Guidance for Industry 

Q4B Evaluation and Recommendation 

of Pharmacopoeial Texts for Use in the 

ICH Regions 

Annex 1 

Residue on Ignition/Sulphated Ash 

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) 

February 2008 

ICH 
Guidance for Industry 

Q4B Evaluation and Recommendation 

of Pharmacopoeial Texts for Use in the 

ICH Regions 

Annex 1 

Residue on Ignition/Sulphated Ash 

General Chapter 

Additional copies are available from: 

Office of Training and Communication 

Division of Drug Information, HFD-240 

Center for Drug Evaluation and Research 

Food and Drug Administration 

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(Tel) 301-827-4573 

 http://www.fda.gov/cder/guidance/index.htm 

Office of Communication, Training and 

Manufacturers Assistance, HFM-40 

Center for Biologics Evaluation and Research 

 Food and Drug Administration 

1401 Rockville Pike, Rockville, MD 20852-1448 

 http://www.fda.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) 

February 2008 

ICH 
i

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

1

Guidance for Industry1

Q4B Evaluation and Recommendation of Pharmacopoeial Texts 

for Use in the ICH Regions 

Annex 1 

Residue on Ignition/Sulphated Ash 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 Residue on Ignition/Sulphated Ash. 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 

 

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 2007. 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 2007. 

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.
Contains Nonbinding Recommendations

2

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. 20414 

Sulphated Ash, JP 2.44 Residue on Ignition Test, and USP <281> Residue on Ignition 

can be used as interchangeable in the ICH regions given the following: 

1. (2.1.1) Unless otherwise specified in a monograph, an appropriate sample weight is 

chosen, typically 1-2 g, to result in a level of residue sufficient to be accurately 

measurable by weight (typically 1 mg). If not specified in the monograph, the 

appropriate sample weight should be justified, and the sample weight and the acceptance 

criteria should be specified in the application dossier. 

2. (2.1.2) The muffle furnace should be appropriately calibrated to ensure compliance 

with regional GMP requirements. 

B. Acceptance Criteria (2.2) 

The proposed 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 may 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 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 in accordance with the conditions set forth in this 

annex, the pharmacopoeial texts referenced in section II.A (2.1) of this annex can be 
Contains Nonbinding Recommendations

3

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) 

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

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, 

Sulphated Ash: 20414, 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. 

V. REFERENCES USED FOR THE Q4B EVALUATION (5) 

A. (5.1) The PDG Stage 5B sign-off document: Japanese Pharmacopoeial Forum Volume 

14, Number 4 (December 2005). (Note: the PDG cover letter published in this 

volume was subsequently changed based on Q4B comments.) 

B. (5.2) The pharmacopoeial references for Residue on Ignition/Sulphated Ash for this 

annex are: 

1. (5.2.1) European Pharmacopoeia (Ph. Eur.): Supplement 5.6 (official on January 

2007) (reference Sulphated Ash 01/2007:20414) 

2. (5.2.2) Japanese Pharmacopoeia (JP): 2.44 Residue on Ignition Test as it appears 

in the JP Fifteenth Edition (March 31, 2006, The Ministry of Health, Labour 

and Welfare Ministerial Notification No. 285) 

3. (5.2.3) United States Pharmacopeia (USP): <281> Residue on Ignition official in 

USP 29, 2nd Supplement, August 2006