Q4B Evaluation and Recommendation 
of Pharmacopoeial Texts for Use in the 
ICH Regions 
 
Annex 8(R1) 
Sterility Test General Chapter  
Guidance for Industry 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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) 
 
September 2017 
ICH 
 
Revision 1  
 
Q4B Evaluation and Recommendation of 
Pharmacopoeial Texts for Use in the  
ICH Regions 
 
Annex 8(R1) 
Sterility Test General Chapter 
Guidance for Industry 
 
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 https://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.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) 
 
September 2017 
ICH 
 
Revision 1 
   
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) ............................................................................................................... 3 
C.  EU Consideration (4.3) .................................................................................................................. 3 
D.  MHLW Consideration (4.4) .......................................................................................................... 3 
E.  Canada Consideration (4.5) .......................................................................................................... 3 
V.  REFERENCES USED FOR THE Q4B EVALUATION (5) ........................................ 3 
  Contains Nonbinding Recommendations 
 
Q4B Evaluation and Recommendation of Pharmacopoeial Texts  
for Use in the ICH Regions 
 
Annex 8(R1) 
Sterility Test General Chapter 
1
Guidance for Industry  
 
 
This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on 
this topic.  It does not create or confer any rights for any person and is not binding on FDA or the public.  
You can use an alternative approach if it satisfies the requirements of the applicable statutes and 
regulations.  To discuss an alternative approach, contact the FDA office responsible for this guidance as 
listed on the title page.  
 
 
 
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 the Sterility Test General Chapter.  The proposed 
texts were submitted by the Pharmacopoeial Discussion Group (PDG).  This revision, Q4B 
Annex 8(R1), adds the Health Canada interchangeability statement in section IV.E (4.5). 
 
 
                                                 
1 This guidance was developed within the Expert Working Group (Quality) of the International Council for 
Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), formerly the International 
Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, 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, September 2010.  At Step 4 of the 
process, the final draft is recommended for adoption to the regulatory agencies. 
 
2 Arabic numbers reflect the organizational breakdown of the document endorsed by the ICH Steering Committee at 
Step 4 of the ICH process, September 2010. 
 
3We update guidance documents periodically.  To make sure you have the most recent version of a guidance, check 
the FDA Drugs guidance page at https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/ 
Guidances/default.htm or the FDA Biologics guidance page at 
https://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm. 
1  Contains Nonbinding Recommendations 
In general, FDAs guidance documents do not establish legally enforceable responsibilities.  
Instead, guidances describe the Agencys current thinking on a topic and should 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. 2.6.1. Sterility, JP 4.06 
Sterility Test, and USP <71> Sterility Tests, can be used as interchangeable in the ICH regions 
subject to the conditions detailed below. Testing conditions for medical devices, such as sutures, 
are outside the scope of the ICH recommendation.   
 
1. (2.1.1)  Diluting and rinsing fluids should not have antibacterial or antifungal 
properties if they are to be considered suitable for dissolving, diluting, or rinsing an 
article under test for sterility. 
 
2. (2.1.2)  When testing liquid parenteral preparations with a nominal volume of 100 
milliliters in batches of more than 500 containers, the test is considered interchangeable if 
the minimum number of containers selected is either 20 or is 2 percent of the total 
number of containers, whichever is lower. 
 
B.  Acceptance Criteria (2.2) 
 
The acceptance criteria are harmonized between the three pharmacopoeias.   
 
 
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 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 Q4B-
evaluated 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. 
 
2  Contains Nonbinding Recommendations 
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 II.A (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.  
 
C.  EU Consideration (4.3) 
 
For the European Union (EU), 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, Sterility: 2.6.1., 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. 
 
E.  Canada Consideration (4.5) 
 
In Canada, any of the pharmacopoeial texts cited in section II.A (2.1) of this annex and used in 
accordance with the conditions set out in this annex can be considered interchangeable. 
 
 
V.  REFERENCES USED FOR THE Q4B EVALUATION (5) 
 
A. (5.1)  The PDG Stage 5B sign-off document:  Japanese Pharmacopoeial Forum, 
Volume 16, number 4 (December 2007). 
 
B. (5.2)  The pharmacopoeial references for Sterility Test for this annex are: 
 
1. (5.2.1)  European Pharmacopoeia (Ph. Eur.):   Supplement 6.3 (official in 
January 2009), Sterility (reference 01/2009:20601). 
 
2. (5.2.2)  Japanese Pharmacopoeia (JP):  The 4.06 Sterility Test as it appeared in 
the partial revision of the JP 15th edition (made official March 31, 2009, by the 
Ministry of Health, Labour and Welfare Ministerial Notification No. 190).  
 
3  Contains Nonbinding Recommendations 
3. (5.2.3)  United States Pharmacopeia (USP):  <71> Sterility Tests as presented in 
Pharmacopeial Forum, Volume 34(6), Interim Revision Announcement No. 6, 
December 1, 2008, official on May 1, 2009. 
 
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