FDA official gives insight into heparin case

By Nick Taylor

- Last updated on GMT

Related tags: Chondroitin sulfate, Heparin

Following fresh criticism of the agency’s handling of the heparin case, in-PharmaTechnologist reports on a FDA official’s explanation of the what, the when and the why of the scandal, from first deaths to continued vigilance.

The details were given in a speech at this year’s AAPS by Ali Al-hakim, a US Food and Drug Administration (FDA) official involved in the heparin case. Al-hakim discussed the ongoing activities of the FDA, which include research into development of better screening methods.

Currently there is only one method accepted by the FDA but the agency is attempting to develop others. The intention is that the new test would identify not only oversulfated chondroitin sulfate (OSCS) but also other compounds that could in theory be added to heparin.

Al-hakim explained that polysaccharides from bacteria, plants and animals can be manipulated so that they resemble heparin and avoid detection by current testing systems. In previous talks he had shown a slide detailing the composition of the potential contaminants but had been warned against doing so in case it helped fraudsters.

Although he has stopped showing the slide Al-hakim said the cost of developing these potential candidates would make it uneconomical for fraudsters.

Nonetheless the FDA is continuing to update its detection methods and is also working with the US Pharmacopeia (USP) to revise the current monograph, which has been in use since 1950. This is one aspect of the continuing cooperation between the FDA and international bodies to ensure safe supplies of heparin.

An additional layer of security is also being implemented, with the FDA working with heparin manufacturers to incorporate new contaminant tests into their specifications.

These measures are deemed necessary as the world will always need to source the majority of its heparin from China owing to the large number of pigs the nation kills, according to Al-hakim.

He added that the US alone uses two tonnes of heparin a month, with 70 per cent of this originating in China.

A dark and complex tale

Al-hakim also spoke about how the factors that enabled the contaminant to enter the supply chain and difficulties the FDA faced in identifying and dealing with the contaminant.

The complexity of heparin, which contains 1000s of molecules, makes it very difficult to identify impurities. Consequently the USP’ tests were unable to detect the OSCS used by the fraudsters, who Al-hakim described as “very clever​”, as it is incredibly similar to heparin.

Al-hakim said that research had been published in journals in early 2000 detailing the synthesis of OSCS and its similarity to heparin; seven years later allergic or hypotensive reactions to heparin skyrocketed.

The FDA worked with others around the globe to identify the contaminant, using capillary electrophoretic (CE) and nuclear magnetic resonance analysis.

OSCS was identified as the contaminant but the FDA still had the problem of locating the source of the problem. This was complicated as the chondroitin was taken from a variety of sources and the solvents and reagents used were not known.

In addition the composition of the adulterated batches varied and some of the facilities were found to have produced clean and contaminated batches of heparin.

This complicated and lengthy process has resulted in 16 Chinese facilities being implicated in the contamination but as detailed above, the FDA’s battle is far from over.

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