What We Don't Know May, In Fact, Hurt Us

Finally, some positive movement is taking place in Washington to fund the FDA and increase its capacity to monitor foreign manufacturers. The agency has asked for more money (finally), and Sen. Edward Kennedy proposed upping the FDA's 2009 budget by $375 million, to reach the level recommended by the Science Board. The agency also took steps to establish a permanent presence in China, and Sen. Chuck Grassley suggested creating a registration fee for foreign companies as a way to fund inspections.

Laura Bush

Yet event these important steps may not be enough to protect us from tragedies like the current heparin crisis. Because a new spectre has emerged: counterfeiting.

On March 19, the FDA said that it had identified a previously announced contaminant in Baxter's heparin as over-sulfated chondroitin sulfate. The presence of this substance leads to suspicions of counterfeiting, for several reasons. First, according to sources I spoke to, there is no obvious way this contaminant would appear in heparin by accident. Second, chondroitin is cheaper than heparin. And third, over-sulfated chondroitin is similar enough to heparin to make it hard to detect in standard assays—a big advantage for a counterfeit ingredient.

So if this is in fact a case of counterfeiting, would a better FDA foreign inspection program have been enough to protect us? That seems doubtful.

So what can we do? Unfortunately, there are no simple answers.

In the heparin case, we now know which analytical tests can detect this particular contaminant. But are these tests that any reasonable Quality Control director would have required as standard practice before this all happened? Probably not. Even though Baxter was thoroughly testing all of its incoming API, it had not foreseen the need for these specialized analyses.

Many pharma companies, however, don't conduct the level of testing that is standard at Baxter. Once a supplier has undergone extensive qualification and has a history of supplying a quality raw material, FDA regulations (see 21 CFR 211.84) permit a finished product manufacturer to conduct only one identity test and rely on the qualified supplier's certificate of analysis for the rest. I am told this is a fairly common practice in the industry. Now is a good time to reconsider that approach.

It is also a good time for companies to ensure they know their suppliers well. "I know of a few big companies with really good audit programs that include visiting suppliers several times a year," said one consultant. "But those good programs are more the exception than the rule."

To reinforce the importance of audits, that consultant cites an example from a trip to a Chinese chondroitin plant. There, he witnessed a visit by a rabbi, during which operators processed material from a bovine source. After the rabbi left, the plant went back to processing chondroitin from pig's noses. "You are not going to mix the material from the two sources, are you?" asked the consultant. "Oh yes," said the Chinese operators, unmoved by the rabbi's concerns for kosher standards. "After all, it's all the same molecule."

The management at that plant seemed to think that "what they don't know won't hurt them." The problem is, what we don't know may indeed hurt us.

Therefore, perhaps all companies should follow the example of an auditor for a Japanese cosmetics company. During his audits of his Chinese suppliers of chondroitin, the Japanese auditor drops in on the plant at all hours, including the middle of the night.

In other words, harking back to an old public service message to parents, perhaps we should ask: "It's 3:00 am in China. Do you know what your API supplier is doing?"

Laura Bush is the editor in chief of BioPharm International, lbush@advanstar.com