APIs produced in third countries in Asia (like China and India) can only be imported into the EU if the regulatory authority of the exporting country issues a written confirmation that those APIs have been manufactured in GMP-compliant conditions which comply with the European regulations. Moreover, the statement must also comply with the European regulations and ensure that information about non-Compliance shall be immediately reported by the authority of the third country to the EU.
It seems that neither authorities operating in the Indian provinces nor those operating in China have recognised the requirement of the EU and taken adequate measures. Although the API industry in India is concerned by the new requirement, no measure has been taken. As a consequence, some APIs might not be available in 2013. This scenario has already been raised by different industry organisations. Now the British Authority (MHRA) has also expressed their concern.
In the letter from the MHRA which was addressed to the European Commission Unit SANCO, the authority states: “the EU authorities need, urgently, to engage much more extensively with third country regulators to inform them about the changes in the legislation and to ensure that countries will issue the written confirmations that will need to accompany active substances from July 2013 onwards”. The letter goes on by saying: "we are extremely concerned that the additional burden placed on the industry may make European companies consider moving finished product manufacture offshore to reduce those burdens - this is because the requirements apply to the import of active substances only and not finished products…if the conditions for import cannot be satisfied it could potentially lead to a shortage of medicines."
How to solve this issue? Currently many APIs are manufactured outside the EU in manufacturing sites without the necessary GMP supervision. The heparin scandal has recently shown the dramatic consequences of insufficient GMP monitoring of APIs. People died in the USA after heparin batches from different workshops have been processed to APIs without any control and falsified with the cheapest oversulfated chondroitin sulphate made of partly synthetic cartilage.
If manufacturing sites within the EU have to meet the latest GMP requirements (EU GMP Part 2 equivalent to ICH Q7) why should the EU authorities allow the import of APIs which may not meet the same standards? There is clearly a challenge to assure the availability of APIs on one hand but on the other hand also to guarantee that manufacturing sites outside the EU have no cost advantages due to the fact that GMP has not been implemented and supervised.
Also in terms of quality of medicinal products, the manufacture of APIs without GMP compliance can’t be acceptable. If no “written confirmation” is provided, the pressure remains in the hands of the European authorities which should perform inspections in the third countries. The significance of the QP Declaration as well as the underlying audits of pharmaceutical manufacturers keep on increasing.
One possible solution to the problem is that EU authorities provide regulators in India and China with much more information about new regulations than they have so far. Both ministries and administrative bodies have been extensively exchanging information with these two countries for years already. Another option would be to postpone the implementation deadline for some months.
MHRA_Comments.pdf (78.5 KB)
UK_comments.pdf (75.0 KB)