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.
Zip with all ICH Quality Guidelines in word format

  • Q1A - Q1F Stability

    Code Document Title Previously coded
    • Finalised Guideline:
      February 2003

      Description:

      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.

      Implementation:

      Step 5

      EU:

      Adopted by CPMP, March 2003, issued as CPMP/ICH/2736/99

      MHLW:

      Adopted 3 June 2003, PFSB/ELD Notification No. 0603001

      FDA:

      Published in the Federal Register, 21 November 2003, Vol. 68, No. 225, p. 65717-18

    • Finalised Guideline:
      November 1996

      Description:

      The tripartite harmonised ICH Guideline was finalised under Step 4 in November 1996. This forms 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.

      Implementation:

      Step 5

      EU:

      Adopted by CPMP, December 1996, issued as CPMP/ICH/279/95

      MHLW:

      Adopted May 1997, PAB/PCD Notification No. 422

      FDA:

      Published in the Federal Register, 16 May 1997, Vol. 62, No. 95, p. 27115-27122

    • Finalised Guideline:
      November 1996

      Description:

      The tripartite harmonised ICH 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.

      Implementation:

      Step 5

      EU:

      Adopted by CPMP, December 1996, issued as CPMP/ICH/280/95

      MHLW:

      Adopted May 1997, PAB/PCD Notification No. 425

      FDA:

      Published in the Federal Register, 9 May 1997, Vol. 62, No. 90, p. 25634-5

    • Finalised Guideline:
      February 2002

      Description:

      The tripartite harmonised ICH Guideline was finalised under Step 4 in February 2002. This document describes general principles for reduced stability testing and provides examples of bracketing and matrixing designs.

      Implementation:

      Step 5

      EU:

      Adopted by CPMP, February 2002, issued as CPMP/ICH/4104/00

      MHLW:

      Adopted 31 July 2002 as PFSB/ELD Notification No. 0731004

      FDA:

      Published in the Federal Register, Vol. 68, No. 11, p. 2339-2340, 16 January 2003

    • Finalised Guideline:
      February 2003

      Description:

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

      Implementation:

      Step 5

      EU:

      Adopted by CPMP, March 2003, issued as CPMP/ICH/420/02

      MHLW:

      Adopted 3 June 2003, PFSB/ELD Notification No. 0603004

      FDA:

      Published in the Federal Register, 8 June 2004, Vol. 69, No. 110, p. 32010-11

    • Guideline Withdrawal:
      June 2006

      Description:

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

      Implementation:

      Guideline withdrawn on 8 June 2006

      EU:

      Withdrawal notification and Explanatory Note, issued as CPMP/ICH/421/02, June 2006

      MHLW:

      Withdrawal 3 July 2006, PFSB/ELD Notification No. 0703001

      FDA:

      Withdrawn from CDER's guidance page on 6 June 2006 and has been listed in the FDA annual guidance agenda published in the Federal Register.

  • Q2 Analytical Validation

    Code Document Title Previously coded
    • Finalised Guidelines:
      October 1994/November 1996

      Description:

      The tripartite harmonised ICH Guideline on Text (previously coded Q2A) was finalised under Step 4 in October 1994. This identifies the validation parameters needed for a variety of analytical methods. It also discusses the characteristics that must be considered during the validation of the analytical procedures which are included as part of registration applications.

      The tripartite harmonised ICH Guideline on Methodology (previously coded Q2B) was finalised under Step 4 in November 1996. It extends the Guideline Q2A to include the actual experimental data required, along with the statistical interpretation, for the validation of analytical procedures.

      The Guideline on Methodology has been incorporated into the Guideline on Text in November 2005 and then renamed Q2(R1), without any changes in the contents of the two Guidelines.

      Guideline on Text Implementation:

      Step 5

      EU:

      Adopted by CPMP, November 1994, issued as CPMP/ICH/381/95

      MHLW:

      Adopted July 1995, PAB/PCD Notification No. 755

      FDA:

      Published in the Federal Register, 1 March 1995, Vol. 60, p. 11260

      Validation of Analytical Procedures: Methodology

      Implementation:

      Step 5

      EU:

      Adopted by CPMP, December 1996, issued as CPMP/ICH281/95

      MHLW:

      Adopted October 1997, PMSB/ELD Notification No. 338

      FDA:

      Published in the Federal Register, 19 May 1997, Vol. 62, No. 96, p. 27463-7

  • Q3A - Q3D Impurities

    Code Document Title Previously coded
    • Finalised Guideline:
      October 2006

      Description:

      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 harmonize 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)).

      Implementation:

      Step 5

      EU:

      Adopted by CPMP, October 2006, issued as CPMP/ICH/142/95

      MHLW:

      Adopted 4 December 2006, PFSB/ELD Notification No. 1204001

      FDA:

      Published in the Federal Register on June 2008

    • Finalised Guideline:
      June 2006

      Description:

      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)).

      Implementation:

      Step 5

      EU:

      Adopted by CPMP, June 2006, issued as CPMP/ICH/2738/99

      MHLW:

      Adopted 3 July 2006, PFSB/ELD Notification No. 0703004

      FDA:

      Published in the Federal Register, 14 November 2003, Vol, 68, No. 220, p. 64628-9 with the Revised Attachment 2

    • Finalised Guideline:
      February 2011

      Description:

      The core tripartite harmonised ICH Guideline was finalised under Step 4 in July 1997. This recommends the use of less toxic solvents in the manufacture of drug substances and dosage forms, and sets pharmaceutical limits for residual solvents (organic volatile impurities) in drug products.

      Maintenance Process

      A Maintenance process has been done to revise Permitted Daily Exposure (PDE), as new toxicological data for solvents become available. 

      Limit values for three residual solvents in drug products were revised on basis of the newly recognised toxicity data; lower PDE for N-Methylpyrrolidone being kept in Class 2 (limited by health-basis) and for Tetrahydrofuran and Cumene being placed into Class 2 from Class 3 (no health-based).

      Both revisions (PDE for THF and PDE for NMP) reached Step 4 of the process in September 2002. A corrigendum to calculation formula for NMP was subsequently approved on 28 October 2002. As per the new coding rule, they were incorporated into the core Guideline in November 2005.

      In February 2009, Table 2, Table 3 and Appendix 1 of the Core Guideline were updated to reflect the revision of the PDEs for N-Methylpyrrolidone and Tetrahydrofuran (Q3C(R4)).

      The revision of the PDE for Cumene reached Step 4 of the process in February 2011 and was integrated as part IV in the core Guideline (Q3C(R5)).

      Implementation:

      Step 5

      EU:

      Core Guideline adopted by CPMP, September 1997, issued as CPMP/ICH/283/95

      MHLW:

      Core Guideline adopted March 1998, PMSB/ELD Notification No. 307

      FDA:

      Core Guideline published in the Federal Register, 24 December 1997, Vol. 62, No. 247, p. 67377; Q3C Tables and list published in FR, Vol. 68, No. 219, p. 64352-64353, 13 November 2003

      Revised PDE for N-Methylpyrrolidone (September 2002) - View subsequent Correction

      Implementation:

      Step 5

      EU:

      Adopted by CPMP, September 2002, issued as CPMP/ICH/1940/00

      MHLW:

      Adopted 25 December 2002, ELD Notification No. 1225006

      FDA:

      The revised PDE is reflected in the Q3C Tables and List published in the Federal Register, Vol. 68, No. 219, p. 64352-3, 13 November 2003

      Revised PDE for Tetrahydrofuran (September 2002)

      Implementation:

      Step 5

      EU:

      Adopted by CPMP, September 2002, issued as CPMP/ICH/1940/00

      MHLW:

      Adopted 25 December 2002, ELD Notification No. 1225006

      FDA:

      The revised PDE is reflected in the Q3C Tables and List published in the Federal Register, Vol. 68, No. 219, p. 64352-64353, 13 November 2003

      Q3C(R4)

      Implementation:

      Step 5

      EU:

      Adopted by CPMP, February 2009, issued as CPMP/ICH/28395

      Q3C(R5) Revised PDE for Cumene (February 2011)

      Implementation:

      Step 5

      EU:

      Adopted by CHMP, March 2011, issued as EMA/CHMP/ICH/82260/2006

      MHLW:

      Adopted 21 February 2011, PFSB/ELD Notification No. 0221-1

      FDA:

      The revised PDE is reflected in the Q3C Tables and List published in the Federal Register, 23 February 2012, Vol. 77, No. 36, p. 10754-5

    • Draft Document:
      July 2013

      Description:

      The Q3D draft Guideline has been relased for consultation under Step 2B of the ICH process in July 2013.

      This new guidance is proposed to provide a global policy for limiting metal impurities qualitatively and quantitatively in drug products and ingredients. The existing ICH Q3A Guideline classifies impurities as organic, inorganic, and residual solvents. The Q3A and Q3B Guidelines effectively address the requirements for organic impurities. An additional Guideline Q3C was developed to provide clarification of the requirements for residual solvents. The proposed new Guideline Q3D would provide similar clarification of the requirements for metals, which are included in the ICH inorganic impurities classification.

       

      Status:

      Step 2b

      EU:

      Transmission to CHMP in June 2013, issued as EMA/CHMP/ICH/353369/2013. Deadline for comments: 31 December 2013

      MHLW:

      Released for consultation, 4 October 2013, PFSB/ELD. Deadline for comments: 29 November 2013

      FDA:

      Published in the Federal Register 23 October 2013, Vol. 78, No. 205, p. 63219-20. Deadline for comments: 23 December 2013

  • Q4 - Q4B Pharmacopoeias

    Code Document Title Previously coded
    • Description:

      Q6A activity provided the framework on how to set specifications for drug substances to address how regulators and manufacturers might avoid setting or agreeing to conflicting standards for the same product, as part of the registration in different regions.  The resulting ICH Q6A Guideline provides harmonised guidance in this area.  With the passage of the Chemical Substances (Q6A) ICH Guideline, the harmonisation of several compendial test chapters has been considered as critical by the ICH Steering Committee. These chapters are at various stages of harmonisation among the three pharmacopeial organisations (USP, JP & EP). The three organisations conduct their harmonisation efforts through a tripartite pharmacopeial harmonisation program known as the Pharmacopoeial Discussion Group (PDG).

    • Description:

      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. The ICH Steering Committee receives regular reports on the status of pharmacopoeial harmonisation at its meetings.

    • Finalised Guideline:
      November 2007

      Description:

      The tripartite harmonised ICH 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 and since 2010 in Canada. Following favourable evaluations, ICH will 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.

      Implementation:

      Step 5

      EU:

      Adopted by CHMP, December 2007, issued as EMEA/CHMP/ICH/222007/2006

      MHLW:

      Adopted 26 May 2009, PFSB/ELD Notification No. 0526001

      FDA:

      Published in the Federal Register, 21 February 2008, Vol. 73, No. 35, p. 9575-6

      Frequently Asked Questions

      Finalised Document:
      April 2012

      Description:

      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.

    • Finalised Annex:
      September 2010

      Description:

      The tripartite harmonised ICH 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- to include the Interchangeability Statement from Health Canada on 27 September 2010.

      Implementation:

      Step 5

      EU:

      Adopted by CHMP, December 2007, issued as EMEA/CHMP/ICH/222063/2006

      MHLW:

      Adopted 26 May 2009, PFSB/ELD Notification No. 052 6002

      FDA:

      Published in the Federal Register, 21 February 2008, Vol. 73, No. 35, p. 9576-7

      Frequently Asked Questions

      Finalised Document:
      April 2012

      Description:

      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.

    • Finalised Annex:
      September 2010

      Description:

      The tripartite harmonised ICH 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- to include the Interchangeability Statement from Health Canada on 27 September 2010.

      Implementation:

      Step 5

      EU:

      Adopted by CHMP, June 2008, issued as EMEA/CHMP/ICH/559409/2007

      MHLW:

      Adopted 8 February 2010, PFSB/ELD Notification No. 0208-1

      FDA:

      Published in the Federal Register, 9 January 2009, Vol. 74, No. 6, p. 908-9

      Frequently Asked Questions

      Finalised Document:
      April 2012

      Description:

      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.

    • Finalised Annex:
      September 2010

      Description:

      The tripartite harmonised ICH 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- to include the Interchangeability Statement from Health Canada on 27 September 2010.

      Implementation:

      Step 5

      EU:

      Adopted by CHMP, June 2008, issued as EMEA/CHMP/ICH/561176/2007

      MHLW:

      Adopted 8 February 2010, PFSB/ELD Notification No. 0208-2

      FDA:

      Published in the Federal Register, 9 January 2009, Vol. 74, No. 6, p. 909-10

      Frequently Asked Questions

      Finalised Document:
      April 2012

      Description:

      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.

    • Finalised Annex:
      September 2010

      Description:

      The tripartite harmonised ICH 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- to include the Interchangeability Statement from Health Canada on 27 September 2010.

      Implementation:

      Step 5

      EU:

      Adopted by CHMP, December 2008, issued as CHMP/ICH/308671/07

      MHLW:

      Adopted 17 September 2010, PFSB/ELD Notification No. 0917-2

      FDA:

      Published in the Federal Register, 8 April 2009, Vol. 74, No. 66, p. 15991-2

      Frequently Asked Questions

      Finalised Document:
      April 2012

      Description:

      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.

    • Finalised Annex:
      September 2010

      Description:

      The tripartite harmonised ICH 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- to include the Interchangeability Statement from Health Canada on 27 September 2010.

      Implementation:

      Step 5

      EU:

      Adopted by CHMP, December 2008, issued as CHMP/ICH/308817/07

      MHLW:

      Adopted 17 September 2010, PFSB/ELD Notification No. 0917-2

      FDA:

      Published in the Federal Register, 8 April 2009, Vol. 74, No. 66, p. 15989-90

      Frequently Asked Questions

      Finalised Document:
      April 2012

      Description:

      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.

    • Finalised Annex:
      September 2010

      Description:

      The tripartite harmonised ICH 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- to include the Interchangeability Statement from Health Canada on 27 September 2010.

      Implementation:

      Step 5

      EU:

      Adopted by CHMP, December 2008, issued as CHMP/ICH/308867/08

      MHLW:

      Adopted 17 September 2010, PFSB/ELD Notification No. 0917-2

      FDA:

      Published in the Federal Register, 8 April 2009, Vol. 74, No. 66, p. 15992-3

      Frequently Asked Questions

      Finalised Document:
      April 2012

      Description:

      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.

    • Finalised Annex:
      September 2010

      Description:

      The tripartite harmonised ICH 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- to include the Interchangeability Statement from Health Canada on 27 September 2010.

      Implementation:

      Step 5

      EU:

      Adopted by CHMP, June 2009, issued as CHMP/ICH/308895/08

      MHLW:

      Adopted 17 September 2010, PFSB/ELD Notification No. 0917-3

      FDA:

      Published in the Federal Register, 23 December 2009, Vol. 74, No. 245, Docket No. FDA-2009-D-0399, p. 68270-1

      Frequently Asked Questions

      Finalised Document:
      April 2012

      Description:

      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.

    • Finalised Annex:
      November 2013

      Description:

      The tripartite harmonised ICH 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.

      Implementation:

      Step 5

      EU:

      Adopted by CHMP, December 2013, issued as EMA/CHMP/ICH/645408/2008

      MHLW:

      Adopted 17 April 2014, PFSB/ELD Notification No. 0417-1

      FDA:

      Published in the Federal Register, 16 June 2014, Vol. 79, No. 115, p. 34314-5

      Frequently Asked Questions

      Finalised Document:
      April 2012

      Description:

      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.

    • Finalised Annex:
      November 2010

      Description:

      The tripartite harmonised ICH 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- to include the Interchangeability Statement from Health Canada on 27 September 2010.

      This annex was revised -R2- under Step 4 without further public consultation on 11 November 2010.

      Implementation:

      Step 5

      EU:

      Adopted by CHMP, December 2010, issued as EMA/CHMP/ICH/645469/2008

      MHLW:

      Adopted 26 July 2011, PFSB/ELD Notification No. 0726-1

      FDA:

      Published in the Federal Register, 24 June 2011, Vol. 76, No. 122, p. 37129-31

      Frequently Asked Questions

      Finalised Document:
      April 2012

      Description:

      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.

    • Finalised Annex:
      September 2010

      Description:

      The tripartite harmonised ICH 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- to include the Interchangeability Statement from Health Canada on 27 September 2010.

      Implementation:

      Step 5

      EU:

      Adopted by CHMP, June 2009, issued as CHMP/ICH/645592/0

      MHLW:

      Adopted 17 September 2010, PFSB/ELD Notification No. 0917-1

      FDA:

      Published in the Federal Register, 22 December 2009, Vol. 74, No. 244, Docket No. FDA-2009-D-0013, p. 68068-9

      Frequently Asked Questions

      Finalised Document:
      April 2012

      Description:

      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.

    • Finalised Annex:
      September 2010

      Description:

      The tripartite harmonised ICH guideline was finalised underStep 4 in October 2009.
      This annex is the result of the Q4B process for Tablet Friability General Chapter.

      This annex was revised -R1- to include the Interchangeability Statement from Health Canada on 27 September 2010.

      Implementation:

      Step 5

      EU:

      Adopted by CHMP, November 2009, issued as CHMP/ICH/379801/2009

      MHLW:

      Adopted 27 January 2011, PFSB/ELD Notification No. 0127-2

      FDA:

      Published in the Federal Register, 5 April 2010, Vol. 75, No. 64, Docket No. FDA-2009-D-0343, p. 17147

      Frequently Asked Questions

      Finalised Document:
      April 2012

      Description:

      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.

    • Finalised Annex:
      September 2010

      Description:

      The tripartite harmonised ICH 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- to include the Interchangeability Statement from Health Canada on 27 September 2010.

      Implementation:

      Step 5

      EU:

      Adopted by CHMP, November 2009, issued as CHMP/ICH/381133/2009

      MHLW:

      Adopted 27 January 2011, PFSB/ELD Notification No. 0127-1

      FDA:

      Published in the Federal Register, 12 April 2010, Vol. 75, No. 69, Docket No. FDA-2009-D-0342, p. 18509

      Frequently Asked Questions

      Finalised Document:
      April 2012

      Description:

      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.

    • Finalised Annex:
      June 2010

      Description:

      The tripartite harmonised ICH 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.

      Implementation:

      Step 5

      EU:

      Adopted by CHMP, September 2010, issued as EMA/CHMP/ICH/730028/2009

      MHLW:

      Adopted 27 January 2011, PFSB/ELD Notification No. 0127-3

      FDA:

      Published in the Federal Register 3 September 2010, Vol. 75, No. 171, p. 54153-4

      Frequently Asked Questions

      Finalised Document:
      April 2012

      Description:

      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.

    • Finalised Annex:
      June 2010

      Description:

      The tripartite harmonised ICH 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.

      Implementation:

      Step 5

      EU:

      Adopted by CHMP, September 2010, issued as EMA/CHMP/ICH/730808/2009

      MHLW:

      Adopted 27 January 2011, PFSB/ELD Notification No. 0127-4

      FDA:

      Published in the Federal Register, 2 September 2010, Vol. 75, No. 170, p. 53973-4

      Frequently Asked Questions

      Finalised Document:
      April 2012

      Description:

      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.

    • Finalised Annex:
      June 2012

      Description:

      The tripartite harmonised ICH 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.

      Implementation:

      Step 5

      EU:

      Adopted by CHMP, July 2012, issued as EMA/CHMP/ICH/405290/2010

      MHLW:

      Adopted 8 November 2012, PFSB/ELD Notification No. 1108-3

      FDA:

      Published in the Federal Register, 28 May 2013, Vol. 75, No. 102, p. 31944-5

      Frequently Asked Questions

      Finalised Document:
      April 2012

      Description:

      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.

    • Finalised Annex:
      October 2012

      Description:

      The tripartite harmonised ICH 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.

      Implementation:

      Step 5

      EU:

      Adopted by CHMP, November 2012, issued as EMA/CHMP/ICH/529785/2010

      MHLW:

      Adopted 21 March 2013, PFSB/ELD Notification No. 0321-1

      FDA:

      Published in the Federal Register, 23 October 2013, Vol. 78, No. 205, p. 63221-2

    • Finalised Document:
      April 2012

      Description:

      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.

  • Q5A - Q5E Quality of Biotechnological Products

    Code Document Title Previously coded
    • Finalised Guideline:
      September 1999

      Description:

      The tripartite harmonised ICH Guideline was finalised  under Step 4 in March 1997. This is concerned with testing and evaluation of the viral safety of biotechnology products derived from characterised cell lines of human or animal origin. The purpose is to provide a general framework for virus testing experiments for the evaluation of virus clearance and the design of viral tests and clearance evaluation studies.

      (Please note that a typographic error has been corrected on 23 September 1999 on Table A-1. the Genome of the Reovirus 3 is RNA (and not DNA as previously printed). The correction was integrated in the Guideline that was then renamed Q5A(R1)).

      Implementation:

      Step 5

      EU:

      Adopted by CPMP, April 1997, issued as CPMP/ICH/295/95

      MHLW:

      Adopted, 22 February 2000, PMSB/ELD Notification No. 329

      FDA:

      Published in the Federal Register, 24 September 1998, Vol. 63, No. 185, p. 51074

    • Finalised Guideline:
      November 1995

      Description:

      The tripartite harmonised ICH Guideline was finalised under Step 4 in November 1995. It advises on the types of information that are considered valuable in assessing the structure of the expression construct used to produce recombinant DNA derived proteins.

      Implementation:

      Step 5

      EU:

      Adopted by CPMP, December 1995, issued as CPMP/ICH/139/95

      MHLW:

      Adopted January 1998, PMSB/ELD Notification No. 3

      FDA:

      Published in the Federal Register, 23 February 1996, Vol. 61, p. 7006

    • Finalised Guideline:
      November 1995

      Description:

      The tripartite harmonised ICH Guideline was finalised under Step 4 in November 1995. This document augments the stability Guideline (Q1A above) 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.

      Implementation:

      Step 5

      EU:

      Adopted by CPMP, December 1995, issued as CPMP/ICH/138/95

      MHLW:

      Adopted January 1998, PMSB/ELD Notification No. 6

      FDA:

      Published in the Federal Register, 10 July 1996, Vol. 61, p. 36466

    • Finalised Guideline:
      July 1997

      Description:

      The tripartite harmonised ICH 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 microbes used to prepare biotechnological/biological products and for the preparation and characterisation of cell banks to be used for production.

      Implementation:

      Step 5

      EU:

      Adopted by CPMP, September 1997, issued as CPMP/ICH/294/95

      MHLW:

      Adopted 14 July 2000, PMSB/ELD Notification No. 873

      FDA:

      Published in the Federal Register, 21 September 1998, Vol. 63, No. 182, p. 50244-9

    • Finalised Guideline:
      November 2004

      Description:

      The tripartite harmonised ICH 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.

      Implementation:

      Step 5

      EU:

      Adopted by CPMP, December 2004, CPMP/ICH/5721/03

      MHLW:

      Adopted 26 April 2005, PFSB/ELD Notification No. 0426001

      FDA:

      Published in the Federal Register, 30 June 2005, Vol. 70, No. 125, p. 37861-2

  • Q6A- Q6B Specifications

    Code Document Title Previously coded
    • Finalised Guideline:
      October 1999

      Description:

      The tripartite harmonised ICH Guideline was finalised under Step 4 in October 1999. This addresses the process of selecting tests and methods and setting specifications for the testing of drug substances and dosage forms. Account has been taken of the considerable guidance and background information which are present in existing regional documents.

      Implementation:

      Step 5

      EU:

      Adopted by CPMP, November 1999, issued as CPMP/ICH/367/96

      MHLW:

      Adopted May 2001, PMSB/ELD Notification No. 568

      FDA:

      Published in the Federal Register, 29 December 2000, Vol. 65, No. 251, p. 83041-63

    • Finalised Guideline:
      March 1999

      Description:

      The tripartite harmonised ICH Guideline was finalised under Step 4 in March 1999. This document provides guidance on justifying and setting specifications for proteins and polypeptides which are derived from recombinant or non-recombinant cell cultures. The scope of this part is initially limited to well-characterised biotechnological products, although the concepts may be applicable to other biologicals as appropriate. In view of the nature of the products, the topic of specifications include in-process controls, bulk drug, final product and stability specifications and give guidance for a harmonised approach to determining appropriate specifications based on safety, process consistency, purity, analytical methodology, product administration and clinical data considerations.

      Implementation:

      Step 5

      EU:

      Adopted by CPMP, March 1999, issued as CPMP/ICH/365/96

      MHLW:

      Adopted May 2001, PMSB/ELD Notification No. 571

      FDA:

      Published in the Federal Register, 18 August 1999, Vol. 64, p. 44928

  • Q7 Good Manufacturing Practice

    Code Document Title Previously coded
    • Finalised Guideline:
      November 2000

      Description:

      Early in the ICH Process it was agreed that there was adequate international agreement on the technical aspects of Good Manufacturing Practices (GMP) for Pharmaceutical Products and that further harmonisation action through ICH was not needed. Recently, however, attention has focused on the need to formalise GMP requirements for the components of pharmaceutical products - both active and inactive. In February 1998, the ICH Steering Committee agreed that GMP for Active Pharmaceutical Ingredients (APIs) should be adopted as an ICH Topic.

      When this topic was adopted, the Steering Committee took steps to ensure that due account was taken of the work already in progress by PIC/S, FDA and other parties. In view of the unusually wide implications of this Topic, a much extended EWG has been established which includes, in addition to the six ICH parties and the Observers, experts representing IGPA (generics industry), WSMI (self medication industry) and PIC/S. With respect to the latter representatives from China, India and Australia have been invited to participate.

      Implementation:

      Step 5

      EU:

      Adopted by CPMP, November 2000, issued as CPMP/ICH/4106/00

      MHLW:

      Adopted November 2001, PMSB/ELD Notification No. 1200

      FDA:

      Published in the Federal Register, 25 September 2001, Vol. 66, No. 186, p. 49028-9

    • Description:

      This Implementation Working Group was endorsed by the ICH Steering Committee in October 2012.

      Experience gained with the implementation of the ICH Q7 Guideline since its finalisation in 2000 shows 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 - will be addressed in this Question and Answer document in order to harmonize expectations during inspections, to remove ambiguities and uncertainties and also to harmonise the inspections of both small molecules and biotech APIs.

      Status:

      Step 1

  • Q8 Pharmaceutical Development

    Code Document Title Previously coded
    • Finalised Guideline:
      August 2009

      Description:

      The core tripartite harmonised ICH 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 tripartite 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 Summer 2009 to reflect minor corrections to Example 2 on page 23 (Q8(R2)).

      Implementation:

      Step 5

      EU:

      Adopted by CHMP, June 2009, issued as CHMP/ICH/167068/04

      MHLW:

      Adopted 28 June 2010, PFSB/ELD Notification No. 0628-1

      FDA:

      Published in the Federal Register, November 2009, Vol. 71, No. 98

    • Description:

      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 and second set of Q&As was finalised under Step 4 in April and June 2009, respectively.

      In October 2009, a third set of Q&As was developed and approved by the Steering Committee for integration in the Q&A document (Q8/Q9/Q10 Q&As (R3)).

      In November 2010, a fourth set of Q&As was developed and approved by the Steering Committee for integration in the Q&A document (Q8/Q9/Q10 Q&As (R4)).

      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 Document was finalised in June and November 2011, respectively.  

      Implementation Q&As:

      Step 5

      EU:

      Transmission to CHMP and release for information, December 2010, issued as EMA/CHMP/ICH/265145/2009

      MHLW:

      Adopted 29 August 2011

      FDA:

      Posted on FDA website on 1 November 2011

  • Q9 Quality Risk Management

    Code Document Title Previously coded
    • Description:

      The tripartite harmonised ICH Guideline was finalised under Step 4 in November 2005.
      This Guideline provides principles and examples of tools of quality risk management that can be applied to all aspects of pharmaceutical quality including development, manufacturing, distribution, and the inspection and submission/review processes throughout the lifecycle of drug substances and drug (medicinal) products, biological and biotechnological products, including the use of raw materials, solvents, excipients, packaging and labeling materials.

      Implementation:

      Step 5

      EU:

      Published on the EMA website with an Explanatory Note, January 2006, issued as EXT/24235/2006

      MHLW:

      Adopted September 2006, PFSB/ELD Notification No. 0901004

      FDA:

      Published in the Federal Register, 2 June 2006, Vol. 71, No. 106, p. 32105-6

    • Description:

      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 and second set of Q&As was finalised under Step 4 in April and June 2009, respectively.

      In October 2009, a third set of Q&As was developed and approved by the Steering Committee for integration in the Q&A document (Q8/Q9/Q10 Q&As (R3)).

      In November 2010, a fourth set of Q&As was developed and approved by the Steering Committee for integration in the Q&A document (Q8/Q9/Q10 Q&As (R4)).

      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 Document was finalised in June and November 2011, respectively.  

      Implementation Q&As:

      Step 5

      EU:

      Transmission to CHMP and release for information, December 2010, issued as EMA/CHMP/ICH/265145/2009

      MHLW:

      Adopted 29 August 2011

      FDA:

      Posted on FDA website on 1 November 2011

  • Q10 Pharmaceutical Quality System

    Code Document Title Previously coded
    • Description:

      The tripartite harmonised ICH Guideline was finalised under Step 4 in June 2008.
      This Guideline applies to 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.

      Implementation:

      Step 5

      EU:

      Adopted by CHMP, July 2008, issued as CHMP/ICH/214732/04

      MHLW:

      Adopted 19 February 2010, PFSB/ ELD Notification No. 0219-1 & PFSB/ NCD Notification No. 0219-1

      FDA:

      Published in the Federal Register, 8 April 2009, Vol. 74, No. 66, p. 15990-1

    • Description:

      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 and second set of Q&As was finalised under Step 4 in April and June 2009, respectively.

      In October 2009, a third set of Q&As was developed and approved by the Steering Committee for integration in the Q&A document (Q8/Q9/Q10 Q&As (R3)).

      In November 2010, a fourth set of Q&As was developed and approved by the Steering Committee for integration in the Q&A document (Q8/Q9/Q10 Q&As (R4)).

      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 Document was finalised in June and November 2011, respectively.  

      Implementation Q&As:

      Step 5

      EU:

      Transmission to CHMP and release for information, December 2010, issued as EMA/CHMP/ICH/265145/2009

      MHLW:

      Adopted 29 August 2011

      FDA:

      Posted on FDA website on 1 November 2011

  • Q11 Development and Manufacture of Drug Substances

    Code Document Title Previously coded
    • Finalised Guideline:
      May 2012

      Description:

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

      This new guidance is proposed for Active Pharmaceutical Ingredients (APIs) harmonising the scientific and technical principles relating to the description and justification of the development and manufacturing process (CTD sections S 2.2. - S 2.6) of Drug Substances including both chemical entities and biotechnological/biological entities.

      Implementation:

      Step 5

      EU:

      Adopted by CHMP, May 2012, issued as EMA/CHMP/ICH/425213/2011

      MHLW:

      Adopted July 2014, PFSB/ELD Notification No. 0710-9

      FDA:

      Published in the Federal Register 20 November 2012, Vol. 77, No. 224, p. 69634-5

  • Cross-cutting Topics

    Code Document Title Previously coded