Drugmaker GlaxoSmithKline settled for $750 million in federal court yesterday over charges this that it knowingly sold unsafe drugs that didn’t meet quality standards set by the company and the FDA. The drugs include Paxil CR, an antidepressant, Bactroban, an ointment, Tagamet, an acid-reflux medication, and Kytril, an anti-nausea drug.

The quality problems at the center of the case occurred at its flagship Puerto Rico plant in Cidra, which made $5.5 billion worth of drugs each year but closed in 2009 after contamination problems could not be resolved. In 2002, Cheryl Eckard, GSK’s quality assurance manager, found major contamination problems at the facility after she was sent to address an FDA warning letter. She complained to executives but the problems went unresolved. Her requests to recall drugs for quality problems were not authorized (more evidence of the problem of leaving companies to conduct voluntary recalls), and in 2003 Eckard was let go.

The company allegedly failed to guarantee that some of the drugs were free from bacterial contamination, and in the case of Paxil, a chemical separation meant some patients may have been getting the wrong amount of the drug, causing it to be less effective. According to news reports, there were no reported illnesses linked to the drugs in the case.

According to the New York Times, “the case may lead to a collective industry shiver because it opens a new frontier for whistle-blower suits. Nearly all previous cases against the industry involved illegal marketing. This is the first successful case ever to assert that a drug maker knowingly sold contaminated products.”

Though Eckard’s findings came during a follow-up to an FDA warning letter, the Times report suggests that FDA inspectors also missed some of the quality problems identified in the suit.

Ensuring companies adhere to manufacturing quality standards is a critical oversight role of the FDA, and one that has been made more difficult as manufacturing increasingly occurs outside of the U.S. The announcement of GSK’s settlement comes as a new GAO report on the FDA’s foreign inspection program shows better resourcing for overseas inspection — the agency devoted four times as much money to foreign inspection in 2009 as it did in 2007 — but still suggests that the number of plants making raw materials and drugs for the U.S. far exceeds the FDA’s resources to inspect them. This leaves thousands of uninspected plants each year — plants that potentially manufacture raw materials for prescription and over-the-counter drugs on American pharmacy shelves. Often, as with the Lipitor recall announced earlier this month, companies are wary to name the source supplier of suspect or contaminated materials.

Several bills before Congress would increase FDA’s authority to guarantee the safety and efficacy of drugs, and establish more stringent supply chain management requirements for drug makers that regulators could use to better enforce drug quality and safety, both in the drug application and post-market phase. They would also create important new whistleblower protections for industry employees bringing information on violations of the FDCA and the Public Health Service Act. Currently, whistleblowers not employed by the government are covered by federal protections under the False Claims Act, when they can show that a false claim has been made against the government (in GSK’s case this was sub-standard medications sold to Medicare/Medicaid). But employees that want to alert regulators to a public health threat where evidence of a false claim against the government is not available or easily demonstrated are not specifically covered by those protections.

–Kate Petersen, PostScript blogger.

Using public reports from seven drug companies about their payments to doctors, a wide-ranging investigative report by ProPublica revealed this week that tens of thousands of U.S. doctors and health practitioners were paid over $250 million by pharmaceutical companies since 2009, much of it to give promotional talks for the companies. Among them, ProPublica found that hundreds have been cited for serious sanctions and misconduct, lack expertise such as publications or even board certification, or are in violation of their medical institution’s or hospital’s conflict-of-interest policies.

This report, in cooperation with the Boston Globe, the Chicago Tribune, NPR, PBS Nightly Business Report and Consumer Reports, suggests that when it comes to selecting opinion leaders, drug companies have often created their own from sheer volume of talks a doctor is hired for. The report also suggests a eye-opening failure to perform due diligence in investigating the records of those speaking to other physicians about their products. ProPublica reports:

A review of physician licensing records in the 15 most-populous states and three others found sanctions against more than 250 speakers, including some of the highest paid. Their misconduct included inappropriately prescribing drugs, providing poor care or having sex with patients. Some of the doctors had even lost their licenses.

More than 40 have received FDA warnings for research misconduct, lost hospital privileges or been convicted of crimes. And at least 20 more have had two or more malpractice judgments or settlements. This accounting is by no means complete; many state regulators don’t post these actions on their web sites.

Only two of the seven companies said they looked routinely into state licensing boards before hiring doctors to speak for them.

These frightening findings—made possible by the fraction of payment data currently available from companies–remind us that complete and mandatory disclosure of payments made to doctors is a critical crosscheck for consumers who want to know whether their doctor has been paid by industry, and for public and private payers and institutions interested in the compliance of health practitioners with state or institutional policies. ProPublica collected the data from the seven companies that publicly report some physician payments—AstraZeneca, Cephalon, GlaxoSmithKline, Eli Lilly, Johnson & Johnson, Merck and Pfizer—in a database that consumers and medical school compliance officers can use to make these searches.

That’s a good thing, but these companies represent just over a third of prescription drug sales in the U.S.; extrapolating, significantly more money trading hands isn’t being captured. That’s why the Physician Payments Sunshine law, which will require all U.S. drug, device and biotech companies to disclose all payments over $10 to physicians beginning in 2013, is so critical to completing the picture.

Despite the hundreds of millions of dollars that doctors are being paid to give drug talks—many making the equivalent of a second salary to do so—a survey done by Consumer Reports as part of the series suggests that consumers are clearly fed up and understand the dangers of bias that attend marketing relationships between industry and physicians: Nearly three-quarters of Americans are concerned that taking pharma money affects patient care, and more than two-thirds think that their doctor should tell them if he or she has been paid by a company whose drug they plan to prescribe.

The survey underscores a 2008 Pew Prescription Project consumer survey (pdf) that showed the public was similarly concerned that being paid to talk about a company’s drug could bias their health provider.  In the absence of professionwide self-regulation by physicians, many of whom continue to take these large sums, medical schools, hospitals, and states have stepped forward, creating new policies and regulations that put distance between doctors and drug marketing departments.

The American Medical Student Association Scorecard, which assesses the conflict-of-interest policies of every U.S. medical school each year, is a powerful tool that consumers and administrators can use alongside ProPublica’s database to check compliance of their doctor with his or her school’s policy, and to get ideas for how some medical centers have gone about strengthening their policies.

One example is Harvard Medical School’s new policy banning faculty from doing industry speaking gigs, which goes into effect early next year. Using the 2009-2010 data, the Boston Globe found that nearly half of the $6.3 million paid to Massachusetts physicians went to those affiliated with Harvard, and several doctors told the Globe they had stopped the speaking arrangements in order to comply with Harvard’s new rules.

But the Globe story also showed that just having a rule or strong policy isn’t enough. The Globe found that numerous clinicians whose Massachusetts hospitals had rules against giving promotional talks, including Beth Israel Deaconess Medical Center and Boston Medical Center, continued to perform such talks for drug companies.  These institutional policies and state laws need diligent and rigorous enforcement.  Having good intra-institutional compliance structures and information-sharing among medical schools about implementation are key to the success of these policies. Disclosure tools like Sunshine database, when it is complete, and others like ProPublica will reveal health providers who violate these rules.

One final point: the fact that the news outlets here found so much misconduct connected to drug company money in the incomplete records they have suggests there may be much more that remains undiscovered. Rigorous enforcement of existing policies and laws, and comprehensive disclosure from good work like ProPublica’s database and the future Sunshine Act, have never been more important in making sure that patients are getting the best medicine from their doctors, and that physicians are getting the best unbiased information about drugs.

Find the full series and searchable database at: http://www.propublica.org/topic/dollars-for-doctor

–Kate Petersen, PostScript blogger

A U.S. wholesaler of heparin sat on a complaint of contamination for nearly a year, an FDA investigation has revealed, well after the blood-thinner was recalled in 2008 for contaminated raw materials.

According to the Wall Street Journal, which reviewed the September FDA report, Wisconsin-based wholesaler Scientific Protein Laboratories (SPL) received a complaint from a company that had detected contaminants in one of the SPL heparin lots in October 2008, but did not look into it until September 2009. When SPL did finally investigate, the Journal reports, “it found that the contaminated raw material was used in two processed batches of heparin,” but it stopped reviewing one batch in June 2010 and never investigated the second.

SPL sold batches of the blood-thinner imported from a Chinese subsidiary to Baxter International, whose heparin was linked to numerous deaths and patient injury in 2007 and 2008 from contaminants that were later discovered to have originated in Chinese plants.

“I think it is deeply concerning that even after the national recall of heparin, which had been sourced from SPL, that the company would…fail to investigate a report of contaminated heparin in a timely way,” the Pew Health Group’s Allan Coukell told FDA Week, which also reviewed the FDA report.

“This is clearly a supplier of active ingredient that should have been under a lot of scrutiny from early 2008, so it’s hard to understand why these concerns apparently aren’t identified until a 483 that was issued in 2010,” Coukell said. “It’s really ultimately the company’s responsibility to ensure that the appropriate quality standards are in place and that reports of contamination are investigated in a timely way and FDA is saying that did not happen here.”

A source for the Journal indicated that the SPL contamination complaint may have come from Momenta, a Boston-based biotech firm, which won FDA approval this summer for a generic form of the drug.

For more on proposals and regulations to help secure the safety of the drug supply, visit the Pew Prescription Project, and follow SafeRxWatch on Twitter and Facebook.

–Kate Petersen, PostScript blogger

Want to find out about drug recalls when they happen? It seems FDA may need to get more involved. That may be one lesson to take from last week’s announcement that in August, Pfizer recalled 191,000 bottles of Lipitor after several patients reported a musty odor. Though it’s link to the Lipitor complaints is yet unconfirmed, a Pfizer test revealed low levels of 2,4,6 tribromoanisole in one of the lots, the same chemical used to coat wood shipping pallets that was linked to the delayed recall of millions of bottles of J&J’s Tylenol last winter.

Under current rules, companies that recall medications do not have to tell the FDA about a recall at all, much less within a certain timeframe. Though companies are required to notify the agency of chemical or physical changes, deterioration or contamination, J&J’s delayed recall and FDA notification (the company started receiving consumer complaints of musty odors in early 2008) suggests that even that reporting rule may be broadly, or loosely, interpreted by companies.

Pfizer has indicated that the recalled bottles of its blockbuster cholesterol medication came from a third-party supplier, but would not name the supplier or its location. A spokesman for the company told in-pharma Technologist that it is working with the FDA to “[change] the way that the bottles are packaged at the bottle supplier, decreasing time to delivery, and relocating some bottle production to other facilities operated by the supplier.”

Without sounding like a broken record (or an iPod on repeat), the amount of irregular, voluntary, and sometimes significantly delayed public notice of drugs pulled from the market is stacking up faster than it should, at least for the comfort of those on the public side of the equation.  Drugmakers’ conflict of interest – that is, a fear of potential sales lost by telling the public the full and timely facts about why, where, and when a drug was recalled – may be just too great to overcome with cautionary tales and promises at Congressional hearings to do better.

The FDA, free of that conflict and charged first with protecting the public’s health, is a fundamentally better steward of a recall, setting requirements for timeliness and disclosure, and overseeing–not just reactively advising–a company on when and how to remove risky drugs from the shelves. Several bills before Congress would give FDA that authority, and the Lipitor recall joins the list of reasons to give them consideration.

For more, see PostScript’s drug safety archive.

Speaking of more rapid responses, consider following “SafeRxWatch,” Community Catalyst’s new Facebook page and Twitter feed on drug safety issues.

–Kate Petersen, PostScript blogger

The FDA has made strengthening the safety and integrity of the global drug supply chain one of its top four strategic priorities for FY2011-2015, and is seeking public comment on refining these agency-wide goals.

Community Catalyst, which has been working with the Pew Prescription Project and the Alliance for a Safe Drug Supply to secure the global supply chain through legislative and regulatory measures, has been supportive of the agency’s efforts and applauds the prioritization of these critical issues now. The groups plan to comment in support of them.

In FDA’s draft strategy document, the agency said it aims to improve its oversight capacity by expanding risk-based quality checks, ensure that drugs being manufactured conform to established quality standards, and build good communication lines so the public is kept informed of drug quality and safety issues that arise.

Establishing better supply chain controls, the agency said, will entail coordination among foreign, federal and state regulators, gathering more and higher quality information from companies about their supply chains, and improving enforcement and inspection duties – which means newer tools and equipment, more inspection resources and the adoption of newer technology systems (read: FDA needs new computers.)

The FDA is already taking steps in this direction. It is working to prioritize follow-up with companies after warning letters and other enforcement actions have been issued, and developing deadlines by which drug makers must respond to critical or problematic inspection results.

The agency has also gone before Congress numerous times in the past two years to ask for more inspection resources and regulatory authority. Several bills before Congress now, including the Drug Safety and Accountability Act in the Senate, and a draft bill from the House Energy and Commerce Committee, would give the agency those things, among others.

Read more on Community Catalyst and Pew Prescription Project efforts to secure a safe drug supply here.

–Kate Petersen, PostScript blogger

Though Congress adjourned Wednesday, the House Oversight and Government Reform Committee went ahead and heard yesterday from two Johnson & Johnson/McNeil executives and the FDA over the ‘phantom recall’ of defective adult Motrin earlier this year.

To refresh, J&J has been in the news quite a bit this year, primarily for its recall of more than 135 million bottles of children’s liquid medications in May after numerous consumer complaints and an FDA inspection of the plant in Fort Washington, Pennsylvania turned up raw materials that were contaminated with gram-negative bacteria.

At the hearing Thursday, J&J CEO Bill Weldon admitted that the company did not notify FDA that it was purchasing product in an April sweep of stores now known as the phantom recall. Emails obtained by the committee revealed that J&J contractors were instructed to buy up deficient bottles of Motrin while acting like regular customers so as not to alert employees or the public.  Both Weldon and Consumer Group Chairwoman Colleen Goggins backpedaled on the “unfortunate language” and poor quality and notification systems, things that should have been done differently. There was a lot of Won’t Happen Again.

But these recalls were not just a case of unfortunate language and isolated mistakes, FDA Deputy Commissioner Joshua Sharfstein said: J&J had a big systemic quality problem.  The FDA inspected every McNeil plant at least once in the last year, and every one was found to have “inspectional deficiencies,” which the agency has been working with McNeil to clean up.

Weldon, too, highlighted the cooperation with the agency on fixing the quality systems and said that the children’s medicines recalled earlier this year would be back on shelves next week.

But members of the committee were unmollified. Ohio Rep. Dennis Kucinich said that there was a pattern of concealment, and was incredulous when Goggins maintained she was unaware of a series of emails discussing the advantages of the “soft market withdrawal” of the Motrin over a regular recall.

And Missouri Rep. Lacy Clay grew impatient when he tried to get a straight answer on why the company didn’t even get to close to meeting an FDA rule that requires companies to notify the agency within three days of any suspected contamination, irregularity or other change in a drug:

Clay: You can twist my words if you want, but why didn’t you report it within three days?
…
Goggins: I don’t know which instance you’re talking about. If we did not sir, we should have.

Clay: Any of the incidents! You didn’t report it in a timely fashion, within three days.

Weldon: Sir if–

Clay: So why didn’t you? Simple question.

Weldon: Yes, that I cannot answer. I would say though in all instances, in some instances, I know that we did. I don’t know the specific instance. If we did not, it was a mistake on our part and we should have.

The FDA’s Sharfstein didn’t get a free pass, either. Though he said there was no evidence that FDA was aware of or had condoned the phantom recalls, Ranking Member Darrell Issa tore into the deputy commissioner for requesting recall authority, waving a binder of inspection reports from the Fort Washington plant at him and suggesting FDA should have shut the plant down instead of asking for more authority.

But Sharfstein made a clear and compelling case for why the agency should have mandatory recall authority: The agency currently cannot tell a company how to recall product, he said, or influence the timeline or execution of a recall, and if a company refuses to recall a product FDA believes to be unsafe, the agency can only take product off shelves through complicated and time-intensive court channels (you can read his full prepared testimony here).

“The event of the phantom recall raises important questions about the current voluntary recall system,” he said. “In this case, if FDA had had the authority simply to order a recall to be done in the right way, I do not believe these events would have occurred.”

Two bills before Congress now, the Drug Safety and Accountability Act and a House bill introduced by Committee Chairman Edolphus Towns, would give the FDA that authority.  A third draft bill in Energy and Commerce would give FDA the same power.

Congresswoman Eleanor Norton from D.C. agreed with Sharfstein’s assessment that the current voluntary system depends totally “on companies providing accurate and complete information” to the FDA:

A voluntary system would assume all that to be the case. But I must say, it makes the same kind of assumption that was made for 10 years about the financial system, that voluntarily letting them go without regulations will do it.

In the same way, this voluntary recall notion is not only an oxymoron, I don’t see how we can continue to abide it, and expect companies to act any way but the way people do: to protect themselves, to protect their shareholders. And the only way to pierce that is with some form of regulation. If we haven’t learned that from financial reform, and now we’ve got to learn it through children’s medicines, we’ll never learn it.”

You can watch the full hearing at C-SPAN.

–Kate Petersen, PostScript blogger