Explosion of an API Manufacturing Site: Supply of Medicinal Products Endangered

In the past, if one spoke about supply shortages of medicinal products it was usually with a view to the Third World. But then the issue arrived in the USA. Regularly, diverse medicinal products are not available. We - in Europe - have so far believed that the supply of medicinal products would always be guaranteed: after all, we have a functioning health system. Far from it ... The number of cases and their consequences have reached a new level. Moreover, the focus is moving stronger and stronger to the manufacturing sites.

In October 2016, a facility of the company Qilu manufacturing the antibiotic Piperacillin exploded. Piperacillin  "is a broad-spectrum beta-lactam antibiotic of the ureidopenicillin class. The chemical structure of piperacillin and other ureidopenicillins incorporates a polar side chain that enhances penetration into Gram negative bacteria and reduces susceptibility to cleavage by Gram negative beta lactamase enzymes. [...] piperacillin is sometimes referred to as an "anti-pseudomonal penicillin" (Source: Wikipedia).

This accident at one production site has serious consequences in Germany. The Federal Institute for Drugs and Medical Devices (BfArM) announced that In Germany there is a supply shortage of mono-preparations containing Piperacillin and fixed-dose combination products (piperacillin with the beta lactamase inhibitor). It further states that on the basis of the notice made by the Federal Ministry of Health (BMG) according to § 79 section 5 of the German Medicines Act (AMG), the competent Federal authorities are now entitled to allow a temporary deviation from the AMG (German Drug Law) to allow treatments with medicinal products which are not authorised in Germany.

In one word, in Germany there is such a huge dependency on one single facility in China that a vital medicinal product is no longer available. This means that because of an accident (as in the present case) or GMP non-compliance (in other cases), a whole supply chain even in one of the richest countries in the world can be endangered. Especially the price competition has led to APIs being manufactured in Asia, i.e. in low-wage countries where safety and environmental regulations are far less stringent than in Europe. This is another factor which increases the cost advantage. According to the branch service Apotheke Adhoc, this is not a new situation: one year ago, the Ampicillin/Sulbactam combination was concerned. For around a year, doctors have had to forego fosfomycin because of the disaster in Fukushima. Furthermore, the BMG (German Ministry of Health) has declared a state of emergency already three times so far. The last time was in June. GlaxoSmithKline (GSK) was not able to deliver Infanrix hexa and Sanofi Pasteur MSD Hexyon.

The German legislator is currently examining ways of reducing such risks (and similar activities can be observed in other European countries and in the US). In addition to a reporting obligation regarding supply shortages (which is legally not required in Germany and many other EU countries yet) there should be an obligation to check whether the dependency on a few facilities (e.g. located in India and China) doesn't hinder the guarantee of patient safety. It is hoped that such initiatives won't be taken first when harms to patients have already occurred. Just recall the problems and risks around the manufacture of Heparin in China. They had been known for a long time to insiders. But it was only after Heparin had been falsified in China and led to around 250 deaths in the USA that extensive measures had been taken. At that time, manufacturing Heparin in Europe was unthinkable - mainly because of the costs. Today, Heparin is manufactured in one of the world's countries with the highest labour costs: in Germany - under strict GMP regulations!