The European Commission's latest revision of its GMP guide, effective from Jan. 31, 2012, shows the degree to which it is
responding to calls for ICH guidelines to be given greater prominence in EU rules on quality in pharmaceuticals. Chapter
1 of the guide has been changed to align it with the concepts and terminology of the ICH Q10 guideline on pharmaceutical
quality systems. It makes clear that this new chapter will also apply to two existing pieces of EU legislation on the principles
and guidelines of GMP—one, for medicines for human use, and other, for veterinary applications. References in the legislation
to "an effective quality-assurance system" that manufacturers must establish and implement will now be taken to mean the
ICH pharmaceutical quality system. "For the purposes of this chapter, these terms can be considered to be interchangeable,"
states the revised guide.
Chapter 7 of the guide on outsourced activities has also been revised to take into account the ICH Q10 guideline. The biggest
change in the GMP guide is a massive extension of Annex 2 on the manufacture of biological active substances, which has been
extended from five to 32 pages and from 43 sub-items to 70.
"The enlargement has been necessitated by the introduction of new manufacturing technologies and the increased breadth of
biological medicines into areas like gene and cell therapy," says the Commission. It is also because of the incorporation
of components of the ICH guideline on QRM. "These biological principles may display inherent variability," the new annex
states. "As a result, QRM principles are particularly important for this class of materials." The annex includes a new section
on operating principles emphasizing the need for control strategies based on QRM principles to cover various key features
of production processes.
The GMP guide may have to be further updated to highlight the importance of certain aspects of ICH guidelines because of what
EMA describes as "public health crises" due to disruption to drug supplies caused by manufacturing problems. In a discussion
paper issued in late 2012, the agency pinpointed the need for tighter controls on outsourced manufacturing to ensure that
it is GMP compliant. EMA also thought that details of the "pre-planned inclusion of failsafe manufacturing site capacity"
should possibly be included in marketing authorizations. In the longer term, the agency is considering making some QbD elements
mandatory rather than optional by requiring submissions by all marketing authorization holders of risk analyses of their
manufacturing processes to identify weaknesses.
REDUCING MEDICINE SHORTAGES
EMA is also looking to collaborate with other licensing agencies outside Europe on ways to reduce drug scarcities, including
the sharing of information about product-supply issues. EMA is already involved in a joint program with FDA on the parallel
assessment of marketing authorization and new drug applications, which include QbD approaches.
One key objective of the three-year program, due to end in March next year, is to ensure consistency between the EU and the
US in the implementation of ICH Q8, Q9, and Q10 guidelines. Assessments of applications are being done in parallel by the
two agencies after which the review teams will discuss lessons to be learned and identify knowledge gaps. The pilot scheme
should increase the momentum behind the uptake of QbD principles in Europe among both regulators and pharmaceutical manufacturers
as well as lead to a more uniform policy between the EU and the US in the use of QbD to tackle issues like drug shortages
due to production disruptions.
Sean Milmo is a freelance writer based in Essex, UK, firstname.lastname@example.org