Yet again, FDA has come under siege for failing to inspect a Chinese manufacturing facility. The mix-up of names because of a paperwork glitch has proven costly, not just for the US regulator, but for Baxter (IL, USA), which dominates 50% of the US heparin market.

Heparin is administered as an injection to thin blood and prevent blood clots from forming during surgery. It is a complex biologic derived from the intestinal muscose of pigs.

It seems to be a clear-cut case. Apparently, FDA confused the name of one company with another that had already received approval. Whatever the case, Baxter is feeling the heat as the latest report confirms that it is linked to a Chinese manufacturing plant.

Based on investigations, it appears that a manmade contaminant compound was used as a substitute for raw heparin. Known as oversulfated chondroitin, the compound is made from animal cartilage and is not approved for use in medicines. Norbet Riedel, Baxter's Corporate Vice President and CEO, commented that there is speculation that it is a case of counterfeit and that it may have been introduced at workshop or consolidator level.

According to Robert Rhoades, a pharmaceutical consultant for Becker & Associates (WA, USA), the contamination was found in the powdered form of raw heparin that was purchased by Scientific Protein Laboratories' (SPL [WI, USA]) suppliers in China. SPL supplies a refined form of the heparin API to Baxter from a plant in China called Changzhou SPL, along with another plant it owns in the US. The use of the heparin has been linked to four deaths in the US, which have been associated with high doses, and there have been more than 300 reported cases of allergic reactions.

FDA has been quick to go on the defensive. It claims the event is an "isolated incident" and, according to a spokeswoman, FDA is not required by law to inspect foreign manufacturing facilities. Furthermore, regular routine checks are not standard practice and the Chinese government does not inspect plants dealing with exports.

All fingers seem to point at FDA and the agency has a lot of work to do as it only inspected 13 Chinese plants last year out of a few hundred. Many have also wondered whether FDA even has details of the exact number of API manufacturers in China, as the market has grown at an exponential rate during recent years.

In the meantime, Baxter has ceased current production and initiated a thorough inquiry with FDA to establish the number of reported cases. According to the company's updated investigation report, its pharmacovigilance (safety surveillance) group is working closely with FDA and has been examining the number and types of adverse reaction, and the casual association of these reactions to the drugs.

FDA may have fallen short with foreign inspection, but it is not turning its back on the situation. Janet Woodcock, FDA's Acting Director for the Center for Drug Evaluation and Research, says: "FDA is vigorously investigating to determine the root cause of these serious reactions."

As the investigation continues, the agency is seeking advice from experts of the manufacture and clinical use of heparin. Meanwhile in the US, FDA is monitoring its post-marketing safety database for additional cases and is in touch with international regulators to determine whether similar cases have surfaced elsewhere. It has also decided to continue with the distribution of the existing heparin released by Baxter to ensure an undisrupted supply, while at the same time looking for alternate sources

However, not everyone has lost out in the heparin mess. At least APP Pharmaceuticals (Il, USA), an equally strong player as Baxter in the US heparin market, has every reason to pop the champagne bottle. It is now solely in the driver's seat to ensure a seamless supply of heparin to the US market. It has left nothing to chance and has given total assurance that its heparin sources are checked and FDA approved, including the one in China. It is also actively coordinating with suppliers to increase and arrange deliveries, and has advocated a direct shipment programme to meet emergency needs.

Tom Silberg, President of APP, says, "We have actively worked to secure sufficient raw materials and have increased production to respond swiftly to those in need of the product for the entire country."

Just as we thought the situation was more than the industry could come to terms with, FDA has also been admonished for its lack of inspection on medical devices, according to a report by the Government Accountability Office. Once again, the agency fell short on inspecting domestic establishments manufacturing Class II (e.g., hearing aids) and Class III (high risk, e.g., pacemakers) medical devices, as well as foreign facilities.

The proven bad track record of FDA has left behind a black mark. The International Trade Association and industry players are left wondering when this will ever end.