Q4B Evaluation and Recommendation of 

Pharmacopoeial Texts for Use in the ICH Regions 

Annex 6: Uniformity of Dosage Units 

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This draft guidance, when finalized, will represent the Food and Drug Administration's (FDA's) 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 UNIFORMITY OF DOSAGE UNITS GENERAL CHAPTER 

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19 Q4B ANNEX 6 

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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 6 

51 Document History 

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53 Current Step 2 version 

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Code History Date 

Q4B Annex 6 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 UNIFORMITY OF DOSAGE UNITS GENERAL CHAPTER 

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63 Q4B Annex 6 

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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...........................................................2 

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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.................................................................................2 

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92 5. REFERENCES USED FOR THE Q4B EVALUATION.......................................2 

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95 EVALUATION AND RECOMMENDATION OF 

96 PHARMACOPOEIAL TEXTS FOR USE IN THE ICH REGIONS 

97 ON 

98 UNIFORMITY OF DOSAGE UNITS GENERAL CHAPTER

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100 Q4B Annex 6 101

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103 1. INTRODUCTION 104 

105 This annex is the result of the Q4B process for Uniformity of Dosage Units. 

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

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109 2. Q4B OUTCOME 

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111 2.1 Analytical Procedures 112 

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

114 Group (EWG), recommends that the official pharmacopoeial texts, Ph.Eur. 2.9.40. 

115 Uniformity of Dosage Units, JP 6.02 Uniformity of Dosage Units, and USP General 

116 Chapter <905> Uniformity of Dosage Units, can be used as interchangeable in the 

117 ICH regions subject to the following conditions: 

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119 2.1.1 The Uniformity of Dosage Unit test is not considered to be interchangeable in 

120 the three regions unless the target test sample amount at time of manufacture 

121 (T) is 100% (i.e., T=100%). 

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123 2.1.2 Unless the 25 milligrams (mg)/25% threshold limit is met, the use of the 

124 Mass/Weight Variation test as an alternative test for Content Uniformity is not 

125 considered interchangeable in all ICH regions. 

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127 2.1.3 For specific dosage forms which have been indicated in local text in the 

128 pharmacopoeias by enclosing the text within the black diamond symbols, 

129 application of the Uniformity of Dosage Units test is not considered 

130 interchangeable in all ICH regions. 

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132 2.1.4 For Mass/Weight Variation, the PDG-harmonised definition for ‘W Bar’
 

133 should be used. 

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135 2.1.5 If a correction factor is called for when different procedures are used for assay
 

136 of the preparation and for the Content Uniformity Test, the correction factor 

137 should be specified and justified in the application dossier. 138 

139 2.2 Acceptance Criteria
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141 The acceptance criteria are harmonized between the three pharmacopoeias. 

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143 Uniformity of Dosage Units General Chapter 144 

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146 3. TIMING OF ANNEX IMPLEMENTATION 147 

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

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

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151 4. CONSIDERATIONS FOR IMPLEMENTATION 152 

153 4.1 General Consideration 154 

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

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

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

158 in accordance with established regional regulatory mechanisms pertaining to 

159 compendial changes. 160 

161 4.2 FDA Consideration 162 

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

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

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

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

167 or product, irrespective of the origin of the method. 168 

169 FDA finds unsuitable for regulatory purposes the not more than (NMT) 2% relative 

170 standard deviation (RSD) exception to the 25 mg/25% threshold. Accordingly, for 

171 those items below the 25 mg/25% threshold, testing by Content Uniformity should be 

172 performed. 173 

174 4.3 EU Consideration 175 

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

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

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

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

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

181 compliance with the Ph. Eur. Chapter 2.9.40. on the basis of the declaration of 

182 interchangeability made above. 183 

184 4.4 MHLW Consideration 185 

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

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

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

189 annex is implemented. 

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192 5. REFERENCES USED FOR THE Q4B EVALUATION 193 

194 5.1 The PDG Stage 5B sign-off document: Japanese Pharmacopoeial Forum, Volume 

195 13, number 2 (May 2004). 196 

197 5.2 The pharmacopoeial references for Uniformity of Dosage Units for this annex are: 

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199 5.2.1 European Pharmacopoeia (Ph. Eur.): 

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201 Uniformity of Dosage Units General Chapter 202 

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204 Supplement 6.1 (official April 2008) Uniformity of Dosage Units (reference 

205 01/2008: 20940) 

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207 5.2.2 Japanese Pharmacopoeia (JP): 

208 6.02 Uniformity of Dosage Units, as it appears in the JP Fifteenth Edition 

209 (March 31, 2006, The Ministry of Health, Labour and Welfare Ministerial 

210 Notification No. 285). 

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212 5.2.3 United States Pharmacopeia (USP): 

213 <905> Uniformity of Dosage Units, Pharmacopeial Forum, Volume 34, 

214 Number 5, to be official December 2009. 

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