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The EU Stiffens its Requirements for Imported APIs with New Rules

“As of 2 January 2013, all imported active substances must have been manufactured in compliance with standards of good manufacturing practices (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.”

With these words, the EU has stepped up its war on counterfeit and substandard imports of APIs and drug substances into member countries. This new regulation requires that GMP compliance of the API manufacture for all products imported into the EU must be confirmed in writing by the regulatory authority of the exporting country. This document should also confirm that the manufacturing plant is subject to regulatory control and enforcement of GMP practices at least equivalent to that in Europe. This written documentation of GMP compliance must cover both the API manufacturing site and specific APIs (drug substances) produced at the facility. Once the EMA has accepted this documentation, additional batches of the same API from the same facility can be imported into EU Member States provided that each imported consignment is accompanied by a copy of the approved certificate. The certification will be required even if the manufacturing site has recently been inspected by an EU Member State or by the European Directorate for the Quality of Medicines (EDQM) of the Council of Europe.

Countries can, however, request that they be included on a list to be compiled by the Commission which specifies the country as having equivalent GMP rules to those of the EU. Active substances manufactured in such countries will not require written confirmation of GMP compliance for each batch of product imported. So far, only Switzerland and Israel have made a formal request.

While it is likely that licensed API manufacturers in the USA will eventually become exempt from the new regulation, this will only happen after FDA has made a formal request to have the United States included on the list. We expect that pressure from US exporters of APIs and DS will encourage the FDA to do the same, but the Agency may raise a question of priorities – how important are these exports? Do they warrant the additional paperwork involved? FDA’s website states that export certificates for finished pharmaceuticals carry a fee of $175.00 if the certificate is issued within 20 government working days. Since the export of finished products is much larger than that of APIs, one might expect that this is where the priority will rest, and the API exporters may have to wait.

FDA is also tightening the importation of APIs into the US. Under an Import Alert issued on August 14, 2012, field officers are being advised to employ the Establishment Evaluation System to determine whether an imported API and its manufacturer are actually covered by a valid NDA/IND. The notice also includes a “Red List” of overseas companies whose specified products will be detained without examination.

We support this move by the Europeans and hope that other major manufacturing countries will soon enact similar legislation to control the global flow of APIs. The new rule should be sufficient to control imports from those countries with an efficient regulatory authority and help pave the road for more efficient importation of APIs into the EU from manufacturers located in countries that are in compliance with these rules as the GMP certification should remove the need for time consuming and costly retesting of APIs.

But the question still remains – is a GMP certificate going to guarantee the quality of the imported API, if it comes from a less reliable source? While a big step forward in ensuring product quality, we believe that it will not replace the need to test the material received, as relying solely on the manufacturer’s CoA will still present risks of product quality and patient safety. Caveat emptor (“Let the buyer beware”) still rules the day.


Blog article by: Lars Skriver, Alex Kanarek, and Howard Levine