Guidance for Industry 

 
Q4B Evaluation and Recommendation 

of Pharmacopoeial Texts for Use in the 

ICH Regions 

 
Annex 7(R2) 

Dissolution Test 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) 

 
June 2011 

ICH 

 
Revision 2 

   
Guidance for Industry 

 
Q4B Evaluation and Recommendation 

of Pharmacopoeial Texts for Use in the 

ICH Regions 
 
 
Annex 7(R2) 

Dissolution Test General Chapter 

 
Additional copies are available from: 

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

 
or 
 
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 Food and Drug  Administration 
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 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) 

 
June 2011 

ICH 

 
Revision 2 

   
TABLE OF CONTENTS 

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

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

for Use in the ICH Regions 

 
Annex 7(R2) 

Dissolution Test 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.  
 
 
 
1.   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 guidance is a revision of the ICH guidance entitled Q4B Evaluation and Recommendation 
of Pharmacopoeial Texts for Use in the ICH Regions; Annex 7:  Dissolution Test General 
Chapter (April 2010). In September 2010, the April 2010 guidance was revised to add guidance 
on Health Canada consideration.  This second revision, Q4B Annex 7(R2), specifies additional 
dissolution apparatuses to which interchangeability applies in the ICH regions:  the Basket 
                                                 
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, November  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,  November 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  
 
Apparatus (Apparatus 1), the Paddle Apparatus (Apparatus 2), and the Flow-Through Cell.  Q4B 
Annex 7(R2) also updates the considerations for implementation for the FDA; the European 
Union (EU); and the Ministry of Health, Labour and Welfare (MHLW) of Japan.  In addition, it 
updates the references used for the Q4B evaluation. 
 
This annex is the result of the Q4B process for the Dissolution Test General Chapter.  The 
proposed texts were submitted by the Pharmacopoeial Discussion Group (PDG).  
 
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 official pharmacopoeial texts, Ph. Eur. 2.9.3. Dissolution Test for 
Solid Dosage Forms, JP 6.10 Dissolution Test, and USP <711> Dissolution, can be used as 
interchangeable in the ICH regions subject to the following conditions: 
 
1. (2.1.1)  The declaration of interchangeability applies to the Basket Apparatus 
(Apparatus 1), the Paddle Apparatus (Apparatus 2), and the Flow-Through Cell. The 
Flow-Through Cell should be referred to in the dossier by an unambiguous descriptive 
title or compendial reference because it is referred to by different numbers in the three 
pharmacopoeias. 
 
2. (2.1.2) The Dissolution Test is not considered to be interchangeable in the ICH 
regions when enzymes are used in the media. 
  
3. (2.1.3)  The dissolution apparatus should be appropriately calibrated to ensure 
compliance with regional good manufacturing practice (GMP) requirements.  For 
example, an appropriately designed and executed mechanical calibration strategy should 
be in compliance with good manufacturing practice requirements.     
  
4. (2.1.4)  The Dissolution Test is not considered to be interchangeable in the three ICH 
regions for dosage forms referred to in the regional compendia as delayed-release, 
gastro-resistant, or enteric-coated.  
 
5. (2.1.5)  Validation studies should be conducted to demonstrate that the test results are 
not adversely affected if the thermometer is to remain in the dissolution vessel per 
regional good manufacturing practice. 
 
2 
 Contains Nonbinding Recommendations  
 
6. (2.1.6) The Dissolution Test is not considered to be interchangeable in the ICH 
regions for JP Interpretation 2. 
 
7. (2.1.7) The Dissolution Test is not considered to be interchangeable in the ICH 
regions for use of large vessels (greater than 1 liter). 
 
8. (2.1.8)  Product-specific parameters such as media, stirring rate, sampling time, and the 
use and type of sinkers should be specified and justified in the application dossier. 
 
B.  Acceptance Criteria (2.2) 
 
Acceptance criteria should be specified in the application dossier.   
 
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.  
 
An appropriately rigorous mechanical calibration method,4 when properly executed, should 
satisfy the current good manufacturing practice (CGMP) requirement for dissolution apparatus 
calibration under 21 CFR 211.160(b)(4). 
 
C.  EU Consideration (4.3) 
 
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 
                                                 
4 See the  guidance for industry,  The Use of Mechanical Calibration of Dissolution Apparatus 1 and 2  
Current Good Manufacturing Practice (CGMP), available on the Internet at 
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.  
3 
 Contains Nonbinding Recommendations  
 
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 2.9.3. on the basis of the declaration of interchangeability made above. 
 
EU considers that it could accept the approach to the dissolution test for delayed-release 
products, as published in the USP, as meeting the criteria of the Ph. Eur.  The validation studies 
referred to in section II.A.5 (2.1.5) of this annex would normally be submitted in the marketing 
authorization dossier. 
 
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. 
 
MHLW considers that it could accept the approach to the dissolution test for reciprocating 
cylinder apparatus as published in Ph. Eur. and USP, if the validation studies have been 
submitted in the marketing authorization dossier. 
 
 E. 	 Health Canada Consideration (4.5) 
 
In Canada any of the pharmacopoeial 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. 
 
The dissolution tests for delayed-release/enteric coated products as published in the USP and in 
the Ph. Eur. can be considered interchangeable in Canada. 
 
V.  REFERENCES USED FOR THE Q4B EVALUATION (5) 
 
A. (5.1) 	The PDG Stage 5B sign-off document (Rev. 2):  Japanese Pharmacopoeial 
Forum, Volume 18, number 1 (April 2009). 
 
B. (5.2)  The pharmacopoeial references for Dissolution Test for this annex are: 
 
1. (5.2.1)   European Pharmacopoeia (Ph. Eur.):  Supplement 6.6 (official January 
2010), Dissolution Test for Solid Dosage Forms (reference 01/2010: 20903).  
 
2. (5.2.2)   Japanese Pharmacopoeia (JP): 6.10 Dissolution Test as it appears in 
Supplement I to the JP Fifteenth edition (September 28, 2007, The Ministerial 
Notification No. 316) and in the partial revision of the JP 15th edition made official 
March 31, 2009, by the Ministry of Health, Labour and Welfare Ministerial 
Notification No. 190, and in the partial revision of the JP 15th edition made official 
July 30, 2010, by the Ministry of Health, Labour and Welfare Ministerial 
Notification No. 322.  
 
4 
 Contains Nonbinding Recommendations  
 
3. (5.2.3)   United States Pharmacopeia (USP):  <711> Dissolution as presented in 
Pharmacopeial Forum, Volume 35(3), May/June 2009, published in USP 33-
Reissue, official October 1, 2010.  
 
5