In Britain alone - the transit point for a second fake batch of the cancer drug uncovered in the U.S. market - there are around 1,800 licensed wholesalers, according to the Medicines and Healthcare products Regulatory Agency (MHRA).

That is the second highest number of pharmaceutical middlemen in Europe after Germany, where there are more than 3,000 - simply too many to allow for proper supervision, according to drug manufacturers, who have long complained about the ease with which medicines are shipped across borders.

"We are concerned that the MHRA doesn't have sufficient resources to inspect all the premises that have a wholesale dealer license," said Malcolm West, a supply chain expert at the Association of the British Pharmaceutical Industry.

Lack of regular inspections increases the risk of things going wrong, which is what happened in the latest case involving bogus vials shipped from Turkey via Britain. The fake drugs contained none of Avastin's active ingredient, bevacizumab.

Two UK-based wholesalers - Richard's Pharma and River East Supplies - exported the fake versions of the injectable drug to the United States. The supplies were labeled as Altuzan, which is the Turkish brand name for Avastin, according to the MHRA.

That pattern of trade from the Middle East through Europe to the U.S. mirrors what was seen when fake Avastin first hit the headlines in February, underscoring the vulnerability of the global medicine supply chain.

The initial case also involved River East.

Officials at Richard's Pharma and River East - both of which have UK licenses allowing them to trade in "biological products" such as Avastin - did not respond to repeated telephone calls asking for comment.

PARALLEL TRADE

The vast majority of medicines dispensed in Britain come from big multinational wholesalers like Celesio and Alliance Boots, but the MHRA figures show there is also a long tail of such smaller companies.

These independent firms typically buy products in one country and sell them in another at a higher price in a short-term arbitrage trade.

This "parallel" trade is perfectly legal, under European laws protecting free movement of goods, and also helps keep prices down, according to the European Association of Euro-Pharmaceutical Companies, representing parallel traders.

But the practice is still controversial.

In Britain, a parliamentary committee has been investigating shortages of some medicines in the wake of complaints that supplies are being sucked out of the country by parallel trade. The final session of the inquiry was held last week.

Exports from Britain have been encouraged by a weak pound, which makes the country a cheap place for middlemen to source medicines. A few years back, British prices were relatively high and, as a result, there were extensive parallel imports.

(Editing by Andrew Callus)

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