Boehringer Ingelheim is a Germany-based drug manufacturer. Boehringer has affiliates in 142 international areas, including the U.S. and is one of the 20 largest pharmaceutical manufacturers in the world. The company had 2013 revenue of nearly $18 billion with products in Consumer Health Care (over-the-counter), Animal Health, and Prescription Medicine.
Boehringer describes their mission as “Value through Innovation” and has produced several unique medications including Flomax for enlarged prostate, Viramune for HIV in adults and infants over the age of 15 days, Spiriva for pulmonary disorders, Tradjenta for diabetes and Pradaxa for blood clot prevention.
Though Boehringer has maintained a reputation of advanced research and philanthropy, it has been warned by the Food and Drug Administration on more than one occasion for poor quality control and safety violations at some production facilities. Some Boehringer products have caused serious side effects resulting in permanent injury or death. The company was accused of failure to adequately warn patients and the medical community about potential risks and is facing thousands of lawsuits over the medications Pradaxa and Tradjenta.
History of Boehringer Ingelheim
Boehringer Ingelheim was founded in 1885 by Albert Boehringer in Nieder-Ingelheim, Germany as a tartar factory, manufacturing pharmaceutical acid salts and textile dyes. In 1893, Boehringer developed a process by which bacteria could be used to produce lactic acid to be used in the food, dye, and leather industries, which led to dramatic growth of the company.
Through the first and second World Wars, the company suspended the production of organic acids but continued Research and Development, and introduced new pharmaceutical products in pulmonary, gastrointestinal, and cardiovascular medicine. During World War II, the Ingelheim factory was forced to close but for only a few months until production was resumed with Allied permission.
During the 1950’s through the 1980’s the company continues international expansion, acquisition and mergers and a number of new-category medications were produced in the same therapeutic areas (cardiac, pulmonary and GI) such as Atrovent and Alupent for pulmonary disorders, Catapresan, Persantine, and Mexitil for cardiac disorders, and Buscospan for GI disorder. In 1977, the company’s first medication to treat thrombosis and embolisms (blood clots), Asasantin was launched and in 1987, the first thrombolytic for acute heart attacks was launched, Actilyse.
In 1991, the family owned company shifted management to the Board of Managing Directors and restructured R&D activities and in 1994, the formation of separate companies for each division was announced. A number of notable products have since been introduced as the company has continued development in its primary therapeutic areas with expansion into additional areas.
Notable products include Flomax for the treatment of prostate enlargement, Viramune and Aptivus for the treatment of HIV, Aggrenox for the treatment of strokes, Micardis for the treatment of hypertension, Metalyse for the treatment of heart attack, Spiriva for the treatment of COPD, Pradaxa for blood clot prevention and Tradjenta for the treatment of Type 2 Diabetes, both released in 2011.
Boehringer Manufacturing Issues
Despite a mostly good reputation, the company has a spotty history involving drug manufacturing, clinical testing and safety issues.
In 2013, a report in the German weekly magazine, Der Speigel, indicated that at least 50,000 patients including premature infants had been involved in over 600 clinical trials at hospitals in East Germany beginning in 1983, before the reunification. The article indicated that for each trial, “Western” pharmaceutical companies had paid up to 800,000 Deutsche Marks (about $2.1 million) to be split between the hospitals and the East German government.
International companies such as Sanofi of France, Ciba Geigy (now part of Novartis), Schering AG (now part of Roche), Bayer and Boehringer Ingelheim. Allegations indicate that the trials could not have been conducted in West Germany or other Western nations due to safety concerns.
Patients used in the trials were reportedly not given or unable to provide for informed consent required by global standards such as ICH and as adopted by the FDA. The government of Germany has been unable to confirm or deny these allegations and companies involved have provided no comment or denied violation of standards.
In 2012, the company paid $64,475 to settle EPA violations regarding mishandled mercury waste and was required to spend hundreds of thousands to develop a qualified hazardous waste facility. After a serious of missteps in manufacturing, the management of Boehringer Ingelheim was restructured. Violations included:
- 2008 – 2009 – Foreign material discovered in pharmaceutical ingredients and failure to adequately investigate the contamination
- 2009-2012 – Contaminated batches identified in 2009 were used to produce medications until 2012
- 2013 – Failure of Spiriva inhaler lots to meet dose uniformity product specifications which were released for shipment
- 2013 – Inconsistent reports filed with FDA in response to warning letters
Particular issues were noted at Ben Venue Laboratories, a U.S. subsidiary of Boehringer which led the FDA to issue an injunction against the manufacturing plant until it complied with regulations. Though Boehringer spent hundreds of millions of dollars on the plant, it was closed in December of 2013.
Boehringer Ingelheim was forced to pay $931,000 by a U.S. District Court Judge for withholding or failing to preserve “countless” files regarding Pradaxa drug development, marketing plans or employee phone message related to the requests of the records sought by litigants who had sued the company over injuries caused by Pradaxa in December of 2013, prior to the first Pradaxa lawsuit court dates.
The company claimed that they had made 32 million pages of documents available but they had been bombarded with “overly burdensome” requests by patient lawyers. The company also claimed that many of the documents were not relevant.
In March of 2014, Boehringer Ingelheim and Eli Lilly announced that a new diabetes drug that was intended for co-promotion would not be approved by the FDA due to previous cGMP violations at the Boehringer plant in Ingelheim that had not been corrected. A warning letter had been issued by the FDA in May of 2013 regarding a reinspection conducted 6 months after the original violation in 2012. Empagliflozine was not approved until August of 2014.
Boehringer Product Issues
Pradaxa (dabigatran), was approved in 2010 as a new type of anticoagulant to prevent clot formation in heart arrhythmia. It is a type of drug known as a factor Xa inhibitor that, unlike the older medication Coumadin, does not require routine blood testing. It was developed as an improvement over Coumadin but unlike the older medication, does not have an antidote.
Pradaxa is one of Boehringer’s bestselling products and produced over $1.5 billion in 2013 revenue for the company but many patients have reported serious side effects. Pradaxa may cause uncontrolled bleeding leading to hemorrhage and death in some cases which cannot be reversed.
Thousands of lawsuits regarding injury and death caused by Pradaxa have been filed against Boehringer Ingelheim. Patients have claimed that the company failed to adequately warn patients and the medical community about the bleeding risks and lack of antidote.
Boehringer has settled 4,000 lawsuits for $650 million but many more remain and more are expected against Pradaxa and similar medications such as Eliquis.
Tradjenta or Trajenta (linagliptin) is an anti-diabetic medication used for the treatment of Type 2 Diabetes. It is manufactured in partnership with Eli Lilly & Company and is in the same medication class as Byetta, which has caused numerous problems.
Tradjenta is a member of the “incretin” group of anti-diabetics such as Byetta and Bydureon but Tradjenta is taken as a pill and not an injection. Byetta and Bydureon have been implicated in a number of lawsuits due to serious side effects such as hypoglycemia, pancreatitis and pancreatic cancer.
The manufacturer of Byetta has faced hundreds of lawsuits with claims of failure to adequately warn the public about potential risks. Some of those lawsuits have been settled but many remain and more are expected.
Tradjenta is new on the market so no long-term safety evaluations are available but as it is in the same class of medications, it may cause similar serious adverse events as Byetta and may be subject to future lawsuits, particularly if long-term studies link the medication to pancreatic disorder or deaths.
The active ingredient in Tradjenta, linagliptin is also part of a combination product, Jentadueto which also contains metformin. Due to its composition, Jentadueto may also be subject to future lawsuits.
Boehringer in the Future
The changing healthcare market including the enactment of the Affordable Care Act, known as Obamacare and complexities in the Japanese market has concerned Boehringer management but it continues aggressive development in the diabetes, pulmonary and oncology arena.
Boehringer cut 1,100 jobs with the U.S. closure of Ben Venue in Ohio and has announced plans to cut 500 to 600 jobs in Germany due to lagging sales that dropped 3 percent overall in the first half of 2014, with a 5.4 percent drop in the pharmaceuticals market and has said they will be looking for additional cost cutting measures.
It is clear that Pradaxa lawsuits have also impacted the company’s financial future and may continue to do so as additional lawsuits are filed.