FDA regulation

Scientists: Watch these off-label uses

Tracy Staton — Tue, 25 Nov 2008 11:15:50 -0500

Are you ready for a new debate over off-label use of prescription drugs? A new study almost guarantees it. Going off-label with drugs may be perfectly legal, this report in Pharmacotherapy states, but those unapproved uses should at least be studied for safety and effectiveness. Without that research, off-label prescribing can easily be influenced by "opinion leaders" who sometimes are paid by drug companies to support unapproved uses, USA Today reports.

"Clearly, for many of these off-label uses, the manufacturers are benefiting enormously, and in some cases I think one could argue that off-label use has allowed them to circumvent the regulatory process," Randall Stafford, associate professor of medicine at the Stanford Prevention Research Center, told the newspaper. Although the regulatory process is not infallible, he says, "it does provide a level of scrutiny" beyond what the off-label uses have received.

The researchers identified 14 drugs whose off-label uses should be studied ASAP. Many of them are psychotropic drugs that are approved for one mental illness--such as depression--but often used for another. At the top of the list is AstraZeneca's Seroquel, approved for use in schizophrenia, but often prescribed as maintenance therapy for bipolar patients. And No. 3, Lexapro, is an approved antidepressant, but it's commonly used against bipolar disorder, too.

But psychiatric meds aren't the only ones in need of scrutiny, the researchers said. Ranking second on their list is Warfarin, approved to treat atrial fibrillation, but also prescribed to patients with hypertensive heart disease. And then there's Merck's Singulair, approved for asthma, but used also in chronic obstructive pulmonary disease. For the full 14-drug ranking, see the link below.

- check out the release
- read the USA Today story

Pharma bets its chips in developing countries

Tracy Staton — Mon, 17 Nov 2008 11:51:59 -0500

We've been talking a lot about drug sales in the developing world lately, as Big Pharma eyes markets such as Brazil, China and India--the so-called BRIC countries--to make up for stalling sales in the U.S. This week's Economist comes to the party, taking a look at America's declining contribution to pharma profits, and just how developing countries might help take up the slack.

As the magazine rightly notes, pharma's a bit late. Other industries started targeting the growing markets in Asia and Latin America years ago. While consumer brands and high-tech companies poured billions into those countries, drugmakers sniffed about weak intellectual property laws and low per-capita incomes. Now, however, that's changed, partly because other countries have started to beef up IP protections and partly because incomes have been growing.

But at least half the reason is that China, India, et al, are among the only countries pharma hasn't fully tapped. Consider a new report from Decision Resources, which predicts that China's market for antidepressants will triple by 2012 to $226 million. The research firm expects SSRI sales to post continuing double-digit growth there. Plus, Chinese docs and patients consider Western-made antidepressants to be better-quality than those made domestically.

The roll call of companies looking eastward and southward includes GlaxoSmithKline and Pfizer, which just announced that it would put emerging markets on its priority list. And then there's Abbott Laboratories, which has quietly been building up its Chinese business and now ranks as that countries' No. 1 outside pharma firm. Plus, news is just now breaking that AstraZeneca is building up a supply hub in China that's aimed at helping the company not only build its "In China for China" manufacturing strategy, but also its "In China for Global" business.

Meanwhile, look no further than the FDA, which is cutting ribbons at three new offices in China this week: Beijing, Guangzhou and Shanghai. "Establishing a permanent FDA presence in China will greatly enhance the speed and effectiveness of our regulatory cooperation and our efforts to protect consumers in both countries," HHS Secretary Michael Leavitt said in a statement.

So pharma appears to be meeting itself coming and going, from developed nations to developing countries and back again. And the FDA won't be the only ones watching.

- read the story in The Economist
- see the AstraZeneca news at Supply Chainer
- check out the release on China's antidepressant market
- see the AP article about new FDA offices

Is the FDA persecuting India's generics makers?

Tracy Staton — Mon, 17 Nov 2008 10:36:02 -0500

Indian drugmakers are feeling a bit paranoid these days. Big Brother, a.k.a. the FDA, is looking over their shoulders, and they're not happy about it.

There appears to be reason to fear, Pharmalot reports: Three major Indian pharma companies have felt the long arm of the law in recent months. First, the FDA banned 30 Ranbaxy Laboratories drugs because of manufacturing irregularities at two of its Indian plants. Then the agency nixed drugs made at Sun Pharma's Detroit plant. And last week, FDA warned Lupin about 15 manufacturing problems at a plant in Madhya Pradesh.

Some Indian pharma types are even wondering whether the regulatory scrutiny amounts to a sort of trade barrier. "[T]here may be an attempt by global innovator majors to question the standards of Indian drugs and stop their entry," Daara Patel, chief of India's pharma trade association, told the Economic Times.

But others say Indian generics makers just need to toughen up. The companies have an edge in the copycat-med market, and with the U.S. government and other payers looking to control healthcare costs, Indian drugmakers can certainly benefit. One expert told the Times, "The three companies who have come under (the FDA) scanner should be ready for any test conducted by any regulator, anytime." Hear, hear.

- check out the Economic Times story
- see the Pharmalot post
- get the Lupin news from NDTV

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

Ranbaxy waves white flag at Feds

Tracy Staton — Fri, 10 Oct 2008 10:54:07 -0400

Call it a truce between Ranbaxy Laboratories and U.S. law enforcement. The Department of Justice has dropped its legal action against Ranbaxy, now that the company has agreed to hand over audits of its manufacturing facilities. For months the FDA has been trying to get the documents as part of an inquiry into allegations that the company falsified records, allowing the company to sell substandard generic meds.

Ranbaxy claimed the audits--conducted by Parexel--were privileged info. The FDA struck back, banning nearly 30 Ranbaxy products from entering the U.S., citing two Ranbaxy plants in India for inadequate manufacturing controls and procedures.

Since then, Ranbaxy hired former NYC mayor Rudy Giuliani for advice. And now, the cease fire. Presumably we'll eventually find out what those contested audits actually reveal.

- read the item at Pharmalot

FDA halts eye wash and skin cream

Christe Bruderlin-Nelson — Wed, 24 Sep 2008 04:29:06 -0400

The FDA came down on a group of companies that it says is marketing prescription medications without approval.

The medications are topical skin creams and eyewashes.

One is a skin cream containing a unique enzyme, called papain, derived from papaya plants, which have been in use for over a century. FDA, however, says it has never approved the use of these creams, which at least 10 companies market for the treatment of skin ulcers and other skin ailments.

As for the eyewashes, Alcon Laboratories and Akorn, Inc. have balanced salt solutions that the FDA has approved for use during surgical procedures, but none of the other three companies (Braun, Baxter and Hospira) marketing the eyewashes are approved.

The FDA has given the companies exactly two months to file for FDA approval or stop making the products. If they do not comply, the FDA can take legal action or initiate product seizures.

Customer complaints are likely the impetus behind the move: The FDA said it received hundreds of reports of serious eye reactions in people using the eyewash and close to 40 reports of everything from no benefit to severe allergic reactions from people using the papain-containing skin creams.

- get the FDA release
- read the Associated Press story

FDA names 20 drugs in safety probes

Tracy Staton — Mon, 08 Sep 2008 10:17:31 -0400

In a move sure to cause controversy, the FDA will let some sunshine in on its investigations of adverse event reports. Every quarter, the agency will release a list of drugs under investigation because of complaints about side effects. The nature of the complaints will be included in the report, but the number of complaints--or their seriousness--won't be. So is this too much information? Or not enough context?

Though this disclosure is required by the new FDA law enacted last year, the reports are already being greeted with concern by drugmakers--and even agency officials. Both worry that patients might stop taking their meds because of the disclosed investigations, even though many of them may turn out to be false alarms.

The FDA has already warned patients and docs about some of the drugs on the first list of 20 under scrutiny, such as TNF blockers, in the news last week. But some of the listed meds are new. For instance, Biogen Idec and Elan's Tysabri is listed because of reported cases of melanoma in patients taking the drug. Others named in the report include Eli Lilly's antidepressant Cymbalta and Purdue Pharma's Oxycontin. (See the entire list via the FDA link below.)

- check out the FDA's release
- read the Washington Post story
- see the article in the Wall Street Journal

Will FDA label regs shield pharma?

Tracy Staton — Mon, 25 Aug 2008 11:05:21 -0400

The draft rules on labeling updates are now a reality. Next month, regulations about safety warnings will take effect, aimed at offering clarity for drugmakers and increased confidence among patients, the FDA says. Critics say the new regs could shield drugmakers from product liability suits.

One new rule in particular states that companies only have to rush out safety warnings when there's clear evidence of a serious risk that the FDA hasn't reviewed. In every other case, FDA will review safety data and consider labeling changes after that.

A lawyers' association (which of course has its own vested interest) says the rule sets the bar too high for the scientific evidence needed to impel a warning. The group says that will make it easier for drugmakers to say they weren't obligated to alert the public about a particular safety risk. "This rule is going to be a total shield against all 'failure to warn' claims," the association's director said.

The big Vioxx case, for instance, alleged that Merck failed to warn consumers about the painkiller's heart attack and stroke risks. That lawsuit wouldn't have been possible under this new rule, according to the lawyers' association.

- read the story at CNN Money

FDA to revamp rules on kids' cold meds

Tracy Staton — Mon, 25 Aug 2008 10:28:15 -0400

Remember all the brouhaha last fall about children's cold medicines? Well, the controversy is back. And this time the FDA says it's going to thoroughly review the safety and effectiveness of those products, revamping the criteria used to determine whether they should remain on the market. "Modern science has advanced...and this is an opportunity to apply modern science to evaluate these products," said Janet Woodcock, CDER director.

You could say that about any drug that's been on the market awhile, though. The reason these drugs are drawing scrutiny is that pediatricians have been lobbying for it, saying there's little evidence they help kids and lots of evidence that they can cause severe side effects. Plus, these products were approved back before pediatric drugs had to be tested in kids, so they never were.

Last year, the FDA convened an advisory panel to look at the meds, and in advance of that meeting, drugmakers voluntarily withdrew all over-the-counter cough and cold products for kids younger than 2. The panel itself recommended against their use in children younger than 6, and called for new studies to assess them when used in children. Now, the agency plans a hearing Oct. 2 to start figuring out what sorts of studies should be done and what other steps should be taken in the interim.

- read the article in the Washington Post

FDA might mandate drug training

Christe Bruderlin-Nelson — Mon, 18 Aug 2008 00:59:18 -0400

Perhaps triplicate prescriptions are not enough of a safety measure when it comes to powerful narcotics. At least, that's what the FDA might be thinking. The agency is considering mandatory training for clinicians who prescribe certain narcotic medications, including methadone, fentanyl and some versions of oxycodone.

It's a move that would be controversial and one that the FDA cannot make in a vacuum, according to Bob Rappaport, the agency's director for the division of Anesthesia, Analgesia and Rheumatology Products, as states usually have jurisdiction over regulatory and education issues when it comes to physicians.

As it stands, a state medical license and a simple registration with the Drug Enforcement Administration are all that are necessary for a physician to prescribe narcotics. At present, states like California that require additional training are the exception rather than the norm.

- read the full story in the New York Times

Are black box warnings inevitable?

Tracy Staton — Mon, 11 Aug 2008 11:22:08 -0400

A sociologist and health policy researcher has some stern language for drugmakers and their regulators. "Drug disasters are literally built into the current system of drug testing and approvals in the United States," Donald Light said in presenting his figures on new drugs to the American Sociological Association.

According to Light's data review, one in seven new drugs is superior to existing ones, but two in every seven end up emblazoned with a black box, an adverse reaction warning--or they're withdrawn.

And all those post-marketing adverse event reports and black box warnings? They're almost inevitable, given the fact that drugmakers test their products on patients that are typically healthier than the entire population actually targeted by the drugs. And trials are long enough only to pick up short-term side effects, Light said.

Some would argue that the uptick in drug warnings is actually a reflection of the FDA's newly cautionary stance rather than an indication that drug safety is slipping overall. Check out Light's data and see what you think.

- read the post at Pharmalot

Marketing lessons from FDA warnings

Tracy Staton — Mon, 11 Aug 2008 11:12:21 -0400

The FDA's marketing regulators have either been pulling their punches lately or drugmakers are complying with promo rules better than usual, because the number of warning letters about advertising and brochures and mailers last quarter could be counted on one hand--and so far this quarter, there hasn't even been one. As Eye on FDA notes, the letters can be mini-lessons in compliance, so here's the summary of the second quarter action:

Pfizer was cited for a sildenafil citrate video that didn't include any risk information. The video referred viewers to that info on a web page, but the FDA didn't see that info. Lesson? Even online videos should include risk info, just like TV commercials.
Zila Pharmaceuticals got tagged for a professional mailer about its oral rinse Peridex. The mailing included the rinse's package insert. But because that insert wasn't physically attached to the promotional brochure, it didn't count. Lesson? No detachable risk info.
Novartis was cited for a Trileptal magnet because the risk info was on the back, where it couldn't be seen. Lesson? Risk info in view at all times.
Shire got its hand slapped for a reminder ad that wasn't. A reminder ad, as you know, is supposed to just include the drug name--no indications, dosage, or other info. FDA said the Shire ad looked like a reminder ad, but contained language about indications. Lesson? Calling an ad a reminder ad doesn't make it one.

- read the post at Eye on FDA

House votes to treat tobacco as a drug

Tracy Staton — Thu, 31 Jul 2008 10:10:40 -0400

If the U.S. House gets its way, the FDA soon may have even more power--to regulate tobacco as a drug. Reps voted overwhelmingly to charge the agency with overseeing the tobacco industry, in spite of a veto threat by President Bush. It's a move long sought by anti-smoking advocates, and one lobbied for, as you may recall, by ex-FDA chief David Kessler.

Under the bill the agency would be able to reduce the amount of addictive nicotine in cigarettes and smokeless tobacco--though not remove it altogether--plus ban various additives, such as candy and fruit flavorings designed to appeal to youngsters. And tobacco makers would have to disclose all the different additives in their products and hand over research into their effects.

In declaring its opposition, the White House said that the FDA is already overstretched as it is. But that didn't seem to bother frequent agency critic John Dingell, a vehement supporter of the measure. It's not clear as yet whether the Senate can come up with a veto-proof majority for the bill. Stay tuned; it's sure to cause lots of debate.

- read the Washington Post story
- see the article in the New York Times

SPOTLIGHT: FDA forces contract manufacturer to reform

Tracy Staton — Mon, 19 May 2008 11:07:14 -0400

Contract manufacturer Scientific Laboratories is in a world of hurt today, as FDA has barred it from manufacturing or distributing drug products until it brings its operations up to par. The company, which makes various prescription cough-and-cold meds, didn't ask FDA for approval for some of its drugs--a dozen of them--and didn't comply with required manufacturing protocols. The consent decree Scientific Labs signed requires it to get the FDA's blessing for any product it sells and to conform to good manufacturing practices. The drugs it's already made all have to be destroyed. And the agreement comes with a big or-else: If Scientific Labs doesn't comply, FDA can shut it down completely. Story | Item

Pharma drags feet on promised studies

Thu, 24 Apr 2008 06:59:55 -0400

We once saw a sign in a newsroom that said, "Deadlines, schmedlines, as long as I get paid." Maybe Big Pharma has similar signage posted at its various HQs. According to newly released FDA data, drug makers haven't even started more than 1,000 post-marketing studies they promised to do after their products were approved. And some of that research has been in the promised-but-not-started phase for years. Almost 450 have been on the pledge rolls since way back in 2004.

Now, some of that is the FDA's fault; the agency doesn't always set deadlines for this research. And some drug makers are doing their duties. About 16 percent of post-marketing research was on or ahead of schedule and 14 percent had been submitted to FDA or terminated before completion.

What we're wondering, though, is what FDA will do with its new powers to compel those studies, granted by Congress in the agency funding bill last fall. Will FDA start cracking the whip? Will drug makers shift these studies into high gear? We'll be watching the agency's numbers to find out.

- read the item at Pharmalot

Woodcock: FDA wary of Vytorin debate

Wed, 09 Apr 2008 06:59:56 -0400

Expect the FDA to stay out of the Vytorin fray, at least for now. So Janet Woodcock (photo), CDER chief, told FDAWeb in an interview (recounted, in turn, by Pharmalot). The agency is afraid of seeming "defensive" if it weighs in now. But Woodcock did make clear that FDA still considers lowering "bad" cholesterol--which Vytorin did quite well in the Enhance study--to be a valid surrogate for heart-disease prevention.

Scientific nitpicking about LDL is misleading people, Woodcock said: "[T]here is some little point that the scientists are arguing about, and then the media get on it, and they start throwing the baby out with the bathwater," she said. "...[but if] people think we're just being defensive, we wouldn't make a difference in this environment."

Meanwhile, new data is in on the expected drop-off in Vytorin and Zetia scrips. A Deutsche Bank analyst surveyed primary care docs and found that 75 percent expect usage of both drugs will drop in their practices. The analyst now predicts that market share for Vytorin will drop to 9 percent from 16 percent. Zetia, one of the drugs in the Vytorin combo, will see its share drop to 6 percent from 9.5 percent, the analyst concluded.

Some of that drop-off will be in new scrips, some from patients switching. In an investor note, the analyst predicted "increased utilization of other statins, especially [Pfizer's] Crestor."

- see the Woodcock interview excerpt at Pharmalot
- check out the scrip numbers
- see Pharmalot's analysis of Deutsche Bank's predictions

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Planning for the FDA's overhaul

Tue, 08 Apr 2008 06:59:58 -0400

Just about everybody agrees that the FDA needs a safety overhaul--including Commissioner Andrew von Eschenbach, who recently admitted the agency is in crisis. The agency itself drafted a five-year plan that would channel user fees into more safety evaluators, epidemiologists, regulatory project managers, and risk experts, all to beef up post-marketing drug-safety oversight. In addition to new staff, the plan calls for technology and communications systems, plus two or three years of intense staff training.

Meanwhile, Rep. John Dingell has been working on a plan of his own. According to Congressional Quarterly, Dingell would expand the FDA's regulatory authority by funding a team of full-time overseas inspectors. He'd require drugs, devices, and food products to be labeled according to country of origin. He'd levy new user fees to pay for spot checks at overseas plants and U.S. ports. Sweeping change is absolutely necessary, Dingell tells CQ, saying that the agency doesn't have "the vaguest idea who's producing these things, whether they're safe or not, whether they're using good manufacturing practices or not...or anything else that might relate to seeing to it that the safety of the American people is attended to." Ouch.

- read the Dingell item at Pharmalot
- see a summary of the FDA plan at FDANews
- check out the FDA's plan draft (.pdf)

ALSO: The San Jose Mercury News' editorial board says the FDA should be embarrassed by its lack of attention to the ingredients in prescription drugs--and that its laissez-faire foreign inspections make its refusal to import cheaper prescription meds (for "safety reasons") into "hypocrisy." Report

Related Articles:
FDA chief admits need for funding, reform. Report
FDA can't guarantee drug safety. Report
FDA wants satellite offices overseas. Report
FDA badly needs more money, staff. Report

Supreme Court shields device makers

Thu, 21 Feb 2008 06:59:58 -0500

Medical device makers got some supreme protection yesterday. The highest court raised a partial shield against lawsuits, saying that devices that passed the FDA's most stringent premarketing review are exempt from consumer lawsuits. Essentially, the justices ruled that federal law--i.e., FDA regulation--preempts liability under state law for these devices.

Can drugmakers anticipate their own celebration when the Supreme Court decides a couple of other preemption cases that involve meds instead of a device? Don't buy the champagne yet, some legal experts say. In ruling for Medtronic yesterday, the Court relied on a federal law specific to medical devices, not drugs. The Medical Device Amendments of 1976 set up detailed requirements for FDA testing of devices, wrote Justice Antonin Scalia in the majority opinion, and prohibited states from imposing different requirements.

The ruling will affect numerous outstanding lawsuits, but some pending cases will still be allowed to go forward; the ruling doesn't keep consumers from suing if a device was made improperly, contrary to FDA specifications.

The Court will hear one drug-related case Monday and will consider another in October. Ironically, the justices are considering these rules just as big questions have been raised about the FDA's ability to effectively regulate drugs and devices. Several recent reports have castigated the agency for scientific shortcomings, outdated technology, and mismanagement. Experts say the agency is way underfunded and understaffed. If the courts want FDA as our final authority, then shouldn't it be good at its job?

- read the story in the Washington Post
- see this New York Times article
- check out the NYT's take on preemption under an inadequate FDA
- find this Q&A with a consumer in a preemption case at Pharmalot

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FDA experts mull ban on child cold meds

Fri, 19 Oct 2007 06:59:54 -0400

Did drug makers go far enough when they pulled infant cough-and-cold remedies from store shelves last week? Maybe not, the FDA says. An advisory panel convened to discuss the over-the-counter meds is weighing the evidence: that every study of pediatric cold products shows they don't work; that dosing is confusing; and that some research concludes the meds are dangerous. One FDA official told the committee to consider banning them.

Obviously, the drug industry doesn't want to lose these products. The Consumer Health Productions Association is promising an educational campaign to teach parents to use the products properly and avoid overdose. But another powerful group is set against them: pediatricians, who originally lobbied the FDA to take up the issue.

- read the New York Times report

Related Articles:
Drug makers recall infant cold meds. Report
FDA to review OTC cough medicine safety. Report

Lilly diabetes med linked to pancreatitis

Wed, 17 Oct 2007 06:59:57 -0400

A fast-growing Eli Lilly med may be held back by a new warning linking it to acute pancreatitis. After 30 reports of pancreatitis in patients using the injectable diabetes drug Byetta--five of which led to serious complications such as kidney failure--the FDA has asked Lilly and its partner on the drug, Amylin, to revise its labeling.

With $430.2 million in 2006 sales, Byetta delivered some $219 million in revenues to Lilly. The rest went to Amylin, accounting for 90 percent of that company's sales. Amylin stock fell sharply on the news.

- check out the report from the Indianapolis Star

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Read more on: Eli Lilly | Diabetes | Amylin