Changeflow GovPing Pharma Standards ICH Q1A(R2) Stability Testing Guideline Finalized

Routine Guidance Amended Final

ICH Q1A(R2) Stability Testing Guideline Finalized

ICH Guidelines News

Published February 6th, 2003

Detected March 13th, 2026

Summary

The International Council for Harmonisation (ICH) has finalized its Q1A(R2) guideline on stability testing of new drug substances and products. This revised guideline, effective February 6, 2003, provides updated recommendations for stability testing protocols across different climatic zones.

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What changed

The International Council for Harmonisation (ICH) has finalized the Q1A(R2) guideline on Stability Testing of New Drug Substances and Products. This revision, reaching Step 4 in February 2003, provides updated recommendations for stability testing protocols, including temperature, humidity, and trial duration, specifically addressing requirements for Climatic Zones III and IV to facilitate global dossier submissions. The guideline aims to harmonize stability testing requirements internationally.

While this guideline was finalized in 2003, the document lists various implementation dates by regulatory authorities worldwide, with some as recent as October 2023. Regulated entities, particularly drug manufacturers and pharmaceutical companies, should ensure their stability testing practices align with the latest ICH Q1A(R2) recommendations as adopted by their respective national regulatory agencies. Compliance with these harmonized guidelines is crucial for the successful registration and marketing of new drug substances and products globally.

What to do next

Review ICH Q1A(R2) guideline for current stability testing requirements.
Ensure internal stability testing protocols align with the guideline and relevant national regulatory agency implementations.
Verify that stability testing data supports global dossier submissions as per ICH recommendations.

Source document (simplified)

Home \ ICH Guidelines \ Quality Guidelines

Quality Guidelines

Harmonisation achievements in the Quality area include pivotal milestones such as the conduct of stability studies, defining relevant thresholds for impurities testing and a more flexible approach to pharmaceutical quality based on Good Manufacturing Practice (GMP) risk management.

Q1A - Q1F Stability

Q1A(R2) Stability Testing of New Drug Substances and Products

This Guideline has been revised a second time and has reached Step 4 of the ICH process in February 2003. This Guideline provides recommendations on stability testing protocols including temperature, humidity and trial duration for Climatic Zone I and II. Furthermore, the revised document takes into account the requirements for stability testing in Climatic Zones III and IV in order to minimise the different storage conditions for submission of a global dossier.

Date of Step 4:

6 February 2003

Status: Step 5

Implementation status:

ANMAT, Argentina - Implemented; Date: 17 October 2023; Reference: ANMAT Regulation 4061/2023 ANVISA, Brazil - Implemented; Date: 7 November 2019; Reference: RDC nº 318/2019 and RDC 359/2020 COFEPRIS, Mexico - Implemented; Date: 1 September 2015; Reference: NOM-073-SSA1-2015 Stability Testing of New Drug Substances and Products EC, Europe - Implemented; Date: 1 August 2003; Reference: CPMP/ICH/2736/99 EDA, Egypt - Implemented; Date: 31 December 2015; Reference: Guidelines On Stability Testing Of Finished Pharmaceutical Products and Active Drug Substance FDA, United States - Implemented; Date: 1 November 2003; Reference: Vol. 68, No. 225, p. 65717-18 HSA, Singapore - Implemented; Date: 1 January 2008; Reference: ASEAN Common Technical Dossier (ACTD) for the registration of pharmaceuticals for human use, Part II: Quality Health Canada, Canada - Implemented; Date: 25 September 2003; Reference: File #: 03-118437-914 JFDA, Jordan - Implemented; Date: 1 March 2008; MFDS, Republic of Korea - Implemented; Date: 14 June 2016; Reference: Regulation on Stability Test of Pharmaceuticals [Appendix 4] Stability Testing Standard of New Drugs MFDS, Republic of Korea Notification MHLW/PMDA, Japan - Implemented; Date: 1 June 2003; Reference: PFSB/ELD Notification No. 0603001 MHRA, UK - Implemented; Date: 1 August 2003; NMPA, China - Implemented; Date: 5 February 2015; Reference: Technical Guideline for the Study of Stability of Chemical Drugs (APIs and Preparations) (published by CFDA)(2015) SFDA, Saudi Arabia - Implemented; Date: 3 May 2011; Swissmedic, Switzerland - Implemented; Date: 1 February 2003; Reference: ICH Guidelines apply in Switzerland automatically upon reaching Step 4: Swissmedic Journal 05/2006, p. 504 TFDA, Chinese Taipei - Implemented; Date: 1 April 2005; Reference: Guideline on Stability Testing of Drug Substances and Products TITCK, Türkiye - Implemented; Date: 17 July 2017; Reference: NA

Guideline Q1A(R2) Guideline

Q1B Stability Testing : Photostability Testing of New Drug Substances and Products

The ICH Harmonised Guideline was finalised under Step 4 in November 1996. This document is an annex to the main stability Guideline, and gives guidance on the basic testing protocol required to evaluate the light sensitivity and stability of new drugs and products.

Date of Step 4:

6 November 1996

Status: Step 5

Implementation status:

ANMAT, Argentina - Implemented; Date: 17 October 2023; Reference: ANMAT Regulation 4061/2023 ANVISA, Brazil - Implemented; Date: 7 November 2019; Reference: RDC nº 318/2019 and RDC 359/2020 COFEPRIS, Mexico - Implemented; Date: 1 September 2015; Reference: NOM-073-SSA1-2015 Stability Testing of New Drug Substances and Products EC, Europe - Implemented; Date: 1 January 1998; Reference: CPMP/ICH/279/95 EDA, Egypt - Implemented; Date: 31 December 2015; Reference: Guidelines On Stability Testing Of Finished Pharmaceutical Products and Active Drug Substance FDA, United States - Implemented; Date: 1 May 1997; Reference: Vol. 62, No. 95, p. 27115-27122 HSA, Singapore - Implemented; Date: 1 January 2008; Reference: ASEAN Common Technical Dossier (ACTD) for the registration of pharmaceuticals for human use, Part II: Quality Health Canada, Canada - Implemented; Date: 12 February 1999; Reference: Catalogue No. H42-2/77-1998E JFDA, Jordan - Implemented; Date: 1 March 2008; MFDS, Republic of Korea - Implemented; Date: 14 June 2016; Reference: Regulation on Stability Test of Pharmaceuticals [Appendix 6] Photostability Testing of New Drugs MFDS, Republic of Korea Notification; Guideline on photostability testing of Drugs [Guideline-0205-01] MHLW/PMDA, Japan - Implemented; Date: 1 May 1997; Reference: PAB/PCD Notification No. 422 MHRA, UK - Implemented; Date: 1 January 1998; NMPA, China - Implemented; Date: 5 February 2015; Reference: Technical Guideline for the Study of Stability of Chemical Drugs (APIs and Preparations) (published by CFDA)(2015) SFDA, Saudi Arabia - Implemented; Date: 3 May 2011; Swissmedic, Switzerland - Implemented; Date: 6 November 1996; Reference: ICH Guidelines apply in Switzerland automatically upon reaching Step 4: Swissmedic Journal 05/2006, p. 504 TFDA, Chinese Taipei - Implemented; Date: 22 July 1998; Reference: Guideline on Stability Testing of Drug Substances and Products TITCK, Türkiye - Implemented; Date: 17 July 2017; Reference: NA

Guideline Q1B Guideline

Q1C Stability Testing for New Dosage Forms

The ICH Harmonised Guideline was finalised under Step 4 in November 1996. It extends the main stability Guideline for new formulations of already approved medicines, and defines the circumstances under which reduced stability data can be accepted.

Date of Step 4:

6 November 1996

Status: Step 5

Implementation status:

ANMAT, Argentina - Implemented; Date: 17 October 2023; Reference: ANMAT Regulation 4061/2023 ANVISA, Brazil - Implemented; Date: 7 November 2019; Reference: RDC nº 318/2019 COFEPRIS, Mexico - Implemented; Date: 1 September 2015; Reference: NOM-073-SSA1-2015 Stability Testing of New Drug Substances and Products EC, Europe - Implemented; Date: 1 January 1998; Reference: CPMP/ICH/280/95 EDA, Egypt - Implemented; Date: 31 December 2015; Reference: Guidelines On Stability Testing Of Finished Pharmaceutical Products and Active Drug Substance FDA, United States - Implemented; Date: 1 May 1997; Reference: Vol. 62, No. 90, p. 25634-5 HSA, Singapore - Implemented; Date: 1 January 2008; Reference: ASEAN Common Technical Dossier (ACTD) for the registration of pharmaceuticals for human use, Part II: Quality Health Canada, Canada - Implemented; Date: 18 January 1999; Reference: Catalogue No. H42-2/78-1998E JFDA, Jordan - Implemented; Date: 1 March 2008; MFDS, Republic of Korea - Implemented; Date: 14 June 2016; Reference: Regulation on Stability Test of Pharmaceuticals [Appendix 5] Stability Testing of New Dosage Forms of New Drugs [ MFDS, Republic of Korea Notification] MHLW/PMDA, Japan - Implemented; Date: 1 May 1997; Reference: PAB/PCD Notification No. 425 MHRA, UK - Implemented; Date: 1 January 1998; NMPA, China - Implemented; Date: 5 February 2015; Reference: Technical Guideline for the Study of Stability of Chemical Drugs (APIs and Preparations) (published by CFDA)(2015) SFDA, Saudi Arabia - Implemented; Date: 3 May 2011; Swissmedic, Switzerland - Implemented; Date: 6 November 1996; Reference: ICH Guidelines apply in Switzerland automatically upon reaching Step 4: Swissmedic Journal 05/2006, p. 504 TFDA, Chinese Taipei - Implemented; Date: 22 July 1998; Reference: Guideline on Stability Testing of Drug Substances and Products TITCK, Türkiye - Implemented; Date: 17 July 2017; Reference: NA

Guideline Q1C Guideline

Q1D Bracketing and Matrixing Designs for Stability Testing of New Drug Substances and Products

The ICH Harmonised Guideline was finalised under Step 4 in February 2002. This document is intended to address recommendations on the application of bracketing and matrixing to stability studies conducted in accordance with principles outlined in the main stability Guideline.

Date of Step 4:

7 February 2002

Status: Step 5

Implementation status:

ANMAT, Argentina - Implemented; Date: 17 October 2023; Reference: ANMAT Regulation 4061/2023 ANVISA, Brazil - Implemented; Date: 7 November 2019; Reference: RDC nº 318/2019 and RDC 359/2020 COFEPRIS, Mexico - Implemented; Date: 1 September 2015; Reference: NOM-073-SSA1-2015 Stability Testing of New Drug Substances and Products EC, Europe - Implemented; Date: 1 August 2002; Reference: CPMP/ICH/4104/00 EDA, Egypt - Implemented; Date: 31 December 2015; Reference: Guidelines On Stability Testing Of Finished Pharmaceutical Products and Active Drug Substance FDA, United States - Implemented; Date: 1 January 2003; Reference: Vol. 68, No. 11, p. 2339-2340 HSA, Singapore - Implemented; Date: 1 January 2008; Reference: ASEAN Common Technical Dossier (ACTD) for the registration of pharmaceuticals for human use, Part II: Quality Health Canada, Canada - Implemented; Date: 25 September 2003; Reference: File #: 03-118449-498 JFDA, Jordan - Implemented; Date: 1 March 2011; MFDS, Republic of Korea - Implemented; Date: 14 June 2016; Reference: Regulation on Stability Test of Pharmaceuticals [Appendix 7] Bracketing and Matrixing Designs for New Drugs [ MFDS, Republic of Korea Notification] MHLW/PMDA, Japan - Implemented; Date: 1 July 2002; Reference: PFSB/ELD Notification No. 0731004 MHRA, UK - Implemented; Date: 1 August 2002; NMPA, China - Implemented; Date: 5 February 2015; Reference: Technical Guideline for the Study of Stability of Chemical Drugs (APIs and Preparations) (published by CFDA)(2015)
http://www.sfda.gov.cn/WS01/CL1616/114289.html SFDA, Saudi Arabia - Implemented; Date: 3 May 2011; Swissmedic, Switzerland - Implemented; Date: 7 February 2002; Reference: ICH Guidelines apply in Switzerland automatically upon reaching Step 4: Swissmedic Journal 05/2006, p. 504 TFDA, Chinese Taipei - Implemented; Date: 1 April 2005; Reference: Guideline on Stability Testing of Drug Substances and Products TITCK, Türkiye - Implemented; Date: 17 July 2017; Reference: NA

Guideline Q1D Guideline

Q1E Evaluation of Stability Data

The ICH Harmonised Guideline was finalised under Step 4 in February 2003. This document extends the main stability Guideline by explaining possible situations where extrapolation of retest periods or shelf-lives beyond the real-time data may be appropriate. Furthermore, it provides examples of statistical approaches to stability data analysis.

Date of Step 4:

6 February 2003

Status: Step 5

Implementation status:

ANMAT, Argentina - Implemented; Date: 17 October 2023; Reference: ANMAT Regulation 4061/2023 ANVISA, Brazil - Implemented; Date: 7 November 2019; Reference: RDC nº 318/2019 and RDC 359/2020 and RDC 413/2020 COFEPRIS, Mexico - Implemented; Date: 1 September 2015; Reference: NOM-073-SSA1-2015 Stability Testing of New Drug Substances and Products EC, Europe - Implemented; Date: 1 August 2003; Reference: CPMP/ICH/420/02 EDA, Egypt - Implemented; Date: 31 December 2008; Reference: (Egyptian Guidelines on CTD Quality Module for Human Pharmaceuticals) and (Regulatory guide for mechanisms, procedures and rules of implementing the decree of Egyptian Drug Authority No.343 of 2021) FDA, United States - Implemented; Date: 1 June 2004; Reference: Vol. 69, No. 110, p. 32010-11 HSA, Singapore - Implemented; Date: 1 January 2008; Reference: ASEAN Common Technical Dossier (ACTD) for the registration of pharmaceuticals for human use, Part II: Quality Health Canada, Canada - Implemented; Date: 25 September 2003; Reference: File #: 03-118451-122 JFDA, Jordan - Implemented; Date: 1 March 2008; MFDS, Republic of Korea - Implemented; Date: 14 June 2016; Reference: Regulation on Stability Test of Pharmaceuticals [Appendix 8] Evaluation of Stability Data [ MFDS, Republic of Korea Notification] MHLW/PMDA, Japan - Implemented; Date: 1 June 2003; Reference: PFSB/ELD Notification No. 0603004 MHRA, UK - Implemented; Date: 1 August 2003; NMPA, China - Implemented; Date: 5 February 2015; Reference: Technical Guideline for the Study of Stability of Chemical Drugs (APIs and Preparations) (published by CFDA)(2015) SFDA, Saudi Arabia - Implemented; Date: 22 September 2011; Swissmedic, Switzerland - Implemented; Date: 6 February 2003; Reference: ICH Guidelines apply in Switzerland automatically upon reaching Step 4: Swissmedic Journal 05/2006, p. 504 TFDA, Chinese Taipei - Implemented; Date: 1 April 2005; Reference: Guideline on Stability Testing of Drug Substances and Products TITCK, Türkiye - Implemented; Date: 17 July 2017; Reference: NA

Guideline Q1E Guideline

WG Presentations / Trainings Q1E Presentation

Q1F Stability Data Package for Registration Applications in Climatic Zones III and IV

The ICH Steering Committee endorsed the withdrawal of the Q1F Guideline at Yokohama meeting in June 2006, and decided to leave definition of storage conditions in Climatic Zones III and IV to the respective regions and WHO.

Status: Withdrawn

Other documents Q1F Stability Guideline WHO 2018 Q1F Explanatory Note

Q1 EWG Stability Testing of Drug Substances and Drug Products

This topic was endorsed by the ICH Assembly in June 2021.

Further to the ICH Management Committee’s endorsement of the Q1/Q5C Concept Paper and Business Plan in November 2022, the Q1/Q5C EWG was established to revise the current ICH Stability Guideline Series Q1A-F and Q5C by:

Streamlining the series, combining the various guidelines into a single guideline focused on core stability principles;
Promoting harmonised interpretation by addressing potential gaps and areas of ambiguity; Addressing additional technical issues, including relevant stability strategies and innovative tools that strengthen the application of risk management;
Considering inclusion of new topics, such as stability considerations for advanced therapies.

The envisioned result is a combined guideline, ICH Q1, with integrated annexes and/or appendices that address specific topics beyond the core stability recommendations and principles. Addressing drug product types including substances, intermediates, and devices.

Further information can be found in the Q1/Q5C Concept Paper and Business Plan.

Rapporteur: Dr. Ashutosh Rao (FDA, United States)

Regulatory Chair: Ms. Ana Cerúlia Moraes do Carmo (ANVISA, Brazil)

Date of Step 2b:

11 April 2025

Status: Step 3

Public consultation dates:

ANVISA, Brazil - Deadline for comments by 3 August 2025 EDA, Egypt - Deadline for comments by 31 July 2025 FDA, United States - Deadline for comments by 25 August 2025 HSA, Singapore - Deadline for comments by 11 July 2025 Health Canada, Canada - Deadline for comments by 31 August 2025 MFDS, Republic of Korea - Deadline for comments by 20 July 2025 MHLW/PMDA, Japan - Deadline for comments by 28 August 2025 SFDA, Saudi Arabia - Deadline for comments by 29 August 2025 Swissmedic, Switzerland - Deadline for comments by 30 July 2025 TFDA, Chinese Taipei - Deadline for comments by 29 August 2025 TITCK, Türkiye - Deadline for comments by 15 July 2025

Guideline ICH Q1 Draft Guideline

Endorsed Documents Q1/Q5C Concept Paper Q1/Q5C Business Plan Q1 Work Plan

WG Presentation/ Trainings Q1 Step 2 Presentation
WG list

Q2 Analytical Validation

Q2(R2) Revision of Q2(R1) Analytical Validation

The ICH Q2(R2) revised Guideline Step 4 of the ICH process on 1 November 2023.

The Q2(R2) EWG revised the ICH Q2(R1) Guideline on Validation of Analytical Procedures.

Q2(R1) Revision

The scope of the revision of ICH Q2(R1) includes validation principles that cover analytical use of spectroscopic or spectrometry data (e.g., NIR, Raman, NMR or MS) some of which often require multivariate statistical analyses. The guideline continues to provide a general framework for the principles of analytical procedure validation applicable to products mostly in the scope of Q6A and Q6B. These guidelines (Q2(R2) and Q14) are intended to complement ICH Q8 to Q12 Guidelines, as well as ICH Q13 for Continuous Manufacturing.

Date of Step 4:

1 November 2023

Status: Step 5

Implementation status:

ANMAT, Argentina - Not yet implemented; ANVISA, Brazil - Not yet implemented; COFEPRIS, Mexico - Implemented; Date: 25 February 2022; Reference: Pharmacopeia of the United Mexican States 13.0. EC, Europe - Implemented; Date: 14 June 2024; Reference: EMA/CHMP/ICH/82072/2006 EDA, Egypt - Implemented; Date: 1 June 2024; Reference: (Guidelines for File Assessment for Pharmaceutical Products for Human Use) and (Regulatory Guide for mechanisms, procedures and rules of implementing the Decree of Egyptian Drug Authority No.343 of 2021) FDA, United States - Implemented; Date: 7 March 2024; Reference: 89 FR 16582 HSA, Singapore - Implemented; Health Canada, Canada - Implemented; Date: 15 October 2025; Reference: File #: 25-105890 – 674 JFDA, Jordan - Not yet implemented; MFDS, Republic of Korea - In the process of implementation; Date: 1 December 2026; MHLW/PMDA, Japan - Implemented; Date: 9 October 2025; Reference: PSB/ PED Notification No. 1009-1 MHRA, UK - Not yet implemented; NMPA, China - Implemented; Date: 24 November 2024; Reference: NMPA, China Announcement No.65(2024) SFDA, Saudi Arabia - Implemented; Date: 22 September 2011; Swissmedic, Switzerland - Implemented; Date: 1 November 2023; Reference: ICH Guidelines apply in Switzerland automatically upon reaching Step 4: Swissmedic Journal 05/2006, p. 504 TFDA, Chinese Taipei - Not yet implemented; TITCK, Türkiye - Not yet implemented;

Guideline Q2(R2) Guideline

Endorsed Documents Q2(R2)/Q14 Concept Paper Q2(R2)/Q14 Business Plan

WG Presentations/Trainings Q2(R2)/Q14 Step 4 Presentation

Q2(R2)/Q14 Training on Validation of Analytical Procedures and Q14: Analytical Procedure Development

Further to the ICH Management Committee’s endorsement of the Q2(R2)/Q14 IWG Concept Paper in October 2023, the Q2(R2)/Q14 IWG was established to prepare and deliver training materials which will facilitate an aligned interpretation and a harmonised implementation of Q2(R2) “Validation of Analytical” Procedures and Q14 “Analytical Procedure Development” Guideline in ICH and non-ICH regions by:

Illustrating the general concepts of ICH Q2(R2) and Q14;
Providing more depth to the discussion of the Annexes in ICH Q2(R2) and Q14 to address some specific implementation aspects relevant for different cases; Further information can be found in the Q2(R2)/Q14 IWG Concept Paper

Endorsed Documents Q2(R2)/Q14 IWG Concept Paper

WG Presentations / Trainings Q2(R2)/Q14 Training Material Map of Contents Q2(R2)/Q14 Training Material Module 1 Q2(R2)/Q14 Training Material Module 2 Q2(R2)/Q14 Training Material Module 3 Q2(R2)/Q14 Training Material Module 4 Q2(R2)/Q14 Training Material Module 5 Q2(R2)/Q14 Training Material Module 6 Q2(R2)/Q14 Training Material Module 7

Q3A - Q3E Impurities

Q3A(R2) Impurities in New Drug Substances

First recommended for adoption at Step 4 of the ICH Process on 30 March 1995, the Guideline was revised under Step 2 of the ICH Process on 7 October 1999 and finalised under Step 4 on 7 February 2002 (Q3A(R1)).

The Guideline addresses the chemistry and safety aspects of impurities, including the listing of impurities in specifications and defines the thresholds for reporting, identification and qualification. The revision of the Guideline has allowed clarifying some inconsistencies, to revise the decision tree, to harmonise with Q3B and to address some editorial issues.

The Attachment 2 of this Guideline has been revised under Step 4 without further public consultation on 25 October 2006 (Q3A(R2)).

Date of Step 4:

25 October 2006

Status: Step 5

Implementation status:

ANMAT, Argentina - Not yet implemented; ANVISA, Brazil - Implemented; Date: 3 August 2020; Reference: RDC 359/2020 and RDC 753/2022 COFEPRIS, Mexico - In the process of implementation; Date: 25 February 2022; Reference: Pharmacopeia of the United Mexican States 13.0. EC, Europe - Implemented; Date: 1 October 2006; Reference: CPMP/ICH/2737/99 EDA, Egypt - Implemented; Date: 31 December 2015; Reference: (Egyptian Guidelines on CTD Quality Module for Human Pharmaceuticals) and (Guidelines for File Assessment for Pharmaceutical Products for Human Use) FDA, United States - Implemented; Date: 1 June 2008; Reference: Published in the Federal Register HSA, Singapore - Implemented; Date: 1 January 2008; Reference: These guidelines are cross-referred in M4Q and applied in the routine evaluation. See regulatory guidance. Health Canada, Canada - Implemented; Date: 5 June 2015; Reference: File #: 15-106606-354 JFDA, Jordan - Implemented; Date: 1 March 2008; MFDS, Republic of Korea - Implemented; Date: 22 June 2018; Reference: Regulation on Pharmaceuticals Approval, Notification and Review [MFDS, Republic of Korea Notification] MHLW/PMDA, Japan - Implemented; Date: 1 December 2006; Reference: PFSB/ELD Notification No. 1204001 MHRA, UK - Implemented; Date: 1 October 2006; NMPA, China - Implemented; Date: 21 July 2020; Reference: NMPA, China Announcement No. 7 (2020) SFDA, Saudi Arabia - Implemented; Date: 22 September 2011; Swissmedic, Switzerland - Implemented; Date: 25 October 2006; Reference: ICH Guidelines apply in Switzerland automatically upon reaching Step 4: Swissmedic Journal 05/2006, p. 504 TFDA, Chinese Taipei - Implemented; Date: 26 October 2021; Reference: Guidance for Impurities in New Drug Substances and New Drug Products TITCK, Türkiye - Implemented; Date: 11 December 2021; Reference: NA

Guideline Q3A(R2) Guideline

Q3B(R2) Impurities in New Drug Products

This Guideline has been first revised and finalised under Step 4 in February 2003. It complements the Guideline on impurities in new drug substances and provides advice in regard to impurities in products containing new, chemically synthesized drug substances. The Guideline specifically deals with those impurities which might arise as degradation products of the drug substance, or arising from interactions between drug substance and excipients or components of primary packaging materials. The Guideline sets out a rationale for the reporting, identification and qualification of such impurities based on a scientific appraisal of likely and actual impurities observed, and of the safety implications, following the principles elaborated in the parent Guideline. Threshold values for reporting and control of impurities are proposed, based on the maximum daily dose of the drug substance administered in the product.

The Attachment 2 of this Guideline has been revised under Step 4 without further public consultation on 2 June 2006 (Q3B(R2)).

Date of Step 4:

2 June 2006

Status: Step 5

Implementation status:

ANMAT, Argentina - Not yet implemented; ANVISA, Brazil - In the process of implementation; Date: 24 February 2025; Reference: RDC 964/2025 COFEPRIS, Mexico - In the process of implementation; Date: 25 February 2022; Reference: Pharmacopeia of the United Mexican States 13.0. EC, Europe - Implemented; Date: 1 June 2006; Reference: CPMP/ICH/2738/99 EDA, Egypt - Implemented; Date: 31 December 2015; Reference: (Egyptian Guidelines on CTD Quality Module for Human Pharmaceuticals) and (Guidelines for File Assessment for Pharmaceutical Products for Human Use) FDA, United States - Implemented; Date: 1 November 2003; Reference: Vol, 68, No. 220, p. 64628-9 HSA, Singapore - Implemented; Date: 1 January 2008; Reference: These guidelines are cross-referred in M4Q and applied in the routine evaluation. See regulatory guidance. Health Canada, Canada - Implemented; Date: 15 June 2015; Reference: File #: 15-106634-508 JFDA, Jordan - Implemented; Date: 1 March 2008; MFDS, Republic of Korea - Implemented; Date: 30 July 2018; Reference: Impurities in New Drug Products[Guideline-0877-01] MHLW/PMDA, Japan - Implemented; Date: 1 July 2006; Reference: PFSB/ELD Notification No. 0703004 MHRA, UK - Implemented; Date: 1 June 2006; NMPA, China - Implemented; Date: 21 July 2020; Reference: NMPA, China Announcement No. 7 (2020) SFDA, Saudi Arabia - Implemented; Date: 22 September 2011; Swissmedic, Switzerland - Implemented; Date: 2 June 2006; Reference: ICH Guidelines apply in Switzerland automatically upon reaching Step 4: Swissmedic Journal 05/2006, p. 504 TFDA, Chinese Taipei - Implemented; Date: 26 October 2021; Reference: Guidance for Impurities in New Drug Substances and New Drug Products TITCK, Türkiye - Implemented; Date: 11 December 2021; Reference: NA

Guideline Q3B(R2) Guideline

Endorsed Document Q3B(R2) Concept Paper

Q3C(R9) Guideline for Residual Solvents

The Q3C ICH Guideline was finalised under Step 4 in July 1997, providing recommendations on the use of less toxic solvents in the manufacture of drug substances and dosage forms, and setting pharmaceutical limits for residual solvents (organic volatile impurities) in drug products.

Maintenance Process

As part of the Maintenance process, the Q3C Guideline incorporated the revision and inclusion of new Permitted Daily Exposure (PDE) levels as new toxicological data for solvents became available.

Date of Step 4:

24 January 2024

Status: Step 5

Implementation status:

ANMAT, Argentina - Not yet implemented; ANVISA, Brazil - In the process of implementation; COFEPRIS, Mexico - Not yet implemented; EC, Europe - Implemented; Date: 29 April 2024; Reference: EMA/CHMP/ICH/82260/2006 EDA, Egypt - Implemented; Date: 1 June 2024; Reference: (Guidelines for File Assessment for
Pharmaceutical Products for Human
Use) and (Regulatory Guide for mechanisms, procedures and rules of implementing the Decree of Egyptian Drug Authority No.343 of 2021) FDA, United States - Not yet implemented; HSA, Singapore - Implemented; Date: 1 July 2024; Reference: These guidelines are cross-referred in M4Q and applied in the routine evaluation. See regulatory guidance. Health Canada, Canada - Implemented; Date: 27 June 2025; Reference: 25-102237-854 JFDA, Jordan - Not yet implemented; MFDS, Republic of Korea - In the process of implementation; Date: 31 December 2025; Reference: Korean Pharmacopoeia : Guideline of Residual Solvents Test; Question & Answers : Guideline of Residual Solvents Test MHLW/PMDA, Japan - Implemented; Date: 15 April 2024; Reference: PSB/ PED Notification No. 0415-1 MHRA, UK - Not yet implemented; NMPA, China - Implemented; Date: 20 June 2024; Reference: NMPA, China Announcement No. 76(2024) SFDA, Saudi Arabia - Implemented; Swissmedic, Switzerland - Implemented; Date: 24 January 2024; Reference: ICH Guidelines apply in Switzerland automatically upon reaching Step 4: Swissmedic Journal 05/2006, p. 504 TFDA, Chinese Taipei - Implemented; Date: 19 June 2025; Reference: Updated-Announcement for ICH Guidelines Recognition List TITCK, Türkiye - Not yet implemented;

Guideline Q3C(R9) Guideline

Endorsed Documents Q3C(R9) Concept Paper

Implementation status:

ANMAT, Argentina - Not yet implemented; ANVISA, Brazil - In the process of implementation; Date: 1 December 2027; Reference: Partial implementation for synthetic and semi-synthetic API - RDC 359/2020 and RDC 361/2020 COFEPRIS, Mexico - Not yet implemented; EC, Europe - Implemented; Date: 24 September 2022; Reference: EMA/CHMP/ICH/353369/2013 EDA, Egypt - Implemented; Date: 31 December 2015; Reference: Egyptian Guidelines on CTD Quality Module for Human Pharmaceuticals FDA, United States - Implemented; Date: 15 September 2022; Reference: Vol 87 No. 178 p.56683-56684 HSA, Singapore - Implemented; Date: 26 May 2022; Health Canada, Canada - Implemented; Date: 29 August 2022; Reference: File #: 22-105313-723 JFDA, Jordan - Not yet implemented; MFDS, Republic of Korea - Implemented; Date: 31 March 2022; Reference: Guideline for Elemental Impurities[Guideline-0224-03] MHLW/PMDA, Japan - Implemented; Date: 20 January 2023; Reference: PSEHB/PED Notification No. 0120-1 MHRA, UK - Implemented; Date: 1 January 2024; NMPA, China - Implemented; Date: 29 July 2023; Reference: NMPA, China Announcement No. 16 (2023) SFDA, Saudi Arabia - Implemented; Swissmedic, Switzerland - Implemented; Date: 26 April 2022; Reference: ICH Guidelines apply in Switzerland automatically upon reaching Step 4: Swissmedic Journal 05/2006, p. 504 TFDA, Chinese Taipei - Implemented; Date: 30 May 2023; Reference: 1. Chinese Pharmacopeia
2. Updated-Announcement for ICH Guidelines Recognition List TITCK, Türkiye - Implemented; Date: 11 December 2021; Reference: NA

Guideline Q3D(R2) Guideline

Endorsed Documents Q3D(R2) Maintenance Concept Paper Q3D(R2) Maintenance Work Plan

WG Presentations / Trainings Q3D(R2) Step 4 Presentation

Q3D(R3) Maintenance Maintenance of the Guideline for Elemental Impurities

The ICH Q3D Guideline was finalised under Step 4 in November 2014. It is a quality guideline for the control of elemental impurities in new drug products (medicinal products), and it establishes Permitted Daily Exposures (PDEs) for Elemental Impurities (EIs) for drug products administered by the oral, parenteral and inhalation routes of administration. In addition, guidance is provided in ICH Q3D on how to develop an acceptable level for EIs for drug products administered by other routes of administration.

The Q3D(R1) and Q3D(R2) Guidelines reached Step 4 of the ICH process in March 2019 and April 2022, respectively.

Maintenance Process
A maintenance procedure for the Q3D Guideline was setup to enable incorporation of Permitted Daily Exposure (PDE) for new elemental impurities (EI)/routes of administration and revising the PDE for EI as new toxicological data for EI becomes available.

Endorsed Documents

Maintenance Procedure Maintenance Procedure for Q3C, Q3D and M7

Q3D training Implementation of Guideline for Elemental Impurities

The Q3D Implementation Working Group (IWG) was endorsed by the ICH Steering Committee in October 2014. Throughout the development of the Q3D Guideline, external audiences, constituents and interested parties have clearly communicated the complexity of the implementation approaches for this Guideline. The ICH Steering Committee considered that the development of a comprehensive training programme and supporting documentation sponsored by ICH was necessary to ensure the proper interpretation and effective utilisation by industry and regulators alike to enable a Harmonised and smooth implementation of Q3D on a global basis. The first training package (Modules 0-7) was endorsed by the ICH Assembly in December 2015. The final Modules 8-9 of the Q3D training package were endorsed by the ICH Assembly in June 2016.

Endorsed Documents Q3D Training Concept Paper Q3D Training Business Plan

WG Presentations / Trainings Q3D Training Package Module 0-9

Q3E EWG Guideline for Extractables and Leachables

This topic was endorsed by the ICH Assembly in June 2019.

Further to the MC's endorsement of the Q3E Concept Paper and Business Plan in July 2020, the Q3E EWG was established to work on the development of the Q3E Guideline on the assessment and control of extractables and leachables (E&L), and is expected would assist both
applicants and regulators by providing focus on critical aspects, and improving transparency in requirements for medicinal products including drug delivery device components.

Further information can be found in the Q3E Concept Paper and Business Plan.

Rapporteur: Dr. Dan Mellon (FDA, United States)

Regulatory Chair: Dr. Katrin Buss (EC, Europe)

Date of Step 2b:

1 August 2025

Status: Step 3

Public consultation dates:

ANVISA, Brazil - Deadline for comments by 11 November 2025 FDA, United States - Deadline for comments by 30 January 2026 HSA, Singapore - Deadline for comments by 30 November 2025 MFDS, Republic of Korea - Deadline for comments by 19 December 2025 NMPA, China - Deadline for comments by 15 December 2025 SFDA, Saudi Arabia - Deadline for comments by 15 December 2025 TFDA, Chinese Taipei - Deadline for comments by 25 November 2025

Guideline ICH Q3E Draft Guideline Guideline Supporting Documentation

Endorsed Documents Q3E Concept Paper Q3E Business Plan Q3E Work Plan

WG Presentations / Trainings Q3E Step 2 Presentation
WG list

Q4A - Q4B Pharmacopoeias

Q4A Pharmacopoeial Harmonisation

The pharmacopoeial authorities, working together through the Pharmacopoeial Discussion Group (PDG), have been closely involved with the work of ICH since the outset and harmonisation between the major pharmacopoeias, which started before ICH, has proceeded in parallel.

Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions

The ICH Harmonised Guideline was finalised under Step 4 in November 2007. This document describes a process for the evaluation and recommendation 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. Following favourable evaluations, ICH decided to issue topic-specific annexes with information about these texts and their implementation. Implementation of the Q4B annexes is intended to avoid redundant testing by industry. Given the nature of this topic, no Concept Paper was developed for Q4B.

Date of Step 4:

1 November 2007

Status: Step 5

Implementation status:

ANMAT, Argentina - Not applicable; ANVISA, Brazil - In the process of implementation; Date: 1 November 2010; Reference: RDC 49/2010

RDC 511/2021 COFEPRIS, Mexico - Implemented; Date: 5 March 2021; Reference: Mexican Official Standard NOM-001-SSA1-2020, that establishes the structure of the Pharmacopeia of the United Mexican States and its supplements and the procedure for its review, updating, editing and dissemination. EC, Europe - Implemented; Date: 1 December 2007; Reference: CHMP/ICH/222007/2006 EDA, Egypt - Implemented; Date: 12 December 2022; Reference: Egyptian Guidelines on CTD Quality Module for Human Pharmaceuticals and the Egyptian Pharmacopeia 5th edition FDA, United States - Implemented; Date: 1 February 2008; Reference: Vol. 73, No. 35, p. 9575-6 HSA, Singapore - Not applicable; Health Canada, Canada - Implemented; Date: 29 September 2010; Reference: File #: 10-120634-491 JFDA, Jordan - Not yet implemented; MFDS, Republic of Korea - Implemented; Date: 5 December 2014; Reference: Korean Pharmacopoeia [MFDS, Republic of Korea Notification] MHLW/PMDA, Japan - Implemented; Date: 1 May 2009; Reference: PFSB/ELD Notification No. 0526001 MHRA, UK - Implemented; Date: 1 December 2007; NMPA, China - Implemented; Date: 1 October 2025; Reference: Chinese Pharmacopoeia (2025 edition) SFDA, Saudi Arabia - Implemented; Swissmedic, Switzerland - Implemented; Date: 1 November 2007; Reference: ICH Guidelines apply in Switzerland automatically upon reaching Step 4: Swissmedic Journal 05/2006, p. 504 TFDA, Chinese Taipei - Implemented; Date: 10 October 2011; Reference: 1. Chinese Phamacopeia
2. Public Announcement for ” List for ICH Guidelines Adopted.” TITCK, Türkiye - Implemented; Date: 11 December 2021; Reference: NA

Guideline Q4B Guideline

WG Presentations / Trainings Q4B Presentation

Other documents Q4B Frequently Asked Questions (FAQs)

Maintenance Procedure Maintenance of Q4B

Q4B(R1) Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions

The ICH Harmonised Guideline was finalised under Step 4 in June 2024. This document describes a process for the evaluation and recommendation 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. Following favourable evaluations, ICH decided to issue topic-specific annexes with information about these texts and their implementation. Implementation of the Q4B annexes is intended to avoid redundant testing by industry. Given the nature of this topic, no Concept Paper was developed for Q4B(R1).

Date of Step 4:

5 June 2024

Status: Step 5

Guideline Q4B(R1) Guideline

Q4B Annex 1(R1) Residue on Ignition/Sulphated Ash General Chapter

The ICH Harmonised Annex was finalised under Step 4 in November 2007. This annex is the result of the Q4B process for Residue on Ignition/Sulphated Ash General Chapter. This annex was revised (R1) on 27 September 2010 to include the Interchangeability Statement from Health Canada, Canada.

Date of Step 4:

27 September 2010

Status: Step 5

Implementation status:

ANMAT, Argentina - Implemented; Date: 12 April 2023; ANVISA, Brazil - In the process of implementation; Reference: RDC 298/2019: publication of the 6th edition of the Brazilian Pharmacopoeia COFEPRIS, Mexico - Implemented; Date: 25 February 2022; Reference: Pharmacopeia of the United Mexican States 13.0. EC, Europe - Implemented; Date: 1 June 2008; Reference: CHMP/ICH/222063/2006 EDA, Egypt - Implemented; Date: 13 November 2024; Reference: Residue on ignition Egy.Ph. GC (B.2.19) FDA, United States - Implemented; Date: 1 June 2017; Reference: Vol. 73, No. 35, p. 9576-7 HSA, Singapore - Not applicable; Health Canada, Canada - Implemented; Date: 13 October 2010; Reference: File #: 10-121155-764 JFDA, Jordan - Not yet implemented; MFDS, Republic of Korea - Implemented; Date: 28 December 2007; Reference: Korean Pharmacopoeia : Residue on Ignition Test [MFDS, Republic of Korea Notification] MHLW/PMDA, Japan - Implemented; Date: 1 May 2009; Reference: PFSB/ELD Notification No. 052 6002 MHRA, UK - Implemented; Date: 1 September 2010; NMPA, China - Implemented; Date: 1 October 2025; Reference: Chinese Pharmacopoeia (2025 edition) SFDA, Saudi Arabia - Implemented; Swissmedic, Switzerland - Implemented; Date: 27 September 2010; Reference: ICH Guidelines apply in Switzerland automatically upon reaching Step 4: Swissmedic Journal 05/2006, p. 504 TFDA, Chinese Taipei - Implemented; Date: 10 October 2011; Reference: 1. Chinese Phamacopeia
2. Public Announcement for ” List for ICH Guidelines Adopted.” TITCK, Türkiye - Not yet implemented;

Guideline Q4B Annex 1(R1)

Other documents Q4B Frequently Asked Questions (FAQs)

Q4B Annex 2(R1) Test for Extractable Volume of Parenteral Preparations General Chapter

The ICH Harmonised Annex was finalised under Step 4 in June 2008. This annex is the result of the Q4B process for the Test for Extractable Volume of Parenteral Preparations General Chapter. This annex was revised (R1) on 27 September 2010 to include the Interchangeability Statement from Health Canada, Canada.

Date of Step 4:

27 September 2010

Status: Step 5

Implementation status:

ANMAT, Argentina - Implemented; Date: 12 April 2023; ANVISA, Brazil - In the process of implementation; Reference: RDC 49/2010

RDC 298/2019 COFEPRIS, Mexico - Implemented; Date: 25 February 2022; Reference: Pharmacopeia of the United Mexican States 13.0. EC, Europe - Implemented; Date: 1 September 2010; Reference: CHMP/ICH/559409/2007 EDA, Egypt - Implemented; Date: 13 November 2024; Reference: Container content for injection Egy.Ph.GC (B.3.66) FDA, United States - Implemented; Date: 1 June 2017; Reference: Vol. 74, No. 6, p. 908-9 HSA, Singapore - Not applicable; Health Canada, Canada - Implemented; Date: 13 October 2010; Reference: File #: 10-121172-973 JFDA, Jordan - Implemented; MFDS, Republic of Korea - Implemented; Date: 28 December 2007; Reference: Korean Pharmacopoeia : Determination of Volume of Injection in Containers [MFDS, Republic of Korea Notification] MHLW/PMDA, Japan - Implemented; Date: 1 February 2010; Reference: PFSB/ELD Notification No. 0208-1 MHRA, UK - Implemented; Date: 1 September 2010; NMPA, China - Implemented; Date: 1 October 2025; Reference: Chinese Pharmacopoeia (2025 edition) SFDA, Saudi Arabia - Implemented; Swissmedic, Switzerland - Implemented; Date: 27 September 2010; Reference: ICH Guidelines apply in Switzerland automatically upon reaching Step 4: Swissmedic Journal 05/2006, p. 504 TFDA, Chinese Taipei - Implemented; Date: 10 October 2011; Reference: 1. Chinese Phamacopeia
2. Public Announcement for ” List for ICH Guidelines Adopted.” TITCK, Türkiye - Not yet implemented;

Guideline Q4B Annex 2(R1)

Other document Q4B Frequently Asked Questions (FAQs)

Q4B Annex 3(R1) Test for Particulate Contamination: Sub-Visible Particles General Chapter

The ICH Harmonised Annex was finalised under Step 4 in June 2008. This annex is the result of the Q4B process for Test for Particulate Contamination: Sub-Visible Particles General Chapter. This annex was revised (R1) on 27 September 2010 to include the Interchangeability Statement from Health Canada, Canada.

Date of Step 4:

27 September 2010

Status: Step 5

Implementation status:

ANMAT, Argentina - In the process of implementation; ANVISA, Brazil - Implemented; Date: 1 November 2010; Reference: RDC 49/2010

RDC 298/2019 COFEPRIS, Mexico - Implemented; Date: 25 February 2022; Reference: Pharmacopeia of the United Mexican States 13.0. EC, Europe - Implemented; Date: 1 September 2010; Reference: CHMP/ICH/561176/2007 EDA, Egypt - Implemented; Date: 13 November 2024; Reference: Particulate matter in injections Egy.Ph. CG (B.3.43) FDA, United States - Implemented; Date: 1 June 2017; Reference: Vol. 74, No. 6, p. 909-10 HSA, Singapore - Not applicable; Health Canada, Canada - Implemented; Date: 22 October 2010; Reference: File #: 10-121191-626 JFDA, Jordan - Implemented; MFDS, Republic of Korea - Implemented; Date: 28 December 2007; Reference: Korean Pharmacopoeia : Insoluble Particulate Matter Test for Injections [MFDS, Republic of Korea Notification ] MHLW/PMDA, Japan - Implemented; Date: 1 February 2010; Reference: PFSB/ELD Notification No. 0208-2 MHRA, UK - Implemented; Date: 1 September 2010; NMPA, China - Implemented; Date: 1 October 2025; Reference: Chinese Pharmacopoeia (2025 edition) SFDA, Saudi Arabia - Implemented; Swissmedic, Switzerland - Implemented; Date: 27 September 2010; Reference: ICH Guidelines apply in Switzerland automatically upon reaching Step 4: Swissmedic Journal 05/2006, p. 504 TFDA, Chinese Taipei - Implemented; Date: 11 October 2011; Reference: 1. Chinese Phamacopeia
2. Public Announcement for ” List for ICH Guidelines Adopted.” TITCK, Türkiye - Not yet implemented;

Guideline Q4B Annex 3(R1)

Other documents Q4B Frequently Asked Questions (FAQs)

Q4B Annex 4A(R1) Microbiological Examination of Non-Sterile Products: Microbial Enumeration Tests General Chapter

The ICH Harmonised Annex was finalised under Step 4 in November 2008. This annex is the result of the Q4B process for Microbiological Examination of Non-Sterile Products: Microbial Enumeration Tests General Chapter. This annex was revised (R1) on 27 September 2010 to include the Interchangeability Statement from Health Canada, Canada.

Date of Step 4:

27 September 2010

Status: Step 5

Implementation status:

ANMAT, Argentina - In the process of implementation; ANVISA, Brazil - Not yet implemented; Reference: RDC 298/2019 COFEPRIS, Mexico - Implemented; Date: 25 February 2022; Reference: Pharmacopeia of the United Mexican States 13.0. EC, Europe - Implemented; Date: 1 September 2010; Reference: CHMP/ICH/308671/2008 EDA, Egypt - Implemented; Date: 13 November 2024; Reference: Microbiological examination of non sterile products-microbial enumeration test Egy.Ph.GC (B.5.5) FDA, United States - Implemented; Date: 1 June 2017; Reference: Vol. 74, No. 66, p. 15991-2 HSA, Singapore - Not applicable; Health Canada, Canada - Implemented; Date: 13 October 2010; Reference: File #: 10-121518-692 JFDA, Jordan - Implemented; MFDS, Republic of Korea - Implemented; Date: 27 December 2012; Reference: Korean Pharmacopoeia : Microbial Limit Test [MFDS, Republic of Korea Notification] MHLW/PMDA, Japan - Implemented; Date: 1 September 2010; Reference: PFSB/ELD Notification No. 0917-2 MHRA, UK - Implemented; Date: 1 September 2010; NMPA, China - Implemented; Date: 1 October 2025; Reference: Chinese Pharmacopoeia (2025 edition) SFDA, Saudi Arabia - Implemented; Swissmedic, Switzerland - Implemented; Date: 27 September 2010; Reference: ICH Guidelines apply in Switzerland automatically upon reaching Step 4: Swissmedic Journal 05/2006, p. 504 TFDA, Chinese Taipei - Implemented; Date: 12 October 2011; Reference: 1. Chinese Phamacopeia
2. Public Announcement for ” List for ICH Guidelines Adopted.” TITCK, Türkiye - Not yet implemented;

Guideline Q4B Annex 4A(R1)

Other documents Q4B Frequently Asked Questions (FAQs)

Q4B Annex 4B(R1) Microbiological Examination of Non-Sterile Products: Tests for Specified Micro-Organisms General Chapter

The ICH Harmonised Annex was finalised under Step 4 in November 2008. This annex is the result of the Q4B process for Microbiological Examination of Non-Sterile Products: Tests for Specified Micro-organisms General Chapter. This annex was revised (R1) on 27 September 2010 to include the Interchangeability Statement from Health Canada, Canada.

Date of Step 4:

27 September 2010

Status: Step 5

Implementation status:

ANMAT, Argentina - In the process of implementation; ANVISA, Brazil - Not yet implemented; Reference: RDC 298/2019 COFEPRIS, Mexico - Implemented; Date: 25 February 2022; Reference: Pharmacopeia of the United Mexican States 13.0. EC, Europe - Implemented; Date: 1 September 2010; Reference: CHMP/ICH/308817/2008 EDA, Egypt - Implemented; Date: 13 November 2024; Reference: Microbiological examination of non sterile products tests for specified microorganisms Egy.Ph.GC (B.5.6) FDA, United States - Implemented; Date: 1 June 2017; Reference: Vol. 74, No. 66, p. 15989-90 HSA, Singapore - Not applicable; Health Canada, Canada - Implemented; Date: 18 October 2010; Reference: File #: 10-121745-378 JFDA, Jordan - Implemented; MFDS, Republic of Korea - Implemented; Date: 27 December 2012; Reference: Korean Pharmacopoeia : Microbial Limit Test [MFDS, Republic of Korea Notification] MHLW/PMDA, Japan - Implemented; Date: 1 September 2010; Reference: PFSB/ELD Notification No. 0917-2 MHRA, UK - Implemented; Date: 1 September 2010; NMPA, China - Implemented; Date: 1 October 2025; Reference: Chinese Pharmacopoeia (2025 edition) SFDA, Saudi Arabia - Implemented; Swissmedic, Switzerland - Implemented; Date: 27 September 2010; Reference: ICH Guidelines apply in Switzerland automatically upon reaching Step 4: Swissmedic Journal 05/2006, p. 504 TFDA, Chinese Taipei - Implemented; Date: 13 October 2011; Reference: 1. Chinese Phamacopeia
2. Public Announcement for ” List for ICH Guidelines Adopted.” TITCK, Türkiye - Not yet implemented;

Guideline Q4B Annex 4B(R1)

Other documents Q4B Frequently Asked Questions (FAQs)

Q4B Annex 4C(R1) Microbiological Examination of Non-Sterile Products: Acceptance Criteria for Pharmaceutical Preparations and Substances for Pharmaceutical Use General Chapter

The ICH Harmonised Annex was finalised under Step 4 in November 2008. This annex is the result of the Q4B process for Microbiological Examination of Non-Sterile Products: Acceptance Criteria for Pharmaceutical Preparations and Substances for Pharmaceutical Use General Chapter. For each regulatory region this pharmacopoeial text is non-mandatory and is provided for informational purposes only. This annex was revised (R1) on 27 September 2010 to include the Interchangeability Statement from Health Canada, Canada.

Date of Step 4:

27 September 2010

Status: Step 5

Implementation status:

ANMAT, Argentina - In the process of implementation; ANVISA, Brazil - Not yet implemented; Reference: RDC 298/2019 COFEPRIS, Mexico - Implemented; Date: 25 February 2022; Reference: Pharmacopeia of the United Mexican States 13.0. EC, Europe - Implemented; Date: 1 September 2010; Reference: CHMP/ICH/308867/2008 EDA, Egypt - Implemented; Date: 2 July 2025; Reference: MICROBIOLOGICAL EXAMINATION OF NONSTERILE PRODUCTS:
ACCEPTANCE CRITERIA FOR PHARMACEUTICAL PREPARATIONS
AND SUBSTANCES FOR PHARMACEUTICAL USE
(D.34) FDA, United States - Implemented; Date: 1 June 2017; Reference: Vol. 74, No. 66, p. 15992-3 HSA, Singapore - Not applicable; Health Canada, Canada - Implemented; Date: 20 October 2010; Reference: File #: 10-121780-106 JFDA, Jordan - Implemented; MFDS, Republic of Korea - Implemented; Date: 27 December 2012; Reference: Korean Pharmacopoeia : Microbial Limit Test [MFDS, Republic of Korea Notification] MHLW/PMDA, Japan - Implemented; Date: 1 September 2010; Reference: PFSB/ELD Notification No. 0917-2 MHRA, UK - Implemented; Date: 1 September 2010; NMPA, China - Implemented; Date: 1 October 2025; Reference: Chinese Pharmacopoeia (2025 edition) SFDA, Saudi Arabia - Implemented; Swissmedic, Switzerland - Implemented; Date: 27 September 2010; Reference: ICH Guidelines apply in Switzerland automatically upon reaching Step 4: Swissmedic Journal 05/2006, p. 504 TFDA, Chinese Taipei - Implemented; Date: 14 October 2011; Reference: 1. Chinese Phamacopeia
2. Public Announcement for ” List for ICH Guidelines Adopted.” TITCK, Türkiye - Not yet implemented;

Guideline Q4B Annex 4C(R1)

Other documents Q4B Frequently Asked Questions (FAQs)

Q4B Annex 5(R1) Disintegration Test General Chapter

The ICH Harmonised Annex was finalised under Step 4 in June 2009. This annex is the result of the Q4B process for Disintegration Test General Chapter. This annex was revised (R1) on 27 September 2010 to include the Interchangeability Statement from Health Canada, Canada.

Date of Step 4:

27 September 2010

Status: Step 5

Implementation status:

ANMAT, Argentina - In the process of implementation; ANVISA, Brazil - In the process of implementation; Reference: RDC 298/2019 COFEPRIS, Mexico - Implemented; Date: 25 February 2022; Reference: Pharmacopeia of the United Mexican States 13.0. EC, Europe - Implemented; Date: 1 September 2010; Reference: CHMP/ICH/308895/2008 EDA, Egypt - Implemented; Date: 13 November 2024; Reference: Disintegration Egy.Ph.GC (B.3.29) FDA, United States - Implemented; Date: 1 June 2017; Reference: Vol. 74, No. 245, p. 68270-1 HSA, Singapore - Not applicable; Health Canada, Canada - Implemented; Date: 22 October 2010; Reference: File #: 10-121831-758 JFDA, Jordan - Implemented; MFDS, Republic of Korea - Implemented; Date: 27 December 2012; Reference: Korean Pharmacopoeia : Disintegration Test [MFDS, Republic of Korea Notification] MHLW/PMDA, Japan - Implemented; Date: 1 September 2010; Reference: PFSB/ELD Notification No. 0917-3 MHRA, UK - Implemented; Date: 1 September 2010; NMPA, China - Implemented; Date: 1 October 2025; Reference: Chinese Pharmacopoeia (2025 edition) SFDA, Saudi Arabia - Implemented; Swissmedic, Switzerland - Implemented; Date: 27 September 2010; Reference: ICH Guidelines apply in Switzerland automatically upon reaching Step 4: Swissmedic Journal 05/2006, p. 504 TFDA, Chinese Taipei - Implemented; Date: 15 October 2011; Reference: 1. Chinese Phamacopeia
2. Public Announcement for ” List for ICH Guidelines Adopted.” TITCK, Türkiye - Not yet implemented;

Guideline Q4B ANNEX 5(R1)

Other documents Q4B Frequently Asked Questions (FAQs)

Q4B Annex 6 Uniformity of Dosage Units General Chapter

The ICH Harmonised Annex was finalised under Step 4 in November 2013. This annex is the result of the Q4B process for Uniformity Dosage Units General Chapter. It contains the Interchangeability Statement from Health Canada, Canada.

Date of Step 4:

13 November 2013

Status: Step 5

Implementation status:

ANMAT, Argentina - Implemented; Date: 11 May 2013; ANVISA, Brazil - Implemented; Reference: RDC 298/2019, Resolução da Diretoria Colegiada - RDC nº 832, de 11 de dezembro de 2023 COFEPRIS, Mexico - Implemented; Date: 25 February 2022; Reference: Pharmacopeia of the United Mexican States 13.0. EC, Europe - Implemented; Date: 1 December 2013; Reference: CHMP/ICH/645408/2008 EDA, Egypt - Implemented; Date: 13 November 2024; Reference: Uniformity of dosage units Egy.Ph.GC (B.3.32) FDA, United States - Implemented; Date: 1 June 2014; Reference: Vol. 79, No. 115, p. 34314-5 HSA, Singapore - Not applicable; Health Canada, Canada - Implemented; Date: 29 May 2015; Reference: File #: 15-106278-499 JFDA, Jordan - Implemented; MFDS, Republic of Korea - Implemented; Date: 27 December 2012; Reference: Korean Pharmacopoeia : Uniformity of Dosage Units [MFDS, Republic of Korea Notification] MHLW/PMDA, Japan - Implemented; Date: 1 April 2014; Reference: PFSB/ELD Notification No. 0417-1 MHRA, UK - Implemented; Date: 1 December 2013; NMPA, China - Implemented; Date: 1 October 2025; Reference: Chinese Pharmacopoeia (2025 edition) SFDA, Saudi Arabia - Implemented; Swissmedic, Switzerland - Implemented; Date: 13 November 2013; Reference: ICH Guidelines apply in Switzerland automatically upon reaching Step 4: Swissmedic Journal 05/2006, p. 504 TFDA, Chinese Taipei - Implemented; Date: 12 December 2016; Reference: 1. Chinese Phamacopeia
2. Public Announcement for ” List for ICH Guidelines Adopted.” TITCK, Türkiye - Not yet implemented;

Guideline Q4B Annex 6

Other documents Q4B Frequently Asked Questions (FAQs)

Q4B Annex 7(R2) Dissolution Test General Chapter

The ICH Harmonised Annex was finalised under Step 4 in October 2009. This annex is the result of the Q4B process for Dissolution Test General Chapter. This annex was revised (R1) on 27 September 2010 to include the Interchangeability Statement from Health Canada, Canada. On 11 November 2010 the ICH Steering Committee approved the second revision (R2) directly under Step 4 without further public consultation.

Date of Step 4:

11 November 2010

Status: Step 5

Implementation status:

ANMAT, Argentina - In the process of implementation; ANVISA, Brazil - Implemented; Reference: RDC 49/2010, RDC 298/2019, Resolução da Diretoria Colegiada - RDC nº 844, de 22 de fevereiro de 2024 COFEPRIS, Mexico - Implemented; Date: 25 February 2022; Reference: Pharmacopeia of the United Mexican States 13.0. EC, Europe - Implemented; Date: 1 December 2010; Reference: CHMP/ICH/645469/2008 EDA, Egypt - Implemented; Date: 13 November 2024; Reference: Dissolution Egy.Ph.GC (B.3.28) FDA, United States - Implemented; Date: 1 June 2011; Reference: Vol. 76, No. 122, p. 37129-31 HSA, Singapore - Not applicable; Health Canada, Canada - Implemented; Date: 22 October 2010; Reference: File #: 10-121855-881 JFDA, Jordan - Implemented; MFDS, Republic of Korea - Implemented; Date: 27 December 2012; Reference: Korean Pharmacopoeia : Dissolution Test [MFDS, Republic of Korea Notification] MHLW/PMDA, Japan - Implemented; Date: 1 July 2011; Reference: PFSB/ELD Notification No. 0726-1 MHRA, UK - Implemented; Date: 1 December 2010; NMPA, China - Implemented; Date: 1 October 2025; Reference: Chinese Pharmacopoeia (2025 edition) SFDA, Saudi Arabia - Implemented; Swissmedic, Switzerland - Implemented; Date: 11 November 2010; Reference: ICH Guidelines apply in Switzerland automatically upon reaching Step 4: Swissmedic Journal 05/2006, p. 504 TFDA, Chinese Taipei - Implemented; Date: 15 October 2011; Reference: 1. Chinese Phamacopeia
2. Public Announcement for ” List for ICH Guidelines Adopted.” TITCK, Türkiye - Not yet implemented;

Guideline Q4B Annex 7(R2)

Other documents Q4B Frequently Asked Questions (FAQs)

Q4B Annex 8(R1) Sterility Test General Chapter

The ICH Harmonised Annex was finalised under Step 4 in June 2009. This annex is the result of the Q4B process for Sterility Test General Chapter. This annex was revised (R1) on 27 September 2010 to include the Interchangeability Statement from Health Canada, Canada.

Date of Step 4:

27 September 2010

Status: Step 5

Implementation status:

ANMAT, Argentina - In the process of implementation; ANVISA, Brazil - Implemented; Date: 1 November 2010; Reference: RDC 49/2010

RDC 298/2019 COFEPRIS, Mexico - Implemented; Date: 25 February 2022; Reference: Pharmacopeia of the United Mexican States 13.0. EC, Europe - Implemented; Date: 1 September 2010; Reference: CHMP/ICH/645592/2008 EDA, Egypt - Implemented; Date: 13 November 2024; Reference: Sterility Egy.Ph. GC (B.5.9) FDA, United States - Implemented; Date: 1 June 2017; Reference: Vol. 74, No. 244, p. 68068-9 HSA, Singapore - Not applicable; Health Canada, Canada - Implemented; Date: 26 October 2010; Reference: File #: 10-121878-840 JFDA, Jordan - Implemented; MFDS, Republic of Korea - Implemented; Date: 27 December 2012; Reference: Korean Pharmacopoeia : Sterility Test [MFDS, Republic of Korea Notification] MHLW/PMDA, Japan - Implemented; Date: 1 September 2010; Reference: PFSB/ELD Notification No. 0917-1 MHRA, UK - Implemented; Date: 1 September 2010; NMPA, China - Implemented; Date: 1 October 2025; Reference: Chinese Pharmacopoeia (2025 edition) SFDA, Saudi Arabia - Implemented; Swissmedic, Switzerland - Implemented; Date: 27 September 2010; Reference: ICH Guidelines apply in Switzerland automatically upon reaching Step 4: Swissmedic Journal 05/2006, p. 504 TFDA, Chinese Taipei - Implemented; Date: 16 October 2011; Reference: 1. Chinese Phamacopeia
2. Public Announcement for ” List for ICH Guidelines Adopted.” TITCK, Türkiye - Not yet implemented;

Guideline Q4B Annex 8(R1)

Other documents Q4B Frequently Asked Questions (FAQs)

Q4B Annex 9(R1) Tablet Friability General Chapter

The ICH Harmonised guideline was finalised under Step 4 in October 2009. This annex is the result of the Q4B process for Tablet Friability General Chapter. This annex was revised (R1) on 27 September 2010 to include the Interchangeability Statement from Health Canada, Canada.

Date of Step 4:

27 September 2010

Status: Step 5

Implementation status:

ANMAT, Argentina - In the process of implementation; ANVISA, Brazil - Implemented; Reference: RDC 49/2010, RDC 298/2019, Resolução da Diretoria Colegiada - RDC nº 832, de 11 de dezembro de 2023 COFEPRIS, Mexico - Implemented; Date: 25 February 2022; Reference: Pharmacopeia of the United Mexican States 13.0. EC, Europe - Implemented; Date: 1 September 2010; Reference: CHMP/ICH/379801/2009 EDA, Egypt - Implemented; Date: 13 November 2024; Reference: Tablet Friability Egy.Ph.GC (D.61) FDA, United States - Implemented; Date: 1 June 2017; Reference: Vol. 75, No. 64, p. 17147 HSA, Singapore - Not applicable; Health Canada, Canada - Implemented; Date: 26 October 2010; Reference: File #: 10-121949-582 JFDA, Jordan - Implemented; MFDS, Republic of Korea - Implemented; Date: 5 December 2014; Reference: Korean Pharmacopoeia : Tablet Friability [MFDS, Republic of Korea Notification] MHLW/PMDA, Japan - Implemented; Date: 1 January 2011; Reference: PFSB/ELD Notification No. 0127-2 MHRA, UK - Implemented; Date: 1 September 2010; NMPA, China - Implemented; Date: 1 October 2025; Reference: Chinese Pharmacopoeia (2025 edition) SFDA, Saudi Arabia - Implemented; Swissmedic, Switzerland - Implemented; Date: 27 September 2010; Reference: ICH Guidelines apply in Switzerland automatically upon reaching Step 4: Swissmedic Journal 05/2006, p. 504 TFDA, Chinese Taipei - Implemented; Date: 17 October 2011; Reference: 1. Chinese Phamacopeia
2. Public Announcement for ” List for ICH Guidelines Adopted.” TITCK, Türkiye - Not yet implemented;

Guideline Q4B Annex 9(R1)

Other documents Q4B Frequently Asked Questions (FAQs)

Q4B Annex 10(R1) Polyacrylamide Gel Electrophoresis General Chapter

The ICH Harmonised Annex was finalised under Step 4 in October 2009. This annex is the result of the Q4B process for Polyacrylamide Gel Electrophoresis General Chapter. This annex was revised (R1) on 27 September 2010 to include the Interchangeability Statement from Health Canada, Canada.

Date of Step 4:

27 September 2010

Status: Step 5

Implementation status:

ANMAT, Argentina - In the process of implementation; ANVISA, Brazil - Implemented; Date: 1 November 2010; Reference: RDC 298/2019: publication of the 6th edition of the Brazilian Pharmacopoeia COFEPRIS, Mexico - In the process of implementation; Date: 25 February 2022; Reference: Pharmacopeia of the United Mexican States 13.0. EC, Europe - Implemented; Date: 1 May 2010; Reference: CHMP/ICH/381133/2009 EDA, Egypt - Implemented; Date: 13 November 2024; Reference: Polyacrylamide gel electrophoresis Egy.Ph.GC (D.110) FDA, United States - Implemented; Date: 1 June 2017; Reference: Vol. 75, No. 69, Docket No. FDA, US-2009-D-0342, p. 18509 HSA, Singapore - Not applicable; Health Canada, Canada - Implemented; Date: 26 October 2010; Reference: File #: 10-122178-463 JFDA, Jordan - Not yet implemented; MFDS, Republic of Korea - Implemented; Date: 24 March 2017; Reference: Korean Pharmacopoeia : Polyacrylamide Gel Electrophoresis [MFDS, Republic of Korea Notification ] MHLW/PMDA, Japan - Implemented; Date: 1 January 2011; Reference: PFSB/ELD Notification No. 0127-1 MHRA, UK - Implemented; Date: 1 September 2010; NMPA, China - Implemented; Date: 1 October 2025; Reference: Chinese Pharmacopoeia (2025 edition) SFDA, Saudi Arabia - Implemented; Swissmedic, Switzerland - Implemented; Date: 27 September 2010; Reference: ICH Guidelines apply in Switzerland automatically upon reaching Step 4: Swissmedic Journal 05/2006, p. 504 TFDA, Chinese Taipei - Implemented; Date: 10 October 2011; Reference: 1. Chinese Phamacopeia
2. Public Announcement for ” List for ICH Guidelines Adopted.” TITCK, Türkiye - Not yet implemented;

Guideline Q4B Annex 10(R1)

Other documents Q4B Frequently Asked Questions (FAQs)

Q4B Annex 11 Capillary Electrophoresis General Chapter

The ICH Harmonised Annex was finalised under Step 4 in June 2010. This annex is the result of the Q4B process for Capillary Electrophoresis General Chapter. It contains the Interchangeability Statement from Health Canada, Canada.

Date of Step 4:

9 June 2010

Status: Step 5

Implementation status:

ANMAT, Argentina - Implemented; Date: 12 April 2023; ANVISA, Brazil - Implemented; Date: 1 November 2010; Reference: RDC 298/2019: publication of the 6th edition of the Brazilian Pharmacopoeia COFEPRIS, Mexico - Implemented; Date: 25 February 2022; Reference: Pharmacopeia of the United Mexican States 13.0. EC, Europe - Implemented; Date: 1 December 2010; Reference: CHMP/ICH/730028/2009 EDA, Egypt - Implemented; Date: 13 November 2024; Reference: Capilliary electrophoresis Egy.Ph. GC (D.40) FDA, United States - Implemented; Date: 1 September 2010; Reference: Vol. 75, No. 171, p. 54153-4 HSA, Singapore - Not applicable; Health Canada, Canada - Implemented; Date: 29 May 2015; Reference: File #: 15-106291-302 JFDA, Jordan - Not yet implemented; MFDS, Republic of Korea - Implemented; Date: 28 December 2007; Reference: Korean Pharmacopoeia : Capillary Electrophoresis [MFDS, Republic of Korea Notification] MHLW/PMDA, Japan - Implemented; Date: 1 January 2011; Reference: PFSB/ELD Notification No. 0127-3 MHRA, UK - Implemented; Date: 1 September 2010; NMPA, China - Implemented; Date: 1 October 2025; Reference: Chinese Pharmacopoeia (2025 edition) SFDA, Saudi Arabia - Implemented; Swissmedic, Switzerland - Implemented; Date: 9 June 2010; Reference: ICH Guidelines apply in Switzerland automatically upon reaching Step 4: Swissmedic Journal 05/2006, p. 504 TFDA, Chinese Taipei - Implemented; Date: 10 October 2011; Reference: 1. Chinese Phamacopeia
2. Public Announcement for ” List for ICH Guidelines Adopted.” TITCK, Türkiye - Not yet implemented;

Guideline Q4B Annex 11

Other documents Q4B Frequently Asked Questions (FAQs)

Q4B Annex 12 Analytical Sieving General Chapter

The ICH Harmonised Annex was finalised under Step 4 in June 2010. This annex is the result of the Q4B process for Analytical Sieving General Chapter. It contains the Interchangeability Statement from Health Canada, Canada.

Date of Step 4:

9 June 2010

Status: Step 5

Implementation status:

ANMAT, Argentina - In the process of implementation; ANVISA, Brazil - In the process of implementation; COFEPRIS, Mexico - Implemented; Date: 25 February 2022; Reference: Pharmacopeia of the United Mexican States 13.0. EC, Europe - Implemented; Date: 1 December 2010; Reference: CHMP/ICH/730808/2009 EDA, Egypt - Implemented; Date: 13 November 2024; Reference: Particle size distribution estimation by analytical sieving Egy.Ph. GC (B.3.41) FDA, United States - Implemented; Date: 1 September 2010; Reference: Vol. 75, No. 170, p. 53973-4 HSA, Singapore - Not applicable; Health Canada, Canada - Implemented; Date: 3 June 2015; Reference: File #: 15-106304-540 JFDA, Jordan - Not yet implemented; MFDS, Republic of Korea - Implemented; Date: 28 December 2007; Reference: Korean Pharmacopoeia : Particle Size Distribution Test for Preparation [MFDS, Republic of Korea Notification] MHLW/PMDA, Japan - Implemented; Date: 1 January 2011; Reference: PFSB/ELD Notification No. 0127-4 MHRA, UK - Implemented; Date: 1 September 2010; NMPA, China - Implemented; Date: 1 October 2025; Reference: Chinese Pharmacopoeia (2025 edition) SFDA, Saudi Arabia - Implemented; Swissmedic, Switzerland - Implemented; Date: 9 June 2010; Reference: ICH Guidelines apply in Switzerland automatically upon reaching Step 4: Swissmedic Journal 05/2006, p. 504 TFDA, Chinese Taipei - Implemented; Date: 10 October 2011; Reference: 1. Chinese Phamacopeia
2. Public Announcement for ” List for ICH Guidelines Adopted.” TITCK, Türkiye - Not yet implemented;

Guideline Q4B Annex 12

Other documents Q4B Frequently Asked Questions (FAQs)

Q4B Annex 13 Bulk Density and Tapped Density of Powders General Chapter

The ICH Harmonised Annex was finalised under Step 4 in June 2012. This annex is the result of the Q4B process for Bulk Density and Tapped Density of Powders General Chapter. It contains the Interchangeability Statement from Health Canada, Canada.

Date of Step 4:

7 June 2012

Status: Step 5

Implementation status:

ANMAT, Argentina - In the process of implementation; ANVISA, Brazil - Not yet implemented; Reference: RDC 298/2019: publication of the 6th edition of the Brazilian Pharmacopoeia COFEPRIS, Mexico - Implemented; Date: 25 February 2022; Reference: Pharmacopeia of the United Mexican States 13.0. EC, Europe - Implemented; Date: 1 January 2013; Reference: CHMP/ICH/405290/2010 EDA, Egypt - Implemented; Date: 13 November 2024; Reference: Bulk density and tapped density of powders Egy.Ph.GC (B.3.47) FDA, United States - Implemented; Date: 1 May 2013; Reference: Vol. 75, No. 102, p. 31944-5 HSA, Singapore - Not applicable; Health Canada, Canada - Implemented; Date: 29 May 2015; Reference: File #: 15-106311-850 JFDA, Jordan - Not yet implemented; MFDS, Republic of Korea - Implemented; Date: 28 December 2007; Reference: Korean Pharmacopoeia : Determination of Bulk and Tapped Densities [MFDS, Republic of Korea Notification] MHLW/PMDA, Japan - Implemented; Date: 1 November 2012; Reference: PFSB/ELD Notification No. 1108-3 MHRA, UK - Implemented; Date: 1 July 2012; NMPA, China - Implemented; Date: 1 October 2025; Reference: Chinese Pharmacopoeia (2025 edition) SFDA, Saudi Arabia - Implemented; Swissmedic, Switzerland - Implemented; Date: 7 June 2012; Reference: ICH Guidelines apply in Switzerland automatically upon reaching Step 4: Swissmedic Journal 05/2006, p. 504 TFDA, Chinese Taipei - Implemented; Date: 12 December 2016; Reference: 1. Chinese Phamacopeia
2. Public Announcement for ” List for ICH Guidelines Adopted.” TITCK, Türkiye - Not yet implemented;

Guideline Q4B Annex 13

Other documents Q4B Frequently Asked Questions (FAQs)

Q4B Annex 14 Bacterial Endotoxins Test General Chapter

The ICH Harmonised Annex was finalised under Step 4 in October 2012. This annex is the result of the Q4B process for Bacterial Endotoxins Test General Chapter. It contains the Interchangeability Statement from Health Canada, Canada.

Date of Step 4:

18 October 2012

Status: Step 5

Implementation status:

ANMAT, Argentina - In the process of implementation; ANVISA, Brazil - Implemented; Date: 1 November 2010; Reference: RDC 49/2010

RDC 298/2019 COFEPRIS, Mexico - Implemented; Date: 25 February 2022; Reference: Pharmacopeia of the United Mexican States 13.0. EC, Europe - Implemented; Date: 1 May 2013; Reference: CHMP/ICH/529785/2010 EDA, Egypt - Implemented; Date: 13 November 2024; Reference: Bacterial endotoxins test Egy.Ph.GC (B.5.10) FDA, United States - Implemented; Date: 1 October 2013; Reference: Vol. 78, No. 205, p. 63221-2 HSA, Singapore - Not applicable; Health Canada, Canada - Implemented; Date: 29 May 2015; Reference: File #: 15-106315-995 JFDA, Jordan - Implemented; MFDS, Republic of Korea - Implemented; Date: 27 December 2012; Reference: Korean Pharmacopoeia : Bacterial Endotoxins Test [MFDS, Republic of Korea Notification] MHLW/PMDA, Japan - Implemented; Date: 1 March 2013; Reference: PFSB/ELD Notification No. 0321-1 MHRA, UK - Implemented; Date: 1 November 2012; NMPA, China - Implemented; Date: 1 October 2025; Reference: Chinese Pharmacopoeia (2025 edition) SFDA, Saudi Arabia - Implemented; Swissmedic, Switzerland - Implemented; Date: 18 October 2012; Reference: ICH Guidelines apply in Switzerland automatically upon reaching Step 4: Swissmedic Journal 05/2006, p. 504 TFDA, Chinese Taipei - Implemented; Date: 12 December 2016; Reference: 1. Chinese Phamacopeia
2. Public Announcement for ” List for ICH Guidelines Adopted.” TITCK, Türkiye - Not yet implemented;

Guideline Q4B Annex 14

Other documents Q4B Frequently Asked Questions (FAQs)

Q4B FAQs Frequently Asked Question

The Q4B Expert Working Group (EWG) developed a set of Frequently Asked Questions (FAQs) to help users of the Q4B Guideline and Annexes to understand the use and implication of these documents.

Other documents Q4B FAQs Frequently Asked Questions (FAQs)

Q5A - Q5E Quality of Biotechnological Products

Q5A(R2) Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin

The ICH Q5A Guideline reached Step 4 of the ICH process on 1 November 2023.

The revision retains key principles of the original Guideline and provides additional recommendations on the established and complementary approaches to control the potential viral contamination of biotechnology products and describes the evaluation of the viral safety of biotechnology products including viral clearance and testing, and outlines what data should be submitted in marketing applications for those products.

Date of Step 4:

1 November 2023

Status: Step 5

Implementation status:

ANMAT, Argentina - Not yet implemented; ANVISA, Brazil - In the process of implementation; COFEPRIS, Mexico - Not yet implemented; EC, Europe - Implemented; Date: 14 June 2024; Reference: EMA/CHMP/ICH/804363/2022 EDA, Egypt - Implemented; Date: 25 September 2024; Reference: Regulatory Guide for mechanisms, procedures and rules of implementing the Decree of Egyptian Drug Authority No.343 of 2021 FDA, United States - Implemented; Date: 11 January 2024; Reference: Vol. 89, p. 1925 (89 FR 1925) HSA, Singapore - Implemented; Date: 1 April 2024; Reference: These guidelines are cross-referred in M4Q and applied in the routine evaluation. See regulatory guidance. Health Canada, Canada - Implemented; Date: 27 June 2025; Reference: 25-102237-854 JFDA, Jordan - Not yet implemented; MFDS, Republic of Korea - Implemented; Date: 17 December 2024; Reference: VIRAL SAFETY EVALUATION OF BIOTECHNOLOGY PRODUCTS DERIVED FROM CELL LINES OF HUMAN OR ANIMAL ORIGIN [Guideline-0263-02] MHLW/PMDA, Japan - Implemented; Date: 9 January 2025; Reference: PSB/PED Notification No. 0109-4 MHRA, UK - In the process of implementation; NMPA, China - Implemented; Date: 21 May 2025; Reference: NMPA, China Announcement No. 63 (2024) SFDA, Saudi Arabia - Implemented; Date: 1 October 2025; Swissmedic, Switzerland - Implemented; Date: 1 November 2023; Reference: ICH Guidelines apply in Switzerland automatically upon reaching Step 4: Swissmedic Journal 05/2006, p. 504 TFDA, Chinese Taipei - Implemented; TITCK, Türkiye - Not yet implemented;

Guideline Q5A(R2) Guideline

Endorsed Documents Q5A(R2) Concept Paper Q5A(R2) Business Plan

WG Presentations / Trainings Q5A(R2) Step 4 Presentation
WG list

Q5A(R2) Training on Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin

Further to the ICH Management Committee’s endorsement of the Q5A(R2) IWG Concept Paper in December 2023, the Q5A(R2) IWG was established to develop and deliver training materials that focus on up to four key case studies and associated materials to describe use cases for the new principles described in the ICH Q5A(R2) “Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin” Guideline.

The ICH Q5A(R2) “Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin” Guideline training materials were finalised in May 2025.

Further information can be found in the Q5A(R2) IWG Concept Paper.

Endorsed Documents Q5A(R2) IWG Concept Paper

WG Presentations / Trainings Q5A(R2) Training Materials

Q5B Analysis of the Expression Construct in Cells Used for Production of r-DNA Derived Protein Products

The ICH Harmonised Guideline was finalised under Step 4 in November 1995. This document is intended to describe the types of information that are considered valuable in assessing the structure of the expression construct used to produce recombinant DNA derived proteins.

Date of Step 4:

30 November 1995

Status: Step 5

Implementation status:

ANMAT, Argentina - Not yet implemented; ANVISA, Brazil - Implemented; Date: 4 January 2021; Reference: RDC 413/2020 COFEPRIS, Mexico - Not yet implemented; EC, Europe - Implemented; Date: 1 July 1996; Reference: CPMP/ICH/139/95 EDA, Egypt - Implemented; Date: 31 December 2013; Reference: Regulatory guide for mechanisms, procedures and rules of implementing the decree of Egyptian Drug Authority No.343 of 2021 FDA, United States - Implemented; Date: 1 February 1996; Reference: Vol. 61, p. 7006 HSA, Singapore - Implemented; Date: 1 January 2008; Reference: These guidelines are cross-referred in M4Q and applied in the routine evaluation. See regulatory guidance. Health Canada, Canada - Implemented; Date: 5 January 2001; Reference: Catalogue No. H42-2/67-19-2000E JFDA, Jordan - Not yet implemented; MFDS, Republic of Korea - Implemented; Date: 31 July 2019; Reference: Guidelines on the Evaluation of quality, safety and efficacy of recombinant protein products [Guideline-0317-02] MHLW/PMDA, Japan - Implemented; Date: 1 January 1998; Reference: PMSB/ELD Notification No. 3 MHRA, UK - Implemented; Date: 1 December 1995; NMPA, China - Implemented; Date: 21 July 2020; Reference: NMPA, China Announcement No. 7 (2020) SFDA, Saudi Arabia - Implemented; Date: 22 September 2011; Swissmedic, Switzerland - Implemented; Date: 30 November 1995; Reference: ICH Guidelines apply in Switzerland automatically upon reaching Step 4: Swissmedic Journal 05/2006, p. 504 TFDA, Chinese Taipei - Implemented; Date: 22 December 2014; Reference: 1. Public Announcement for ” List for ICH Guidelines Adopted.”
2. Guidance for Quality Of Biotechnological Products: Analysis Of The Expression Construct In Cells Used For Production Of r-DNA Derived Protein Products TITCK, Türkiye - Not yet implemented;

Guideline Q5B Guideline

Q5C Quality of Biotechnological Products: Stability Testing of Biotechnological/Biological Products

The ICH Harmonised Guideline was finalised under Step 4 in November 1995. This document augments the stability Guideline (Q1A) and deals with the particular aspects of stability test procedures needed to take account of the special characteristics of products in which the active components are typically proteins and/or polypeptides.

Date of Step 4:

30 November 1995

Status: Step 5

Implementation status:

ANMAT, Argentina - In the process of implementation; ANVISA, Brazil - Implemented; Date: 4 January 2021; Reference: RDC 412/2020 COFEPRIS, Mexico - Implemented; Date: 1 September 2015; Reference: NOM-073-SSA1-2015 Stability Testing of New Drug Substances and Products; Pharmacopeia of the United Mexican States 13.0. EC, Europe - Implemented; Date: 1 July 1996; Reference: CPMP/ICH/138/95 EDA, Egypt - Implemented; Date: 31 December 2013; Reference: Regulatory guide for mechanisms, procedures and rules of implementing the decree of Egyptian Drug Authority No.343 of 2021 FDA, United States - Implemented; Date: 1 July 1996; Reference: Vol. 61, p. 36466 HSA, Singapore - Implemented; Date: 1 January 2008; Reference: These guidelines are cross-referred in M4Q and applied in the routine evaluation. See regulatory guidance. Health Canada, Canada - Implemented; Date: 5 January 2001; Reference: Catalogue No. H42-2/67-20-2000E JFDA, Jordan - Implemented; Date: 2 January 2016; MFDS, Republic of Korea - Implemented; Date: 30 November 2015; Reference: Guidelines on Stability Testing of Biological Product [Guideline-0328-01] MHLW/PMDA, Japan - Implemented; Date: 1 January 1998; Reference: PMSB/ELD Notification No. 6 MHRA, UK - Implemented; Date: 2 December 1995; NMPA, China - Implemented; Date: 21 July 2020; Reference: NMPA, China Announcement No. 7 (2020) SFDA, Saudi Arabia - Implemented; Date: 3 February 2011; Swissmedic, Switzerland - Implemented; Date: 30 November 1995; Reference: ICH Guidelines apply in Switzerland automatically upon reaching Step 4: Swissmedic Journal 05/2006, p. 504 TFDA, Chinese Taipei - Implemented; Date: 11 December 2003; Reference: Guideline on Stability Testing of Drug Substances and Products TITCK, Türkiye - Implemented;

Guideline Q5C Guideline

Q5D Derivation and Characterisation of Cell Substrates Used for Production of Biotechnological/Biological Products

The ICH Harmonised Guideline was finalised under Step 4 in July 1997. This document provides broad guidance on appropriate standards for the derivation of human and animal cell lines and microbial cells used to prepare biotechnological/biological products, and for the preparation and characterisation of cell banks to be used for production.

Date of Step 4:

16 July 1997

Status: Step 5

Implementation status:

ANMAT, Argentina - In the process of implementation; ANVISA, Brazil - Implemented; Date: 4 January 2021; Reference: RDC 413/2020 COFEPRIS, Mexico - In the process of implementation; Date: 25 February 2022; Reference: Pharmacopeia of the United Mexican States 13.0. EC, Europe - Implemented; Date: 1 March 1998; Reference: CPMP/ICH/294/95 EDA, Egypt - Implemented; Date: 31 December 2013; Reference: Regulatory guide for mechanisms, procedures and rules of implementing the decree of Egyptian Drug Authority No.343 of 2021 FDA, United States - Implemented; Date: 1 September 1998; Reference: Vol. 63, No. 182, p. 50244-9 HSA, Singapore - Implemented; Date: 1 January 2008; Reference: These guidelines are cross-referred in M4Q and applied in the routine evaluation. See regulatory guidance. Health Canada, Canada - Implemented; Date: 5 January 2001; Reference: Catalogue No. H42-2/67-21-2000E JFDA, Jordan - Implemented; Date: 2 January 2016; MFDS, Republic of Korea - Implemented; Date: 1 December 2010; Reference: Guidance on the Characterization of Cell Substrates Used to Produce Biologicals [Guideline-0264-01] MHLW/PMDA, Japan - Implemented; Date: 1 July 2000; Reference: PMSB/ELD Notification No. 873 MHRA, UK - Implemented; Date: 3 December 1995; NMPA, China - Implemented; Date: 7 November 2021; Reference: NMPA, China Announcement No. 61 (2021) SFDA, Saudi Arabia - Implemented; Date: 22 September 2011; Swissmedic, Switzerland - Implemented; Date: 16 July 1997; Reference: ICH Guidelines apply in Switzerland automatically upon reaching Step 4: Swissmedic Journal 05/2006, p. 504 TFDA, Chinese Taipei - Implemented; Date: 22 December 2014; Reference: 1. Public Announcement for ” List for ICH Guidelines Adopted.”
2. Guidance for 'Derivation and Characterisation of Cell Substrates Used for Production of Biotechnological/Biological Products.' TITCK, Türkiye - Implemented; Date: 11 December 2021;

Guideline Q5D Guideline

Q5E Comparability of Biotechnological/Biological Products Subject to Changes in their Manufacturing Process

The ICH Harmonised Guideline was finalised under Step 4 in November 2004.

The objective of this document is to provide principles for assessing the comparability of biotechnological/biological products before and after changes are made in the manufacturing process for the drug substance or drug product.

Therefore, this Guideline is intended to assist in the collection of relevant technical information which serves as evidence that the manufacturing process changes will not have an adverse impact on the quality, safety and efficacy of the drug product.

The document does not prescribe any particular analytical, nonclinical or clinical strategy. The main emphasis of the document is on quality aspects.

Date of Step 4:

18 November 2004

Status: Step 5

Implementation status:

ANMAT, Argentina - In the process of implementation; ANVISA, Brazil - Implemented; Date: 4 January 2021; Reference: RDC 413/2020 COFEPRIS, Mexico - In the process of implementation; Date: 20 September 2013; Reference: Mexican Official Standard NOM-177-SSA1-2013 EC, Europe - Implemented; Date: 1 June 2005; Reference: CPMP/ICH/5721/03 EDA, Egypt - Implemented; Date: 31 December 2013; Reference: Regulatory guide for mechanisms, procedures and rules of implementing the decree of Egyptian Drug Authority No.343 of 2021 FDA, United States - Implemented; Date: 1 June 2005; Reference: Vol. 70, No. 125, p. 37861-2 HSA, Singapore - Implemented; Date: 1 January 2008; Health Canada, Canada - Implemented; Date: 15 June 2015; Reference: File #: 15-107053-353 JFDA, Jordan - Implemented; Date: 2 January 2016; MFDS, Republic of Korea - Implemented; Date: 1 June 2009; Reference: Guidelines on comparability of biological products after change in the manufacturing process [Guideline-0316-01] MHLW/PMDA, Japan - Implemented; Date: 1 April 2005; Reference: PFSB/ELD Notification No. 0426001 MHRA, UK - Implemented; Date: 4 December 1995; NMPA, China - Implemented; Date: 21 July 2020; Reference: NMPA, China Announcement No. 7 (2020) SFDA, Saudi Arabia - Implemented; Date: 22 August 2017; Swissmedic, Switzerland - Implemented; Date: 18 November 2004; Reference: ICH Guidelines apply in Switzerland automatically upon reaching Step 4: Swissmedic Journal 05/2006, p. 504 TFDA, Chinese Taipei - Implemented; Date: 22 December 2014; Reference: Public Announcement for ” List for ICH Guidelines Adopted.” TITCK, Türkiye - Implemented;

Guideline Q5E Guideline

Endorsed Document Q5E Concept Paper

Q5E Annex EWG Comparability of Advanced Therapy Medicinal Products (ATMPs) Subject to Changes in Their Manufacturing Process

This topic was endorsed by the ICH Assembly in April 2025, and the Q5E Annex Working Group has been established to develop a final Concept Paper.

Rapporteur: Dr. Kathleen Francissen (BIO)

Regulatory Chair: Dr. Andrew Timmons (FDA, United States)

Files
WG list

Q6A- Q6B Specifications

Q6A Specifications : Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances

The ICH Harmonised Guideline was finalised under Step 4 in October 1999. This document provides guidance on the setting and justification of acceptance criteria and the selection of test procedures for new drug substances of synthetic chemical origin, and new drug products produced from them, which have not been registered previously in the ICH regions.

Date of Step 4:

6 October 1999

Status: Step 5

Implementation status:

ANMAT, Argentina - In the process of implementation; ANVISA, Brazil - Implemented; Date: 3 August 2020; Reference: RDC 359/2020 and RDC 753/2022 COFEPRIS, Mexico - In the process of implementation; Date: 25 February 2022; Reference: Pharmacopeia of the United Mexican States 13.0. EC, Europe - Implemented; Date: 1 May 2000; Reference: CPMP/ICH/367/96 EDA, Egypt - Implemented; Date: 31 December 2015; Reference: Egyptian Guidelines on CTD Quality Module for Human Pharmaceuticals FDA, United States - Implemented; Date: 1 December 2000; Reference: Vol. 65, No. 251, p. 83041-63 HSA, Singapore - Implemented; Date: 1 January 2008; Reference: These guidelines are cross-referred in M4Q and applied in the routine evaluation. See regulatory guidance. Health Canada, Canada - Implemented; Date: 29 January 2016; Reference: File #: 16-100136-12 JFDA, Jordan - Implemented; Date: 1 March 2008; MFDS, Republic of Korea - Implemented; Date: 23 September 2020; Reference: Specification: Test procedures and acceptance criteria for new drug substances and new drug products: chemical substances [Guideline-1053-01] MHLW/PMDA, Japan - Implemented; Date: 1 May 2001; Reference: PMSB/ELD Notification No. 568 MHRA, UK - Implemented; Date: 5 December 1995; NMPA, China - Implemented; Date: 21 July 2020; Reference: NMPA, China Announcement No. 7 (2020) SFDA, Saudi Arabia - Implemented; Date: 22 September 2011; Swissmedic, Switzerland - Implemented; Date: 6 October 1999; Reference: ICH Guidelines apply in Switzerland automatically upon reaching Step 4: Swissmedic Journal 05/2006, p. 504 TFDA, Chinese Taipei - Implemented; Date: 22 December 2014; Reference: Public Announcement for ” List for ICH Guidelines Adopted.” TITCK, Türkiye - Implemented; Date: 11 December 2021;

Guideline Q6A Guideline

Implementation status:

ANMAT, Argentina - In the process of implementation; ANVISA, Brazil - Implemented; Date: 1 August 2011; Reference: RDC 413/2020 COFEPRIS, Mexico - In the process of implementation; Date: 25 February 2022; Reference: Pharmacopeia of the United Mexican States 13.0. EC, Europe - Implemented; Date: 1 September 1999; Reference: CPMP/ICH/365/96 EDA, Egypt - Implemented; Date: 31 December 2008; Reference: Regulatory guide for mechanisms, procedures and rules of implementing the decree of Egyptian Drug Authority No.343 of 2021 FDA, United States - Implemented; Date: 1 August 1999; Reference: Vol. 64, p. 44928 HSA, Singapore - Implemented; Date: 1 January 2008; Reference: These guidelines are cross-referred in M4Q and applied in the routine evaluation. See regulatory guidance. Health Canada, Canada - Implemented; Date: 20 December 2001; Reference: File #: 01-118655-734 JFDA, Jordan - Implemented; Date: 1 March 2008; MFDS, Republic of Korea - Implemented; Date: 30 December 2014; Reference: Regulation on Approval and Review for Biologics, ETC. [MFDS, Republic of Korea Notification]; Guidelines on the Evaluation of quality, safety and efficacy of recombinant protein products [Guideline-0324-01] MHLW/PMDA, Japan - Implemented; Date: 1 May 2001; Reference: PMSB/ELD Notification No. 571 MHRA, UK - Implemented; Date: 6 December 1995; NMPA, China - In the process of implementation; SFDA, Saudi Arabia - Implemented; Date: 22 September 2011; Swissmedic, Switzerland - Implemented; Date: 10 March 1999; Reference: ICH Guidelines apply in Switzerland automatically upon reaching Step 4: Swissmedic Journal 05/2006, p. 504 TFDA, Chinese Taipei - Implemented; Date: 3 January 2002; Reference: 1.Regulation for Registration for Biotechnological Products for Human Use
2. Guidance for Specifications: Test Procedures and Acceptance Criteria for Biotechnological/ Biological Products TITCK, Türkiye - Implemented; Date: 11 December 2021;

Guideline Q6B Guideline

Q6(R1) EWG Revision of the Specifications Guidelines

This topic was endorsed by the ICH Assembly in June 2021.

Further to the ICH Management Committee’s endorsement of the Q6(R1) Concept Paper in July 2024, the Q6(R1) Guideline aims to update and modernise simultaneously the ICH Q6A and Q6B guidelines by promoting consistency between ICH Q6A and Q6B and establish general principles in setting specifications for all product modalities; aligning with other relevant ICH guidelines and current approaches; and revising the scope of the guideline to incorporate contemporary modalities. In addition, the Q6(R1) EWG aims to develop complementary training material with relevant examples/case studies.

Rapporteur: Ms. Silmara Cristiane da Silveira Andreoli (ANVISA, Brazil)

Rapporteur: Dr. Olivier Dirat (PhRMA)

Regulatory Chair: Dr. Robin Levis (FDA, United States)

Endorsed Documents Q6(R1) Concept Paper Q6(R1) Work Plan
WG list

Q7 Good Manufacturing Practice

Q7 Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients

The ICH Harmonised Guideline was finalised under Step 4 in November 2000. This document is intended to provide guidance regarding Good Manufacturing Practice (GMP) for the manufacturing of Active Pharmaceutical Ingredients (APIs) under an appropriate system for managing quality. It is also intended to help ensure that APIs meet the requirements for quality and purity that they purport or are represented to possess.

This Guideline applies to the manufacture of APIs for use in human drug (medicinal) products. It applies to the manufacture of sterile APIs only up to the point immediately prior to the APIs being rendered sterile. The sterilization and aseptic processing of sterile APIs are not covered by this guidance, but should be performed in accordance with GMP guidelines for drug (medicinal) products as defined by local authorities.

Date of Step 4:

10 November 2000

Status: Step 5

Implementation status:

ANMAT, Argentina - Implemented; Date: 28 July 2023; Reference: ANMAT Regulation 4159/2023 ANVISA, Brazil - Implemented; Date: 1 December 2014; Reference: RDC 654/2022 COFEPRIS, Mexico - Implemented; Date: 1 September 2016; Reference: NOM-164-SSA1-2015 EC, Europe - Implemented; Date: 1 November 2000; Reference: CPMP/ICH/4106/00 EDA, Egypt - Implemented; Date: 1 January 2005; FDA, United States - Implemented; Date: 1 September 2001; Reference: Vol. 66, No. 186, p. 49028-9 HSA, Singapore - Implemented; Date: 22 May 2001; Health Canada, Canada - Implemented; Date: 7 December 2002; Reference: Guide GUI-0104 JFDA, Jordan - Implemented; Date: 1 January 2007; MFDS, Republic of Korea - Implemented; Date: 16 February 2015; Reference: Regulation on Pharmaceutical Good Manufacturing Practice [MFDS, Republic of Korea Notification No.2015-35]; Guidance on Good Manufacturing Practices for Active Pharmaceutical Ingredients[Guideline-0042-01] MHLW/PMDA, Japan - Implemented; Date: 1 November 2001; Reference: PMSB/ELD Notification No. 1200 MHRA, UK - Implemented; Date: 7 December 1995; NMPA, China - Implemented; Date: 31 December 2015; Reference: Good Manufacturing Practice(2010 Revision, Order No.79 of the Ministry of Health)
Notice on Implementation of Good Manufacturing Practice(2010 Revision), No. 101 of CFDA, 2011 SFDA, Saudi Arabia - Implemented; Date: 26 July 2011; Swissmedic, Switzerland - Implemented; Date: 1 May 2001; Reference: ICH Guidelines apply in Switzerland automatically upon reaching Step 4: Swissmedic Journal 05/2006, p. 504 TFDA, Chinese Taipei - Implemented; Date: 22 May 2013; Reference: 1.Regulation for Pharmaceutical Good Manufacturing Practice
2.Public Announcement for API of Biological Products should comply with GMP TITCK, Türkiye - Implemented;

Guideline Q7 Guideline

Endorsed Document Q7 Concept Paper

Q7 Q&As Questions and Answers: Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients

The document was finalised under Step 4 in June 2015.

Experience gained with the implementation of the ICH Q7 Guideline since its finalisation in 2000 showed that uncertainties related to the interpretation of some sections exist.

Technical issues with regard to GMP of APIs – also in context with new ICH Guidelines - are addressed in this Questions and Answers document in order to harmonise expectations during inspections, to remove ambiguities and uncertainties, and to harmonise the inspections of both small molecules and biotech APIs.

Date of Step 4:

10 June 2015

Status: Step 5

Implementation status:

ANMAT, Argentina - Not yet implemented; ANVISA, Brazil - Implemented; Date: 11 March 2020; Reference: Perguntas & Respostas: RDC 69/14 - Boas Práticas de Fabricação de Insumos Farmacêuticos Ativos COFEPRIS, Mexico - Implemented; Date: 30 July 2024; Reference: Questions and Answers Guide for the Official Mexican Standard NOM-164-SSA1-2015 Good Mnufacturing Practices for Active Pharmaceutical Ingredients EC, Europe - Implemented; Date: 1 February 2016; Reference: CHMP/ICH/468930/2015 EDA, Egypt - Implemented; Date: 1 January 2022; FDA, United States - Implemented; Date: 1 April 2018; Reference: Vol. 83, No. 77 p. 17556-17557 HSA, Singapore - Implemented; Date: 1 June 2015; Health Canada, Canada - Implemented; Date: 10 June 2016; Reference: File # 16-106660-852 JFDA, Jordan - Not yet implemented; MFDS, Republic of Korea - Implemented; Date: 5 September 2018; Reference: ICH Q7 Q&A [Guideline-0888-01] MHLW/PMDA, Japan - Implemented; Date: 1 March 2016; Reference: PSEHB/CND Administrative Notice MHRA, UK - Implemented; Date: 8 December 1995; NMPA, China - Implemented; Date: 31 December 2015; Reference: Good Manufacturing Practice(2010 Revision, Order No.79 of the Ministry of Health)
Notice on Implementation of Good Manufacturing Practice(2010 Revision), No. 101 of CFDA, 2011 annexs: computerized system validation and verification(published by CFDI )(2015) SFDA, Saudi Arabia - Implemented; Date: 26 July 2011; Swissmedic, Switzerland - Implemented; Date: 23 July 2015; Reference: Swissmedic, Switzerland press release TFDA, Chinese Taipei - Implemented; Date: 22 May 2013; Reference: 1.Regulation for Pharmaceutical Good Manufacturing Practice
2.Public Announcement for API of Biological Products should comply with GMP TITCK, Türkiye - Not yet implemented;

Questions & Answers Q7 Q&As Questions & Answers

Endorsed Document Q7 Q&As Concept Paper

WG Presentations / Trainings Q7 Q&As Step 4 Presentation

Q8 Pharmaceutical Development

Q8(R2) Pharmaceutical Development

The core ICH Harmonised Guideline was finalised under Step 4 in November 2005.

This Guideline is intended to provide guidance on the contents of Section 3.2.P.2 (Pharmaceutical Development) for drug products as defined in the scope of Module 3 of the Common Technical Document (ICH topic M4). The guideline does not apply to contents of submissions for drug products during the clinical research stages of drug development. However, the principles in this guideline are important to consider during these stages. This guideline might also be appropriate for other types of products. To determine the applicability of this guideline for a particular type of product, applicants should consult with the appropriate regulatory authorities.

The annex to the Harmonised ICH text was finalised under Step 4 in November 2008 and incorporated into the core Guideline, which was then renamed Q8(R1). The annex provides further clarification of key concepts outlined in the core Guideline. In addition, this annex describes the principles of quality by design (QbD). The annex is not intended to establish new standards: however, it shows how concepts and tools (e.g., design space) outlined in the parent Q8 document could be put into practice by the applicant for all dosage forms. Where a company chooses to apply quality by design and quality risk management (Q9: Quality Risk Management), linked to an appropriate pharmaceutical quality system, then opportunities arise to enhance science- and risk-based regulatory approaches (see Q10: Pharmaceutical Quality System).

The Q8(R1) Guideline was revised in August 2009 to reflect minor corrections to Example 2 on page 23 (Q8(R2)).

Date of Step 4:

1 August 2009

Status: Step 5

Implementation status:

ANMAT, Argentina - Not yet implemented; ANVISA, Brazil - Implemented; Date: 1 October 2024; Reference: RESOLUÇÃO RDC Nº 658/2022 COFEPRIS, Mexico - Not yet implemented; EC, Europe - Implemented; Date: 1 August 2009; Reference: CHMP/ICH/167068/2004 EDA, Egypt - Implemented; Date: 31 December 2015; Reference: (Regulatory guide for mechanisms, procedures and rules of implementing the decree of Egyptian Drug Authority No.343 of 2021) and (Egyptian Guidelines on CTD Quality Module for Human Pharmaceuticals) FDA, United States - Implemented; Date: 1 November 2009; Reference: Vol. 71, No. 98 HSA, Singapore - Implemented; Date: 1 January 2013; Reference: Reference made to these guidelines in Draft ASEAN Guidance for Quality By Design as an Alternative Approach to Process Validation which is adopted and published on HSA, Singapore website Health Canada, Canada - Implemented; Date: 11 February 2016; Reference: File #: 16-101390-659 JFDA, Jordan - Implemented; Date: 1 January 2016; MFDS, Republic of Korea - Implemented; Date: 28 November 2018; Reference: Quality Review Guidance for the Introduction of Quality by Design [Guideline-0214-02] MHLW/PMDA, Japan - Implemented; Date: 1 June 2010; Reference: PFSB/ELD Notification No. 0628-1 MHRA, UK - Implemented; Date: 9 December 1995; NMPA, China - Implemented; Date: 21 January 2020; Reference: NMPA, China Announcement No. 6 (2020) SFDA, Saudi Arabia - Implemented; Date: 26 July 2011; Swissmedic, Switzerland - Implemented; Date: 1 August 2009; Reference: ICH Guidelines apply in Switzerland automatically upon reaching Step 4: Swissmedic Journal 05/2006, p. 504 TFDA, Chinese Taipei - Implemented; Date: 22 December 2014; Reference: 1. Updated-Guide to Good Manufacturing Practice for Medicinal Products
2. Updated-Announcement for ICH Guidelines Recognition List TITCK, Türkiye - Not yet implemented;

Guideline Q8(R2) Guideline

Endorsed Document Q8(R2) Concept Paper

WG Presentations/Trainings ICH Q8/Q9/Q10 Training Material

Q8/9/10 Q&As (R5) Q8/Q9/Q10 - Implementation

Since reaching Step 4 and publication within the ICH regions, experiences by all parties with the implementation of the ICH Q8(R2), Q9 and Q10 Guidelines have resulted in the need for some clarification. The Questions and Answers developed by the Quality Implementation Working Group (IWG) are intended to facilitate the implementation of the Q8(R2), Q9 and Q10 Guidelines, by clarifying key issues.

The document with the first set of Q&As was finalised under Step 4 in April 2009. Since then, new sets of questions were added three times, with the most recent version (Q8/Q9/Q10 Q&As (R4)) approved by the Steering Committee in November 2010. The ICH Quality IWG also prepared “Points to Consider” covering topics relevant to the implementation of Q8(R2), Q9 and Q10, which supplement the existing Questions & Answers and workshop training materials already produced by this group.

The document with the first and second set of Points to Consider was finalised in June and November 2011, respectively.

In October 2024 the Q&As were updated to Q8/Q9/Q10 Questions & Answers (R5) by removing outdated text and rephrasing the Q&As considered in view of the implementation of ICH Q8, Q9 and Q10, with minor additions to address minor content gaps in the document. Furthermore, minor edits have been made to improve the readability of the document.

Date of Step 4:

11 November 2010

Status: Step 5

Implementation status:

ANMAT, Argentina - Not yet implemented; ANVISA, Brazil - Not yet implemented; EC, Europe - Implemented; Date: 3 February 2025; Reference: EMA/CHMP/ICH/265145/2009 EDA, Egypt - Implemented; Date: 1 February 2025; Reference: Adoption of The International Council for
Harmonizations (ICH);
Quality Guidelines Notice to Applicant FDA, United States - Not yet implemented; HSA, Singapore - Implemented; Date: 1 January 2013; Health Canada, Canada - Not yet implemented; JFDA, Jordan - Not yet implemented; MFDS, Republic of Korea - Not yet implemented; MHLW/PMDA, Japan - Not yet implemented; MHRA, UK - Not yet implemented; NMPA, China - In the process of implementation; SFDA, Saudi Arabia - Implemented; Swissmedic, Switzerland - Implemented; Date: 1 November 2010; Reference: ICH Guidelines apply in Switzerland automatically upon reaching Step 4: Swissmedic Journal 05/2006, p. 504 TFDA, Chinese Taipei - Implemented; Date: 19 June 2025; Reference: 1. Updated-Guide to Good Manufacturing Practice for Medicinal Products
2. Updated-Announcement for ICH Guidelines Recognition List

Questions & Answers Q8/Q9/Q10 Q&As (R5) Questions & Answers

Other Document Q8/Q9/Q10 Q&As (R2) Points to Consider

Endorsed Document Q8/Q9/Q10 Q&As (R4) Concept Paper

WG Presentations/Trainings ICH Q8/Q9/Q10 Training Material

Q9 Quality Risk Management

Q9(R1) Quality Risk Management

The ICH Q9(R1) Guideline reached Step 4 of the ICH process on 18 January 2023.

The ICH Q9(R1) Quality Risk Management Guideline is intended to provide guidance on the principles and examples of tools for quality risk management that can be applied to different aspects of pharmaceutical quality and make limited and specific adjustments to specific chapters and annexes of the current ICH Q9 Guideline on Quality Risk Management (QRM).

Further to reaching Step 4 Guideline adoption, the WG continues to work to develop specific training materials (with examples) to supplement the existing ICH briefing pack on ICH Q9, as well as to explain and facilitate the implementation and application of the proposed revisions.

Further information can be found in the Q9(R1) Concept Paper and Business Plan.

Date of Step 4:

18 January 2023

Status: Step 5

Implementation status:

ANMAT, Argentina - Not yet implemented; ANVISA, Brazil - Implemented; Date: 19 July 2023; Reference: Guia nº 62/2023 versão 01 COFEPRIS, Mexico - Implemented; Date: 3 August 2016; Reference: Mexican Official Standard NOM-059-SSA1-2015, Good Manufacturing Practices for Drugs EC, Europe - Implemented; Date: 26 July 2023; Reference: EMA/CHMP/ICH/24235/2006 EDA, Egypt - Implemented; Date: 9 November 2023; Reference: (Guideline for Registration of Biosimilar Products
in Egypt) and (Adoption of The International Council for
Harmonizations (ICH);
Quality Guidelines Notice to Applicant) FDA, United States - Implemented; Date: 4 May 2023; Reference: Vol. 88 pg. 28565-28566 HSA, Singapore - In the process of implementation; Health Canada, Canada - In the process of implementation; JFDA, Jordan - Not yet implemented; MFDS, Republic of Korea - In the process of implementation; Date: 31 December 2024; MHLW/PMDA, Japan - Implemented; Date: 11 November 2025; Reference: PSEHB/PED Notification No. 0831-1 & PSEHB/CND Notification No. 0831-2 MHRA, UK - Implemented; NMPA, China - Implemented; Date: 4 March 2024; Reference: NMPA, China Announcement No. 114 (2023) SFDA, Saudi Arabia - Implemented; Date: 26 July 2011; Swissmedic, Switzerland - Implemented; Date: 18 January 2023; Reference: ICH Guidelines apply in Switzerland automatically upon reaching Step 4: Swissmedic Journal 05/2006, p. 504 TFDA, Chinese Taipei - Implemented; TITCK, Türkiye - Not yet implemented;

Guideline Q9(R1) Guideline

Endorsed Documents Q9(R1) Concept Paper Q9(R1) Business Plan Q9(R1) Work Plan

WG Presentations / Trainings Q9(R1) Step 4 Presentation Q9(R1) Training Materials

Q9(R1) IWG 2006-2010 Training on Quality Risk Management

Further to the ICH Management Committee’s endorsement of the Q9(R1) IWG Concept Paper in April 2023, the Q9(R1) IWG was established to review and update the existing training materials in relation to Quality Risk Management (QRM). These materials, include a) the ICH Q9 Briefing Pack and b) the ICH Q8/Q9/Q10 Training Material which were developed in 2006-2010.

The objective of this IWG would be to:

Address the discrepancies and conflicts that exist between these training materials and the revised ICH Q9(R1) Guideline;
Address discrepancies and conflicts between the 2006-2010 training materials and the new training materials that were finalised by the ICH Q9(R1) Expert Working Group (EWG) in 2023 to reflect the changes that were made to the Guideline. Further information can be found in the Q9(R1) IWG Concept Paper.

Endorsed Documents Q9(R1) Concept Paper

Q9(R1) Training Group Quality Risk Management

Further to the Q9(R1) IWG completion of updates and revisions to the Q8/Q9/Q10 Training materials, the Q9(R1) Training Group was established in August 2024 to review and develop the Q9 Briefing Pack training materials.

Rapporteur: Dr. Kevin James O'Donnell (EC, Europe)

Regulatory Chair: Mr. Alex Viehmann (FDA, United States)

Endorsed Documents Q9(R1) Training Group Work Plan
WG list

Q8/9/10 Q&As (R5) Q8/Q9/Q10 - Implementation

The document with the first and second set of Points to Consider was finalised in June and November 2011, respectively.

Date of Step 4:

11 November 2010

Status: Step 5

Implementation status:

Questions & Answers Q8/Q9/Q10 Q&As (R5) Questions & Answers

Other Document Q8/Q9/Q10 Q&As (R2) Points to Consider

Endorsed Document Q8/Q9/Q10 Q&As (R4) Concept Paper

WG Presentations/Trainings ICH Q8/Q9/Q10 Training Material

Q10 Pharmaceutical Quality System

The ICH Harmonised Guideline was finalised under Step 4 in June 2008.

This Guideline applies to the systems supporting the development and manufacture of pharmaceutical drug substances and drug products, including biotechnology and biological products, throughout the product lifecycle.

The elements of Q10 should be applied in a manner that is appropriate and proportionate to each of the product lifecycle stages, recognising the differences among, and the different goals of each stage.

Date of Step 4:

4 June 2008

Status: Step 5

Implementation status:

ANMAT, Argentina - Not yet implemented; ANVISA, Brazil - Implemented; Date: 21 August 2019; Reference: RESOLUÇÃO RDC Nº 658/2022 COFEPRIS, Mexico - Implemented; Date: 3 August 2016; Reference: Mexican Official Standard NOM-059-SSA1-2015, Good Manufacturing Practices for Drugs EC, Europe - Implemented; Date: 1 June 2008; Reference: CHMP/ICH/214732/2007 EDA, Egypt - Implemented; Date: 31 December 2020; Reference: Guideline for Registration of Biosimilar Products
in Egypt FDA, United States - Implemented; Date: 1 April 2009; Reference: Vol. 74, No. 66, p. 15990-1 HSA, Singapore - Implemented; Date: 1 January 2013; Reference: Reference made to these guidelines in Draft ASEAN Guidance for Quality By Design as an Alternative Approach to Process Validation which is adopted and published on HSA, Singapore website Health Canada, Canada - Implemented; Date: 15 February 2016; Reference: File #: 16-101419-273 JFDA, Jordan - Implemented; Date: 7 January 2008; MFDS, Republic of Korea - Implemented; Date: 5 September 2018; Reference: Guideline on Pharmaceutical Quality System [Guideline-0889-01] MHLW/PMDA, Japan - Implemented; Date: 1 February 2010; Reference: PFSB/ ELD Notification No. 0219-1 & PFSB/ NCD Notification No. 0219-1 MHRA, UK - Implemented; Date: 1 July 2008; NMPA, China - Implemented; Date: 21 January 2020; Reference: NMPA, China Announcement No. 6 (2020) SFDA, Saudi Arabia - Implemented; Date: 26 July 2011; Swissmedic, Switzerland - Implemented; Date: 4 June 2008; Reference: ICH Guidelines apply in Switzerland automatically upon reaching Step 4: Swissmedic Journal 05/2006, p. 504 TFDA, Chinese Taipei - Implemented; Date: 22 December 2014; Reference: Public Announcement for ” List for ICH Guidelines Adopted.” TITCK, Türkiye - Not yet implemented;

Guideline Q10 Guideline

Endorsed Documents Q10 Concept Paper Q10 Business Plan

WG Presentations / Trainings Q10 Presentation ICH Q8/Q9/Q10 Training Material

Q8/9/10 Q&As (R5) Q8/Q9/Q10 - Implementation

The document with the first and second set of Points to Consider was finalised in June and November 2011, respectively.

Date of Step 4:

11 November 2010

Status: Step 5

Implementation status:

Questions & Answers Q8/Q9/Q10 Q&As (R5) Questions & Answers

Other Document Q8/Q9/Q10 Q&As (R2) Points to Consider

Endorsed Document Q8/Q9/Q10 Q&As (R4) Concept Paper

WG Presentations/Trainings ICH Q8/Q9/Q10 Training Material

Q11 Development and Manufacture of Drug Substances

Q11 Development and Manufacture of Drug Substances (Chemical Entities and Biotechnological/Biological Entities)

The Guideline reached Step 4 of the ICH process on 1 May 2012.

This Guideline describes approaches to developing and understanding the manufacturing process of the drug substance, and also provides guidance on what information should be provided in Module 3 of the Common Technical Document (CTD) Sections 3.2.S.2.2 – 3.2.S.2.6 (ICH M4Q). It addresses aspects of development and manufacture that pertain to drug substance, including the presence of steps designed to reduce impurities.

This Guideline is applicable to drug substances as defined in the Scope sections of ICH Guidelines Q6A and Q6B but might also be appropriate for other types of products following consultation with the appropriate regulatory authorities.

Date of Step 4:

1 May 2012

Status: Step 5

Implementation status:

ANMAT, Argentina - Not yet implemented; ANVISA, Brazil - Implemented; Date: 3 August 2020; Reference: RDC 359/2020 and RDC 753/2022 and RDC Nº 658/2022 COFEPRIS, Mexico - In the process of implementation; Date: 2 August 2016; Reference: Mexican Official Standard NOM-164-SSA1-2015 Good Mnufacturing Practices for Active Pharmaceutical Ingredients EC, Europe - Implemented; Date: 1 November 2012; Reference: CHMP/ICH/425213/2011 EDA, Egypt - Implemented; Date: 31 December 2020; Reference: Guideline for Registration of Biosimilar Products
in Egypt FDA, United States - Implemented; Date: 1 November 2012; Reference: Vol. 77, No. 224, p. 69634-5 HSA, Singapore - Implemented; Date: 1 January 2013; Reference: Reference made to these guidelines in Draft ASEAN Guidance for Quality By Design as an Alternative Approach to Process Validation which is adopted and published on HSA, Singapore website Health Canada, Canada - Implemented; Date: 12 February 2016; Reference: File #: 16-100199-626 JFDA, Jordan - Implemented; Date: 2 January 2016; MFDS, Republic of Korea - Implemented; Date: 20 July 2017; Reference: Guideline of Development and Manufacture of Drug Substances [Guideline-0218-02] MHLW/PMDA, Japan - Implemented; Date: 1 July 2014; Reference: PFSB/ELD Notification No. 0710-9 MHRA, UK - Implemented; Date: 1 May 2012; NMPA, China - Implemented; Date: 21 January 2020; Reference: NMPA, China Announcement No. 6 (2020) SFDA, Saudi Arabia - Implemented; Date: 26 July 2011; Swissmedic, Switzerland - Implemented; Date: 1 May 2012; Reference: ICH Guidelines apply in Switzerland automatically upon reaching Step 4: Swissmedic Journal 05/2006, p. 504 TFDA, Chinese Taipei - Implemented; Date: 22 December 2014; Reference: Public Announcement for ” List for ICH Guidelines Adopted.” TITCK, Türkiye - Not yet implemented;

Guideline Q11 Guideline

Endorsed Documents Q11 Concept Paper Q11 Business Plan

WG Presentations / Trainings Q11 Training Material

Q11 Q&As Questions & Answers: Selection and Justification of Starting Materials for the Manufacture of Drug Substances

Since reaching Step 4 in 2012, worldwide experience with implementation of the ICH Q11 Guideline and its recommendations on the development and manufacture of drug substances has given rise to requests for clarification relating to the selection and justification of starting materials.

The Q11 Implementation Working Group (IWG), established by ICH in 2014, developed a Questions and Answers (Q&A) document which reached Step 4 of the ICH Process in August 2017.

These Q&As are intended to provide additional clarification, and to promote convergence and improve harmonisation of the considerations for the selection and justification of starting materials and on the information that should be provided in marketing authorisation applications and/or Master Files.

The focus of the Q&A document is on chemical entity drug substances. Training materials and a training video on Q11 Q&As are also available.

Date of Step 4:

23 August 2017

Status: Step 5

Implementation status:

ANMAT, Argentina - Not yet implemented; ANVISA, Brazil - Implemented; Date: 3 August 2020; Reference: RDC 359/2020 and RDC 753/2022 and RDC Nº 658/2022 COFEPRIS, Mexico - Not yet implemented; EC, Europe - Implemented; Date: 28 February 2018; Reference: CHMP/ICH/809509/2016 EDA, Egypt - Implemented; Date: 31 December 2020; Reference: Guideline for Registration of Biosimilar Products
in Egypt FDA, United States - Implemented; Date: 26 February 2018; Reference: Vol. 83, No. 38, p. 8279-8280 HSA, Singapore - Implemented; Date: 4 January 2021; Health Canada, Canada - Implemented; Date: 4 April 2018; Reference: File #: 18-103369-70 JFDA, Jordan - Not yet implemented; MFDS, Republic of Korea - Implemented; Date: 5 July 2018; Reference: Questions and Answers of Development and Manufacturing of Drug Substance [Guideline-0874-01] MHLW/PMDA, Japan - Implemented; Date: 14 September 2018; Reference: PSEHB/PELD Administrative Notice MHRA, UK - Implemented; Date: 1 March 2018; NMPA, China - Implemented; Date: 21 January 2020; Reference: NMPA, China Announcement No. 6 (2020) SFDA, Saudi Arabia - Implemented; Swissmedic, Switzerland - Implemented; Date: 23 August 2017; TFDA, Chinese Taipei - Implemented; Date: 4 December 2017; Reference: Updated-Announcement for ICH Guidelines Recognition List TITCK, Türkiye - Not yet implemented;

Questions & Answers Q11 Q&As Questions & Answers

Endorsed Documents Q11 Q&As Concept Paper Q11 Q&As Business Plan

WG Presentations / Trainings Q11 Q&As Step 4 Presentation Q11 Q&As Training Material Q11 - training video (mp4) Q11 - training video (youtube)

Q12 Lifecycle Management

Q12 Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management

This topic was endorsed by the ICH Steering Committee in September 2014.

This new Guideline is proposed to provide a framework to facilitate the management of post-approval Chemistry, Manufacturing and Controls (CMC) changes in a more predictable and efficient manner across the product lifecycle.

Adoption of this new ICH Guideline will promote innovation and continual improvement in the biopharmaceutical sector, and strengthen quality assurance and reliable supply of product, including proactive planning of supply chain adjustments. It will allow regulators (assessors and inspectors) to better understand the firms’ Pharmaceutical Quality Systems (PQSs) for management of post-approval CMC changes.

This new Guideline is intended to complement the existing ICH Q8 to Q11 Guidelines, and is composed of a core Guideline and Annexes.

Date of Step 4:

20 November 2019

Status: Step 5

Implementation status:

ANMAT, Argentina - Not yet implemented; ANVISA, Brazil - In the process of implementation; Date: 1 November 2029; Reference: RDC 690/2022 COFEPRIS, Mexico - In the process of implementation; Date: 24 August 2023; Reference: Modifications to the registration conditions EC, Europe - In the process of implementation; Reference: EMA/CHMP/ICH/804273/2017,EMA/CHMP/ICH/831751/2017,EMA/CHMP/ICH/78332/2020 EDA, Egypt - Not yet implemented; FDA, United States - Implemented; Date: 11 May 2021; Reference: Posted on FDA, US website HSA, Singapore - In the process of implementation; Health Canada, Canada - In the process of implementation; Reference: File #: 25-105890-674 JFDA, Jordan - Not yet implemented; MFDS, Republic of Korea - In the process of implementation; Date: 1 December 2026; MHLW/PMDA, Japan - Implemented; Date: 29 October 2021; Reference: PSEHB/PED Notification No. 1029-1 & PSEHB/CND Notification No. 1029-1 MHRA, UK - In the process of implementation; NMPA, China - Implemented; Date: 25 August 2023; Reference: NMPA, China Announcement No. 108 (2023) SFDA, Saudi Arabia - Not yet implemented; Swissmedic, Switzerland - In the process of implementation; TFDA, Chinese Taipei - In the process of implementation; TITCK, Türkiye - Not yet implemented;

Guideline Q12 Guideline Q12 Annexes

Endorsed Documents Q12 Business Plan Q12 Concept Paper

WG Presentations / Trainings Q12 Step 4 Presentation

Q12 Training on Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management

Further to the Q12 Guideline reaching Step 4 in November 2019, the Q12 IWG was established to prepare a comprehensive training programme and associated materials to facilitate an aligned interpretation and a harmonized implementation of ICH Q12 in ICH and non-ICH regions.

Endorsed Documents Q12 IWG Concept Paper

Training Materials Q12 Training Material Modules 0-8 Q12 Training Material Video Q12 Training Material Video Subtitles

Q13 Continuous Manufacturing of Drug Substances and Drug Products

The ICH Q13 Guideline reached Step 4 of the ICH process on 16 November 2022.

The guideline:

Builds on existing ICH Quality Guidelines, provides clarification on continuous manufacturing (CM) concepts, describes scientific approaches, and presents regulatory considerations specific to CM of drug substances and drug products;
Focuses on the integrated aspects of a CM system in which two or more unit operations are directly connected;
Describes scientific and regulatory considerations for the development, implementation, operation, and lifecycle management of CM. Date of Step 4:

16 November 2022

Status: Step 5

Implementation status:

ANMAT, Argentina - Not yet implemented; ANVISA, Brazil - Implemented; Date: 11 January 2024; Reference: Guia nº 71/2024 v.01 COFEPRIS, Mexico - In the process of implementation; Date: 1 September 2016; Reference: Mexican Official Standard NOM-164-SSA1-2015 Good Mnufacturing Practices for Active Pharmaceutical Ingredients; Mexican Official Standard NOM-059-SSA1-2015, Good Manufacturing Practices for Drugs EC, Europe - Implemented; Date: 10 July 2023; Reference: EMA/CHMP/ICH/427817/2021 EDA, Egypt - Implemented; Date: 25 September 2024; Reference: Regulatory guide for mechanisms, procedures and rules of implementing the decree of Egyptian Drug Authority No.343 of 2021 FDA, United States - Implemented; Date: 1 March 2023; Reference: Vol. 88, No. 40, p. 12941-12942 HSA, Singapore - In the process of implementation; Health Canada, Canada - Implemented; Date: 27 June 2025; Reference: File #: 25-102237-854 JFDA, Jordan - Not yet implemented; MFDS, Republic of Korea - Implemented; Date: 26 October 2023; Reference: Guideline of Continuous Manufacturing of Drug Substances and Drug Products [Guideline-1310-01] MHLW/PMDA, Japan - Implemented; Date: 31 May 2023; Reference: PSEHB/PED Notification No. 0531-1 MHRA, UK - In the process of implementation; NMPA, China - Implemented; Date: 13 June 2024; Reference: NMPA, China Announcement No. 158 (2023) SFDA, Saudi Arabia - Implemented; Swissmedic, Switzerland - Implemented; Date: 16 November 2022; Reference: ICH Guidelines apply in Switzerland automatically upon reaching Step 4: Swissmedic Journal 05/2006, p. 504 TFDA, Chinese Taipei - Implemented; TITCK, Türkiye - Not yet implemented;

Guideline Q13 Guideline

Endorsed Documents Q13 Business Plan Q13 Concept Paper

WG Presentations / Trainings Q13 Step 4 Presentation

Q13 Training on Continuous Manufacturing of Drug Substances and Drug Products

The Q13 Training Modules 1-12 aim to facilitate an aligned interpretation and a harmonised implementation of the ICH Q13 Continuous Manufacturing of Drug Substances and Drug Products Guideline in ICH and non-ICH regions by:

Illustrating the general concept of Continuous Manufacturing (CM) process operation;
Providing detailed clarification of novel scientific concepts and regulatory expectations pertinent to CM;
Expanding discussion of Annex I-V in Q13 to address some specific CM implementation aspects relevant for different modalities.
Further information can be found in the Q13 IWG Concept Paper and Video Training Modules 1-12:
Module 1: Introduction and Training Overview
Module 2: Batch Definition and Batch Size
Module 3: State of Control and Steady State
Module 4: Principles of Process Dynamics and Residence Time Distribution
Module 5: Case-studies on Process Dynamics, Material Traceability, and Sampling Frequency
Module 6: Case-studies on RTD Model Development and Setting Alarm Limits
Module 7: General Pharmaceutical Quality System (PQS) Considerations for Continuous Manufacturing (CM)
Module 8: Demonstration of Material Diversion
Module 9: Process Monitoring and Control
Module 10: Process Models
Module 11: Drug Substance and Drug Product Stability
Module 12: Batch to CM Conversion for Small Molecule Oral Solid

Endorsed Documents Q13 IWG Concept Paper

WG Presentations / Trainings Q13 Module 1 Q13 Module 2 Q13 Module 3 Q13 Module 4 Q13 Module 5 Q13 Module 6 Q13 Module 7 Q13 Module 8 Q13 Module 9 Q13 Module 10 Q13 Module 11 Q13 Module 12

Q14 Analytical Procedure Development

The ICH Q14 Guideline reached Step 4 of the ICH process on 1 November 2023.

The Q14 EWG developed a new ICH Quality Guideline, ICH Q14, on Analytical Procedure Development.

Q14 Analytical Procedure Development Guideline

The new guideline harmonises the scientific approaches of Analytical Procedure Development and provides the principles relating to the description of Analytical Procedure Development process. This new guideline intends to improve regulatory communication between industry and regulators and facilitate more efficient, sound scientific and risk-based approval as well as post-approval change management of analytical procedures.

Date of Step 4:

1 November 2023

Status: Step 5

Implementation status:

ANMAT, Argentina - Not yet implemented; ANVISA, Brazil - Not yet implemented; COFEPRIS, Mexico - Not yet implemented; EC, Europe - Implemented; Date: 14 June 2024; Reference: EMA/CHMP/ICH/195040/2022 EDA, Egypt - Implemented; Date: 25 September 2024; Reference: Regulatory guide for mechanisms, procedures and rules of implementing the decree of Egyptian Drug Authority No.343 of 2021 FDA, United States - Implemented; Date: 7 March 2024; Reference: 89 FR 16582 HSA, Singapore - In the process of implementation; Health Canada, Canada - Implemented; Date: 12 January 2026; Reference: File#: 25-105890-674 JFDA, Jordan - Not yet implemented; MFDS, Republic of Korea - In the process of implementation; Date: 1 December 2027; MHLW/PMDA, Japan - Implemented; Date: 9 October 2025; Reference: PSB/ PED Notification No. 1009-2 MHRA, UK - In the process of implementation; NMPA, China - Implemented; Date: 24 November 2024; Reference: NMPA, China Announcement No.65(2024) SFDA, Saudi Arabia - Not yet implemented; Swissmedic, Switzerland - Implemented; Date: 1 November 2023; Reference: ICH Guidelines apply in Switzerland automatically upon reaching Step 4: Swissmedic Journal 05/2006, p. 504 TFDA, Chinese Taipei - Not yet implemented; TITCK, Türkiye - Implemented; Date: 1 July 2014; Reference: NA

Guideline Q14 Guideline

Endorsed Documents Q2(R2)/Q14 Concept Paper Q2(R2)/Q14 Business Plan

WG Presentations/ Trainings Q2(R2)/Q14 Step 4 Presentation

Q2(R2)/Q14 Training on Validation of Analytical Procedures and Q14: Analytical Procedure Development

Illustrating the general concepts of ICH Q2(R2) and Q14;
Providing more depth to the discussion of the Annexes in ICH Q2(R2) and Q14 to address some specific implementation aspects relevant for different cases; Further information can be found in the Q2(R2)/Q14 IWG Concept Paper

Endorsed Documents Q2(R2)/Q14 IWG Concept Paper

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Source

ICH Guidelines News ich.org/page/articles-press-releases

Pharma Standards

Analysis generated by AI. Source diff and links are from the original.

Classification

Agency

Various

Published

February 6th, 2003

Instrument

Guidance

Legal weight

Non-binding

Stage

Final

Change scope

Minor

Who this affects

Applies to

Drug manufacturers Pharmaceutical companies

Geographic scope

International

Taxonomy

Primary area

Pharmaceuticals

Operational domain

Compliance

Topics

Drug Manufacturing Quality Control

Browse Categories

Federal Courts 26 State Courts 91 Securities Regulation 6 Financial Regulation 43 Consumer Protection 5 Drug Safety 45 Data Protection 21 Competition 2 Attorneys General 3 Insurance Regulation 5 Trade & Export 36 Legislation 42 Energy Regulation 13 Environment 3 Labor & Employment 2 Tax 1

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ICH Q1A(R2) Stability Testing Guideline Finalized

Summary

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What to do next

Source document (simplified)

Quality Guidelines

Q1A - Q1F Stability

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Q2 Analytical Validation

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Q4A - Q4B Pharmacopoeias

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Q5A - Q5E Quality of Biotechnological Products

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Q6A- Q6B Specifications

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Q7 Good Manufacturing Practice

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Q8 Pharmaceutical Development

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Q9 Quality Risk Management

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Q10 Pharmaceutical Quality System

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Q11 Development and Manufacture of Drug Substances

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Q12 Lifecycle Management

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Q13 Continuous Manufacturing of Drug Substances and Drug Products

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Q14 Analytical Procedure Development

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