pt">(Ph. Eur.):  5</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:372.80pt;top:4611.75pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 7.98pt">th</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:382.00pt;top:4613.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Edition (official on January</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:130.50pt;top:4627.50pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">2005), Particulate Contamination: Sub-visible Particles (reference 01/2005:20919).</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:130.50pt;top:4655.10pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><i><FONT STYLE="font-size: 12.00pt">2. (5.2.2) Japanese Pharmacopoeia </FONT></i><FONT STYLE="font-size: 12.00pt">(JP):  6.07 Insoluble Particulate Matter Test for</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:130.50pt;top:4668.90pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Injections as it appears in the JP Fifteenth Edition (March 31, 2006, The Ministry of</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:130.50pt;top:4682.70pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">Health, Labour and Welfare Ministerial Notification No. 285). </FONT><FONT STYLE="font-size: 10.98pt">The method was</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:130.50pt;top:4696.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 10.98pt">changed in September 2007 to correct a sentence in the introduction as underlined in the text</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:130.50pt;top:4709.20pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 10.98pt">that is provided by MHLW which is attached.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:130.50pt;top:4735.60pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><i><FONT STYLE="font-size: 12.00pt">3. (5.2.3) United States Pharmacopeia </FONT></i><FONT STYLE="font-size: 12.00pt">(USP): </FONT><FONT STYLE="font-size: 10.98pt"><788> Particulate Matter in Injections,</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:130.50pt;top:4749.45pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 10.98pt">Revision Bulletin, April 4, 2007.</FONT></FONT></FONT></SPAN>
<SPAN STYLE="position:absolute;left:71.76pt;top:4878.00pt"> </SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:205.25pt;top:4914.45pt;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:303.50pt;top:5620.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">4</FONT></FONT></FONT></SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:256.70pt;top:4942.05pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><b><FONT COLOR="000000"><FONT STYLE="font-size: 12.00pt">ATTACHMMENT</FONT></FONT></b></FONT></SPAN>
<span style="color:#000000;background-color:#ffffff;position:absolute;left:0.00pt;top:4878.00pt;z-index:-1;"><img style="width:612pt;height:792pt;" src="outputfile-273907952.htm_files\outputfile-273907952_background6.png"></span>
<SPAN STYLE="position:absolute;left:71.76pt;top:5670.00pt"> </SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:205.25pt;top:5706.45pt;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:303.50pt;top:6412.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">5</FONT></FONT></FONT></SPAN>
<span style="color:#000000;background-color:#ffffff;position:absolute;left:0.00pt;top:5670.00pt;z-index:-1;"><img style="width:612pt;height:792pt;" src="outputfile-273907952.htm_files\outputfile-273907952_background7.png"></span>
<SPAN STYLE="position:absolute;left:71.76pt;top:6462.00pt"> </SPAN>
<SPAN STYLE="color:#000000;position:absolute;left:205.25pt;top:6498.45pt;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:303.50pt;top:7204.55pt;z-index:3;"><FONT FACE ="Times New Roman" style = "font-size: 12.00pt"><FONT COLOR="000000"><FONT STYLE="font-size: 10.02pt">6</FONT></FONT></FONT></SPAN>
<span style="color:#000000;background-color:#ffffff;position:absolute;left:0.00pt;top:6462.00pt;z-index:-1;"><img style="width:612pt;height:792pt;" src="outputfile-273907952.htm_files\outputfile-273907952_background8.png"></span>
<SPAN STYLE="position:absolute;left:71.76pt;top:7254.00pt"> </SPAN>
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