Quality

The QWG is comprised of international regulatory authorities and organisations representing harmonization initiatives, who are interested in the convergence of regulatory approaches for Quality for small molecule/chemical entities and their associated drug products.

The QWG is constituted, in terms of size and representation, as determined by the IPRP Management Committee (MC) and its Terms of Reference. 

The current list of IPRP Members and Observers participating in the Quality Working Group (QWG) is the following: 

The medicines industry operates at a global level.  Drug product manufacturers seek authorisation for the same, or similar, drug product in multiple jurisdictions.  Moreover, a single drug substance manufacturer may be supplying multiple drug product manufacturers with the same drug substance, supported by the same or essentially similar Active Substance Master File (ASMF)/Drug Master File (DMF).

Significant pressures are placed on regulatory authorities and organisations (RAs) tasked with the review and authorisation of these drug products. In addition to an increased workload associated with the growing number of drug applications, RAs must also contend with more sophisticated drug products and issues associated with complex global production and distribution chains.

Different procedures and technical requirements among RAs, together with limited operational mechanisms for effective information sharing among RAs, can present challenges to bringing safe, effective and high-quality medicines to the market in a timely manner.

Despite these pressures, the timely availability of quality medicines, plays an important role in helping to address rising health care costs and in promoting access to essential medicines worldwide.

Quality issues that may arise for a specific drug product or drug substance often have widespread consequences across multiple RAs and a collaborative regulatory response to issues is beneficial.

Given these challenges, the benefits of regulatory cooperation, convergence and information sharing have long been recognised.

The strategic priorities of the IPRP create a pathway to respond to the challenges faced by RAs. They are relevant to information sharing, facilitating collaboration towards harmonisation and promoting regulatory convergence for the assessment of drug substance information (e.g., in ASMFs/DMFs) and drug products applications, to enhance the effectiveness and efficiencies of regulatory programmes.

The scope of the QWG is aligned with that of activities as outlined in the IPRP Terms of Reference, but with a focus on the implementation and interpretation of Quality requirements, the development of common assessment procedures and tools, the sharing of information related to ASMFs/DMFs and applications for drug products. This work is focused on small molecule/chemical entities and their associated drug products.

The QWG’s areas of work will complement and not duplicate established international initiatives and developments that are in progress.

• Developing common assessment tools and approaches for the assessment of quality information related to drug substances and drug products.

• Identifying opportunities and mechanisms to facilitate the sharing of information related to drug substances and drug products.

• Creating and fostering a forum of regulatory authorities and organisations to discuss best practices, regulatory or technical challenges, and supporting convergence of regulatory practices, by identifying and resolving barriers to the implementation of ICH guidelines.

The current Mandate of the Quality Working Group (QWG), approved by the Management Committee of IPRP, is the following: 

The IPRP QWG welcomes comments and questions related to our scope, which focuses on the quality aspects of small molecule/chemical entities and their associated drug products. For more information, please send an email to the IPRP Secretariat at IPRPsecretariat@ich.org. Kindly specify "IPRP QWG-Stakeholders" in the subject line.

The QWG identifies opportunities for regulatory convergence and information sharing by exchanging and discussing information from members’ organisation regarding issues of common interest related to Quality information.

Projects currently active within the QWG include:

• Repository of Technical Issues of Interest (ROTII) – Drug Substances and Drug Products

   

The current Workplan of the Quality Working Group (QWG), approved by the Management Committee of IPRP, is the following: 

ASMF/DMF Lexicon of Quality Terms (version 1.2, finalised May 2015)

IPRP ASMF/DMF Working Group members come from a variety of Regulatory Authorities (RA’s) from around the world; each with their own regulatory terminology.

To ensure a common understanding among members, a Lexicon of Quality Terms has been developed for use by members and for use in documents produced by the IRPR ASMF/DMF Working group. Since this may also be of benefit to the broader regulatory community, the decision was made to publish these terms and the result is the ASMF/DMF Lexicon of Quality Terms.

Common ASMF/DMF Submission Form (version 1.3, finalised March 2016)

The ability of IPRP members to identify common ASMF/DMFs is a key focus of the IPRP ASMF/DMF Working Group. Such identification would be facilitated if a common set of ASMF/DMF characteristics can be compared. Since key ASMF/DMF information is typically recorded by IPRP members at the time of submission, ASMF/DMF Working Group members have worked to provide guidance on the type of information that should be recorded as part of an ASMF/DMF submission.

The resulting guidance is captured in the model Common ASMF/DMF Submission form.

The use of this form, in whole or in part, by IPRP members is not mandatory. Each IPRP member works within their own specific regulatory setting and some or all aspects of a document may, for a variety of reasons, not be applicable. Equally, a given IPRP member may for practical reasons choose to revise the format or written language of a model document.

The following word version is provided as supplemental to the PDF version above.  Non-IPRP member regulators may implement these documents within their own responsibility. IPRP is not responsible for any contents of these documents implemented by non-IPRP member authorities.

Gap Analysis on ASMF/DMF frameworks and procedures

• J Pharm Pharm Sci. 2016 Apr-Jun; 19(2):290-300

By Pharmaceuticals and Medical Devices Agency (PMDA), Japan– 5 August 2016

The PMDA, on behalf of the IPRP, investigated and have published a Gap Analysis on the ASMF/DMF frameworks and procedures of IPRP members. This paper has been published in the Journal of Pharmacy and Pharmaceutical Science entitled: Similarities and Differences of International Practices and Procedures for the Regulation for Active Substance Master Files/Drug Master Files of Human Use: Moving Toward Regulatory Convergence.

Criteria for when a Separate ASMF/DMF should be Submitted

A common question often arises as to what differences in API-details may be included in a single ASMF/DMF and under what circumstances should a separate ASMF/DMF be submitted.

The IPRP performed a Gap Analysis of the ASMF systems in the various IPRP jurisdictions and a questionnaire was also circulated among members to ascertain the criteria for issuing a new ASMF.

The following common criteria have been identified by the IPRP for when a separate ASMF/DMF should be submitted. The list is indicative only and not exhaustive.  Ultimately, the legislation or regulation in force in each country takes precedence.  Nonetheless, this information is deemed useful to ASMF/DMF holders and other regulators.

Guidance for Quality Assessors –Drug Substance (Ver 1.0, finalised June 2017)

This document is primarily intended for Quality Assessors within Regulatory Agencies to facilitate the preparation of the Quality Assessment Reports (QARs), by providing guidance and assistance to Quality Assessors in the review of the technical information contained in the Quality Module (Module 3) of Active Substance Master Files (ASMFs)/Drug Master Files (DMFs) and marketing authorisation applications (MAAs).

In line with IPRP’s broader objectives, the IPRP believes that the publishing of this guidance may also be of benefit to national regulatory agencies who are not members of IPRP, and to parties responsible for the preparation of quality information that is submitted to regulatory agencies.

It should be noted that this document outlines the recommended components in the evaluation of the Quality Module. It is acknowledged that during the assessment, there may be additional components to be considered by each regulatory agency beyond this guidance depending on their legislative/regulatory/policy requirements and review practices.

Guidance for Quality Assessors –Drug Product (Ver 1.0, finalised May 2020)

The purpose of this document is to provide guidance and assistance to new and existing Quality Assessors in the assessment of the technical information contained in Drug Product Quality Module (Module 3.2.P) and to facilitate the preparation of Quality Assessment Reports (QARs).

This guidance document reflects information on the assessment of data contained in marketing authorization applications for chemical entities; it does not include guidance for the assessment of biologicals / biotechnological products.

This Guidance for Quality Assessors follows the format and terminology recommended in ICH’s CTD-Q guideline. This guidance is structured to provide recommendations on the preparation of the Quality Assessment Report (QAR), as indicated by “Information to be stated in the QAR”, followed by further guidance to assist Quality Assessors in the assessment of the technical information, as indicated by “Points to be considered during assessment”.

It should be noted that this document outlines the recommended components of an evaluation of the Drug Product Quality Module (Module 3.2.P) of the application. It is acknowledged that there may be additional components to be considered by each regulatory agency during the assessment of the Quality Module beyond this document, depending on each regulatory agencies’ legislative/regulatory/policy requirements and review practices.

ASMF/DMF Quality Assessment Report (QAR) Template (version 2.0, finalised June 2017)

The sharing of common ASMF/DMF assessment reports among ASMF/DMF Working Group members supports the broader goal of the IPRP to promote collaboration among generic drug regulators and regulatory convergence of technical requirements.

The use and the value of a shared assessment report can be increased if the presentation and placement of assessment information follows a consistent format – such as a Quality Assessment Report (QAR) template. Furthermore, the ASMF/DMF QAR template has the ability to promote regulatory convergence through a series of agreed prompts to be considered throughout the assessment of the technical information contained in an ASMF/DMF. Therefore, the IPRP Quality Working Group (QWG) has developed a Quality Assessment Report template for the Common Technical Document (CTD) Module 3.2.S for use by QWG members.

The ASMF/DMF QAR template was originally finalised in May 2015 (version 1.0) and has since undergone a maintenance process. Revisions have been incorporated into the updated version of the QAR template based on experience gained and to include other enhancements to facilitate its use. The updated version (version 2.0) and has been finalised in June 2017. 

The use of this template, in whole or in part, by IPRP members is not mandatory. Each IGDRP member works within their own specific regulatory setting and some or all aspects of a document may, for a variety of reasons, not be applicable. Equally, a given IPRP member may for practical reasons choose to revise the format or written language of a model document.

Non-IPRP member regulators may implement this document within their own responsibility. IPRP is not responsible for any contents of this document implemented by non-IGDRP member authorities.

The ASMF/DMF QAR template is published in both PDF and Word versions.

Quality Assessment Report (QAR) – Full Dossier template (Ver 1.0, finalised June 2021)

The sharing of Quality Assessment Reports (QARs) among IPRP members and observers supports the goal of the IPRP to promote efficiency and regulatory convergence by sharing best practices and developing tools as a resource for regulators to assist in the regulatory review of applications for marketing authorisation.

The use and the value of sharing QARs can be increased if the presentation and placement of information relating to these assessments follow a consistent format, such as a common template and structure. Furthermore, using a common QAR template has the opportunity to promote regulatory convergence through a series of agreed prompts to be considered throughout the assessment the Quality information contained in applications. Therefore, the IPRP Quality Working Group (QWG) has developed the IPRP Quality Assessment Report (QAR) – Full Dossier template for the assessment of technical information contained in Common Technical Document (CTD) Module 3 for use by IPRP members and observers.

The finalisation of this template now completes the suite of IPRP Quality regulatory tools for the assessment of Quality information related to drug substances and drug products, notably:

• Guidance for Quality Assessors - Drug Substance.
• Guidance for Quality Assessors - Drug Product.
• Quality Assessment Report (QAR) template - ASMFs/DMFs.
• Quality Assessment Report (QAR) template - Full Dossier.

The use of this IPRP QAR – Full Dossier template, in whole or in part, by IPRP members or observers is not mandatory. Each IPRP member or observer works within their own specific regulatory setting and some or all aspects of a document may, for a variety of reasons, not be applicable. Equally, a given IPRP member or observer may for practical reasons choose to revise the format or written language of a model document.

Non-IPRP member regulators may implement this document within their own responsibility. IPRP is not responsible for any contents of this document implemented by non-IPRP members.

The IPRP QAR – Full Dossier template is published in both PDF and Word versions.

Survey on Administrative Procedures and Terminologies for Quality Variations/Post-Approval Changes:

This article prepared by the IPRP Quality Working Group (QWG) describes the results of a survey of members and observers of QWG on their terminologies and procedural aspects for Quality variations/post-approval changes. With input from 16 regulatory authorities and organisations, the paper is intended to assist both regulators and the pharmaceutical industry in clarifying differences and aims to increase an understanding of the procedures used for changes to Active Pharmaceutical Ingredients (APIs) and drug products (e.g., reporting levels, categories of changes for prior-authorisation or notification). In addition, this work could potentially support international collaborative efforts on information sharing and regulatory convergence. Having received input from many regulatory authorities and organisations, the information compiled in this paper creates a unique opportunity to increase the knowledge and comprehension to navigate some of the complexities in regulating pharmaceuticals globally.

It should be noted that this article reflects information that was current at the time of its publication on the IPRP website. It may be updated periodically to reflect further developments or to include information for new regulatory authorities and organisations that have joined IPRP since its original development and publication.

The IPRP QWG Pilot Project of Active Substance Master File (ASMF)/Drug Master File (DMF) Database

The International Pharmaceutical Regulators Programme (IPRP) Quality Working Group (QWG) has established a pilot project to create a database that captures administrative information associated with selected ASMFs/DMFs that are filed with participating Regulatory Authorities/Organisations. The IPRP QWG members participating in this pilot project are listed below:

• Agencia Nacional de Vigilancia Sanitaria (ANVISA).

• European Directorate for the Quality of Medicines and Healthcare (EDQM).

• European Commission (EC) / European Medicines Agency (EMA).

• Federal Commission for the Protection against Sanitary Risk (COFEPRIS).

• Health Canada.

• Health Sciences Authority (HSA).

• Instituto Nacional de Vigilancia de Medicamentos y Alimentos (INVIMA).

• Ministry of Food and Drug Safety (MFDS).

• Ministry of Health, Labour and Welfare (MHLW) / Pharmaceuticals and Medical Devices Agency (PMDA).

• South African Health Products Regulatory Authority (SAHPRA).

• Swissmedic.

• Taiwan Food and Drug Administration (TFDA).

• Therapeutic Goods Administration (TGA).

• World Health Organization (WHO).

The IPRP ASMF/DMF Database has been set up in order for the participating Regulatory Authorities/Organisations to identify common ASMFs/DMFs submitted to them for selected Active Pharmaceutical Ingredients (APIs).  For the pilot phase, only a limited number of APIs are included in the scope of the project (a list of about 20 APIs of common interest has been established by the group).

The IPRP ASMF/DMF Database will include administrative information of selected ASMFs/DMFs submitted into the participating Regulatory Authorities, and will contain only the following specific details:

• Regulatory Authority/Organisation and date of submission of the ASMF/DMF to the agency.

• Active Pharmaceutical Ingredient (API) name.

• Chemical Abstracts Service (CAS) number.

• Applicant’s Part and Restricted Part version numbers and dates.

• ASMF/DMF Holder details (e.g., name, address, contact information).

• Names and address of the manufacturer for the final API.

• Whether the API is manufactured as sterile or non-sterile.

This database is stored in a non-public secure environment, hosted by the EDQM, which is accessible only by the above mentioned participating Regulatory Authorities/Organisations.  The database contains neither the ASMF/DMF dossiers themselves, nor any assessment reports prepared by the participating Regulatory Authorities/Organisations. The participating Regulatory Authorities / Organisations confirm that the information contained in the database will be treated fully confidentially and that they will gather prior consent from the ASMF/DMF holder for each report they wish to exchange.

The database provides a unique opportunity for information sharing with regards to ASMF/DMFs, and the participating Regulatory Authorities/Organisations.  The ultimate goal of these endeavours is greater regulatory cooperation, leading to faster and more consistent ASMF/DMF assessments among Regulatory Authorities/Organisations.  However, the scope of this pilot project is limited only to the sharing of administrative information that describes an ASMF/DMF.   

The pilot phase started on 1st October 2018, and a review of the activities around the database will be carried out.

Additional information:

The IPRP QWG welcomes comments on any practical matters that may need to be considered to make this pilot project a success.  Any question about this project may be sent to the IPRP secretariat - IPRPsecretariat@ich.org.

Additionally, any specific queries may be addressed directly to the regulatory authorities/organisations participating in this pilot.

• ICMRA - Pharmaceutical Quality Knowledge Management System (PQKMS) 
• ICH Quality Guidelines