Guidance for Industry 

 
Q4B Evaluation and Recommendation 

of Pharmacopoeial Texts for Use in the 

ICH Regions 

 
Annex 12 

Analytical Sieving General Chapter 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
U. S. Department of Health and Human Services 

Food and Drug Administration 

Center for Drug Evaluation and Research (CDER) 

Center for Biologics Evaluation and Research (CBER) 

 
September 2010 

ICH 

   
Guidance for Industry 

 
Q4B Evaluation and Recommendation 

of Pharmacopoeial Texts for Use in the 

ICH Regions 
 
 
Annex 12 

Analytical Sieving General Chapter 

 
 
Additional copies are available from: 

 
Office of Communication, Division of  Drug  Information 

Center for Drug Evaluation  and Research 
 
Food and  Drug Administration 

 10903 New Hampshire Ave., Bldg. 51, Room  2201 
 
Silver Spring, MD 20993-0002 
  
Phone: 301-796-3400;  Fax: 301-847-8714; E-mail: druginfo@fda.hhs.gov 

http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm 

 
or 
 
Office of Communication, Outreach  and Development, HFM-40 
Center for Biologics Evaluation and Research 
 Food and Drug  Administration 
1401 Rockville Pike, Rockville, MD  20852-1448 
 (Tel) 800-835-4709  or  301-827-1800 
 http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm   
 
 
U.S. Department of Health and Human Services 

Food and Drug Administration 

Center for Drug Evaluation and Research (CDER) 

Center for Biologics Evaluation and Research (CBER) 

 
September 2010 

ICH 

   
TABLE OF CONTENTS 

 
 
I.   INTRODUCTION (1)....................................................................................................... 1 
 
II.   Q4B OUTCOME (2)......................................................................................................... 2
  
A.   Analytical Procedures (2.1) ...........................................................................................................2
  
B.   Acceptance Criteria (2.2)...............................................................................................................2
  
III.   TIMING OF ANNEX IMPLEMENTATION (3) .......................................................... 2  

IV.   CONSIDERATIONS FOR IMPLEMENTATION (4).................................................. 2 
 
A.   General Consideration (4.1)..........................................................................................................2
  
B.   FDA Consideration (4.2) ...............................................................................................................2
  
C.   EU Consideration (4.3)..................................................................................................................2
  
D.   MHLW Consideration (4.4) ..........................................................................................................3
  
E.   Health Canada Consideration (4.5)..............................................................................................3
  
V.   REFERENCES USED FOR THE Q4B EVALUATION (5) ........................................ 3 
 
i  Contains Nonbinding Recommendations  
 
1
 
Guidance for Industry  
Q4B Evaluation and Recommendation of Pharmacopoeial Texts  

for Use in the ICH Regions 

 
Annex 12 

Analytical Sieving General Chapter 

 
 
This guidance represents the Food and Drug Administration's (FDA's) current thinking on this topic.  It 
does not create or confer any rights for or on any  person and does not operate to bind FDA or the public.  
You can use an alternative approach if the approach satisfies the requirements of the applicable statutes 
and regulations.  If you want to discuss an alternative approach, contact the FDA staff responsible for 
implementing this guidance.  If you cannot identify the appropriate FDA staff, call the appropriate 
number listed on the title page of this guidance.  
 
 
 
 
 
I.   INTRODUCTION (1)2  
 
This annex is one in a series of guidance documents that describe the evaluations and 
recommendations by the Q4B Expert Working Group (EWG) of selected pharmacopoeial texts 
to facilitate their recognition by regulatory authorities for use as interchangeable in the ICH 
regions. Implementation of the Q4B annexes is intended to  avoid redundant testing by industry.  
For general information on the Q4B process, the reader is referred to the core guidance Q4B 
Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions.3  
 
This annex is the result of the Q4B process for the Analytical Sieving General Chapter.  
The proposed texts were submitted by the Pharmacopoeial Discussion Group (PDG). 
 
 
                                                 
1  This guidance was developed within  the Expert Working Group (Quality) of  the International Conference on  
Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) and has been  
subject to consultation by the  regulatory  parties, in accordance with the ICH process.  This document has been  
endorsed by the ICH Steering Committee at Step 4  of the ICH process, June  2010.  At  Step 4  of the process, the final  
draft is recommended for adoption to the regulatory  bodies of the European Union, Japan, and the United States. 
 
2 Arabic numbers reflect the organizational breakdown of the document endorsed  by the ICH Steering Committee at 
Step 4 of  the ICH process,  June 2010. 
 
3We update guidance  documents periodically.  To make sure you have the most  recent version of a guidance, check 
the FDA Drugs guidance page at http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/  
Guidances/default.htm or the  FDA Biologics guidance page at  
http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm. 
1 
 Contains Nonbinding Recommendations  
 
FDA's guidance documents, including this guidance, do not establish legally enforceable 
responsibilities. Instead, guidances describe the Agency's current thinking on a topic and should 
be viewed only as recommendations, unless specific regulatory or statutory requirements are 
cited. The use of the word should in Agency guidances means that something is suggested or 
recommended, but not required. 
 
II.  Q4B OUTCOME (2) 
 
A.  Analytical Procedures (2.1) 
 
The ICH Steering Committee, based on the evaluation by the Q4B Expert Working Group 
(EWG), recommends that the analytical procedures described in the official pharmacopoeial 
texts, Ph. Eur. 2.9.38. Particle-size Distribution Estimation by Analytical Sieving, JP 3.04 
Particle Size Determination entitled Method 2. Analytical Sieving Method, and USP General 
Chapter <786> Particle Size Distribution Estimation by Analytical Sieving, can be used as 
interchangeable in the ICH regions.   
 
B.  Acceptance Criteria (2.2) 
   
The texts evaluated did not contain acceptance criteria.  
 
III.   TIMING OF ANNEX IMPLEMENTATION (3)  
 
When this annex is implemented (incorporated into the regulatory process at ICH Step 5) in a 
region, it can be used in that region.  Timing might differ for each region.  
 
IV.  CONSIDERATIONS FOR IMPLEMENTATION (4) 
 
A.  General Consideration (4.1) 
 
When sponsors or manufacturers change their existing methods to the implemented Q4B-
evaluated pharmacopoeial texts that are referenced in section II.A (2.1) of this annex, any change 
notification, variation, and/or prior approval procedures should be handled in accordance with 
established regional regulatory mechanisms pertaining to compendial changes.  
 
B.  FDA Consideration (4.2) 
 
Based on the recommendation above, and with reference to the conditions set forth in this annex, 
the pharmacopoeial texts referenced in section II.A (2.1) of this annex can be considered 
interchangeable.  However, FDA might request that a company demonstrate that the chosen 
method is acceptable and suitable for a specific material or product, irrespective of the origin of 
the method.  
 
C.  EU Consideration (4.3) 
 
2 
 Contains Nonbinding Recommendations  
 
For the European Union, regulatory authorities can accept the reference in a marketing 
authorization application, renewal or variation application citing the use of the corresponding 
text from another pharmacopoeia as referenced in section II.A (2.1), in accordance with the 
conditions set out in this annex, as fulfilling the requirements for compliance with the Ph. Eur. 
Chapter 2.9.38. on the basis of the declaration of interchangeability made above.  
 
D.  MHLW Consideration (4.4) 
 
The pharmacopoeial texts referenced in section II.A. (2.1) of this annex can be used as 
interchangeable in accordance with the conditions set out in this annex.  Details of 
implementation requirements will be provided in the notification by MHLW when this annex is 
implemented. 
 
E.   Health Canada Consideration (4.5) 
 
In Canada any of the texts cited in section II.A (2.1) of this annex and used in accordance with 
the conditions set out in this annex can be considered interchangeable. 
 
V.  REFERENCES USED FOR THE Q4B EVALUATION (5) 
 
A. (5.1) 	The PDG Stage 5B sign-off document:  Japanese Pharmacopoeial Forum, 
Volume 16, number 2 (June 2007). 
 
B. (5.2) 	The pharmacopoeial references for Analytical Sieving General Chapter for this 
annex are: 
 
1. (5.2.1)    European Pharmacopoeia (Ph. Eur.): Supplement 6.2 (published 
December 11, 2007, and official July 2008), Particle-size Distribution Estimation 
by Analytical Sieving (reference 07/2008:20938). 
 
2. (5.2.2)    Japanese Pharmacopoeia (JP): 3.04 Particle Size Determination as it 
appeared in Supplement II to the JP Fifteenth Edition (September 30, 2009, The 
Ministerial Notification No. 425).  The English version of the JP text was 
published June 4, 2010, and is available at 
www.std.pmda.go.jp/jpPUB/index_e.html. 
 
3. (5.2.3)    United States Pharmacopeia (USP): <786> Particle Size Distribution 
Estimation by Analytical Sieving, USP 32 Supplement 2 (official 12/1/09), and 
Errata in Interim Revision Announcement to USP 32 appearing in Pharmacopeial 
Forum, Vol. 35, no. 5, released September 1, 2009, and official October 1, 2009. 
 
 
3