The European Union is making changes to its good manufacturing practice (GMP) guidelines at a pace that is threatening to
move the region out of sync with global GMP rules, in particular with the US and Japan. The objective of the changes, put
forward by the European Commission, the executive body of the Brussels-based EU, is to help pharmaceutical manufacturers reinforce
quality controls over their suppliers, particularly in the area of active pharmaceutical ingredients (APIs).
The alterations to the EU GMP code (Directives 91/356/EEC, as amended by Directive 2003/94/EC and 91/412/EEC) were originally
drafted to support the 2003 EU legislation on GMP for medicinal products and are considered binding on industry. They are
largely based on the more recent quality guidelines adopted by the International Conference on Harmonization (ICH).
Although the ICH guidelines are meant to harmonize practices between the primary member regions (the European Union, Japan,
and United States), the European Commission and its regulatory authority, the European Medicines Agency, have been acting
ahead of their ICH partners. For example, the Commission recently finalized amendments to its quality risk management of APIs
guideline that incorporated principles introduced in the ICH Q9 Quality Risk Management. The US and Japan, even though they have published ICH Q9 as a guidance for industry, have not gone as far as updating binding
legislation (e.g., the Code of Federal Regulations sections that apply to drug manufacturing) to date.
In November, the Commission and EMA proposed changes to a chapter in the EU GMP Guide on contract manufacturing to broaden
the guideline's coverage of outsourcing activities. The potential changes correspond to language in the ICH Q10 Pharmaceutical Quality System guideline that was adopted by the three ICH regions in June 2008. The alterations make clear the drug manufacturer's responsibilities
for ensuring that quality control systems are in place throughout the supply chain and that suppliers are competent in GMP.
The Commission also put forward in November suggestions for changes to rules on starting materials which are, at the moment,
not covered by any ICH guidelines (ICH Q11, which is still in Step 2 of the harmonization process, may address this topic
in part). The suggestions stipulate that all aspects of the production and control of starting materials be documented, that
purchasing staff should have a "thorough knowledge of suppliers," and that the suppliers themselves be periodically audited.
These modifications, like others proposed by the Commission during the past few months, are now undergoing a consultation
period with industry stakeholders.
"Experience has shown that some manufacturers do not adequately qualify their suppliers, do not have good knowledge of the
supply chain or fail to control it properly," says an EMA spokesperson. "Regulators perceive an increasing risk in this area
and as the heparin incident illustrates, failures can have disastrous consequences."