The European Commission (EC) and the European Medicines Agency (EMA), have been supporting quality-by-design (QbD) concepts
over the past 10 years. In 2003, EMA set up a team to back activities in process analytical technology (PAT) in the EU. The
agency has seen its PAT team as a key element in the implementation of QbD by encouraging process understanding. This knowledge
becomes a basis for achieving quality by ensuring pre-defined quality criteria are met through design rather than ad-hoc testing. However, EMA has not been a strong driving force behind the adoption of QbD in the EU compared with FDA in the United
Recently, both EMA and the EC have experienced pressure from the pharmaceutical industry, particularly in the biopharmaceutical
sector, to do more to encourage QbD. In addition, EU authorities are becoming more concerned about the increasing number
of quality defects in pharmaceutical manufacturing that have been causing a rise in drug scarcities.
The industry has been wanting to see greater use of the Q8, Q9, and Q10 guidelines of the International Conference on Harmonization
(ICH), which contain most of the basic QbD principles. These guidelines cover pharmaceutical development concepts in Q8,
quality risk management (QRM) in Q9, and a pharmaceutical quality system to be implemented in the different stages of a product
lifecycle in Q10. The ICH guidelines offer pharmaceutical manufacturers the option of taking the "minimal" or traditional
approach to quality assurance or an "enhanced" structured approach, which involves concepts like critical quality attributes
(CQA), design space, and control strategies.
The industry has been urging EU authorities to put more emphasis in regulations and guidelines on the enhanced attitude
to quality, particularly because QbD is seen as a means for easing the regulatory burden with less need for inspections and
post-approval submissions. EMA has, however, stressed that the adoption of an enhanced QbD approach by drug producers is
optional rather than a requirement.
In comments published last year on proposed changes yet to be finalized to EU regulations on approval of manufacturing variations
after marketing authorization, pharmaceutical trade associations called for more accommodation of elements of the ICH guidelines
in the legislation. EuropaBio, which represents both biotechnology companies and national associations in Europe, said in
its comments, published in July 2012 on a proposed revised guideline on variations, that greater recognition should be given
to an enhanced QbD approach. This approach would provide opportunities for "a more science- and risk-based approach" in assessing
In a joint comment, the European Federation of Pharmaceutical Industries and Associations (EFPIA), representing original drug
producers, European Biopharmaceutical Enterprises (EBE), and European Vaccine Manufacturers (EVM), urged the EC to make clear
in legal text that changes within a design space did not constitute variations that need to be approved. Design space is defined
as a QbD component that sets the combination of variables and process parameters providing assurance of quality.
The pharmaceutical industry in Europe sees QbD concepts as reflecting existing practices in the sector. Introducing them in
regulations and guidelines gives more emphasis to the important elements in quality assurance.
"The adoption of ICH Q8–10 is not introducing new requirements or expectations," says Julie Marechal-Jamil, senior manager
of quality and regulatory affairs at the European Generic Medicines Association (EGA), Brussels. "But the regulatory adoption
of the guidelines is clarifying what elements are considered essential to support the pharmaceutical development section
of a marketing authorization application dossier." Nonetheless, she claimed that "many practical questions regarding implementation
of QbD remain open—even for medicines originators."