Last year impure heparin from Chinese manufacturers of active pharmaceutical ingredients led to grave side effects in patients in Europe and several deaths in the USA. As a consequence, the FDA intensified its inspection activities and, in doing so, did not only find GMP deficiencies in the inspected firms, but also the firms' massive attempts of concealment and deception by deliberately passing on false information. Inspections of two heparin manufacturers in China at the end of July and in August last year resulted in two warning letters, which were now published on 14 April 2009. These documents describe the facts of the case, which read like a mystery thriller.
What happened beforehand?
In the course of the inspection, the FDA investigators found out the following:
The fact that some batches of heparin were contaminated with over-sulfated chondroitin sulfate, which causes the known grave side effects, supports the suspicion that the FDA had been deceived on purpose with false information.
This case shows how important it is for manufacturers of medicinal products to know in detail the sources and the distribution chain of raw materials and active ingredients including the proceedings at all wholesalers and repackagers, especially if they come from the Far East.
Recommended event: The situation of the API manufacturers in China seen from the point of view of a GMP auditor and China expert is among the topics of the 4th EFCG Conference in Brussels on 13-14 May 2009. The details can be found here.
Dr Gerhard Becker
On behalf of the European Compliance Academy (ECA)