EU reforms rules on importing APIs

The European Union (EU) has reformed the rules for importing active pharmaceutical ingredients (APIs) for human-use medicines into Europe.

The new rules state that, from January 2 2013, all imported APIs will be required to have been manufactured in compliance with standards of Good Manufacturing Practice (GMP) at least equivalent to the GMP of the EU. The manufacturing standards in the EU for active substances are those of the International Conference for Harmonisation (ICH) Q7.

As of July 2 2013, this compliance must be confirmed in writing by the competent authority of the exporting country - the importer will need to request this confirmation from the authority in question. This document must also confirm that the plant where the active substance was manufactured is subject to control and enforcement of GMP at least equivalent to that in the EU.

Written confirmation will not need to be issued for each batch or consignment - this will be issued per manufacturing plant and for each active substance manufactured at that site. Each imported consignment will have to be accompanied by this written confirmation, although it can be a copy of the confirmation issued by the regulatory authority.

Such confirmation will be necessary if even a manufacturing site has recently been the subject of an inspection by an EU member state or by the Council of Europe's European Directorate for the Quality of Medicines (EDQM). However, exceptionally and where necessary to ensure the availability of a particular product, a member state may decide to waive the need for a written confirmation, for a period not exceeding the validity of the GMP certificate.

Also, it will be for each non-EU country to decide which body within that country will issue the confirmation - this may be at central, regional or local level.

Written confirmation will still be required where there is a mutual recognition agreement between the exporting country and the EU. However, the Commission is to publish a list of countries which, following their request, have been assessed and are considered as having equivalent rules for GMP to those in the EU. Active substances manufactured in these countries will not require a written confirmation.

So far, the countries which have requested to be included on the list are Switzerland, Israel, Australia, Singapore and Brazil. Equivalence assessments of all these requests are currently ongoing.

The new rules are contained within Directive 2011/62/EU which amends the EU Code relating to human-use medicines (Directive 2001/83/EC) with the aim of preventing the entry of falsified medicines into the legal supply chain. They do not apply to APIs to be used in investigational medicines or products to be used in R&D trials. Nor do they apply to active substances contained within imported finished medicines - for these, the current rules (importation authorisation and batch release by a qualified person (Articles 40[3] and 51 of Directive 2001/83/EC) will continue to apply.