Guidance for Industry
 

Q4B Evaluation and Recommendation
 

of Pharmacopoeial Texts for Use in the
 

ICH Regions
 

Annex 2
 

Test for Extractable Volume of
 

Parenteral Preparations
 

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)
 

January 2009
 

ICH
 
Guidance for Industry
 

Q4B Evaluation and Recommendation of
 

Pharmacopoeial Texts for Use in the
 

ICH Regions
 

Annex 2
 

Test for Extractable Volume of
 

Parenteral Preparations
 

General Chapter
 

Additional copies are available from:
 

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Division ofDrug Information
 

Center for Drug Evaluation and Research
 

Food and Drug Administration
 

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Bldg. 51, Room 2201
 

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(Tel) 301-796-3400
 

http://wwwjda.gov/cder/guidance/index.htm
 

or 

Office ofCommunication. Training and
 

Manufacturers Assistance, HFM-40
 

Center for Biologics Evaluation and Research
 

Food and Drug Administration
 

1401 Rockville Pike, Rockville, MD 20852-1448
 

http://wwwjda.gov/cber/guidelines.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)
 

January 2009
 

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) 3
 

D. MHLW Consideration (4.4) 3
 

V. REFERENCES USED FOR THE Q4B EVALUATION (5) 3
 
Contains Nonbinding Recommendations 

Guidance for Industryl
 

Q4B Evaluation and Recommendation of Pharmacopoeial Texts
 

for Use in the ICH Regions
 

Annex 2
 

Test for Extractable Volume of Parenteral Preparations
 

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 ifthe approach satisfies the requirements ofthe applicable statutes 

and regulations. If you want to discuss an alternative approach, contact the FDA staff responsible for 

implementing this guidance. If you cannot identitY 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 ofthe 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 ofPharmacopoeial Texts for Use in the ICH Regions.3 

This annex is the result of the Q4B process for the Test for Extractable Volume of Parenteral 

Preparations General Chapter. The proposed texts were submitted by the Pharmacopoeial 

Discussion Group (PDG). 

1 This guidance was developed within the Expert Working Group (Quality) ofthe 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 ofthe ICH process, June 2008. At Step 4 of the process, the final 

draft is recommended for adoption to the regulatory bodies ofthe 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 2008. 

3 We update guidances periodically. To make sure you have the most recent version of a guidance, check the CDER 

guidance page at http://www.fda.gov/cder/guidance/index.htm or the CBER guidance page at 

http://www.fda.gov/cber/guidelines.httn. 
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 ofthe 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. 2.9.17. Test for Extractable 

Volume of Parenteral Preparations, JP 6.05 Test for Extractable Volume of Parenteral 

Preparations, and the section in USP <1> Injections General Chapter entitled "Volume in 

Containers," can be used as interchangeable in the ICH regions. 

B. Acceptance Criteria (2.2) 

The acceptance criteria are the same in the three pharmacopoeias. 

III. TIMING OF ANNEX IMPLEMENTATION (3) 

When this annex has been 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 Q4Bevaluated pharmacopoeial texts that are referenced in section ILA (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 ILA (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. 

2 
Contains Nonbinding Recommendations 

C. EU Consideration (4.3) 

For the European Union, the monographs ofthe Ph. Eur. have mandatory applicability. 

Regulatory authorities can accept the reference in a marketing authorization application, renewal 

or variation application citing the use ofthe 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, Test for Extractable 

Volume ofParenteral Preparations: 2.9.17., on the basis ofthe declaration of interchangeability 

made above. 

D. MHLW Consideration (4.4) 

The pharmacopoeial texts referenced in section II.A (2.1) ofthis 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. 

V. REFERENCES USED FOR THE Q4B EVALUATION (5) 

A. (5.1) The PDG Stage 58 sign-off document: Japanese Pharmacopoeial Forum, 

Volume 13, Number 3 (August 2004). 

B. (5.2) The pharmacopoeial references for Test for Extractable Volume of Parenteral 

Preparations for this annex are: 

1. (5.2.1) European Pharmacopoeia (Ph. Eur.): Supplement 5.3 (official on January 

2006), Test for Extractable Volume of Parenteral Preparations (reference 

01/2006:20917). 

2. (5.2.2) Japanese Pharmacopoeia (JP): 6.05 Test for Extractable Volume of 

Parenteral Preparations as it appears in the JP Fifteenth Edition (March 31, 2006, 

The Ministry ofHealth, Labour and Welfare Ministerial Notification No. 285). 

3. (5.2.3) United States Pharmacopeia (USP): official text published in the Revision 

Bulletin issued November 14, 2006, and as appeared in USP 30, 2nd Supplement, 

official December 1, 2007. The official text is incorporated in <1> Injections 

General Chapter as the section entitled "Volume in Containers." 

3