As of 2 January 2013, all APIs imported in the EU have to be manufactured in accordance with GMP which is at least equivalent with EU-GMP. From 2 July 2013 on, APIs from Third Countries will be allowed for importation into the European Union only if one of the following options is fulfilled:
Option 1: the consignment is accompanied by a 'Written Confirmation' by the authority of the third country, certifying that the plant manufacturing active substances operates in compliance with EU-GMP, or with equivalent rules; or
Option 2: the third country has been listed by the European Commission as a country with an equivalent system of supervision and inspection as in the EU; or
Option 3: on exception and where necessary to ensure the availability of medicinal products, the need for the written confirmation can be waived by a Member State if a Member State has inspected the specific plant.
However at the moment there is still a lot of uncertainty in Europe what the future will bring. There are currently severe doubts that all APIs imported into the EU will comply with these requirements.
Here is an overview of the current status:
Option 1: Challenges with India and China
The EU Commission (COM) has published a progress report giving an overview on 20 major countries and their status of preparation for adhering to the new rules. According to this report, India and China seem to have to do more to comply with the EU requirements. Both countries currently have almost 1.000 API manufacturing sites supplying to the EU. For both, the EU confirms "good progress" but for both more work is needed - "in particular by industry stakeholders". It's similar with countries like Russia, Argentina and Malaysia.
Another thing to consider is the fact that the Chinese State Food and Drug Administration SFDA has already informed the Commission that it would not issue 'written confirmations' for manufacturing sites which are not under SFDA's supervision. These are about 30 sites. EMA is already co-ordinating the inspections of these sites (option 3).
South-Korea, South-Africa and the Ukraine have already started issuing written confirmations. According to the statement, the "situation is under control". Turkey, Mexico, Brazil, Taiwan and Canada will issue written confirmations.
Option 2: Only one country listed yet
To get on the list the EU Commission evaluates the equivalence of control standards in the respective country. So far, only Switzerland is on this list. The U.S. FDA has also filed a request for being evaluated. The authority does not mention in a statement whether they will also issue 'written confirmations' in the case they will not be listed until 2 July. However, it is very likely that the FDA's request will be answered positively. An on-site audit visit by the EU is scheduled for mid-May 2013. Japan also wants to get on the list. An on-site audit visit is planned for mid-April 2013.
The equivalence assessment for Australia is almost concluded and they seem to be the next country on the list.
Brazil has applied for listing. However, the respective documentation has not been received yet. As soon as COM receives the information, COM will start the 'equivalence assessment'.
Israel and also Singapore's request have been rejected. Both countries will start issuing written confirmations.
Option 3: Who will do all these inspections?
In December 2012, the HMA (Head of Medicines Agencies) expressed their concerns about the implementation of the new requirements in a statement which can be found on the HMA webpage. HMA representatives say: "This situation might endanger public health within the EU due to possible shortages of medicinal products for the European market and consequently become a serious public health risk." According to the HMA information 300 sites might have to be inspected. The HMA's protocol shows that the resources available in the EU countries would enable the performance of only 25 inspections by the end of June 2013.
It is impossible to predict whether the current challenges will lead to supply shortage from 2 July on. As a precautionary measure, many pharmaceutical manufacturers are currently increasing their stocks of APIs from non-EU countries.