Q4B Evaluation and Recommendation of 

Pharmacopoeial Texts for Use in the ICH Regions 

Annex 7: Dissolution Test General Chapter 

This draft guidance, when finalized, will represent the Food and Drug Administration's (FDA's) 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. 

For questions regarding this draft document contact (CDER) Robert King 301-796-1242, 

or (CBER) Christopher Joneckis 301-827-0373. 
 

 

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3 INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL 

4 REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE 

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8 DRAFT CONSENUS GUIDELINE
 

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14 EVALUATION AND RECOMMENDATION OF 

PHARMACOPOEIAL TEXTS FOR USE IN THE ICH REGIONS 

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17 DISSOLUTION TEST GENERAL CHAPTER 

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19 Q4B ANNEX 7 

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24 Current Step 2 Version 

dated 13 November 2008 

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At Step 2 of the ICH Process, a consensus draft text or guideline, agreed by the appropriate ICH 

36 Expert Working Group, is transmitted by the ICH Steering Committee to the regulatory 

37 authorities of the three ICH regions (the European Union, Japan and the USA) for internal and 

38 external consultation, according to national or regional procedures. 
 

 

 

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50 Q4B Annex 7 

51 Document History 

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53 Current Step 2 version 

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Code History Date 

Q4B Annex 7 Approval by the Steering Committee under Step 2 and release 

for public consultation. 

13 November 

2008 

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58 EVALUATION AND RECOMMENDATION OF 

59 PHARMACOPOEIAL TEXTS FOR USE IN THE ICH REGIONS 

60 ON 

61 DISSOLUTION TEST GENERAL CHAPTER 

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63 Q4B Annex 7 

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65 Draft ICH Consensus Guideline 

66 Released for Consultation on 13 November 2008, at Step 2 of the ICH Process 

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69 TABLE OF CONTENTS 

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72 1. INTRODUCTION......................................................................................................1 

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74 2. Q4B OUTCOME........................................................................................................1 

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76 2.1 Analytical Procedures................................................................................................1 

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78 2.2 Acceptance Criteria....................................................................................................1 

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80 3. TIMING OF ANNEX IMPLEMENTATION...........................................................1 

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82 4. CONSIDERATIONS FOR IMPLEMENTATION.................................................2 

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84 4.1 General Consideration................................................................................2 

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86 4.2 FDA Consideration....................................................................................2 

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88 4.3 EU Consideration......................................................................................2 

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90 4.4 MHLW Consideration.................................................................................3 

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92 5. REFERENCES USED FOR THE Q4B EVALUATION.......................................3 

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96 EVALUATION AND RECOMMENDATION OF 

97 PHARMACOPOEIAL TEXTS FOR USE IN THE ICH REGIONS 

98 ON 

99 DISSOLUTION TEST GENERAL CHAPTER

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101 Q4B Annex 7 102

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104 1. INTRODUCTION 105 

106 This annex is the result of the Q4B process for Dissolution Test. 

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108 The proposed texts were submitted by the Pharmacopoeial Discussion Group (PDG). 

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110 2. Q4B OUTCOME 

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112 2.1 Analytical Procedures 113 

114 The ICH Steering Committee, based on the evaluation by the Q4B Expert Working 

115 Group (EWG), recommends that the official pharmacopoeial texts, Ph.Eur. 2.9.3. 

116 Dissolution, JP 6.10 Dissolution Test, and USP <711> Dissolution, can be used as 

117 interchangeable in the ICH regions subject to the following conditions: 

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119 2.1.1 The Dissolution Test is not considered to be interchangeable in the ICH regions 

120 when enzymes are used in the media. 

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122 2.1.2 The dissolution apparatus should be appropriately calibrated to ensure 

123 compliance with regional good manufacturing practice (GMP) requirements. 

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125 2.1.3 Except for Apparatus 1 and 2, apparatus numbers are not consistent in the three 

126 pharmacopoeias. Accordingly, other apparatus should be referred to in the 

127 dossier by an unambiguous descriptive title or compendial reference. 

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129 2.1.4 The Dissolution Test is not considered to be interchangeable in the ICH regions 

130 for dosage forms referred to in the regional compendia as delayed-release, 

131 gastro-resistant, or enteric-coated. 

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133 2.1.5 Validation studies should be conducted to demonstrate that the test results are 

134 not adversely affected if the thermometer is to remain in the dissolution vessel 

135 per regional good manufacturing practice (GMP). 

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137 2.1.6 The Dissolution Test is not considered to be interchangeable in the ICH regions 

138 for JP Interpretation 2. 

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140 2.1.7 The Dissolution Test is not considered to be interchangeable in the ICH regions 

141 for use of large vessels (greater than 1 liter). 

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143 2.1.8 Product-specific parameters such as media, stirring rate, sampling time, and the 

144 use and type of sinkers should be specified and justified in the application 

145 dossier. 

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147 Dissolution Test General Chapter 148 

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150 2.1.9 When using the small cell tablet holder with the flow-through cell apparatus, 

151 only the dimensions described in the PDG harmonised text Figure 5 are 

152 considered interchangeable. 

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155 2.2 Acceptance Criteria 156 

157 Acceptance criteria should be specified in the application dossier. 

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160 3. TIMING OF ANNEX IMPLEMENTATION 161 

162 When this annex is implemented (incorporated into the regulatory process at ICH Step 5) in a 

163 region, it can be used in that region. Timing might differ for each region. 

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165 4. CONSIDERATIONS FOR IMPLEMENTATION 166 

167 4.1 General Consideration 168 

169 When sponsors or manufacturers change their existing methods to the implemented 

170 Q4B-evaluated pharmacopoeial texts that are referenced in Section 2.1 of this annex, 

171 any change notification, variation, and/or prior approval procedures should be handled 

172 in accordance with established regional regulatory mechanisms pertaining to 

173 compendial changes. 174 

175 4.2 FDA Consideration 176 

177 Based on the recommendation above, and with reference to the conditions set forth in 

178 this annex, the pharmacopoeial texts referenced in Section 2.1 of this annex can be 

179 considered interchangeable. However, FDA might request that a company 

180 demonstrate that the chosen method is acceptable and suitable for a specific material 

181 or product, irrespective of the origin of the method. 182 

183 An appropriately rigorous mechanical calibration method (such as ASTM 

184 International’s ASTM E2503-07, Standard Practice for Qualification of Basket and 

185 Paddle Dissolution Apparatus, or the procedures for Mechanical Qualification of 

186 Dissolution Apparatus 1 and 2, DPA-LOP.002, on the FDA Web site), when properly 

187 executed, will satisfy the current good manufacturing practice (CGMP) requirement 

188 for dissolution apparatus calibration under § 211.160(b)(4) of Title 21 of the Code of 

189 Federal Regulations. 190 

191 4.3 EU Consideration 192 

193 For the European Union, the monographs of the Ph. Eur. have mandatory 

194 applicability. Regulatory authorities can accept the reference in a marketing 

195 authorisation application, renewal or variation application citing the use of the 

196 corresponding text from another pharmacopoeia as referenced in Section 2.1, in 

197 accordance with the conditions set out in this annex, as fulfilling the requirements for 

198 compliance with the Ph. Eur. Chapter 2.9.3. on the basis of the declaration of 

199 interchangeability made above. 200 

201 EU considers that it could accept the approach to the dissolution test for delayed202 release products as published in the USP as meeting the criteria of the Ph. Eur. The 

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204 Dissolution Test General Chapter 205 

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207 validation studies referred to in Section 2.1.5 of this annex would normally be 

208 submitted in the marketing authorisation dossier. 

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211 4.4 MHLW Consideration 212 

213 The pharmacopoeial texts referenced in Section 2.1 of this annex can be used as 

214 interchangeable in accordance with the conditions set out in this annex. Details of 

215 implementation requirements will be provided in the notification by MHLW when this 

216 annex is implemented. 

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218 MHLW considers that it could accept the approach to the dissolution test for 

219 reciprocating cylinder apparatus as published in Ph. Eur. and USP, if the validation 

220 studies have been submitted in the marketing authorization dossier. 

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222 5. REFERENCES USED FOR THE Q4B EVALUATION 223 

224 5.1 The PDG Stage 5B sign-off document (Rev. 1): Japanese Pharmacopoeial Forum, 

225 Volume 14, number 4 (December 2005).
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227 5.2 The pharmacopoeial references for Dissolution Test for this annex are: 228 

229 5.2.1 European Pharmacopoeia (Ph. Eur.): 

230 6th Edition (official on January 2008) Dissolution Test (reference 01/2008: 

231 20903). 232 

233 5.2.2 Japanese Pharmacopoeia (JP): 

234 6.10 Dissolution Test as it appears in Supplement I to the JP Fifteenth Edition 

235 (September 28, 2007, The Ministerial Notification No. 316). 236 

237 5.2.3 United States Pharmacopeia (USP): 

238 <711> Dissolution Test USP 28, 2nd Supplement, official August 1, 2005.
 

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