FDA update

Study reaffirms safety flags for last-minute meds

Tracy Staton — Thu, 03 Jul 2008 08:52:05 -0400

Remember that study that seemed to show that drugs FDA approved on deadline were more likely to end up with safety problems? Since its March publication in the New England Journal of Medicine, FDA hit back, saying that the Harvard professor who did the research made mistakes. Well, now Daniel Carpenter admits that FDA did find mistakes--but when he corrected those mistakes and added more recent data, he said, his original finding still holds.

Now, Carpenter says, the 88 drugs approved on deadline between 1993 and 2005 had a 15 percent chance of getting tagged with severe safety problems: Either a black-box warning or complete withdrawal. For the 226 other drugs approved the rate was just 5 percent. That compares with 14 percent and 3 percent, respectively, in the original published study. And when Carpenter extended that data through 2007, both groups got red flags: 20 percent of on-deadline drugs were withdrawn or got a black-box warning compared with 9.7 percent of other drugs. And, Carpenter says, he may have missed some warnings in his earlier study, but the FDA data omitted "a whole bunch" of them.

FDA didn't comment for the Wall Street Journal, but when the first study was released, said that its own records showed no statistically significant difference in safety performance among those drugs approved right before deadline and those that weren't.

- see the WSJ article

FDA handed out $35M in bonuses

Tracy Staton — Thu, 26 Jun 2008 10:03:05 -0400

The FDA finds itself in the line of Congressional fire on two different issues today. One, the agency is taking some heat for the $35 million in incentive pay it handed out last fiscal year, a 29 percent hike from the year before. Rep. Bart Stupak, a familiar FDA critic and head honcho of a House panel reviewing FDA compensation, called the bonus increases "outrageous" in light of "the agency's poor management."

The bonus plan has been around since 2004--as a way to compete with the private sector for top talent--but last year marked the biggest payouts; some FDAers got more than $50,000 in incentive pay. And 17 of the highest paid officials at the agency made more than $200,000. That's more than a member of Congress or the U.S. attorney general takes home.

Meanwhile, the agency's animal health division is facing more questions about the return of ProHeart 6, Wyeth's heartworm med that was yanked four years ago after it was linked to serious side effects. Stupak and his colleague John Dingell want the FDA to justify its decision to let the drug back onto the market, saying that ProHeart 6 didn't get a full safety-and-risk evaluation before the go-ahead came.

- read the Wall Street Journal story
- see the item at the WSJ Health Blog
- check out the Pharmalot post

Should FDA outsource inspections?

Tracy Staton — Mon, 16 Jun 2008 08:41:30 -0400

Is what's good for pharma good for its regulators, too? As we all know, Big Pharma's outsourcing of active ingredients and manufacturing has caused a big bout of hand-wringing on the governmental side as FDA has struggled to keep up--and largely failed. Meanwhile, attempting to keep pace with a boom in overseas device manufacturing, FDA tried imitating its regulatees by outsourcing some foreign device-making inspections. Two years and 12 third-party inspections later, critics have declared the program a flop, and even FDA types are underwhelmed.

Despite those ignominious results, the Bush administration has been pushing a plan to expand private inspections to drugs and other imports. Bills are in various stages of draft in Congress. Whether inspection-outsourcing will ever make it past the draft phase remains to be seen, especially given the fact that in a few months, the Bush administration will be no more, and its zeal for privatization could very well exit the White House along with the boxed-up files. Stay tuned.

- see the Pharmalot post

FDA drags feet on generic approvals

Tracy Staton — Mon, 16 Jun 2008 07:20:47 -0400

And you thought the odds on new-drug approvals at the FDA were bad. Generics get the thumbs-down 96 percent of the time, according to a new report from the Inspector General. And agency review of new generics is slow, too--rather than the 180 days required by law, it's 217 days on average, more for those meds that aren't rejected outright. Those that won tentative approval saw their apps languish for an average of 300 days.

Not surprising, really, given the recent spotlight on FDA's lack of resources and staff. And going slow on the generic uptake isn't nearly so worrisome as the other problems FDA has faced because of that lack. But in any case, the IG suggested the FDA give generics makers more guidance up front so that their applications are more worthy of review the first time out.

- see the Wall Street Journal Health Blog item

FDA finally gets long-awaited funds - FDA trends

Tracy Staton — Sun, 15 Jun 2008 16:29:48 -0400

FDA Commissioner Andrew von Eschenbach is no political naïf. He knows that new funding is a double-edged sword. People--a.k.a. Congress--expect something for their money. In other words, more resources, more responsibility to deliver. If your agency isn't ready to turn the moola into results PDQ, then perhaps a big wad of extra cash will only be counterproductive. Instead of showing up at Congressional hearings, armed with a scarcity of resources as a handy reason for poor performance, you have to show up ready to explain why your bungling made a mockery of the taxpayers' generosity.

Perhaps that's why it took so long for von Eschenbach to say, first, that his agency needed more funding at all, and second, just how much might suffice. Late last year, a panel of outside advisers said the FDA didn't have enough money or staff--not to mention scientific expertise, but that's an extension of the staffing problem--to protect Americans from bad food and drugs. By March, von Eschenbach was admitting to the problem, saying the agency could fail to protect the citizenry. Still, funding offers were received coolly. Senators leading the Appropriations subcommittee practically opened their wallets during a hearing back in April, but von Eschenbach demurred, saying he needed to get some scenarios together.

Observers speculated that it was his loyalty to the Bush Administration, which offered only a 3 percent funding increase in its budget, that inspired von Eschenbach's utterly un-greedy behavior. But his loyalty either gave out, or that wasn't the reason for his reticence in the first place, because in May the commissioner named a figure: $275 million. Meanwhile, the agency finagled clearance to hire hundreds of people without the usual bureaucratic red tape and announced a series of job fairs to fill already vacant slots and newly added positions. Then the administration itself came through June 10, asking Congress to give the FDA an extra $275 million.

So if Congress makes good on its open-wallet offers, von Eschenbach and company will soon be able to tap those millions for even more new employees, long overdue technology, new foreign offices, stepped-up import inspections, and more. They'll also be on the hook to demonstrate that the employees, technology, inspections, et al, are making the U.S. safer from tainted food and drugs. The world will be watching.

FDA rolls out Sentinel project - FDA Trends

Tracy Staton — Sun, 15 Jun 2008 16:28:12 -0400

It's been in the works for years: A 21^st century way for the FDA to track drug side effects. That's right, a database, or series of databases, that agency types can sift for adverse-event patterns. Rather than waiting for doctors and patients to voluntarily report possible safety problems, the agency could actively monitor prescription drug use and its effects on people.

Sounds none too difficult in this age of sophisticated data-management software and Google search algorithms. But like many government agencies, FDA isn't exactly on the cutting edge of computer technology. Plus, access to patient information can be problematic; privacy concerns and all that. Building it all from the ground up wasn't an option.

The agency's solution: Partner with people who already have the info, i.e., Medicare and Medicaid and private insurers. FDA has already inked a deal with WellPoint to query its data on more than half of its 35 million members. It got access to info on even more patients via a recent agreement with the Center for Medicare and Medicaid Services. Agreements with additional private insurers are already in the works.

To allay fears that data-mining will turn up a lot of fool's gold, leading to unnecessary safety alerts, WellPoint queried its 1999 data and concluded it could have spotted the withdrawn painkiller's cardiac problems within four months of the drug's introduction. Offering further reassurance, the FDA said it will first focus on mining the databases for information on known safety problems. But CDER chief Janet Woodcock acknowledged that at least at first, there will be some false alarms. But she promised to work to minimize the possibility.

Questions remain -- questions that likely will only be answered once the FDA has had the opportunity to really dig into the data. For instance, how to know when a pattern is a real problem? How can Medicare beneficiaries' side effects be teased apart when they take, on average, 28 meds a year? Presumably that's why the agency will focus on known problems first.

The real fruits of this labor won't be reaped for years, researchers said when the agency announced its Medicare plans. And it won't be easy. One epidemiologist told the New York Times, "This is going to take a lot of work." Good thing the FDA is planning to expand its staff, eh?

- see this FDA report
- read this release for more

FDA finally gets long-awaited funds - FDA trends

Tracy Staton — Sun, 15 Jun 2008 16:25:51 -0400

Observers speculated that it was his loyalty to the Bush Administration, which offered only a 3 percent funding increase in its budget, that inspired von Eschenbach's utterly ungreedy behavior. But his loyalty either gave out, or that wasn't the reason for his reticence in the first place, because in May the commissioner named a figure: $275 million. Meanwhile, the agency finagled clearance to hire hundreds of people without the usual bureaucratic red tape and announced a series of job fairs to fill already vacant slots and newly added positions. Then the administration itself came through June 10, asking Congress to give the FDA an extra $275 million.

Overseas oversight gets serious - FDA trends

Maureen Martino — Sun, 15 Jun 2008 16:24:11 -0400

The heparin scandal threw into sharp relief just how difficult it is to regulate drug ingredients produced overseas. No one was quite sure where in the supply chain the heparin was tainted, and the FDA and China traded blame over the fiasco. FDA Comissioner Andrew Von Eschenbach didn't escape blame though; he 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.

While most drugmakers draw ingredients from overseas, the problems with heparin highlighted just how difficult it is to regulate a drug's supply chain from start to finish. With an increasing amount of drugs and drug ingredients being imported from India, China and the like, the need is increasing for more rigorous overseas inspection. In response, the FDA is working to establish five satellite offices in India, China, Central and South America and the Middle East. But the FDA is already running into a nest of red tape with its China office and undoubtedly more problems lay ahead as the FDA grapples with drug safety on a global scale.

One thing is for sure: in the coming years, the FDA won't be caught flat-footed the way they have been recently, and drugmakers better be prepared to deal with tighter regulations.

An early look at FDA trends

Sun, 15 Jun 2008 16:22:09 -0400

By Maureen Martino and Tracy Staton

It's never too early to identify trends, and what better place to look than the FDA? The environment at the world's premier regulatory agency can have a significant impact the U.S. as well as the world markets, so it's always wise to keep an eye on happenings at the FDA.

In that vein, here's an early look at four FDA trends we've identified so far this year. We'll see how these play out by the end of the year.

FDA toughens up on approval standards - FDA trends

Maureen Martino — Fri, 13 Jun 2008 15:03:01 -0400

First, Merck was dealt a harsh rejection of Coredaptive, a combination of niacin and laropiprant that had been high up on the drug giant's list of potential blockbusters. Then Genzyme and Isis felt the FDA's wrath when the agency voted thumbs down on mipomersen, another cholesterol drug. Mipomersen will be delayed for several years as the drug developers conduct additional trials.

The back-to-back rejections had some analysts wondering whether the FDA is toughening up on the approval of new cholesterol drugs. It appears that it's no longer sufficient for a drug entering an already-crowded market to be safe and effective; the FDA wants to see a clear benefit over existing medications. These days, it isn't enough for companies to show that their drugs lower bad cholesterol. Drugs must demonstrate better outcomes, thanks largely in part to the recent dust-up over Vytorin. A study conducted by Merck and Schering-Plough showed that when it comes to arterial thickness, there was no significant difference between treatment with generic simvastatin (Zocor) and Vytorin, which combines Zocor and Zetia (ezetimibe).

"FDA has long approved drugs based on their ability to lower so-called bad cholesterol, which is widely believed to reduce heart attack and death," noted the AP. "But the Vytorin results suggest the connection between higher cholesterol and negative outcomes may not be as concrete as initially thought."

FDA staffers say there's been no official change in the agency's policy, but drugmakers may be facing long delays if they can't prove their drugs are significantly more effective that those currently available.