Tag Archives: drug companies

U.S. appeals court rejects novel opioid settlement framework

By Nate Raymond

(Reuters) – A federal appeals court on Thursday overturned a judge’s approval of a novel plan by lawyers representing cities and counties suing drug companies over the U.S. opioid crisis that would bring every community nationally into their settlement talks.

The 6th U.S. Circuit Court of Appeals by a 2-1 vote declined to approve an unprecedented “negotiation class” of 33,000 cities, towns and counties who could have a vote on whether to accept any settlements proposed with drug manufacturers and distributors.

U.S. District Judge Dan Polster in Cleveland, who oversees 2,900 opioid lawsuits, approved the framework last year to promote a global settlement.

It would allow cities and counties that have not sued to participate in settlement talks. Any settlement would need to win support of at least 75% of class members to be approved.

While companies do not have to use the negotiation class to settle cases, many including the drug distributors McKesson Corp, Cardinal Health Inc and AmerisourceBergen Corp objected.

Many state attorneys general, who have cases against the companies not before Polster, also objected, arguing the ruling could complicate their own settlement talks and interfere with states’ rights over their political subdivisions.

U.S. Circuit Judge Eric Clay said the federal rule that allows for class actions to jointly litigate cases does not authorize what Polster approved.

“However well-intentioned the district court’s actions might be, the fact of the matter is that the court, when it certified the negotiation class, exercised power it did not have,” he wrote.

The plaintiffs’ lawyers and companies did not immediately comment.

Some companies have proposed deals that do not use the framework including the three distributors and drugmakers Johnson & Johnson and Teva Pharmaceutical Industries Ltd, who in October 2019 proposed deals worth a collective $48 billion.

Negotiations are ongoing and dollar amounts have been shifting.

(Reporting by Nate Raymond in Boston; Editing by Bill Berkrot)

Toxin at heart of drug recall shows holes in medical safety net

FILE PHOTO: The headquarters of the European Medicines Agency (EMA), is seen in London, Britain, April 25, 2017. REUTERS/Hannah McKay -/File Photo

By Alexandra Harney and Ben Hirschler

SHANGHAI/LONDON (Reuters) – A toxin inadvertently produced in the manufacture of a widely prescribed medicine but not spotted for years raises questions about regulators’ ability to detect risks in a sprawling global drug supply chain increasingly reliant on factories in China.

China’s Zhejiang Huahai Pharmaceutical, which produces bulk ingredients for drugmakers, told its customers in late June it had found NDMA in its valsartan, an off-patent blood pressure drug originally developed by Novartis.

The discovery means that some of the 10 billion pills containing valsartan sold worldwide last year to prevent heart attacks and strokes had traces of N-nitrosodimethylamine (NDMA), classified as a probable human carcinogen. No one has been reported as sickened by the toxin, once used in the production of liquid rocket fuel.

Regulators and industry experts say the toxin almost certainly was introduced when Huahai changed the way it produced valsartan in 2012 – a modification that was signed off on by the European body that sets standards. Subsequent inspections by European, U.S., and Chinese regulators also found no problem.

“Everyone failed – the company, the inspectors, the FDA (U.S. Food and Drug Administration), the Europeans, the Chinese,” said Philippe André, an independent pharmaceutical auditor who inspected two Huahai facilities last August and found no critical concerns. “It’s a system failure.”

Reuters was unable to determine how Huahai first discovered the problem. In a July 7 statement released through the Shanghai Stock Exchange, it said it detected the toxin during the “optimization and evaluation” of its manufacturing process.

A Novartis spokesman told Reuters that its generic drugs arm, Sandoz, spotted the NDMA in the course of intensive testing to prepare for expanding its purchases of valsartan. He declined to comment further, including on the identity of the manufacturer or when the tests took place.

Two other smaller bulk suppliers – Zhejiang Tianyu Pharmaceutical and a unit of India’s Hetero Drugs – have since also discovered traces of NDMA in some of their valsartan.

The three companies declined to comment to comment about the case.

REDUCE WASTE

Huahai said in a document released through the Shanghai Stock Exchange it changed the production process to reduce waste and improve yields.

“The NDMA impurity was produced in trace amounts during the normal manufacturing process according to the company’s current registered process,” it said in a statement on July 24.

“All changes in the company’s valsartan manufacturing process have been approved by each country’s drug regulator, and the company manufactures in compliance with legal and regulatory standards.”

The European Medicines Agency (EMA) regulator, which first publicly raised the alarm in a statement on July 5, told valsartan suppliers in a subsequent memo dated July 16 that the NDMA may have been connected to the combined use of the solvent dimethylformamide and sodium nitrite.

The FDA is also going on that hypothesis, said Janet Woodcock, director of its Center for Drug Evaluation and Research. She stressed the investigation was still going on.

“This (NDMA) was not what you look for in an inspection,” Woodcock said in an interview. “If you don’t test for this you’re not going to have an idea that it’s in there, and you’re not going to see it on an inspection.”

The European Directorate for the Quality of Medicines (EDQM), responsible for setting manufacturing standards, told Reuters it was aware the solvent was being used when it approved the changed process, but that NDMA as a by-product was unexpected and not tested for.

Detecting NDMA would have required gas chromatography coupled with mass spectrometry, a very sensitive level of testing, an EDQM spokeswoman said.

“These techniques are not normally used routinely to test pharmaceutical products,” she said.

RECALLS

Built by Novartis into the $6 billion-a-year brand Diovan, valsartan’s European and U.S. patents expired in 2011 and 2012.

Global sales totaled 10.4 billion pills last year, including combination products, healthcare data consultancy IQVIA estimates. People with high blood pressure typically take one pill daily and heart failure patients two.

More than 50 companies around the world making finished tablets from the tainted valsartan have recalled products in recent weeks, according to a Reuters analysis of national medicines agencies’ records. They include major generic drug manufacturers such as Teva Pharmaceutical Industries, Ranbaxy Laboratories, and Sandoz.

Based on the average NDMA impurity detected at Huahai of 60 parts per million (ppm), the EMA says there could be one additional case of cancer in every 5,000 people taking the highest dose for seven years.

The contamination puts a spotlight on manufacturers in China and India, which supply more than two-thirds of all active pharmaceutical ingredients used in medicines, industry executives estimate. China accounts for the lion’s share.

Huahai, founded in 1989 and listed in Shanghai in 2003, was one of the first Chinese companies to get drugs approved in the U.S. market.

The FDA has inspected the site that made the contaminated valsartan three times since 2010, its records show. European inspectors also visited regularly.

The provincial branch of the Chinese FDA (CFDA) also inspected Huahai facilities 10 times in connection with new drug applications between January 2016 and June 2018, the national online database shows.

SCRUTINY

U.S. and European regulators have increased scrutiny of Chinese and Indian drug factories after the adulteration of the blood thinner heparin sickened hundreds and caused the deaths of at least 81 Americans in 2007 and 2008.

The CFDA is also on alert.

Last month, it revealed that Changsheng Bio-technology , a vaccine maker, had fabricated data and sold ineffective vaccines for children. It also found that a diphtheria, tetanus and pertussis vaccine sold by the state-owned Wuhan Institute of Biological Products was substandard.

The fact that international inspections do not appear to have detected the NDMA contamination alarms Anders Fuglsang, a former European medicines regulator who runs a pharmaceutical consultancy in Denmark.

“We need to ask ourselves how it is possible – despite pharmacopoeias and agency guidelines, inspection programs with coordination across continents, a system of public quality control, and companies complying with all rules – that a nasty carcinogen can find its way into our drugs and be there for years without anyone noticing,” he said.

(Additional reporting by Shanghai newsroom, Zeba Siddiqui in Mumbai and Sharnya G in Bengaluru; Editing by Sonya Hepinstall)

Trump: major drug companies to announce voluntary price cuts soon

U.S. President Donald Trump arrives prior to signing the "Right to Try Act," which gives terminally ill patients the right to use experimental medications not yet been approved by the Food and Drug Administration (FDA), at the White House in Washington, U.S., May 30, 2018. REUTERS/Leah Millis

WASHINGTON (Reuters) – President Donald Trump on Wednesday said he expects major drug companies to cut prices on their products in two weeks, but did not provide details on which companies would do so or the means by which they would provide such reductions.

“You’re going to have some big news. I think we’re going to have some of the big drug companies in two weeks said they’re going to announce, because of what we did, they’re going to announce voluntary massive drops in prices,” Trump said at a signing ceremony for a new law making it easier for seriously ill people to try experimental treatments.

Earlier this month, Trump unveiled the administration’s plan to lower prescription drug prices, largely through regulatory authority, calling the plan “the most sweeping action in history” to reduce the cost of medicines for consumers.

But healthcare stocks rose as it became clear that his administration avoided aggressive direct measures to cut prices.

The Health and Human Services Department has put out a request for information for its drug pricing plan, but has yet to issue any new regulations or pilot programs to lower drug prices.

Trump campaigned on lowering drug prices and has said that pharmaceutical companies were “getting away with murder,” but has since backed off that rhetoric.

HHS did not immediately respond to a request for comment on Trump’s announcement.

(Reporting by Steve Holland and Yasmeen Abutaleb; Editing by Chizu Nomiyama and Bill Berkrot)

U.S. states sue Mylan, Teva, others for fixing drug prices

A person holds pharmaceutical tablets and capsules in this picture illustration taken in Ljubljana

y Diane Bartz and Sarah N. Lynch

(Reuters) – Twenty states filed a lawsuit Thursday against Mylan, Teva Pharmaceuticals and four other generic drug makers, saying they conspired on pricing of two common generic drugs, according to a copy of the complaint.

The civil lawsuit is one piece of a broader generic drug pricing probe that remains under way at the state and federal level, as well as in the U.S. Congress. The inquiries have grown over the past two years to include multiple drugs and companies, some of which have disclosed they are being investigated by the Justice Department.

The drugs involved in Thursday’s lawsuit include the delayed release version of a common antibiotic, doxycycline hyclate; and glyburide, an older drug used to treat diabetes.

The lawsuit, filed in the U.S. District Court for the District of Connecticut, names Heritage Pharmaceuticals Inc as a “ring leader” of the price manipulation, and also lists Mayne Pharma, Aurobindo Pharma and Citron Pharma LLC as participants.

Asked for comment on Thursday, a spokesman for Heritage referred to their comment from the previous day, which blamed the former executives for the price-fixing and said that they had been terminated. Heritage is part of Indian company Emcure Pharmaceuticals.

Mylan denied the charge. “To date, we know of no evidence that Mylan participated in price fixing,” Mylan spokeswoman Nina Devlin said by email.

Teva spokeswoman Denise Bradley said by email that the company had just received the complaint and was reviewing it.

The other three companies had no immediate comment.

Teva shares were off 0.4 percent at $36.84 in New York trading. Mylan’s rose 0.9 percent at $38.01. Mylan has also come under fire for hiking the price of the Epipen to $600 for a two-pack, from $100.

The lawsuit alleges that top executives of the drug companies and their sales executives propped up the prices of the two drugs either by setting the prices or allocating markets, the New York attorney general’s office said in the statement.

The states also say in their lawsuit that executives knew that the conduct was illegal and either deleted emails or made efforts to avoid communicating in writing.

“Companies that collude and fix prices for generic drugs in order to pad their profits must be held accountable for the very real harm they inflict on New Yorkers’ ability to pay for life-saving medications,” New York Attorney General Eric Schneiderman said in a statement.

The state attorneys’ investigation into drug price fixing found evidence of broad, well-coordinated schemes on a number of generic drugs and is ongoing, according to the complaint.

The U.S. Department of Justice filed a lawsuit this week against two former Heritage executives alleging that they colluded to fix the prices of doxycycline hyclate, and to split up the market for glyburide.

Generic drug pricing became an issue in 2014, driven in large part by media reports of sharply rising drug prices, and Congress opened an investigation.

The lead state in the probe was Connecticut and the other states involved are Delaware, Florida, Hawaii, Idaho, Iowa, Kansas, Kentucky, Louisiana, Maine, Maryland, Massachusetts, Minnesota, Nevada, New York, North Dakota, Ohio, Pennsylvania, Virginia and Washington.