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New EU rules for importing API’s


The implementation of falsified medicines directive (2011/62/EU) of the European Parliament (dated June 8, 2011) in the EU has significant implications for Indian Generic Industry. These directives have 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 active substances are accompanied by a written confirmation from the competent authority of the exporting third country of the following:

  • The standards of good manufacturing practice applicable to the plant manufacturing the exported active substance are at least equivalent to those laid down by the Union pursuant to the third paragraph of Article 47; (Criteria have been given for equivalency determination by the commission.)
  • The manufacturing plant concerned is subject to regular, strict and transparent controls and to the effective enforcement of good manufacturing practice, including repeated and unannounced inspections, so as to ensure a protection of public health at least equivalent to that in the Union; and
  • In the event of findings relating to non- compliance, information on such findings is supplied by the exporting third country to the Union without any delay.


Changes to the EU’s rules governing the importation of active pharmaceutical ingredients (APIs) were opposed by the governments of India and China, who are reportedly planning a formal protest to the World Trade Organization (WTO). The changes are part of the implementation of the EU falsified medicines directive and are due to come into effect in July 2013, and were prompted by high profile safety scares such as the contaminated heparin incident that led to dozens of deaths around the world a few years ago. At the centre of the disagreements is a controversial new template for use by third country competent authorities to certify that the APIs being managed by companies in their jurisdictions comply with EU standards. The template includes a statement by the third country authority that the standards of good manufacturing practice (GMP) applicable to an API supplier’s manufacturing plant “are at least equivalent to those laid down in the EU”.


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.


Criteria for equivalency determination


In a concept paper published by European Commission titled “IMPLEMENTING ACT ON THE REQUIREMENTS FOR THE ASSEMENT OF THE REGULATORY FRAMEWORK APPLICABLE TO THE MANUFACTURING OF ACTIVE SUBSTANCES OF MEDICINAL PRODUCTS FOR HUMAN USE” has mentioned that the equivalence assessment of regulatory agency will consider:

  • The country’s rules for good manufacturing practice (GMP);
  • The regularity of inspections to verify compliance with GMP;
  • The effectiveness of enforcement of GMP and the regularity and
  • Rapidity of information provided by the third country relating to non-compliant producers of active substances.


Further the paper goes on to clarify that pending the adoption of a delegated act on the principles and guidelines of good manufacturing practice for active substances, the EU rules to be taken into account are contained in Part II of the good manufacturing practice guideline of the EU (Eudralex Volume 4).

The concept paper further gives 10 criteria which will be used for equivalence assessment of the regulatory system with that of the European Union by the EMA. These criteria are:

  • Legislative and Regulatory Requirements and Scope ,
  • Regulatory directives and policies ,
  • GMP Standards,
  • Inspection resources ,
  • Inspection procedures,
  • Inspection performance standard,
  • Enforcement powers and procedures ,
  • Alert and crisis systems, Analytical capability and
  • Quality management system.


These are elaborated further in “Compilation of Community Procedures on Inspections and Exchange of Information (5 July 2011 EMA/INS/GMP/459921/2010 Rev 13 Compliance and Inspection). The Compilation of Community Procedures on Inspections and Exchange of Information, formerly known as the Compilation of Community Procedures on Administrative Collaboration and Harmonization of Inspections, is a tool for facilitating co-operation between the GMP inspectorates of the Member States and a means of achieving harmonization.


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.


India will not be able to export medicines to Europe from 2013 unless the Indian regulatory system becomes equivalent to that in the European Union. Indian authorities recently said they will be prepared to meet the rules by determining what agency will issue the certifications. However the Indian authorities have still not realized that by appointing a new authority to issue a declaration will not meet the EU requirements listed above and that many changes are required to meet the new regulations as listed above.