heparin

FDA seizes tainted Celsus heparin

Tracy Staton — Fri, 07 Nov 2008 10:40:35 -0500

The heparin debacle that began in January is still haunting the drug industry. The FDA actually sent federal marshals to seize 11 lots of the blood thinner from Celsus Laboratories, a Cincinnati company that hadn't complied with the agency's repeated requests for a recall.

Celsus distributes heparin to drug and medical-device manufacturers in the U.S. and abroad. During an April inspection, the FDA found contaminated heparin in two kinds of products, some for use directly in patients and others intended for diagnostic kits and medical devices.

As you know, contaminated lots of the blood thinner--largely sold by Baxter--led to hundreds of allergic reactions and deaths earlier this year, triggering an international recall. The FDA eventually traced the contamination to facilities in China and identified the contaminant as over-sulfated chondroitin sulfate.

FDA found the same contaminant in Celsus' products. That company's heparin had entered the U.S. before the agency slapped import controls on the drug. Celsus notified customers that the contaminant had surfaced in its products, but FDA said that wasn't enough to ensure that the tainted heparin wouldn't be used. After the seizure, Mike Chappell, The FDA's acting associate commissioner for regulatory affairs, said, "This action will help prevent this contaminated heparin fro finding its way into the marketplace."

- read the USA Today story
- see the news from the Associated Press
- check out the article at PharmaTimes

Adverse event reports hit record high

Tracy Staton — Thu, 23 Oct 2008 11:04:40 -0400

Prescription drugs posted a new record during the first quarter of this year, but it's a milestone drugmakers would probably rather forget. The number of deaths and serious injuries associated with prescription drug use rose to new highs, with 4,825 deaths and nearly 21,000 injuries, a watchdog group said. That's nearly a threefold rise from the previous quarter and 38 percent more than last year's quarterly average.

According to the Institute for Safe Medication Practices, the Pfizer stop-smoking drug Chantix tallied the most adverse reports, with 1,001 injuries and 50 deaths. As you know, Chantix has attracted widespread media attention for the psychiatric effects--even suicide attempts--seen in some of its users. (That attention probably boosted the number of reports, too.)

Second on the list was the blood thinner heparin--subject of a much-publicized recall and an international investigation--which was associated with 779 injuries and 102 deaths. These adverse reactions were traced back to contamination of raw heparin used to make the drug.

The Institute took its stats from the FDA's adverse events reporting system, which can be problematic for a couple of reasons. One, adverse events often go unreported, so the numbers can understate the problem. But--and this is the second reason--the individual reports don't prove that the drug caused the problem.

- read the story in the Los Angeles Times
- check out the WSJ Health Blog post

FDA finds 'final link' in heparin case

Tracy Staton — Thu, 31 Jul 2008 09:44:34 -0400

For the first time, the FDA has conclusively tied patients' deaths to the contaminant found in Baxter's heparin blood thinner. Of 10 deaths reported from anaphylactic shock, three of them were traced to lot numbers of the drug that tested positive for oversulfated chondroitin sulfate. (The lot numbers of the other seven weren't known.) "We have what looks like cause and effect in some patients," Dr. Janet Woodcock, CDER chief, told the Chicago Tribune. "This is one of the final links in the chain."

As you know, Baxter recalled its heparin products in February after a spike in severe allergic reactions to the drug. The investigation led to suppliers in China, which, some officials said, may have contaminated raw heparin deliberately to save money. In the process, the probe raised questions about just how close an eye drugmakers keep on their foreign supply chains; Baxter admitted that it didn't know much about the ultimate source of the ingredient it bought from Scientific Protein Laboratories, which operated a plant in China. All told, FDA counted more than reports of more than 90 deaths and 1,000 adverse reactions to heparin.

- read the story in the Tribune

German firm pledges $4.6B for APP Pharma

Tracy Staton — Mon, 07 Jul 2008 08:37:33 -0400

A German company is snapping up APP Pharmaceuticals in a deal worth more than $4.6 billion. Fresenius, an $18 billion company that sells products and services to hospitals and home healthcare groups, says the buyout will expand its presence in the lucrative U.S. market.

APP, you'll recall, has been in the news this year as the sole remaining U.S. producer of the blood thinner heparin. When Baxter saw its heparin production contaminated, it stopped making most of its heparin products; APP didn't have the same contamination problems, so it ramped up to try to fill the supply gap. APP also makes other injectables such as vitamin supplements, hormones, and diruretics.

An interesting side note: APP's recently-ex CEO Patrick Soon-Shiong owns some 83 percent of its stock, so you can bet he's saying ka-ching! Also CEO and a major investor in Abraxis BioScience, Soon-Shiong's share of the APP buyout could amount to as much as $3.8 billion if certain performance targets are met.

- read the Wall Street Journal story
- see the article in the Los Angeles Times

IMS: Pace of outsourcing accelerating

Tracy Staton — Tue, 27 May 2008 09:39:45 -0400

Drugmakers are pulling out of manufacturing at an unprecedented rate, according to a new report from IMS Health. Four of the top 10 pharma players announced big new outsourcing programs last year. That's evidence that pharma execs are thinking in vastly different ways from their predecessors, who believed R&D and manufacturing had to work hand-in-glove, and that the skills required to make drugs couldn't be found in emerging markets.

This shift toward contract manufacturing has risks, IMS concludes. First, there are safety concerns. Just think of Baxter's heparin supplier Scientific Protein, which made crude heparin in partnership with a Chinese manufacturer whose plant was riddled with problems when the FDA finally inspected it after millions of doses of the blood thinner had to be recalled. Then there's Sanofi-Aventis, whose contract manufacturer went bankrupt, leaving Sanofi to deal with its manufacturing breaches. Secondly, in other industries, contract manufacturers have found ways to enter the market as competitors. Finally, there's economic implications of shipping work to emerging markets. Europe, for instance, counts 640,000 pharma jobs. If they are perceived to be under threat from outsourcing, politicians might intervene.

- read the story at Outsourcing Pharma

Leavitt: We'll bar subs-par exporters

Fri, 16 May 2008 06:59:56 -0400

U.S. Health and Human Services honcho Mike Leavitt is baring his teeth at Chinese exporters that don't meet certification standards. Saying that regulators simply can't inspect all imported goods--some $2 trillion this year--companies that don't meet FDA standards won't be allowed to sell their products in the United States.

Leavitt's comments came during a trip to China to follow up on an agreement reached with Chinese regulators in December. Then, officials agreed to boost certification and regulation of exporters and to close some loopholes that have allowed Chinese companies to ship off unsafe food and drugs. Exporters are now required to register with the Chinese government, which will certify that they meet FDA standards.

Among the loopholes left to close: One that allowed chemical companies to produce drug ingredients without being inspected by drug regulators. That, of course, is one of the reasons why heparin tainted with oversulfated chondroitin made its way from Chinese suppliers to the U.S., where it was eventually recalled--but only after being linked to hundreds of severe allergic reactions, including up to 81 deaths.

- see the story in the Wall Street Journal

Leavitt: We'll bar subs-par exporters

Fri, 16 May 2008 06:59:56 -0400

- see the story in the Wall Street Journal

ALSO NOTED: Pfizer gets new cancer team to advance key drugs; Bayer clearing Trasylol off U.S. market;

Fri, 16 May 2008 06:59:50 -0400

> With the clock ticking on its patent for Lipitor, Pfizer has turned to a group of new executives to lead the company to the promised land of new cancer therapies. Report

> Bayer is pulling its remaining stocks of the anti-bleeding drug Trasylol, leaving the drug on the market only under an investigational program, the FDA announced. Release | Report

> Sanofi-Aventis has instituted a precautionary recall of 11 batches of the anti-clotting drug Lovenox after some were found contaminated with low levels of oversulfated chondroitin, the same chemical found in tainted heparin recalled by Baxter earlier this year. Report | Report

> FDA has blessed a new tablet coating ingredient, Kollicoat IR, from the German chemical company BASF. Report

> In more bad news/good news on generics, prices for the copycat meds dropped by 9.6 percent in 2007 as some of the most common drugs had price declines of up to 70 percent. Report

> Canadian regulators may pull the Plan B contraceptive--otherwise known as the "morning-after pill"--out from behind the pharmacy counter. Report

> India's Lupin saw its stock leap on an FDA approval for its version of the Wyeth heart-failure and blood-pressure med Altace, aka ramipril. Report

> Ranbaxy got the FDA nod for its muscle relaxant cyclobenzaprine, a generic form of the Ortho-McNeil drug Flexeril. Report

> Sepracor shares were off 2 percent on news that its CFO was leaving the company. Report

> An older statin, fluvastatin, showed action against the hepatitis C virus in a new study. Report

> Getting an embryonic stem cell therapy through clinical trials in the U.S. is looking like an increasingly tough challenge after Geron announced that the FDA is delaying a study of its experimental therapy for spinal cord injuries. Stem cell reoprt

> Forbes Medi-Tech says it will slash a third of its staff and shelve all in-house drug development work as it focuses its efforts on the nutraceutical business. Report

> Sweden's Biovitrum AB has restructured its R&D operations, winnowing out about 100 people either through layoffs or by reassigning them to other work. Report

> Last year's awful record of new drug approvals by the FDA has been followed by a burst of new activity. Pharmalot reports new analysis indicating 29 new drug approvals through April, the fastest rate of acceptance since 1998 and 2000. Report

And Finally ... Also from the ASCO data dump: Vitamin D may help curb breast cancer. Report

Quaid: Preemption unfair to patients

Thu, 15 May 2008 06:59:54 -0400

Dennis Quaid added some star power--and colorful language--to a dry legal debate yesterday. Testifying before Congress, Quaid backed people's right to sue drugmakers, saying that FDA approval shouldn't automatically negate patient lawsuits. "If preemption of lawsuits is allowed to prevail, it will make all of us--the public--uninformed and uncompensated lab rats," he said.

You'll recall that Quaid and his wife sued Baxter after their twin infants were given an enormous overdose of heparin. The lawsuit alleges Baxter knew other babies had died as a result of improper labeling of the drug, had started making heparin with new labels, but failed to recall the older vials mistakenly given to the Quaid twins. Among Baxter's defenses is the FDA's approval of its product.

The Bush administration has been pushing preemption, saying that approval by FDA, a federal agency, should supersede any state-level claims. This fall the Supreme Court will consider the idea when it hears a case pitting a patient against Wyeth. A Congressional committee met yesterday to hear testimony about preemption; presumably, Congress could circumvent a Supreme Court ruling in favor of it by enacting a law specifically allowing the lawsuits.

- read the Los Angeles Times story
- see the article in the Wall Street Journal

ALSO: Currently the sole supplier of heparin for the U.S. market, APP Pharmaceuticals is increasing its prices because of tightening Chinese stocks of the drug's raw ingredient. Several suppliers there have been shut down in the wake of an investigation of contaminated lots of the drug. Report

Preemption debate heats up

Tue, 13 May 2008 06:59:58 -0400

That little legal argument known as preemption is back in the news. You know the one: That FDA approval, being federal, supersedes any state-court lawsuits over blessed drugs and devices. Pushed by the Bush Administration, it's set for a Supreme test this fall when the U.S.'s highest court hears a case in which Wyeth claims it shouldn't be liable for claims about an FDA-approved med.

The latest? Supreme Court justices have had to recuse themselves from various cases lately because of their pharma-stock holdings. Yesterday, it was Samuel Alito bowing out because of Bristol-Myers stock. (Four of the nine justices had to sit out of that case, which involved a laundry list of big U.S. companies.) Two months ago, it was Chief Justice John Roberts sitting out a case involving Pfizer. Given the fact that ratifying preemption as a legal defense wouldn't simply help Wyeth, but all drugmakers, will the two men recuse themselves from that case, too? Inquiring minds want to know.

Meanwhile, Congress is dipping into the preemption fray with a hearing on the concept tomorrow. The House Committee on Oversight and Government Reform--Rep. Henry Waxman's group--is calling a bunch of preemption opponents to testify. On the roster: Actor Dennis Quaid, who's suing Baxter over a heparin overdose given to his infant twins.

- see the item at Pharmalot
- check out the hearing announcement

Politics hampers heparin probes

Mon, 12 May 2008 06:59:57 -0400

On the one hand, we have Health and Human Services Secretary Mike Leavitt gladhanding Chinese officials as he announced the heparin supply is now safe--including the crude heparin coming from China's workshops. On the other, there's Rep. Bart Stupak (photo), whose congressional committee is investigating the heparin debacle, contending that, "The FDA thinks they have it under control, but they really don't. If I was the FDA director, I'd shut down every drug coming in from China" until they were deemed safe, he told the Wall Street Journal.

Stupak is riled because the FDA won't hand over the names of Chinese heparin suppliers, citing confidentiality agreements. He and his committee worry that Chinese companies aren't fully cooperating with the agency's probe; during recent testimony, an FDA inspector said Chinese manufacturers didn't give them complete access to suppliers of crude heparin. Of course, Chinese officials accused Baxter of stonewalling their investigation, too.

All of which shows that politics is clouding the process of tracing contaminated heparin back to its source or sources--politics that go way beyond the typical Democrats-versus-Republicans grandstanding in our nation's capitol. Because this investigation crosses international boundaries, inspectors are hamstrung by deals higher-ups made on their behalf. As the top brass are smiling and making promises, the on-the-ground investigators are fighting red tape. Yet another unforeseen consequence of the globalization of pharma.

- read the article in the Wall Street Journal
- see Leavitt's pronouncement
- check out the UPI story

ALSO: The FDA sent out a new round of alerts to hospitals, pharma groups, and medical societies after learning that some medical facilities still had contaminated heparin among their supplies. Report

SPOTLIGHT: Heparin prices double since recalls

Fri, 09 May 2008 06:59:52 -0400

Since Baxter recalled virtually all its heparin products on reports of severe reactions and deaths, the price for the blood thinner has doubled. The sole U.S. supplier, APP Pharmaceuticals, says costs for crude Chinese heparin have risen fivefold since last year and recent price increases don't cover all its higher expenses. Report

Blaming Baxter, China denies heparin guilt

Tue, 06 May 2008 06:59:57 -0400

Point fingers at us, we'll point back at you. That's what China appears to be saying about the heparin scandal, claiming that it wasn't the "heparin-like substance" found in batches of the blood thinner that caused hundreds of severe reactions and up to 81 deaths.

Chinese officials are also blaming Baxter, which recalled millions of doses and stopped heparin production; they say the drugmaker won't cooperate with their investigation. The company destroyed some drug samples and production records that China considered important to their probe, one official said. A company spokeswoman denied the allegation, saying Baxter has cooperated "with all parties."

Admittedly, the FDA says it can't prove that the oversulfated chondroitin found in the offending batches actually caused the reactions. But China can't prove its theory that the culprit was actually introduced in the U.S., rather than overseas. Nor will China say where the heparin-like substance came from or how it got into the blood thinner. Until proof is on the table, the blame game will likely continue.

- check out the story in the International Herald Tribune
- see the Pharmalot item

ALSO: Analysts are bullish on Baxter's prospects despite the heparin recall and attending fallout. Report

FDA wants power to police imports

Wed, 30 Apr 2008 06:59:57 -0400

The FDA finally put its mouth where the money is. During congressional hearings yesterday, CDER chief Janet Woodcock said the agency would need $225 million to $250 million in additional funding to inspect foreign plants as frequently as it does in the U.S. And, along with drug compliance director Deborah Autor, Woodcock asked Congress for the power to inspect foreign companies that ship drugs to the U.S., stop imports at the border if necessary, and require U.S. drugmakers to police their foreign suppliers.

"We currently have a crisis and an opportunity to make real change," Autor said.

The requests came during hearings into the heparin-contamination scandal. The blood thinner has been linked to 81 deaths and 785 allergic reactions. In written testimony, Woodcock reiterated the FDA's suspicion that the med was deliberately tainted with oversulfated chondroitin somewhere along the Chinese supply chain. Some batches of the Baxter med consisted of more than 30 percent of the contaminant, "and it does strain one's credulity to suggest that might have been done accidentally," Woodcock said.

Congressional investigator David Nelson, who's leading the heparin inquiry, criticized the FDA for failing to inspect the Chinese plant operated by Baxter's API supplier. But Nelson reserved his most pointed critique for Baxter, saying that the company hadn't adequately inspected that plant, either. For his part, Baxter CEO Robert Parkinson called import oversight problems "a global and industry-wide crisis."

- read the Los Angeles Times story
- see the New York Times coverage
- check out Parkinson's remarks at CNN Money

FDA: Drugmakers responsible for safety

Mon, 28 Apr 2008 06:59:58 -0400

Congress may be all fired up about funding more foreign inspections by the FDA, but the agency itself? Not so much. In multiple appearances before congressional committees, Commissioner Andy von Eschenbach pointedly declined to seek more money for foreign inspections. CDER chief Janet Woodcock went so far as to tell a Senate panel last week that drugmakers need to take responsibility for the quality of their own products.

Increased funding for inspections is all well and good, Woodcock said, but the agency needs better IT systems to track manufacturers and imports, too. And no matter what, the huge volume of pharma ingredients and products made overseas makes it close to impossible to ensure the safety of all drugs sold in the U.S. The FDA can never be "the quality-control unit for the world," she said.

Sounds a lot like the push-back from China early in the heparin scandal, when regulators there said importers needed to bear the responsibility for drug safety. But while China seemed to be simply shoving aside blame, Woodcock is saying that enforcement can't do everything. If drugmakers aren't serious about the quality of their own products from the beginning of their supply chains to the pharmacy shelves, then problem products will get to patients. "We're holding them accountable for their quality system, not being their quality system," she told reporters after her testimony. Maybe what FDA needs as much as new funding is some real power to punish errant manufacturers. Otherwise, this "holding accountable" is nothing more than window-dressing.

- see the story in Pharma Times
- check out the Pharmalot item
- read the Wall Street Journal article on funding
- get the New York Times editorial

Impurities found in Sanofi heparin product

Fri, 25 Apr 2008 06:59:55 -0400

While heparin maker Baxter mulls whether to re-enter the market for that blood thinner, Sanofi-Aventis is announcing that small amounts of an impurity have been found in batches of its heparin injection Lovenox. Batches of contaminated Lovenox have been found in the U.K. and in Sweden, where it is sold under the name Clexane. European regulators said that there's no evidence of any risk to patients, but Sweden has withdrawn the product anyway as a precaution.

Back in Chicago, Baxter CEO is saying that the company is leaving its heparin options open. You'll recall that Baxter recall virtually all its heparin products after the med was linked to severe allergic reactions and deaths; since then, investigators found a contaminant in the problem batches and have said they suspect it was introduced somewhere along the med's Chinese supply chain.

Before deciding whether to sell heparin vials again, CEO Robert Parkinson told analysts, the company needs to understand how the product was contaminated in the first place. "We need to ensure that that supply chain is controlled as effectively as possible," he said.

- check out the Sanofi story in the Wall Street Journal
- see the piece on Baxter in the Chicago Tribune

FDA Commish chided over import safety

Wed, 23 Apr 2008 06:59:57 -0400

FDA Commissioner Andy von Eschenbach found himself in the hot seat again at a Congressional hearing. The House Committee on Energy and Commerce grilled the agency chief about foreign oversight and scolded him for safety lapses that occurred on his watch, including the big heparin debacle that's been unfolding since January. "You presided over this," Dingell said.

The committee wasn't happy with von Eschenbach's overhaul plan, either. And they didn't mince words about it. The GAO had appeared at the hearing earlier, estimating that it would cost $16 million to inspect only the Chinese exporters who hadn't yet seen FDA scrutiny, and $67 million to look at exporters worldwide. But when the commissioner skittered around the numbers himself, Dingell accused him of "toe dancing," saying, "I didn't fall off the cabbage wagon yesterday." (Even more colorfully, a Republican committee member from Texas said drug makers need to be held accountable for supply chain problems, "lest we get a bucket of chicken wings with plutonium in them.")

Dingell, you'll recall, released a draft plan for foreign oversight, and this hearing was supposed to gather fodder for the final bill he and his co-sponsors plan to enter. It looks as if the committee got some hard info from the GAO. It also got a few suggestions from von Eschenbach, namely, that FDA needs to hire contractors and/or depend on foreign regulators to certify foreign drug companies. And upon much pressing from Dingell, von Eschenbach coughed up some inspection figures for drugs: 3,000 facilities times $45,000 per, or $70 million on a biennial inspection schedule. How will this change Dingell's bill? We'll have to wait and see.

- see the Chicago Tribune story
- check out the New York Times article
- find a transcript of a few Dingell-von Eschenbach exchanges at In Vivo

U.S., China trade blame on heparin

Tue, 22 Apr 2008 06:59:58 -0400

Call it the blame game. The U.S. FDA says it's traced contaminated heparin back to 12 companies in China. Chinese officials, however, claim the problem started in the U.S.--and they plan to visit a New Jersey plant this week to investigate. So much for the new spirit of cooperation our drug watchdogs pledged not so many weeks ago.

Now, China doesn't dispute that the blood thinner was adulterated with over-sulfated chondroitin, the almost-heparin contaminant FDA uncovered in batches of the drug linked to allergic reactions and as many as 81 deaths. But Chinese officials say that the contaminant did not cause the allergic reactions. They claim that untainted batches also were linked with 100 adverse events.

The FDA, however, says that China's screening tests aren't as sensitive as the ones the U.S. used, and that the heparin China deems contaminant-free actually is tainted. Baxter, which sold the tainted med until problems with it arose, confirmed the FDA's assessment. Plus, the FDA says contaminated heparin made its way to 11 countries. If the problem originated in the U.S., it would be limited to the U.S.

Meanwhile, the FDA also sent a warning letter to Changzhou SPL, the Scientific Protein facility in China that provided active ingredient to Baxter. Changzhou didn't adequately respond to deficiencies FDA inspectors found at the plant--and some pretty scary ones at that. No adequate systems for evaluating heparin suppliers or their crude materials, for instance.

- find the FDA's letter to Changzhou SPL
- see the story in the Wall Street Journal
- read the New York Times article
- check out the item at Pharmalot
- get the Changzhou news at the LA Times
- see a summary of the FDA's probe at MoneyControl

ALSO: A new bill designed to quash counterfeit meds was introduced in Congress last week. The Safeguarding America's Pharmaceuticals Act would create federal standards for packaging and tracking drugs and establish minimum standards for wholesale licensing. Chain drugstores immediately protested, saying the requirements would be too expensive and complicated to implement. Report

SPOTLIGHT: Baxter: No big legal troubles from heparin

Fri, 18 Apr 2008 06:59:52 -0400

Baxter International said it does not expect its high-profile recall of the blood thinner heparin to trigger big legal troubles despite its links to adverse reactions and patient deaths. Report

Pfizer, Roche suffer as big drugs falter

Thu, 17 Apr 2008 06:59:57 -0400

Today's earnings roundup is a snapshot of pharma's challenges--generic competition, safety problems--and opportunities, namely biotech meds. Big-selling drugs lost ground, bringing their makers down with them. Safety-related charges depressed earnings. Read on, and you'll see.

Pfizer saw first-quarter net income drop by 18 percent as sales of its linchpin med Lipitor fell--and it hasn't even gone off patent yet. Generic competition for the allergy drug Zyrtec cut its sales by 75 percent. Growing drugs included Celebrex, whose sales rose 2.2 percent, and Chantix, which gained 71 percent. Overall, revenues fell by 5 percent to $11.85 billion.
Roche suffered as demand for the cancer med Herceptin slowed and sales of the antiviral drug Tamiflu sank. The flu drug lost 64 percent of its revenues, compared with last year's first quarter, when governments were actively stockpiling for a potential pandemic. Demand for Avastin leapt by 35 percent, offsetting the Herceptin losses. The declining dollar didn't help, either. Overall, revenues declined by 4 percent to $10.4 billion.
Baxter International managed to eke out a 6.5 percent increase in earnings despite two safety-related charges, one of $45 million on its withdrawn Colleague infusion pump and another of $11 million to cover the cost of its heparin recall. Revenues rose 7.6 percent to $2.88 billion. The company boosted its R&D spend to $190 million, a 19 percent increase.
The news from big biotech Gilead Sciences is rosier: The HIV specialist "trounced" Wall Street targets with earnings of $522.1 million, up from $447.6 million first-quarter 2007. Revenues jumped by 22 percent to $1.26 billion as the antiretroviral Truvada bought in $479.4 million, beating analysts' expectations.
Meanwhile, device maker St. Jude Medical reported a 27 percent hike in net income on strong sales of defibrillators. The company posted $184.8 million in profits on sales of $1.01 billion.

- read the Pfizer earnings in the Wall Street Journal
- check out the BBC's take on Roche
- see MarketWatch's Roche coverage
- find the Baxter story in the Chicago Tribune
- get the Gilead news from TheStreet
- check St. Jude's numbers in the WSJ