Ranbaxy Fined, J&J Tylenol Scandal, Bayer Sued Over Vitamins

By Ed Silverman
May 21, 2013

Once again, a plethora of interesting events has occurred since the last time we stopped by. What was the biggest headline? That decision may be up for grabs, but certainly, the $500 million penalty paid by Ranbaxy Laboratories is high on the list. The generic drug maker ponied up to settle criminal and civil charges stemming from a long-running manufacturing failure and cover-up scheme.

The US Justice Department called this the largest “financial” penalty paid by a generic drugmaker for violating the Food, Drug & Cosmetic Act. Ranbaxy pleaded guilty to seven felony counts, including three for making false statements to the FDA; paid a $120 million criminal fine and forfeited $20 million. Another $350 million was paid for causing federal healthcare programs to overpay for various drugs.

For those who may not recall, Ranbaxy used raw chemicals from unapproved sources, fabricated in-house test data to meet FDA standards and concealed these activities from FDA inspectors by falsifying records. These infractions went on for several years, mostly at two plants in India, but also involved senior management there and in the US.

Along the way, the FDA ordered an import ban on 30 different drugs, but not a recall of Ranbaxy medicines that were already circulating. A consent decree was eventually issued, but several months ago, Ranbaxy made headlines once again after recalling generic Lipitor was recalled after particles were found in some lots, embarrassing the FDA and the feds.

The case began nearly a decade ago when a former Ranbaxy executive, Dinesh Thakur, who hired private security after resigning but will receive $48 million, less attorney fees, for his trouble. Despite the severity and scope of the infractions, however, the settlement does not include any sort of penalties for individual Ranbaxy executives.

[Bio-Pharma]

The legal bickering over the Plan B morning after pills is far from over as the government is appealing a scathing ruling by a federal judge, who continues to lambast the Obama administration for purportedly placing politics over science in restricting access to teenage girls. US District Judge Edward Korman had ordered the FDA to make the pill available on an over-the-counter basis to girls of all ages.

In his recent order, Korman rjuled the pill should be available without a prescription of point-of-sale restrictions within 30 days, and accused the White House of acting in “bad faith,” causing “intolerable delays,” engaging in “political interference,” and allowing the FDA to exercise an “administrative agency filibuster.”

The decade-long saga took a decidedly unusual turn in late 2011, when the White House blocked the FDA from allowing the pill to become more widely available prior to the most recent Presidential election, prompting charges the administration was trying to appease conservatives. Some believe Plan B prevents a fertilized egg from implanting in the womb and equate this with abortion.

The administration claims Korman overstepped his authority because such an issue should be decided by agency rulemaking. The White House contends the only to amend distribution is for a manufacturer to submit the appropriate paperwork seeking to ease restrictions. Failing to do so, the feds argue, would harm the public interest, because the public relies on agency decisions, not court dictates.

The issue grew still thornier last month when the FDA approved the newer Plan B One-Step – which is just one pill, unlike the older version – for use for females who are 15 years and older without a prescription. Until then, the pill had been available without a prescription only to women who are 17 years and older. Teva had made an amended request shortly after the December 2011 rejection.

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Yet another Johnson & Johnson manufacturing scandal has erupted, this time in South Korea, where the authorities plan to bring criminal charges against its Janssen unit and ban production of five products – notably, a type of Children’s Tylenol – over the next few months. Moreover, Janssen Korea ceo Kim Oak-Yeon may face three years behind bars.

At issue are manufacturing violations that resulted in some bottles of two types of Children’s Tylenol syrup to contain higher amounts of the acetaminophen active ingredient, which can cause liver damage. The Ministry of Food and Drug Safety had already ordered the recall of nearly 1.7 million bottles, which had to be discarded.

The problems began when Janssen employees manually placed Tylenol syrup into bottles as new automated facilities installed in May 2011 could not completely fill the bottles toward the end of the manufacturing process. Just the same, Janssen Korea took a month before notifying authorities of the problem. By then, some 38,000 bottles had been sold.

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Once again, prescription painkillers made news. This time, the FDA denied a citizen petition that Endo Health Solutions filed in an attempt to thwart generic rivals to its Opana ER treatment. The decision was a big blow to the drugmaker because not only does this mean generics will soon become available, but the agency rationale is expected to diminish the value of the newer, reformulated Opana ER.

Endo wanted the FDA to decide that its original Opana ER was discontinued over safety concerns and, therefore, could no longer serve as the basis for approving any generics. The drugmaker hoped the FDA would only approve generics that contain data demonstrating such a drug is similarly “crush resistant” as the newer Opana ER.

In effect, Endo hoped to convince the agency that its tactic was designed to prevent the sort of abuse and addiction that has prompted a national outcry over the marketing and use of prescription painkillers. To do so, the drugmaker prompted the idea that its original Opana ER was unsafe and any generic that was designed to emulate this drug was also unsafe.

The FDA, however, did not bite. The agency believes the older Opana ER “was not withdrawn from the market for reasons of safety or effectiveness (and) as a result, generic versions” of original Opana ER” can continue to be approved and marketed.” The agency also disagreed with the abuse-resistant features of the newer Opana ER, and smacked down supporting data that had been submitted.

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Earlier this month, the FDA approved a new combination cholesterol pill from Merck that, instead of offering a much-needed medicine to patients who may be at risk of heart attacks and strokes, raised questions about regulatory judgment and marketing motives.

The drug in question is called Liptruzet, which combines Zetia and atorvastation, the active ingredient in Lipitor. However, Merck already sells Vytorin, which combines Zetia with its own Zocor, or simvastatin. And Vytorin has a troubled history, to say the least.

In 2008, a study called Enhance found the drug could LDL cholesterol, but failed to show a benefit over Zocor alone in the key endpoint – reducing plaque in the carotid artery. Along the way, though, Merck changed the primary endpoints, failed to include the lead investigator in the decision and stalled at naming members of a purportedly independent panel for reviewing data.

Moreover, there were ongoing delays in releasing the results, leading to a congressional probe and questions about whether Vytorin patients received sufficient benefit for a heavily promoted pill. Since then, Merck launched an 18,000 patient trial called Improve-It to dispel concerns, although results are not due until September 2014.

Now, here are some questions? What happens if the results are unfavorable? In this event, Merck is left with a pair of cholesterol pills generating declining revenue. But what happens if the results are favorable? Well, Merck still has a dilemma, because the Vytorin patent expires in 2017. By winning approval for Liptruzet, Merck has found a way to bolster its flagging cardiovascular franchise.

But consider this: Merck acknowledges that Lipruzet does not offer any “incremental benefit on cardiovascular morbidity and mortality over and above” what atorvastatin delivers. In other words, patients should not expect the new combination pill to offer any advantage in reducing the chance of developing heart disease. The only true innovation here is in the marketing.

Wall Street, however, sees the proverbial silver lining, at least as far as Merck investors are concerned. One analyst believes that the FDA would not have approved the drug if there were hints the Improve-It trial shows any worrisome signs. If this scenario is correct, then Merck has, indeed, scored a much-needed win for its product portfolio.

But what about the FDA? The agency did not release a statement explaining its rationale, prompting criticism. “I find it astonishing that, after all the controversy about (Vytorin), the FDA would approve another combination product with a drug that has been on the market for a decade and has not been shown to improve cardiovascular outcomes,” Steve Nissen of the Cleveland Clinic told Forbes.

“It seems like the agency is just tone deaf to the concerns raised by many members of the (medical) community about approving drugs with surrogate endpoints like cholesterol without evidence of a benefit for the disease we are truly trying to treat – cardiovascular disease.”

There is some irony here, by the way, because the FDA recently boasted that more new drugs were approved last year than in previous years and amounted to the largest such tally since 1996. And these included many new types of drugs, too. The Liptruzet approval has now prompted speculation that the agency has become too concerned with a “numbers game.”

Of course, the FDA had a regulatory obligation to review Liptruzet and the drug, presumably, passed the necessary hurdles. Just the same, the actual benefit above and beyond what is already to patients remains unclear.

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A non-profit group put Bayer on notice that a lawsuit will be filed charging the drugmaker with making “unsubstantiated and illegal claims” about the ability of its One-A-Day vitamin to prevent various disease, such as breast cancer, bolster physical energy and improve immunity, among other things.

The Center for Science in the Public Interest cites a Bayer web page touting Vitamin D for supporting breath health as an example of these types of claims, but argues that evidence the vitamin plays such a role is inconclusive and noted that supplement makers are prohibited from making claims about disease prevention.

The advocacy group charges Bayer is placing its vitamin on a par with mammograms, because its messages suggest consumers may believe the pill can reduce the risk of breast cancer. CSPI charges Bayer uses “similar tactics” to say its vitamin supports bone strength, joint health or eye health because “consumers will interpret these words to mean that the supplements will help prevent osteoporosis, arthritis or eye diseases, such as glaucoma or macular degeneration.”

In response, Bayer counters that it possesses “strong, competent and reliable science to support all of the structure-function claims,” and never made any claims suggesting that One-A-Day vitamins should be used to mitigate, prevent or treat any disease. The drugmaker also disagreed with CSPI’s assertion that randomized, controlled clinical trials are the standard of clinical evidence required to support dietary supplement claims.

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And finally, GlaxoSmithKline has created an online system for research to request access to patient-level clinical trial data and released the names of a group of experts who will review requestrs from outside researchers seeking to examine trial data. The move comes seven months after the drugmaker promised to create such a system and foster a sense of transparency.

Glaxo maintains the effort will make it possible for outside scientists to study Glaxo data and develop their own conclusions about safety and effectiveness. The move comes after years of controversy over the extent to which drugmakers clinical trial data and various scandals in which side effects were purportedly hidden from view.

The pharmaceutical industry has long been criticized for failing to fully make underlying patient-level data available to others who seek to verify results. Drugmakers have insisted the data is proprietry, but critics say the reluctance to disclose such information can be a red herring for hiding unflattering results that may limit sales.

One member of the Glaxo panel, however, is not wholly independent Brian Strom, a professor of public health and preventive medicine at the University of Pennsylvania, received $5,500 last year from the drugmaker. A spokeswoman insisted there will be no influence over the panel and wants to retain an independent third party to eventually oversee this system and, possibly, supercede the panel.

Separately Strom maintained his independence and that he was paid for providing advice about the panel, which he also insisted that the panel will remain independent. He added that Glaxo should be commended for taking this step and that it can be difficult for drugmakers to find qualified experts who do not have some past tie to industry.

The Author

Ed Silverman

Ed Silverman

Warning & Disclaimer: The pages, articles and comments on IPWatchdog.com do not constitute legal advice, nor do they create any attorney-client relationship. The articles published express the personal opinion and views of the author and should not be attributed to the author’s employer, clients or the sponsors of IPWatchdog.com. Read more.

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