After Heparin: - The Pew Charitable Trusts

—Chapter 1—
Opos, a company making antibiotics for the U.S. market (see case study 4). Pharmaceutical ingredients
made at uncertified plants may be offered at attractively low prices if the factory is not committing
operating expenses to complying with costly quality standards. Economic incentives may also encourage
the introduction of substitute materials specifically designed to thwart standard tests. The adulterant
found in heparin (see case study 1) was almost certainly chosen because it was a cheap substitute for the
genuine product that mimicked the real drug in U.S. Pharmacopeia (USP) assays. 193,194
In some cases, companies may remain unaware for years of supplier deception. One Chinese supplier
to U.S. manufacturer International Medication Systems, Limited (IMS) claimed to be a manufacturer of
heparin but in reality was not. This “show” factory, Shanghai No. 1, was registered with the FDA as an
exporter of heparin active ingredient to the United States and had an authorized U.S. agent, Amphastar
Pharmaceuticals Inc., which in 2004 declared to the FDA that heparin was produced at Shanghai No. 1
under GMP conditions. 195 The FDA claims that Shanghai No. 1 had in fact been shipping heparin made
at two external plants to the United States since 2001. 196 IMS had been importing this falsely labeled
heparin as early as 2001 according to the FDA, but the fraudulent activity was only discovered seven
years later. Further, the FDA alleges that some heparin shipped to the United States by Shanghai No.
1 in 2008 (but made elsewhere) may have contained the same heparin adulterant associated with U.S.
patient adverse events. 197,198,*
APIs are at particular risk of falsification. One pharmaceutical auditor working in China observed during
inspections and audits that for 39 percent of exported APIs, the final European or American customer
was misinformed about the identity of the manufacturing site where all or part of the manufacturing
took place. 199 He occasionally sees uncertified API concealed in hidden factory rooms or warehouses (see
figure 10). 200 Pharmaceutical brokers and traders have also been responsible for concealing the source of
drug products, and failing to adequately verify the products they buy and sell. For instance, diethylene
glycol (an industrial solvent) has been labeled as glycerin (a common inactive ingredient for cold and
cough syrups) and sold into distribution numerous times, causing hundreds of deaths (see case study 5).
Figure 10
European inspectors in Zhejiang, China, found empty drums
blocking access to part of a certified API plant exporting to
Europe and the United States. Further investigation revealed
a vast warehouse of substandard or falsely certified APIs.
Image courtesy of Philippe André, Associate Professor at the School
of Pharmaceutical Science and Technology at Tianjin University,
China (2008). 201
* Shanghai No. 1 was not part of Baxter Inc.’s heparin supply chain.
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Pew Health Group