(Image: Genentech)

By Kamal Menghrajani

Last month the Food and Drug Administration warned 19 doctors and clinics that counterfeit vials of the chemotherapy drug Avastin had been identified in the U.S. Most of those doctors were in California. Today the Wall Street Journal reports that the FDA is investigating two businessmen from Canada who may be the source of these vials. One of them had admitted to shipping fake Avastin last year, although he says he did not know the vials contained counterfeit drugs. While it is generally illegal for anyone but the manufacturer to import prescription drugs into the U.S., it happens frequently and has proven difficult to police, the Journal reports.

“We’re deeply horrified by this counterfeit [product] being sold by one of my companies,” said Thomas Haughton, a Canadian citizen who runs a network of drug distributors that sell to U.S. doctors. At the same time he said that his business operated legally. “We’re doing everything we can to be sure that this never happens again.”

While experts say most U.S. drugs are safe, the probe may raise new concerns about the weakly regulated gray market in foreign drugs aimed at U.S. patients. The importation of foreign drugs by third parties, which takes advantage of the large price differential between the U.S. market and others abroad, is believed to represent a small but growing portion of the $300 billion U.S. prescription pharmaceutical business.

Haughton’s brother-in-law, Kris Thorkelson, is the second man under investigation. Both Haughton and Thorkelson sell low-cost medicines to doctors or directly to patients in the U.S. According to the Journal their Canada-based businesses are thought to be the end of a supply chain of counterfeit Avastin that may have started in China and made its way through Turkey, Egypt, Sweden, and Denmark before going through Canada to get to Tennessee. Tennessee-based Volunteer Distribution was then suspected of funneling those vials out to various clinics throughout the country, most of which were in Southern California. Again, from the Journal:

In the last several days, the U.S. Attorney in Los Angeles has subpoenaed California physicians for documents about their dealings with and products purchased from Messrs. Haughton and Thorkelson, three people who have worked for them and 12 companies that are affiliated with one or the other man, according to a copy of a subpoena reviewed by The Wall Street Journal.

At least some of the doctors who received a subpoena were warned last month by the FDA that they may have purchased fake Avastin from three companies named in the subpoena and linked to Mr. Haughton. The FDA, which is leading the investigation, declined to comment on the subpoenas or the ongoing investigation.

The fake Avastin contained starch, salt, cleaning solvents and other chemicals and none of the drug’s active ingredient, bevacizumab, according to Roche. The packaging didn’t match U.S.-approved labels for the product, regulators said. As of Monday, the FDA hadn’t received any reports of the fake Avastin being administered to patients.

The FDA is pursuing a criminal investigation against the Canadian drug sellers for shipping non-FDA approved drugs into the U.S.

(Zaldylmg: Flickr)

Stories of critical drug shortages–including cancer drugs–have been making news for months. Now the Food and Drug Administration is announcing that replacement supplies of two of those drugs, Doxil and methotrexate, should be available within weeks.

Both drugs are used to treat cancer. Methotrexate is used for many conditions, but of particular concern is its use for a type of childhood leukemia. If a child does not get the drug, the cancer can easily recur.

As the New York Times reports, some experts say the new supplies are only a temporary solution:

Dr. Peter C. Adamson, chairman of the Children’s Oncology Group, which is financed by the National Cancer Institute, said he was pleased that the immediate threat of a methotrexate shortage had passed. “But this is at best a Band-Aid approach to the problem,” he said.

Shortages of both drugs developed when Ben Venue Laboratories temporarily closed its manufacturing facility in Bedford, Ohio, because it could not guarantee product safety.

In the case of Doxil, which is used to treat ovarian cancer, multiple myeloma and AIDS-related Kaposi’s sarcoma, the F.D.A. has decided to allow temporary shipments from India of Lipodox, which is similar to Doxil and is made by Sun Pharma Global.

The FDA says it is also permitting the pharmaceutical company Hospira to ship 31,000 vials of methotrexate from its overseas facilities to hospitals and treatment centers across the U.S. This quantity of vials is enough to meet U.S. demand for one month.

At UC San Francisco, oncologist Alan Venook, said drug shortages have affected his practice as well. But he expressed concern about drugs coming from overseas. “You do worry about quality assurance, this is a real issue,” he told me. “is it a good solution? I don’t think so, but it probably will be fine.”

Venook treats patients with gastrointestinal cancers. Last summer, his group experienced a shortage of a chemotherapy drug. “We didn’t have enough drug for all 40 patients we would have treated,” he said. “Each week we would have a conference call on Thursday where we would decide who we were going to treat next week.”

One of those 40 patients was Jay Cuetara who was being treated for stage 4 rectal cancer. One day last August he came to the clinic, only to discover there was no drug for him. “I was shocked,” he said. “I wasn’t angry. I was shocked.  How can we not have the drug I need in the United States? How does that work?”

Ultimately, that one session was the only one he missed. But that was all it took. He has become an activist on the issue and has testified before Congress. There are bills before both the House and the Senate to give the FDA more legal authority to prevent drug shortages.

(Eric: Flickr)

The announcement by the Food and Drug Administration last week that sixteen California clinics and physicians were sold bogus vials of the cancer drug Avastin did not surprise regulators and researchers who study the counterfeit drug trade.

Indeed, it was after fake AIDS drugs were discovered in California that state legislators passed the “e-pedigree law“ mandating that all prescription drugs carry an electronic tag. The tag could be scanned to show where the drug was first manufactured and every stop along its way to market.

Since the law passed in 2004, biotech and pharmaceutical trade groups fought to delay its implementation. They argued, successfully, that the electronic track-and-trace system would up-end global drug manufacturing.

Finally the system is going into effect, says Virginia Herold, head of the state Board of Pharmacy. But it will still be awhile. “In January 2015, 50 percent of a manufacturer’s products that will be sold into California have to have this unique serialized number of each container,” she says.

The remaining half must have the serialized numbers by the following year — and in subsequent years the system will become more robust. Herold says the the electronic tags can stop incidents like the recent sale of the adulterated Avastin.

“The wholesaler, when it purchased the product would have had to certify, ‘Yes, I just bought this from Roche.’ Well, Roche didn’t manufacture the product. Somebody else did.”

But Brian Liang, Director of the Center for Patient Safety at UC San Diego, says electronic tags won’t end the fake drug business, because counterfeiters often avoid wholesalers. “These are people who are coming at it from a completely different underground approach,” he says.

Liang says counterfeiters will try to sell directly to clinics and doctors by bombarding them with faxes advertising cheap drugs. But there are resources available now, he says, that clinics and patients can turn to.

“We have authorized wholesalers who are in fact listed by the government and National Association of Boards of Pharmacy, they also list wholesalers. If it’s a source you’re not familiar with you really should find out: Is this source legitimate?”

State regulators say about 1 percent of the 400 million prescriptions dispersed in California each year are fake. That’s about four million prescriptions that have too little or too much of the right active ingredients or no active ingredients at all.

Listen to the Story:

(Courtesy: Genentech)

A counterfeit version of the cancer drug Avastin may have made its way into clinics here in California. The medicine is used to treat colon, lung, and other cancers, but several physicians may have unwittingly been giving patients a useless knock-off.

You may remember Avastin because it was considered a blockbuster drug for breast cancer treatment. That was until November of last year, when the Food and Drug Administration (FDA) pulled its approval for treating the disease. However, Avastin is still widely used for other types of cancer.

Earlier this month, the FDA sent letters to 19 doctors around the country warning that they may have fake Avastin. Sixteen of these physicians are here in California, all of them in Southern California.

The FDA says these clinics purchased the medicine from a foreign supplier under the names “Quality Specialty Products” or “Montana Health Care Solutions.” Volunteer Distribution, a company based in Tennessee, funneled the fake vials out to clinics. The company was not licensed by drugmaker Genentech to provide Avastin, and some doctors’ offices were fooled.

“I think we’re all shaken up by it. This isn’t like Viagra – this is life and death when you’re dealing with cancer,” said Tracey Butler, Director of Operations for the Beverly Hills Cancer Center, which received the FDA warning. “We’re in this business so that we can find a cure for cancer, so to think that somebody out there would harm that, is very disturbing.”

Despite having had a past contract with Montana Health Care Solutions, Butler’s clinic did not have the counterfeit Avastin. “We looked through our stocks as soon as the FDA notified us about a month ago and we had nothing from them.”

Calls to Volunteer Distribution went unanswered. Nobody at the Gainesboro, Tennessee company answered the phone when we called.

Andrew Selesnick is a lawyer who represents one of the doctors who received a letter from the FDA. Until this incident, he told me, “I don’t think [doctors] looked at this as an issue to be concerned about, but now I think a lot of physicians are looking at their drug purchasing protocol in a different light.”

“It’s a low person who would replace a cancer-fighting drug with a counterfeit,” he added.

Genentech has been analyzing the counterfeits to determine what is in the vials. Charlotte Arnold, a spokesperson for the company said, “We do know that it doesn’t have the active ingredient for Avastin or any biologic effective for treating cancer,” she said. “We do know that there’s not anti-cancer medicine in there. … It’s not safe or effective and should not be used.”

She says counterfeiting may not be restricted to Avastin, as the FDA is currently investigating whether other fake anti-cancer drugs are circulating in the U.S. “The FDA issued a notice [PDF] in January that mentioned Rituxin and Herceptin, but there was no confirmed counterfeit, as there was in this case.”

Dr. Margaret Hamburg, FDA Commissioner. (US Mission Geneva: Flickr)

Last week, the big story may have been the Susan G. Komen Foundation’s flip-flopping over funding Planned Parenthood. But coming in a close second (at least here at the health desk) was the call for regulating sugar in the same way alcohol and tobacco are. The argument was made by UC San Francisco researchers in the journal Nature. They laid out the science that sugar is behind many of the chronic maladies we see today–diabetes, heart disease and high blood pressure.

Today FDA Commissioner Margaret Hamburg was a guest on KQED’s Forum. Host Michael Krasny asked her if sugar should be removed from the FDA’s “GRAS” category–that’s for Generally Recognized as Safe. Not surprisingly, the Commissioner did not announce imminent action. She said she did have a chance to “look quickly at the initial report” and that “we’ll look very seriously at any new data that’s presented.”

In other words, nothing will be happening soon, just as researcher Robert Lustig expected when I talked to him last week. The commentary was an “opening salvo,” he said. “Nothing in public health changes overnight. It’s not possible to.”

Here’s the Commissioner’s complete response to Krasny’s question:

Sugar is one important area of nutrition where there’s enormous interest in deepening our understanding of the health risks and benefits. It’s an area where consumers want to know more about what’s in the food that they’re eating and where the FDA has a critical role to play in terms of both supporting and building on important new research insights and through our responsibilities for providing accurate information about the content of processed foods.

As the Commissioner continued speaking, she seemed in this next section to be choosing her words very carefully:

So, it’s an important area that sugar, along with other critical nutritional issues, such as sodium and saturated fats and overall calories all require strengthening our understanding of the science and really understanding individual and public health issues and linking that to what we do at the FDA.

Then she picked up steam again here:

But I have had a chance to look quickly at this initial report, I understand the request that’s being made. We’ll look very seriously at any new data that’s presented. In the meantime, consumers should be aware that nutritional information is provided on the back of processed food packages that enables them to look at the relative contribution of different types of sugars in the foods that they’re eating along with other nutritional components and it’s an opportunity to make more informed choices about the food they eat and the food they serve their families.

More:

The Trouble with Sugar on Forum, February 2, 2012

(Courtesy: Genentech)

FDA Commissioner Dr. Margaret Hamburg announced this morning that the agency is revoking approval of Avastin as a treatment for metastatic breast cancer. The Agency had “fast tracked” the approval of the drug in 2008, based on results of one study, but had requested additional research. Those follow up studies did not support the initial findings, the FDA has decided.

NPR’s Shots blog reports on today’s events as well as the history behind the decision.

Hamburg lays out the reasoning for the rare move in a 69-page decision. In a news briefing Friday morning, she said of the drug: “It’s clear there is no benefit to breast cancer patients that would justify its risks.” She said she didn’t “come to this decision lightly but as a result of a rigorous process.”

Roche’s Genentech unit, maker of Avastin said in a statement, “We are disappointed with this outcome.” The company said it will help women “who may be facing obstacles to receiving their treatment” with the drug through a patient-support program. It’s also continuing research on the use of the drug for breast cancer.

Avastin’s side effects are serious, including heart attack or heart failure, severe high blood pressure, and perforations in different parts of the body such as the stomach and intestines.

In a letter to the New England Journal of Medicine, Dr. Mikkael A. Sekeres, an oncologist with the FDA’s Advisory Committee on this issue, summed up the limitations of Avastin in a question he would pose to a patient:

“Well, I can offer you a drug that will not make you live longer, won’t make you feel better, and may have life-threatening side effects, but it will keep your cancer from worsening by an average of 1 to 2 months.”

Hope? Or false hope?

The San Francisco-based advocacy group Breast Cancer Action had opposed the use of Avastin to treat metastatic breast cancer since 2007, before the FDA’s initial approval, over concerns about efficacy and side effects. Today, Karuna Jaggar, Breast Cancer Action’s Executive Director, applauded the FDA’s decision.

“I want to note that we all are on the same side and we absolutely want more effective treatment options for women with metastatic breast cancer. That being said, we cannot allow companies to sell hope and we continue to seek treatments that work.”