Quality by design

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This content applies to human and veterinary medicines.

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.

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.

Parallel assessment with the United States (updated)

EMA published the final report of its join pilot programme with the United States (US) Food and Drug Administration (FDA) for the parallel assessment of sections of applications relevant to quality by design in April 2017:

The pilot aimed to:

  • share knowledge;
  • support consistent implementation of quality by design concepts in international guidelines;
  • promote the availability of medicines of consistent quality throughout the EU and the US.

Based on the experience of conducting joint assessments, EMA and FDA have published three questions-and-answers documents on lessons learnt and to clarify a number of details concerning regulatory submissions. These also addressed comments from the Japanese Pharmaceuticals and Medical Devices Agency (PMDA), which participated as an observer.

The report concludes that the both Agencies are strongly aligned on the implementation of quality by design concepts included in the ICH Q8, Q9 and Q10 guidelines.

It also foresees continued cooperation and support to innovation and global development of medicines of high quality for the benefit of patients.

The agencies are exploring potential joint activities with a focus on continuous manufacturing, additional emerging technologies, and expedited/accelerated assessments. EMA and FDA also host experts from each other’s agencies.

The pilot was initially launched for three years in 2011 and extended until April 2016. 

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
Questions and answers: improving the understanding of normal operating range (NOR), proven acceptable range (PAR), design space (DSp) and normal variability of process parameters (English only)   2017-07-13    
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 2009-06-01 2014-05-28 2006-05-01
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 2006-01-19 2014-05-28  
International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human guideline Q10 on pharmaceutical quality system - Step 5 (English only) adopted 2008-06-01 2014-05-28 2008-06-01
ICH guideline Q11 on development and manufacture of drug substances (chemical entities and biotechnological/biological entities) (English only) adopted 2013-02-11    
Reflection paper: Chemical, pharmaceutical and biological information to be included in dossiers when process analytical technology is employed (English only)   2006-03-20    
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 2000-04-05   1999-08-01
Note for guidance on parametric release (English only) adopted 2001-03-01   2001-09-01

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)   2006-12-08    

Presentations and conference documents

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