In the first lawsuit over Johnson & Johnson’s “phantom recalls,” Oregon’s Attorney General John Kroger argues that Oregon consumers were left in the dark when the company hired parties to covertly buy up potentially defective Motrin from Oregon stores in 2008 and 2009. The lawsuit asserts that J&J’s decision to pursue a secret recall process, rather than a public recall, violated the state’s consumer protections laws.

The complaint cites many disturbing facts that have come out about the phantom recall. As early as Nov. 20 2008, routine testing by J&J showed that some Motrin caplets did not dissolve correctly. Despite notifying the FDA about the defect on Nov. 26,  J&J made “no attempt to notify wholesalers, retailers, or consumers [about] the defective Motrin® . . . .” to stop its shipment or sale.  Weeks later, after J&J “received price estimates from two companies that specialize in product recalls” for a public recall, J&J rejected this approach, choosing instead to ‘remove the defective Motrin® . . . from the market surreptitiously.”

During the “Phase I” of the phantom recall, J&J hired a company to visit 250 stores nationwide to see if any of the defective Motrin remained on the shelves.  In April 2009, five months after J&J knew it was selling a defective product, the company found only 595 packages of defective Motrin on the shelves of these 250 stores.  Two months later, the complaint suggests, a consulting company was hired by J&J to secretly purchase the remaining Motrin from about 5000 convenience stores. How many consumers purchased and consumed these potentially defective drugs remains unknown.

All in all, J&J’s phantom recall turned up only 41 packages of defective Motrin® leaving “787 [packages of defective Motrin®} unaccounted for in Oregon.” But the number of Motrin packages sold isn’t as significant as the fact that “[a]t no point during the entire process did Defendants alert Oregon consumers or retailers that it had distributed the defective Motrin® . . . .” In fact, it was an employee of the company hired to do the phantom recall that alerted the Oregon Board of Pharmacy, who then alerted the FDA in Seattle.

During this five month process, J&J was communicating with the FDA in Puerto Rico, arguing that because so few of the Motrin were still on the shelves, there was no need to do a recall.

So what will this lawsuit mean?  Regardless of whether it yields some recovery for Oregon consumers, it shines light on some of the big problems that can grow out of a regulatory system that relies upon industry to initiate recalls. As we’ve talked about here, the move to give the FDA recall authority over drugs has gained serious traction, appearing in no less than three bills filed in Congress last year. And now a new straw poll at Pharma Tech shows 90 percent of readers think the FDA should be able to hit the recall button.

Of course, J&J is not the only drug-maker that has tried to hide its dirty laundry. Recent revelations on “60 Minutes” document how GlaxoSmithKline tried to silence their own quality control inspectors. At very least, stronger whistleblower protections are needed.

But these problems may be just the tip of the iceberg. Both the J&J and GSK breakdowns in manufacturing standards happened in Puerto Rico-based operations, and like the Deltex factory shuttered in Texas this week, these U.S. plants undergo regular FDA inspections. But many over-the-counter and prescription drug products are manufactured overseas, in locations that FDA inspects less frequently, and whistleblower protections may be non-existent. Congress just expanded FDA funding and authority to regulate imported food sold in the U.S. Doing the same for drugs is a smart move to protect consumers.

–Wells Wilkinson, Director, Prescription Access Litigation

This week’s news that the NIH is going to take up drug discovery where industry well, sort of left off, is big.  The proposed drug development hub, the National Center for Advancing Translational Studies, would move beyond the NIH’s current basic science research mode and usher drugs through clinical trials in an effort to jumpstart a long dried-up (or frozen) industry pipeline.

“Under the plan,” the New York Times reports, “more than $700 million in research projects already under way at various institutes and centers would be brought together at the new center. But officials hope that the prospect of finding new drugs will lure Congress into increasing the center’s financing well beyond $1 billion.”

For those of us who like innovation–and we do–this is good news, since there are plenty of important therapies that have stalled or been left by industry to tackle, as many companies have seemed to grow more risk-averse in recent years.

It’s also funny timing: We’re on the eve of the new House of Representatives’ Symbolic Move No. 3 to cut spending ahead of the State of the Union address today, and deficit concerns and suspicions of government-anything run deep (at least as deep as the 24-hour news cycle.) The Times suggests the agency will pay for it in part by melting down some of the National Center for Research Resources.

Pharma’s pipeline problems are far from new, and neither are the explanations and defenses. Industry tends to point to a slow FDA approval process and the low rate (estimated 3-5%) of phase 1 drugs that ever make it to the phase 3 finish line. And indeed, that process can cost a company a billion dollars.

$1 billion to bring a drug to market sounds expensive until you hear what companies have regularly spent on marketing. In 2007, when just 19 drugs were approved, the industry spent $11.8 billion marketing the drugs it already had – and that’s close to a mean between 2005-2009 (source: IMS Health.)

Companies often use the phase 1-3 fall-off and the steep bench-to-bedside cost to justify exorbitant costs of some brand-name drugs, and to defend their enthusiastic legal pursuits for patent extension and pricing protection (like pay-for-delay). But how much longer can their apologists use innovation as a shield (and sometimes sword) when lately they’ve had so little to show in the way of new cures, and NIH has taken the innovation reins?

Skeptics might ask why the federal government should take up the risks that companies and their shareholder obligations haven’t taken. Or whether this move simply frees up Big Pharma to devote even more of its resources to figuring out how to market the drugs NIH will sell back to them in the brave new world of pen-free physician practices.

As always, Merill Goozner over at Gooznews has a thoughtful take, and we like the historical perspective he brings, offering a cautionary tale in the form of taxol, a tumor-blocking therapy that was discovered in a government program and then handed to Bristol-Myers Squibb, “which in turn proceeded to charge the public exorbitant sums” for the public-backed drug.

But Goozner says he’s all for this drug discovery center, with this request:

All I ask is that on the front end of this program, Congress include in the appropriations bill a clause that states plainly that any products delivered by this program to the private sector be sold to taxpayers and the health care system at a reasonable price. And further the appropriations bill should state plainly that “reasonable” be determined by a carefully audited accounting of what exactly industry put into the drug’s development.

It will be interesting to see whether President Obama mentions the new center in the State of the Union address and if so, how he talks about the decision to take the drug discovery baton and run. And to see, in the longer term, who sees the gains and bears the cost of handing it back.

–Kate Petersen, PostScript blogger

This week Ed Silverman over at Pharmalot asked whether the FDA needed to get tough on some foreign active pharmaceutical ingredients (API) suppliers, citing some pretty hairy findings from inspections of Canadian and Indian factories that triggered the ol’ Warning Letter Machine.

The FDA does need to get tougher, using the authorities it has (seizure, shutting down a plant) and gaining new ones (recall and subpoena are two) to crack down on problem suppliers, since it seems that many manufacturers can’t or aren’t willing to.

As we’ve said here here and oh here, a more splintered supply chain means more places for things to go wrong, and with the number of GMP violations and recalls on the rise, it’s clear that plenty does. (And it’s not just suppliers: see the quality meltdown at GSK’s flagship plant.)

In a recent Pew Prescription Project survey 93 percent of Americans said they favor country of origin labeling on drugs—and the majority had little confidence in drugs coming from major overseas manufacturing hubs like India and China. Recently, drugmakers haven’t given them good reason to. FDA can do its part to change that by taking “louder” actions against suppliers in flagrant violation of safety and quality standards, and use its admittedly limited resources as a megaphone/stick to other suppliers, distributors and drugmakers, and less of a warning-letter/carrot.

Congress can also pass bills before it to bolster the FDA’s authorities and resources. A stronger FDA that can do timely inspections and subpoena documents when asking a company nicely doesn’t work could encourage some members of the supply chain to comply, or at least make it easier to keep them out of the chain when they don’t.

–Kate Petersen, PostScript blogger

As you’ve heard by now, FDA Deputy Commissioner Dr. Joshua Sharfstein is leaving his post at the FDA to become secretary of health and mental hygiene for Maryland. The blogosphere’s abuzz over what Sharfstein’s move means for the FDA and industry at the top of a new Congress, but amidst the speculation, we wanted to take a minute to review some of what Sharfstein did on the drug side of things during his two years at the agency. From an admittedly long and uncountable list, he:

–Oversaw an increase in the number of domestic and foreign inspectors

–Moved to collaborate with industry and lawmakers on improving supply chain security and oversight

–Launched the FDA transparency initiative, a three-phase process to lift the shroud of bureaucracy a bit (more on that soon)

–Engaged the agency in developing social media guidelines for drug and device makers (we await a final guidance).

In fact, Sharfstein was making waves at the FDA prior to being named deputy commissioner. As health commissioner in Baltimore, he and a group of fellow pediatricians filed a citizen petition in 2007 asking the FDA to reconsider the approval of over-the-counter cough and cold meds for small children, citing years of morbidity data and a lack of studies that showed the drugs to be safe or effective. The high-profile case led to manufacturers pulling under-2s’ cough and cold meds off the shelf–a move that was linked in Pediatrics last month in to a drop in related emergency room visits. (To date, we await the FDA’s final ruling on those products.)

In his post as deputy commissioner, Sharfstein was often the voice of the agency’s drug authority, and at a series of Congressional hearings on drug safety bills, heparin, and the J&J recalls, it was a guiding one. He came to the witness stand informed, open, willing to ask for things that the agency needed. As a physician, Sharfstein had the clinical experience and credibility to sign off on advisory committees’ important–and often contentious–approval and post-market debates. As a former Hill staffer, Sharfstein knew what could be done legislatively and how, and Members in turn offered bills that would give the agency authorities and resources that Sharfstein saw were needed.

And as a public health expert, Sharfstein helped recalibrate and rearticulate the agency’s mission in terms of protecting the public health through prevention, transparency, and collaboration. As Mark Senak at Eye on the FDA put it, Sharfstein’s and Commissioner Hamburg’s appointment signaled “that the agency was effectively turning a corner – that public health was the driving force and if you wanted to communicate effectively with the agency, framing a discussion–whether a drug approval or safety considerations or a policy decision – should be in public health vernacular.”

As a new Congress takes over the gavels, the clamor for faster approvals is growing, and several Members of Congress have suggested they intend to do some bureaucracy-busting on the historically beleaguered FDA. We hope that amidst these changes the agency can and will continue to focus on public health the way Sharfstein has, and carry out current initiatives and address new challenges in that spirit.

–Kate Petersen, PostScript blogger

We were glad to see drug safety in the spotlight on Sunday’s 60 Minutes segment on the GlaxoSmithKline quality problems at Cidra, its now-closed flagship plant in Puerto Rico. Cheryl Eckard, the former GSK quality assurance manager and whistleblower at the center of a $750M court settlement in October 2010, talked about the numerous quality and contamination problems her team found at Cidra, which was shut down in 2009 after the company failed to fix the manufacturing problems.

Whistleblowers like Eckard can act as an important safety valve in the current system, exposing potentially harmful safety problems and misconduct by companies that show unwillingness to comply or fix issues on their own.

But the story is a good reminder of the role of the FDA in all this. As the 60 Minutes segment reported, Eckard was sent in to address problems documented by an FDA warning letter, and that’s when her team found even more. Under current rules, companies must report manufacturing problems to the FDA—in a protocol known as “field alerts”—in only very narrow circumstances: when a distributed drug is mislabeled, contaminated, or does not meet required specifications. (And according to allegations in the case, GSK failed to do some of that.)

So how can we make sure that FDA knows whenever there is a quality or safety issue with our drugs that could affect the public health?

Better notification requirements are one way. The Drug Safety Enhancement Act (DSEA) introduced late last month by Rep. John Dingell, would expand notification requirements beyond field alerts in important ways, requiring manufacturers to get more information to the FDA whenever a manufacturing problem is detected.

Currently, many makers of OTC products don’t have to file under the field alert system (for any drug that doesn’t have a New Drug Application on file). But as we were reminded with the flotilla of recent J&J recalls, OTC manufacturers are susceptible to the same splintered manufacturing problems that prescription drugmakers are. The DSEA would include OTC producers.

It would also require companies to inform FDA about all issues with potential impact to the public health, including instances when:
–a drug may cause illness or injury
–possible theft or other loss has occurred
–counterfeit is probable
–the manufacturer has experienced repeated quality failures with a component supplier.

Under the Dingell bill, these reporting requirements would also extend to importers and distributors, which is key in such a fragmented supply chain.  Both that bill and one introduced last year by Rep. Edolphus Towns would bolster the notification systems and give the FDA recall authority, another important tool the agency should have to make sure unsafe or substandard drugs—the kind GSK allowed to get to consumers—are off trucks and pharmacy shelves promptly.

Currently, whistleblower protections under the False Claims Act require the allegation of false claims against the U.S. government. But one can imagine numerous scenarios in which the public health is at risk though no false claim has been made against the feds. Whistleblowers who report such threats would have similar protections under the DSEA.

The Cidra case is evidence that the system partially works. According to allegations, Eckard went to the FDA after her continued petitions to GSK management to fix things went unaddressed. The FDA inspectors of Cidra found quality problems, then Eckard found more. But a better notification system that requires more players to report to regulators all potential problems that could affect the public health puts the emphasis in the right place—in-house quality control and accountability—rather than waiting for outside inspectors to discover just how much has gone wrong.

–Kate Petersen, PostScript blogger

While physicians may be more wary of marketing relationships with industry, a new national survey of nurse practitioners shows that the group, who outnumber family docs, still has extensive ties with the industry and holds favorable views toward marketing tactics such as drug samples, sponsored lunches and dinners, and industry-backed continuing medical education. Considering nurses’ expanding role as primary prescribers in the U.S. health care system and the way the Sunshine provisions in the health reform law require reporting of only physician payments, these data may presage a turn in the industry’s promotional efforts away from physicians and toward nurses.

In the survey of nurse practitioners, “Under the Radar,” conducted in 2007-2008 by Elissa Ladd et al and published in the latest issue of the American Journal of Managed Care, 96 percent of respondents reported having regular interaction with the pharmaceutical industry, and the same number attended an industry-sponsored CME program over the prior five years. Forty-nine percent of nurse practitioners reported that they regularly attended pharma-backed lunches or dinners in the previous six months, and 48 percent said they’d be more likely to prescribe a drug that was highlighted at such a lunch or dinner event.

While the nurses’ survey does not give us trends, it does suggest an openness to industry marketing that may be waning, if slightly, among physicians. In a widely-cited 2004 survey by Eric Campbell et al in the New England Journal of Medicine, 94 percent of physicians reported having a relationship with the pharmaceutical industry. According to a November 2010 follow-up survey in the Archives of Internal Medicine by the same authors, fewer physicians (about 84 percent) reported relationships with pharmaceutical companies and involvement in all domains—samples, gifts, payments, and reimbursement—had decreased over the previous five years. Still lots of ties, but less of them.

Take samples. The number of physicians accepting samples went from 78 percent in 2004 to 64 percent in 2009; that reduced percentage nearly matches the proportion of nurses—66 percent—who reported taking samples between 2007-2008. So while we can’t see trends in the nursing data, we can surmise that policies around physician-industry relationships, coupled with nursing’s favorable attitudes toward promotional activities and its growing prominence (there are now more prescribing nurses in the U.S. than family physicians) could push both exposure and marketing attention toward the nurses’ corner.

If there is a salt-grain alert, it could be that the nurse survey represented a much smaller pool of respondents (263) than the 2009 AIM physician follow-up (1,891). And as they were independently designed and conducted, the surveys are necessarily snapshots, and not designed for perfect comparison.

Still, a few general lessons are worth noting here. While the spotlight has been trained on physician-industry relations in the last six years, the fact that prescribing nurses still hold a very positive attitude toward and active engagement with pharma marketing is an important signal for the nursing profession and those concerned with the influence of marketing to look more closely at the industry’s interaction with prescribing nurses.

State and federal policymakers moving to curb the influence of marketing on prescribing should keep in mind the implications of a group of prescribers whose numbers and prescribing power in the health care industry is growing, but whose involvement with the industry has largely flown “under the radar,” and make sure that policies don’t make a loophole of the nursing profession, and undercut the regulations that seek to protect the integrity of the patient-prescriber relationship.

–Kate Petersen, PostScript blogger