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.

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.

  • Q1A(R2) Guidelines Pdf
  • 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.

  • Q1B Guidelines Pdf
  • 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.

  • Q1C Guidelines Pdf
  • 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.

  • Q1D Guidelines Pdf
  • 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.

  • Q1E Guidelines Pdf
  • Q1E Presentation Pdf
  • 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.

  • Q1F Stability Guideline WHO 2018 Pdf
  • Q1F Explanatory Note Pdf
  • The ICH Harmonised 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 ICH Harmonised 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.

  • Q2 R1 Guideline Pdf
  • This topic was endorsed by the Assembly in June 2018. The Q2(R2)/Q14 EWG will develop a new ICH Quality Guideline, ICH Q14, on Analytical Procedure Development, and revise the ICH Q2(R1) Guideline on Validation of Analytical Procedures, with a view to potentially combine both documents into one, for simplification and clarity.

    Q2(R1) Revision

    The scope of the revision of ICH Q2(R1) will include 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 will continue to provide a general framework for the principles of analytical procedure validation applicable to products mostly in the scope of Q6A and Q6B. These proposed guidelines (Q2(R2) and Q14) are intended to complement ICH Q8 to Q12 Guidelines, as well as on-going ICH Q13 for Continuous Manufacturing.

    14 Analytical Procedure Development Guideline

    The new guideline is proposed to harmonise the scientific approaches of Analytical Procedure Development, and to provide the principles relating to the description of Analytical Procedure Development process. This new guideline is intended 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.

  • Q2R2-Q14 EWG Concept Paper Pdf
  • Q2R2-Q14 EWG Business Plan Pdf
  • Q2-Q14EWG_WorkPlan_2019_0821 Pdf
  • 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)).

  • Q3A_R2 Guideline Pdf
  • 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)).

  • Q3B_R2 Guideline Pdf
  • Q3B_R2 Concept Paper Pdf
  • The 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)).

    In October 2016, the PDE for Methyl isobutyl ketone (MIBK) was revised, and Triethylamine (TEA) was added as a news solvent. Based on new data, MIBK was moved from Class 3 (solvents with low toxic potential) to Class 2 (solvents to be limited). The new solvent Triethylamine was included in Class 3 (solvents with low toxic potential) (Q3C(R6)).

    In October 2018, further to a discrepancy raised regarding the PDE for ethyleneglycol, an error correction procedure was launched and the Q3C(R7) Guideline was released with a new value for the PDE for ethyleneglycol, and the MC further approved the publication of Support Documents 1, 2 and 3, which include the summaries of the toxicity data from which PDEs were derived.

    In October 2019, based on archival documents and a review of the literature, the PDE for ethyleneglycol was reinstated to its previous value (Q3C(R6)). (refer to the Cover Statement for additional information).

    Guideline

  • Q3C-R6 Guideline ErrorCorrection Pdf
  • Q3C-R6 Cover Statement Pdf

  • Endorsed Documents

  • Q3C Concept Paper Pdf

  • WG Presenation/ Trainings

  • Q3C_R6 Step4 Presentation Pdf
  • The Q3C(R8) EWG is currently undertaking a maintenance of the Guideline, which will result in the future Q3C(R8) version, to develop PDE levels for three solvents: 2-methyltetrahydrofuran, cyclopentylmethylether and tert-butanol.

    Endorsed Document

  • Q3C-R8 EWG WorkPlan 2019 Pdf
  • ICH Q3D Elemental Impurities is a quality guideline for the control of elemental impurities in new drug products (medicinal products), and it establishes Permitted Daily Exposures (PDEs) for 24 Elemental Impurities (EIs) for drug products administered by the oral, parenteral and inhalation routes of administration. In addition, guidance is provided in Q3D on how to develop an acceptable level for EIs for drug products administered by other routes of administration.

    In March 2019, the Q3D(R1) Guideline, which was the result of a revision of the PDE level for Cadmium by inhalation in the Q3D Guideline, reached Step 4 of the ICH process.

    Guideline

  • Q3D-R1EWG Document Step4 Guideline 2019 Pdf

  • Endorsed Document

  • Q3D Final Concept Paper Pdf
  • Q3D Final Business Plan Pdf
  • ICH Q3D(R1) Elemental Impurities is a quality guideline for the control of elemental impurities in new drug products (medicinal products), and it establishes Permitted Daily Exposures (PDEs) for 24 Elemental Impurities (EIs) for drug products administered by the oral, parenteral and inhalation routes of administration. In addition, guidance is provided in Q3D(R1) on how to develop an acceptable level for EIs for drug products administered by other routes of administration.

    The Q3D(R2) Maintenance EWG is currently undertaking a maintenance of the Guideline to develop PDE levels for cutaneous and transdermal products.

    Maintenance Process

    A Maintenance Procedure applies to revision of the Q3D(R1) Guideline for Elemental Impurities. These changes includes the incorporation of Permitted Daily Exposure (PDE) for new elemental impurities(EI)/routes of administration and revising the PDE for EI already listed in Q3D(R1) as new toxicological data for EI becomes available.

    Products administered on skin and its appendages (e.g., hair, nails) remain the largest area where PDEs for EIs have not been established. In September 2016, the ICH Management Committee approved the revision of the ICH Q3D Concept Paper to include PDEs for the cutaneous and transdermal Route of Administration to continue the process of harmonisation, where necessary. This leads to the establishment of an Expert Working Group (EWG) to develop PDEs levels for all 24 EI included in the Q3D(R1) Guideline for products administered by the cutaneous and transdermal routes of administration.

    Endorsed Documents

  • Q3D-R2 Maintenance EWG Concept Paper Pdf
  • Q3DEWG WorkPlan 2019 Pdf
  • 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 Pdf
  • Q3D Training Business Plan Pdf
  • This topic was endorsed by the ICH Assembly in June 2019, and an informal Working Group is being established to develop a Concept Paper and Business Plan.

    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 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.

    Guideline

  • Q4B Guideline Pdf

  • WG Presentation/ Trainings

  • Q4B_Presentation Pdf

  • Other Documents

  • Q4B_Frequently Asked Questions Pdf
  • 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.

  • Q4B Annex_1 R1 Annex Pdf
  • Q4B Frequently Asked Questions Pdf
  • 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.

    Guideline

  • Q4B Annex_2 R1 Annex Pdf

  • Other Document

  • Q4B Frequently Asked Questions Pdf
  • 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.

    Guideline

  • Q4B_Annex 3 R1 Annex Pdf

  • Other Documents

  • Q4B_Frequently Asked Questions Pdf
  • 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.

    Guideline

  • Q4B_Annex 4A R1 Annex Pdf

  • Other Documents

  • Q4B_Frequently Asked Questions Pdf
  • 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.

    Guideline

  • Q4B_Annex 4C R1 Annex Pdf

  • Other Documents

  • Q4B_Frequently Asked Questions Pdf
  • 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.

    Guideline

  • Q4B Annex 5 R1 Annex Pdf

  • Other Documents

  • Q4B_Frequently Asked Questions Pdf
  • 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.

    Guideline

  • Q4B Annex 6 Annex Pdf

  • Other Documents

  • Q4B_Frequently Asked Questions Pdf
  • 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.

    Guideline

  • Q4B annex 7 R2 Annex Pdf

  • Other Documents

  • Q4B_Frequently Asked Questions Pdf
  • 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.

    Guideline

  • Q4B Annex 8 R1 Annex Pdf

  • Other Documents

  • Q4B_Frequently Asked Questions Pdf
  • 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.

    Guideline

  • Q4B Annex 9 R1 AnnexPdf

  • Other Documents

  • Q4B_Frequently Asked Questions Pdf
  • 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.

    Guideline

  • Q4B Annex 10 R1 Pdf

  • Other Documents

  • Q4B_Frequently Asked Questions Pdf
  • 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.

    Guideline

  • Q4B Annex 5 R1 Pdf

  • Other Documents

  • Q4B_Frequently Asked Questions Pdf
  • 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.

    Guideline

  • Q4B Annex 12 Pdf

  • Other Documents

  • Q4B_Frequently Asked Questions Pdf
  • 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.

    Guideline

  • Q4B Annex 13 Pdf

  • Other Documents

  • Q4B_Frequently Asked Questions Pdf
  • The ICH Harmonised Annex was finalised under Step 4 in June 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.

    Guideline

  • Q4B Annex 14 Pdf

  • Other Documents

  • Q4B_Frequently Asked Questions Pdf
  • 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_Frequently Asked Questions Pdf
  • The ICH Harmonised Guideline was finalised under Step 4 in March 1997. This document is concerned with testing and evaluation of the viral safety of biotechnology products derived from characterised cell lines of human or animal origin and outlines data that should be submitted in the marketing application/registration package. The purpose of this Guideline is to provide a general framework for virus testing, experiments for the assessment of viral clearance and a recommended approach for the design of viral tests and viral clearance 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). 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.

  • Q5A_R1 Guideline Pdf
  • This topic was endorsed by the ICH Assembly in June 2019. The Q5A(R2) EWG is working on the revision of the of the Q5A(R1) Guideline “Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin” with a view to reflecting new biotechnology product types, advances in manufacturing technology, analytical methods for virus testing, and scientific knowledge that have occurred since publication of the original document in 1999.

    Endorsed Documents

  • Q5A-R2 Final Concept Paper Pdf
  • Q3B_R2 Final Bussiness Plan Pdf
  • 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.

    Guideline

  • Q5B_Guideline Pdf
  • 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.

    Endorsed Document

  • Q5C_Guideline Pdf
  • 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.

    Guidelines

  • Q5D Guideline Pdf
  • 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.

    Guideline

  • Q5E Guideline Pdf

  • Endorsed Document

  • Q5E Concept Paperline Pdf
  • 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.

    Guideline

  • Q6A Guideline Pdf

  • Other Document

  • Q6A Decision Tree Pdf
  • The ICH Harmonised Guideline was finalised under Step 4 in March 1999. This document provides general principles on the setting and justification of a uniform set of international specifications for proteins and polypeptides which are produced from recombinant or non-recombinant cell-culture expression systems. 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.

    Guideline

  • Q6B Guideline Pdf
  • 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.

    Guideline

  • Q7 Guideline Pdf

  • Other Document

  • Q7 Concept Paper Pdf
  • The ICH Harmonised Guideline was finalised under Step 4 in March 1999. This document provides general principles on the setting and justification of a uniform set of international specifications for proteins and polypeptides which are produced from recombinant or non-recombinant cell-culture expression systems. 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.

    Guideline

  • Q6B Guideline Pdf
  • 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.

    Question And Answers

  • Question And Answer Pdf

  • Endorsed Document

  • Concept Paper Pdf

  • WG Presentations / Trainings

  • Presentation Pdf
  • 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)).

    Guideline

  • Q8 R2 Guideline Pdf

  • Endorsed Document

  • Q8_R2 Concept Paper Pdf
  • 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.

    Question And Answers

  • Q8 Q9 Q10 Q&As R4 Q&As Pdf

  • Other Document

  • Q8_Q9_Q10_Q&As_R4 Points Pdf

  • Endorsed Document

  • Q8_Q9_Q10_Q&As_R4 Concept Paper Pdf
  • The ICH Harmonised Guideline was finalised under Step 4 in November 2005. This Guideline provides principles and examples of tools for quality risk management that can be applied to different aspects of pharmaceutical quality. These aspects include development, manufacturing, distribution, and the inspection and submission/review processes throughout the lifecycle of drug substances,drug (medicinal) products, biological and biotechnological products (including the use of raw materials, solvents, excipients, packaging and labeling materials in drug (medicinal) products, biological and biotechnological products).

    Guideline

  • Q9 Guideline Pdf

  • Endorsed Document

  • Q9_Concept Paper Pdf
  • Q9 Business Plan Pdf
  • 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.

    Question And Answers

  • Q8 Q9 Q10 Q&As R4 Q&As Pdf

  • Other Document

  • Q8_Q9_Q10_Q&As_R4 Points Pdf

  • Endorsed Document

  • Q8_Q9_Q10_Q&As_R4 Concept Paper Pdf
  • 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.

    Guideline

  • Q10 Guideline Pdf

  • Endorsed Document

  • Q10 Concept Paper Pdf
  • Q10 Business Plan Pdf

  • WG Presentation / Trainings

  • Q10 Presentation Pdf
  • 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.

    Question And Answers

  • Q8 Q9 Q10 Q&As R4 Q&As Pdf

  • Other Document

  • Q8_Q9_Q10_Q&As_R4 Points Pdf

  • Endorsed Document

  • Q8_Q9_Q10_Q&As_R4 Concept Paper Pdf
  • 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.

    Guideline

  • Q11 Guideline Pdf

  • Endorsed Document

  • Q11 Concept Paper Pdf
  • Q11 Business Plan Pdf
  • 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.

    Question and Answers

  • Q11 Q&As Q&As Pdf

  • Endorsed Document

  • Q11_Q&As Concept Paper Pdf
  • Q11_Q&As Business Plan Pdf

  • WG Presentations/ Trainings

  • Q11_Q&As Step4 Presentation Pdf
  • Q11 Training Deck Final Pdf
  • 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.

    Guideline

  • Q12 Guideline Step4 Pdf
  • Q12 Annexes Step4 Pdf


  • Endorsed Documents

  • Q12 EWG Business_Plan Pdf
  • Q12 EWG Concept Paper Pdf
  • Q12EWG WorkPlan 2019 Pdf

  • WG Presentations/ Trainings

  • Q12EWG_Step4 Intro Training Presentation Pdf
  • This topic was endorsed by the Assembly in June 2018. This new Guideline is proposed to:

    Capture key technical and regulatory considerations that promote harmonisation, including certain Current Good Manufacturing Practices (CGMP) elements specific to Continuous Manufacturing (CM).

    Allow drug manufacturers to employ flexible approaches to develop, implement, or integrate CM for the manufacture – drug substances and drug products – of small molecules and therapeutic proteins for new and existing products.

    Provide guidance to industry and regulatory agencies regarding regulatory expectations on the development, implementation, and assessment of CM technologies used in the manufacture of drug substances and drug products.

    Endorsed Documents

  • Q13 EWG Business_Plan Pdf
  • Q13 EWG Concept Paper Pdf
  • Q13 EWG WorkPlan 2019 Pdf
  • This topic was endorsed by the Assembly in June 2018. The Q2(R2)/Q14 EWG will develop a new ICH Quality Guideline, ICH Q14, on Analytical Procedure Development, and revise the ICH Q2(R1) Guideline on Validation of Analytical Procedures, with a view to potentially combine both documents into one, for simplification and clarity.

    Q2(R1) Revision

    The scope of the revision of ICH Q2(R1) will include 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 will continue to provide a general framework for the principles of analytical procedure validation applicable to products mostly in the scope of Q6A and Q6B. These proposed guidelines (Q2(R2) and Q14) are intended to complement ICH Q8 to Q12 Guidelines, as well as on-going ICH Q13 for Continuous Manufacturing.

    Q14 Analytical Procedure Development Guideline

    The new guideline is proposed to harmonise the scientific approaches of Analytical Procedure Development, and to provide the principles relating to the description of Analytical Procedure Development process. This new guideline is intended 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.

    Endorsed Documents

  • Q2R2-Q14 EWG Concept Paper Pdf
  • Q2R2-Q14 EWG Business Plan Pdf
  • Q2-Q14 EWG WorkPlan Pdf