Multidisciplinary Guidelines

Those are the cross-cutting topics which do not fit uniquely into one of the Quality, Safety and Efficacy categories. It includes the ICH medical terminology (MedDRA), the Common Technical Document (CTD) and the development of Electronic Standards for the Transfer of Regulatory Information (ESTRI).

The development of a Medical Dictionary for Regulatory Activities (MedDRA) was approved by the ICH Steering Committee in 1997, and the terminology was launched in 1999. Due to the development of this topic over the years, all information about MedDRA and the Points to Consider documents developed for every MedDRA version are available on the MedDRA page of the ICH website. Please also visit the official MedDRA website.

The MedDRA (Medical Dictionary for Regulatory Activities) terminology was launched in 1999. To support the use of MedDRA, the M1 PtC WG updates with each MedDRA release the two Points to Consider (PtC) documents on MedDRA Term Selection and MedDRA Data Retrieval and Presentation, available in English and Japanese, as well as condensed versions available in all MedDRA languages. Please refer to the MedDRA page and MedDRA website for information about MedDRA and the Points to Consider documents.

In addition, since 2017, the remit of the M1 PtC WG was extended to include the maintenance of a companion document to the PtC documents, available in English and Japanese, which provides more detailed guidance, examples, and Questions and Answers on topics of regulatory importance such as data quality, medication errors, and product quality issues.

Endorsed documents

  • M1_PtC_WG Concept Paper Pdf
  • M1_PtC WG WorkPlan Pdf
  • The M2 Expert Working Group (EWG) was established by the ICH Steering Committee in 1994 with the objective of facilitating international electronic communication by evaluating and recommending, open and non-proprietary - to the extent possible - Electronic Standards for the Transfer of Regulatory Information (ESTRI) that will meet the requirements of the pharmaceutical companies and regulatory authorities.

    Since its establishment the M2 EWG has been involved in a number of activities including: recommendation for use by ICH of various open international standards (M2 Recommendations); ICH development of specifications for electronic messages for the E2B(R2) ICH Guideline on Clinical Safety Data Management Data Elements for Transmission of Individual Case Safety Reports, as well as the M4 Common Technical Document (CTD); and the provision of technical input to the ICH E2B(R3) and M5 EWGs in their activities to progress their respective standards through the Standards Development Organisation (SDO) process.

    In November 2010, the ICH Steering Committee modified the mandate of the M2 EWG. Important changes included agreement that work related to the Electronic Common Technical Document (eCTD) be undertaken by a newly established M8 EWG, and that the M2 EWG would no longer be directly involved in the development of technical solutions in relation to topics such as E2B(R3) and M5, but would instead provide the framework for the efficient and effective development of the solutions by groups dedicated to these topics. Under its new mandate, the M2 EWG continues to be responsible for the evaluation and recommendation of standards, and also has responsibility for SDO relationship management.

    Endorsed Documents

  • M2_EWG Concept Paper Pdf
  • M2_EWG WorkPlan Pdf
  • The recommendations of this revised Guidance further harmonise the nonclinical safety studies to support the various stages of clinical development among the ICH regions. The present Guidance represents the consensus that exists regarding the type and duration of nonclinical safety studies and their timing to support the conduct of human clinical trials and marketing authorisation for pharmaceuticals.

    Guideline

  • M3_R2 Guideline Pdf

  • Endorsed Document

  • M3_R2 Concept Paper Pdf

  • wG Presentations / Trainings

  • M3_R2 Presentation Pdf
  • The complexity of the M3(R2) Guidance, its broader scope, and numerous changes in recommendations from the M3(R1) Guidance have generated questions that impact its successful implementation. To clarify the key issues of this document, the Steering Committee has endorsed the establishment of a M3(R2) Implementation Working Group (IWG), with the objective of developing the Q&As. The document with the first set of Q&As addressing Limit Dose for Toxicity Studies, Metabolites and Reversibility of Toxicity was finalised under Step 4 in June 2011. In December 2011, a second set of Q&As addressing Combination Drug Toxicity Testing was approved under Step 4 by the Steering Committee, and included in the Q&A document (M3(R2) Q&As (R1)). In March 2012, an additional question on Limit Dose for Toxicity Studies and 4 additional sections addressing Safety Pharmacology, Exploratory Clinical Trials, Reproductive Toxicity and Juvenile Animal Studies were approved under Step 4 by the Steering Committee, and included in the Q&A document (M3(R2) Q&As (R2)).

    Question And Answers

  • M3_R2_Q&As_R2 Q&As Pdf

  • endorsed Document

  • M3_R2_Q&As_R2 Concept Paper Pdf
  • The Common Technical Document was agreed upon by the Steering Committee in November 2000. Due to the development of this topic over the years, all information about the CTD are available on the CTD page under the Work Products.

    In November 2003, the ICH Steering Committee endorsed a Concept Paper for Topic M5 and subsequently formed the M5 EWG to develop ICH requirements for the standardisation of medicinal product identifiers and related terminology. In particular, a need was identified to harmonise product information that would facilitate the electronic exchange of Individual Case Safety Reports (ICSRs) within and across ICH regions using the ICH E2B format in post-marketing pharmacovigilance.

    In May 2005, an M5 consensus draft Guideline containing ICH business requirements for medicinal product identifiers, along with lists of controlled vocabularies for Routes of Administration and Units of Measurements, was published for public consultation at Step 2 of the ICH process. To support the electronic exchange of the M5 data elements proposed by the M5 EWG, technical messaging specifications were needed. Electronic messaging development for utilization by the ICH Parties had been the domain of the ICH M2 EWG, but in June 2006 the ICH Steering Committee took a key decision to develop electronic specifications in collaboration with Standards Development Organisations (SDOs). This would enable wider interoperability across regulatory and healthcare communities.

    The M5 draft Guideline, updated to reflect feedback from the public consultation, was subsequently submitted to the International Organization for Standardization (ISO) for development of electronic messaging specifications in February 2007. Work was conducted as a joint initiative with several other SDOs, including Health Level 7 (HL7), and various global stakeholders, including experts with experience on the ICH M5 EWG. Abbreviated regional testing was performed by the ICH Parties and five International Standards for Identification of Medicinal Products (IDMP) were finalized and published by ISO in November 2012. These five ISO standards not only meet the original ICH needs for electronic exchange of ICSRs in post-marketing pharmacovigilance, but also support broader functionality.

    Having successfully finalised the International Standards for IDMP, the ICH Steering Committee acknowledged the considerable achievements of the M5 EWG and agreed to the sunset of the M5 EWG in June 2013. Subsequently, the ICH Steering Committee formed the new E2B IWG to facilitate implementation of the new E2B(R3) standard for electronic ICSR exchange. The remit of the E2B IWG includes the use of the five ISO IDMP standards (ISO11238:2012, ISO11239:2012, ISO11240:2012, ISO11615:2012, and ISO11616:2012) only for the purpose of electronic ICSR exchange. Therefore, IDMP maintenance and publication requirements are outside the scope of the E2B IWG.

    This new topic was endorsed by the ICH Steering Committee in September 2009. In September 2009, following the finalisation by the ICH Gene Therapy Discussion Group (GTDG) of the ICH Consideration document “General Principles to Address Virus and Vector Shedding”, the ICH Steering Committee endorsed the development of an ICH Guideline on this topic with the aim of providing more extensive information to improve harmonisation amongst the ICH regions. This new topic was subsequently assigned the code “M6”. In April 2011, this topic was ceased following the ICH Steering Committee discussion. The decision was based on the opinion that the current state of science and related resource allocation would not allow this topic to be supported as a topic for harmonisation.

    Endorsed Documents

  • M6_Concept Paper Pdf
  • M6_Business Plan Pdf

  • Other Documents

  • M6_Appendix1 Pdf
  • M6_Appendix2 Pdf
  • The ICH M7 Guideline was finalised in 2014 offering guidance on analysis of Structure Activity Relationships (SAR) for genotoxicity. Furthermore, it is intended to resolve questions such as whether impurities with similar alerts that potentially have similar mechanism of action should not be combined in calculating a Threshold of Toxicological Concern (TTC) and whether the TTC may differ based on differences in the approved duration of use.

    To complement this ICH M7 Guideline an Addendum was finalised in 2017 to summarise known mutagenic impurities commonly found or used in drug synthesis. The intent of this Addendum is to provide useful information regarding the acceptable limits of known mutagenic impurities/carcinogenic and supporting monographs

    Maintenance Process

    A maintenance process has been done to incorporate acceptable limits (Acceptable Intakes (AIs) or Permitted Daily Exposures (PDEs)) for new DNA reactive (mutagenic) impurities and revising acceptable limits for impurities already listed in the Addendum as new data becomes available. Data and/or proposals pertaining to the revision of the ICH M7(R1) Guideline with supporting information can be submitted directly to the ICH Secretariat from either an ICH Member or Observer or other interested ICH stakeholders.

    Guideline

  • M7_R1 Guideline Pdf

  • Endorsed Doeuments

  • M7_R1 Concept Paper Pdf
  • M7_R1 Business Plan Pdf
  • The M7(R2) Maintenance EWG/IWG is currently undertaking a maintenance of the M7(R1) Guideline to incorporate acceptable limits (Acceptable Intakes (AIs) or Permitted Daily Exposures (PDEs)) for new DNA reactive (mutagenic) impurities and revising acceptable limits for impurities already listed in the Addendum as new data becomes available, which will result in the future ICH M7(R2) version.

    In November 2018, the Assembly endorsed the new area of work of the M7(R2) Maintenance EWG/IWG as outlined in the revised Concept Paper which was approved by the ICH Management Committee. As a result, Q&As will be developed to clarify and address Quality and Safety issues and concerns that have been identified from experience through implementation of M7 since its publication in 2014.

    Endorsed Documents

  • M7_R2_Maintenance_EWG-IWG Concept Paper Pdf
  • M7-R2_EWGIWG WorkPlan Pdf
  • The Implementation Guide and related documents for the ICH M8 electronic Common Technical Document (eCTD) v3.2.2 can be found on the ESTRI page.

    The ICH M8 electronic Common Technical Document (eCTD) v4.0 is maintained by the M8 EWG/IWG. The Implementation Guide and related documents can be found on the ESTRI page.

    ICH M8 EWG was formed in November 2010 to take over the development and revision of eCTD v4.0 Implementation Guide and related documents from the ICH M2 eCTD Subgroup. The eCTD v4.0 requirements were addressed by the Standard Development Organisation process and are included in the Health Level Seven Version 3 Regulated Product Submission Release 2 Normative standard. At the ICH Jacksonville meeting in December 2015, the ICH eCTD v4.0 Implementation Package v1.0 and Specification for Submission Formats for eCTD v1.0 was signed off for Step 4 by the Assembly. The package was updated to v1.1 to incorporate minor edits before being published. While the v4.0 is the latest version of the eCTD, v3.2.2, originally released by ICH in July 2008, is still made available in view of time needed for users to transition to the updated version.

    The M8 EWG also provides technical review and impact assessment of issues arising from the use of the ICH M4 CTD Guidelines within the context of the eCTD. This activity includes an update of M4 Annex: Granularity Document in accordance with the agreement by appropriate M4 Working Group whereas the Granularity Document continues to be owned by M4.

    ICH M8 IWG was established in conjunction with the formation of M8 EWG in November 2010, and assumed the responsibility for the implementation and maintenance of eCTD and Study Tagging File specifications from the ICH M2 eCTD Subgroup. The IWG is also responsible for implementation and maintenance of other M8 EWG deliverables (e.g. Specification for Submission Format for eCTD).

    Endorsed Documents

  • M8_EWG_IWG Concept Paper Pdf
  • M8_EWG_IWG_REVISED Concept Paper Pdf
  • M8_EWGIWG WorkPlan Pdf
  • This topic was endorsed by the ICH Assembly in October 2016. This new multidisciplinary Guideline addresses Biopharmaceutics Classification System (BCS)-based biowaivers. BCS-based biowaivers may be applicable to BCS Class I and III drugs, however BCS-based biowaivers for these two classes are not recognised worldwide. This means that pharmaceutical companies have to follow different approaches in the different regions. This Guideline provides recommendations to support the biopharmaceutics classification of medicinal products will provides recommendations to support the waiver of bioequivalence studies. This will result in the harmonisation of current regional guidance and support streamlined global drug development.

    Guideline

  • M9_Guideline_Step4 Pdf

  • Endorsed Document

  • M9_EWG_Concept Paper Pdf
  • M9_EWG_Business Plan Pdf
  • M9EWG_WorkPlan Pdf

  • WG Presentations / Trainings

  • M9_Step_4 Presentation Pdf
  • The ICH M9 Q&As provide clarity to suport the implementation of the ICH M9 Gudieline on Biopharmaceutics Classification System (BCS)-based biowaivers in ICH Regulatory Member countries/regions.

    Question And Answers

  • M9_QAsAnnex_Step4 Pdf
  • This topic was endorsed by the ICH Management Committee in October 2016. This new multidisciplinary guideline will apply to the validation of bioanalytical methods and study sample analyses in non-clinical and clinical studies. Reliable data derived through validated bioanalytical methods are key for the review of marketing authorisation application. This guideline will provide recommendations on the scientific regulatory requirements for bioanalysis conducted during the development of drugs of both chemical and biological origins. It will also address issues on method validation by considering the characteristics of the analytical methods used in bioanalysis, e.g., chromatographic assay and ligand binding assay. A harmonised Bioanalytical method validation guideline will promote the prompt, rational and effective non-clinical and clinical studies, thereby advancing the mission of the ICH.

    Guideline

  • M10_EWG Draft Guideline Pdf

  • Endorsed Documents

  • M10_EWG_Concept Paper Pdf
  • M10_EWG_Business Plan Pdf
  • M10_EWG WorkPlan Pdf

  • Guideline

  • M10_EWG_Step2 Presentation Pdf
  • This topic was endorsed by the ICH Management Committee in November 2018. This new guideline is proposed to provide comprehensive clinical protocol organization with standardised content, with both required and optional components. The guideline will outline two main sets of harmonised approaches:

    1. A template to include identification of headers, common text and a set of data fields and terminologies which will be the basis for efficiencies in data exchange.

    2. A technical specification that uses an open, non-proprietary standard to enable electronic exchange of clinical protocol information.

    Endorsed Document

  • M11_EWG Concept Paper Pdf
  • M11_EWG Business Plan Pdf
  • M11_EWG WorkPlan Pdf
  • This topic was endorsed by the ICH Assembly in June 2018.

    The M12 EWG is working on the development of a new M12 Guideline on “Drug Interaction Studies” with a view to providing a consistent approach in designing, conducting, and interpreting Drug-drug interactions studies during the development of a therapeutic product.

    Endorsed Documents

  • M12_Final Concept Paper Pdf
  • M12_Final Business Plan Pdf
  • M12_WorkPlan Pdf
  • This topic was endorsed by the ICH Assembly in November 2019, and an informal Working Group is being established to develop a Concept Paper and Business Plan.