Implementation of Quality by Design (QbD) Principles in Regulatory Dossiers of Medicinal Products in the European Union (EU) Between 2014 and 2019.

BACKGROUND

Quality by Design (QbD) is a systematic risk-based approach to development, with predefined characteristics and quality risk management throughout the life cycle of a product. International Conference on Harmonization (ICH) guidelines Q8-Q11 give guidance on QbD applications with ICH Q8 (R2)-approved in 2009-describing the principles of QbD in detail. Since its adoption over 10 years ago, more information about QbD usage for the development of medicinal products is expected to be written in regulatory dossiers by companies.

METHODS

The present study set out to evaluate the implementation of QbD principles and elements in all EU approved marketing applications (MA) (n = 494), based on information available in the European Public Assessment Reports (EPARs), for a period of six years (2014-2019), starting 5 years after QbD adoption.

RESULTS

Of the 494 MAs, 271 were submitted with a full dossier (article 8(3)). According to EMA (38%), out of the 271 full dossier submissions, only 104 were developed using full QbD. This figure did not increase during this period. Interestingly, between 2014 and 2019, several MAs were not developed via full QbD implementation but used one or more QbD elements during development, including design space. In addition, a higher percentage of small molecule products were developed with QbD as opposed to biotechnology-derived products (78% vs. 22%, respectively).

CONCLUSION

Overall, QbD during development of medicinal products is still not commonly described in dossiers. However, more companies started mentioning QbD elements, thus making it a promising step toward QbD as the standard for development in the future.