Germany’s Boehringer Ingleheim manufactures drugs that treat a wide variety of conditions. Its blood thinner Pradaxa and type 2 diabetes drug Tradjenta are both linked to serious side effects.
Despite a mostly positive reputation, Boehringer has seen its share of difficulties. The U.S. Food and Drug Administration (FDA) has implicated the company in multiple manufacturing scandals, including poor quality control and failed safety inspections at its production facilities.
In addition, several Boehringer products, including the blood thinner Pradaxa and diabetes drug Tradjenta, have been linked to serious side effects. Complications with Pradaxa have prompted hundreds of lawsuits alleging that Boehringer failed to properly warn consumers about the drug’s potential health risks.
Albert Boehringer founded the company that would later become Boehringer Ingelheim in 1885. What started out as a 28-employee tartar factory that manufactured acid salts for pharmacies and dyeing works soon experienced rapid growth.
In 1893, Boehringer made the groundbreaking discovery that bacteria could be harnessed to mass produce lactic acid. Bacterial production of the acid, widely used in the dyeing, food and leather industries, was a huge innovation in the new arena of “biotech” manufacturing. The new process catapulted the company into the big leagues of manufacturing. By the time of Albert Boehringer’s death in 1939, Boehringer Ingelheim employed 1,500 workers.
|Fast Facts about Boehringer Ingelheim|
|Established: 1885||Founder: Albert Boehringer|
|Headquarters: Ingelheim, Germany||Size: 46,000 employees|
|2012 Sales: $19.4 billion|
Starting in the late 1940s and on through the ensuing decades, Boehringer Ingelheim expanded its operations while launching a number of successful pharmaceutical products. Following World War II, currency reform and a boost in economic growth provided a framework for incredible growth. The company extended its research program to include therapies for new conditions.
Around this time, the drugmaker began to realize the importance of foreign markets. After founding its first foreign subsidiary in 1948, Boehringer expanded to countries in Europe and around the world. The company founded research institutes and production sites In the 1970s and 1980s that led to new proprietary products and continued to fuel its growth. Today, Boehringer operates 145 branches with research centers spanning four continents.
In 1991, Boehringer made fundamental changes to the structure and organization of the company. It established a Board of Managing Directors composed of non-family members and refocused the company’s resources on research and innovation. Since then, Boehringer Ingelheim has done tremendously well, becoming one of the most successful foreign companies in the United States and Japan. It has recently created new companies, formed marketing alliances with other drugmakers and expanded its human and animal health divisions.
Despite a history of success, Boehringer Ingelheim has faced difficulties regarding the safety of some of its pharmaceutical products. Two such products, the blood thinner Pradaxa and the Type 2 diabetes drug Tradjenta, may result in serious legal troubles for the company.
Pradaxa (dabigatran) is a blood thinner approved in 2010 as an alternative to warfarin, the standard blood-thinning medication for more than 50 years. A popular treatment for preventing stroke in patients with atrial fibrillation (irregular heartbeat), Pradaxa topped $1 billion in sales in 2012. Although the drug has brought major success to Boehringer Ingelheim, some patients have reported serious side effects and complications.
While Pradaxa’s most common side effects are mild and may include indigestion, nausea and heartburn, patients have reported serious side effects such as uncontrolled bleeding. Unlike warfarin, Pradaxa has no antidote to stop the bleeding. If a patient begins to bleed uncontrollably, there is no way to make the blood coagulate again, which can lead to death from blood loss or hemorrhage.
In 2011, there were 3,781 reports of serious adverse events related to Pradaxa, according to pharmaceutical watchdog QuarterWatch. Of these, 542 were fatal. Most fatal events appear to be linked to increased risk of heart attack or uncontrollable bleeding associated with Pradaxa.
In response to these complications and deaths, victims and their families filed Pradaxa lawsuits. More than 2,000 Pradaxa cases were consolidated to a Southern District of Illinois court, all alleging that Boehringer failed to adequately warn patients about the drug’s bleeding risks and the lack of an antidote.
According to a May 2014 report on Forbes.com, Boehringer settled 4,000 state and federal Pradaxa lawsuits for $650 million.
Tradjenta (sold generically as linagliptin and as Trajenta in Europe) is an oral medication used to treat Type 2 diabetes. In May 2011, Boehringer Ingelheim gained approval to manufacture the drug in cooperation with Eli Lilly & Co. and experienced immediate success.
Tradjenta works by stopping the production of DPP-4, a protein that breaks down incretin to let the body know to stop producing insulin. As a DPP-4 inhibitor, Tradjenta unfortunately may have many of the same serious side effects as similar drugs in its class, such as Byetta. These include hypoglycemia (low blood sugar), pancreatitis and pancreatic cancer.
Pancreatitis (inflammation of the pancreas) and pancreatic cancer are serious side effects of several new diabetes medications. Byetta and Januvia have been linked to these complications, and lawsuits have already been filed alleging that their manufacturers did not do enough to educate the public about the dangers of the drugs.
Since Tradjenta is new to the market and has no long-term safety studies, there is not enough data to draw conclusions about the prevalence of its serious side effects. However, similarities between the mechanism of action for Tradjenta and embattled drugs like Byetta suggest that adverse event reports are likely. If future studies link the drug to reports of pancreatitis or pancreatic cancer, lawsuits against Tradjenta are likely to follow.
Safety and Quality Control Issues
In addition to legal problems over complications with its drugs, Boehringer also has had issues with safety in drug studies and quality control at its production facilities. Most recently, an article published in the German newspaper Der Spiegel revealed that the company may have been involved in controversial drug trials in the 1980s.
Back when communist East Germany had far less stringent regulations on human medical trials, a troubling number of major drug manufacturers paid doctors and hospitals huge sums of money to test their drugs on patients. Doctors conducting the tests often failed to inform patients about the trial or give them an opportunity to consent to participation.
At least 50,000 people in East Germany participated in more than 600 such clinical trials, some of which resulted in deaths. Although Boehringer Ingelheim officials claim to know of only three such studies conducted on their behalf in East Germany, records show there were at least twice as many.
Boehringer has also faced some conflicts with regulatory agencies. In September 2012, the company paid a civil penalty of $64,475 to settle Environmental Protection Agency (EPA) violations related to improperly handling mercury waste at a veterinary vaccine production facility in Kansas. As part of the settlement, Boehringer was required to spend at least $300,000 on a new hazardous waste storage facility.
In May 2013, the company overhauled its management team after a string of serious quality control problems prompted a sharply worded warning letter from the FDA. The agency cited Boehringer for several manufacturing violations, including:
- Failing to conduct a thorough investigation of foreign particles found in its pharmaceutical ingredients in 2009
- Using contaminated batches identified in 2009 to produce drugs until 2012
- Failing to determine why some shipments of Spiriva Handihaler, a bestselling inhaler, did not pass a test for uniform dose delivery
- Filing inconsistent reports in response to regulators’ complaints
The FDA warning came two years after the company faced severe quality control issues at Ben Venue Laboratories, a sterile injectables plant and U.S. subsidiary of Boehringer. Systemic problems led the FDA to issue a consent decree against the company, preventing the plant from producing and distributing drugs until it complied with safety standards. After spending several years and hundreds of millions of dollars to meet federal standards, Ben Venue ceased production in December 2013.
The Future of Boehringer Ingelheim
Boehringer’s greatest upcoming challenge is the complexity of the international health care marketplace. In its 2012 annual report, the company noted that fundamental health care reform in the United States and uncertainty in the Japanese market are increasing pressure on prices and market access, presenting challenges for Boehringer research-driven pharmaceutical companies.
Although Boehringer has seen substantial growth in recent years from sales of Pradaxa, legal liabilities threaten the future profitability of the flagship drug. Going forward, the company hopes to focus on medical innovation, quality control improvement and refocusing of strategy in stagnating mature markets.