Quality by design

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The European Medicines Agency (EMA) welcomes applications that include quality by design. Quality by design is an approach that aims to ensure the quality of medicines by employing statistical, analytical and risk-management methodology in the design, development and manufacturing of medicines.

One of the goals of quality by design is to ensure that all sources of variability affecting a process are identified, explained and managed by appropriate measures. This enables the finished medicine to consistently meet its predefined characteristics from the start - so that it is 'right first time'.

Quality by design centres on the use of multivariate analysis, often in combination with modern process-analytical chemistry methods and knowledge-management tools to enhance the identification and understanding of critical attributes of materials and critical parameters of the manufacturing process. This enhanced understanding of product and process is used to build quality into manufacturing and provide the basis for continuous improvement of products and processes.

The concepts behind quality by design were introduced in international guidelines intended for the pharmaceutical industry between 2009 and 2012.

Applications including quality by design

The Agency welcomes applications that include quality-by-design aspects. These can include applications for marketing authorisation, variations to existing marketing authorisations and scientific advice.

Applicants wishing to make use quality by design should read the guidance documents below. These include guidelines Q8, Q9, Q10 and Q11 from the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). They explain how aspects related to quality by design should be presented and explained in application dossiers.

Further guidance for applicants is available in quality by design: questions and answers.

Parallel assessment with the United States

In March 2011, the EMA and the United States (US) Food and Drug Administration (FDA) launched a pilot programme for the parallel assessment of sections of applications that are relevant to quality by design, originally for three years.

The EMA and the FDA exended this pilot for a further two years as of 1 April 2014, following a successful first phase, with parallel assessment of one marketing-authorisation application and several requests for scientific advice.

The pilot programme is open to selected procedures, including applications for initial marketing authorisations, type-II variations and scientific advice. Its objectives are to:

  • share knowledge;
  • facilitate consistent implementation of international guidelines;
  • promote the availability of medicines of consistent quality throughout the European Union (EU) and the United States.

Participation in the pilot is voluntary. Interested applicants and sponsors should notify both agencies three months prior to submission of an application.

Both agencies assess the parts of the applications relevant to quality by design, such as development, design space and real-time release testing. The evaluation is performed separately by each agency, with regular communication and consultation throughout the review. The aim is a common list of questions to the applicants and harmonised evaluation of their responses.

The agencies publish question-and-answer documents below reflecting the conclusions reached.

With the agreement of the applicants, experts from the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) participate as observers in the programme.

PAT team

The Agency set up a process analytical technology (PAT) team in November 2003 to support PAT and quality-by-design activities in the EU.

PAT is a system of controlling manufacturing through timely measurements of critical quality attributes of raw and in-process materials. It is often used as part of a quality-by-design approach.

The PAT team reviews the implications of quality by design and ensures that the European regulatory network is prepared for the evaluations of submissions including quality by design.

The team acts as a forum for dialogue between the Quality Working Party, the Biologics Working Party and the Good Manufacturing Practice / Good Distribution Practice Inspectors' Working Group.

Workshops

The Agency hosts workshops to explain the quality-by-design process and how to integrate this into applications:

Contact point

pat@ema.europa.eu

Table of contents


Guidance documents

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Document(s) Language Status First published Last updated Effective Date
International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use considerations (ICH) guideline Q8 (R2) on pharmaceutical development - Step 5 (English only) adopted 01/06/2009 28/05/2014 01/05/2006
International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) guideline Q9 on quality risk management - Step 5 (English only) adopted 19/01/2006 28/05/2014  
International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human guideline Q10 on pharmaceutical quality system - Step 5 (English only) adopted 01/06/2008 28/05/2014 01/06/2008
International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use guideline Q11 on development and manufacture of drug substances (chemical entities and biotechnological / biological entities) - Step 5 (English only) adopted 11/02/2013    
Reflection paper: Chemical, pharmaceutical and biological information to be included in dossiers when process analytical technology is employed (English only)   20/03/2006    
Decision trees for the selection of sterilisation methods (CPMP/QWP/054/98) Annex to note for guidance on development pharmaceutics (CPMP/QWP/155/96) (English only) adopted 05/04/2000   01/08/1999
Note for guidance on parametric release (English only) adopted 01/03/2001   01/09/2001

Parallel assessment with the United States

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PAT team mandate

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Document(s) Language Status First published Last updated Effective Date
Mandate for process-analytical-technology team (English only)   08/12/2006    

Presentations and conference documents

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