Q4B Evaluation and Recommendation of 

Pharmacopoeial Texts for Use in the ICH Regions 

Annex 3: Test for Particulate Contamination: 

Subvisible Particles 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This draft guidance, when finalized, will represent the Food and Drug Administration's (FDA's) current 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 301-435-5681.
 

INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL 

REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE 

Draft Consensus Guideline 

Q4B - Annex 3 

Evaluation and Recommendation of Pharmacopoeial Texts 

for Use in the ICH Regions 

 

ON

Test for Particulate Contamination: Sub-Visible Particles 

Current Step 2 Version 

Dated November 1, 2007

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

Working Group, is transmitted by the ICH Steering Committee to the regulatory authorities of the three 

ICH regions (the European Union, Japan and the USA) for internal and external consultation, according 

to national or regional procedures.
 

Q4B -- Annex 3 

Evaluation and Recommendation of Pharmacopoeial Texts 

for Use in the ICH Regions 

ON 

Test for Particulate Contamination: Sub-Visible Particles 

ICH Consensus Guideline 

Released for Consultation on November 1, 2007, at Step 2 of the ICH Process 

1. Introduction 

This annex is the result of the Q4B process for Test for Particulate Contamination: Sub-Visible 

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

2. Q4B Outcome

2.1. Analytical Procedures 

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

(EWG), recommends that the official pharmacopoeial texts, Ph.Eur. 20919 Particulate 

Contamination: Sub-visible Particles, JP 6.07 Insoluble Particulate Matter Test for Injections, 

and USP <788> Particulate Matter in Injections General Chapter can be used as interchangeable 

in the ICH regions given the following: 

2.1.1 Instrument calibration and system suitability measurements should follow regional GMP 

requirements. 

2.2. Acceptance Criteria 

Except for nominal 100-milliliter (mL) parenteral products, the acceptance criteria are 

interchangeable. At the 100-mL nominal volume, the criteria specified in JP are more stringent 

than those in the other two pharmacopoeias; therefore, the criteria are not interchangeable at that 

volume. 

3. Timing of Annex Implementation 

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. 

4. Considerations for Implementation 

4.1 General consideration: When sponsors or manufacturers change their existing methods to the 

implemented Q4B-evaluated pharmacopoeial texts that are referenced in Section 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. 

4.2 FDA consideration: Based on the recommendation above, and in accordance with the conditions 

set forth in this annex, the pharmacopoeial texts referenced in Section 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.

4.3 EU consideration: For the European Union, the monographs of the Ph. Eur. have mandatory 

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

application, renewal or variation application citing the use of the corresponding text from 

another pharmacopoeia as referenced in Section 2.1, in accordance with the conditions set out in 
 

this annex, as fulfilling the requirements for compliance with the Ph. Eur. Chapter, Particulate 

Contamination: Sub-visible Particles: 20919, on the basis of the declaration of 

interchangeability made above. 

4.4 MHLW consideration: The pharmacopoeial texts referenced in Section 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. 

5. References Used for the Q4B Evaluation 

5.1 The PDG Stage 5B sign-off document: Japanese Pharmacopoeial Forum, Volume 13, 

Number 3 (August 2004) 

5.2 The pharmacopoeial references for Particulate Matter for this annex are: 

5.2.1 European Pharmacopoeia (Ph. Eur.): 5th Edition (official on January 2005) 

Particulate Contamination: Sub-visible Particles (reference 01/2005: 20919) 

5.2.2 Japanese Pharmacopoeia (JP): 6.07 Insoluble Particulate Matter Test for Injections as 

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

and Welfare Ministerial Notification No. 285). The method was changed in 

September 2007 to correct a sentence in the introduction as underlined in the text that 

is appended. 

5.2.3 United States Pharmacopeia (USP): <788> Particulate Matter in Injections, Revision 

Bulletin, April 4, 2007