Q4B Annex 8: Sterility Test General Chapter

Administrative guidance, not enacted legislation. This captured publisher edition preserves the listed document and attachments; later developments are not independently consolidated.

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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Email: ocod@fda.hhs.gov
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
1
Q4B Evaluation and Recommendation of Pharmacopoeial Texts
for Use in the ICH Regions
Annex 8(R1)
Sterility Test General Chapter
Guidance for Industry1
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.

Contains Nonbinding Recommendations
2
In general, FDA’s guidance documents 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 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.

Contains Nonbinding Recommendations
3
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).

Contains Nonbinding Recommendations
4
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.