Grünenthal GmbH

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Grünenthal Group
Type Gesellschaft mit beschränkter Haftung
Industry Pharmaceutical industry
Founded 1946
Founders Hermann Wirtz, Sr.
Headquarters Aachen, Germany
Area served Worldwide
Key people Eric-Paul Pâques
Alberto Grua
Stefan Genten
Klaus D. Langner
Thomas Senderovitz
Heinz-Gerd Suelmann
Products Pharmaceutics
Revenue Increase € 973 million (2012)[1]
Employees ca. 4400 (2012)[1]
Website www.gruenenthal.com
Headquarters in Stolberg

Grünenthal is a pharmaceutical company headquartered in Stolberg, near Aachen in Germany. The company was founded in 1946 as Chemie Grünenthal, and has been continuously family owned. The company was the first to introduce penicillin into the German market in the post-war period, after the Allied Control Council lifted its ban. In the 1960s, Grünenthal became infamous for the development and sale of the teratogenic drug Thalidomide. It was marked as the sleeping pill Contergan, and promoted as a morning sickness preventative. However it caused severe deformities in the children born to mothers who took it.

Today the firm generates more than 50% of its income with pain medications, such as the drug Tramadol which it developed.

It has two offices in Germany. In addition Grünenthal has subsidiaries in Europe, Latin America, the USA and China.

History[edit]

Chemie Grünenthal was founded 1946 by Hermann Wirtz, Sr. as Chemie Grünenthal GmbH in Stolberg (Rhineland), later it was renamed in Grünenthal GmbH and its headquarters were moved to Aachen.

Penicillin[edit]

The occupying powers had prohibited the research and manufacture of penicillin by German companies. When the ban was lifted Grünenthal was the first company, who introduced penicillin in the post-war period onto the German market. This investment achieved a big financial boost for the company.

Thalidomide (Contergan)[edit]

Main article: Thalidomide

Chemie Grünenthal synthezised thalidomide in 1954 and acquired a twenty-year patent. Soon after obtaining a patent in April 1954, the company started clinical trials and as early as November 1956 marketed the drug for the treatment of respiratory infections under the trade name Grippex®, a combination drug that contained thalidomide, quinine, vitamin C, phenacetin and acetylsalicylic acid. Researchers at Chemie Grünenthal also found that the drug was particularly effective for pregnant women suffering from morning sickness. Hence, in 1957, the company began aggressively marketing thalidomide as Contergan®.[2][3]

While initially considered safe, the drug was responsible for deformities in children born after their mothers used it during pregnancy and prior to the third trimester. In November 1961, thalidomide was taken off the market due to massive pressure from the press and public.[4] Experts estimate that the drug thalidomide led to the death of approximately 2,000 children and serious birth defects in more than 10,000 children, about 5,000 of them in West Germany. The regulatory authorities in the German Democratic Republic, as the former Communist East Germany was called, did not approve thalidomide. [5] One reason for the initially unobserved side effects of the drug and the subsequent approval in Germany was that at that time drugs did not have to be tested for teratogenic effects. They had only been tested on rodents, as was usual practice at the time.[6][7]

Thalidomide became one of the most successful prescription drugs in the history of medicine. In the UK, the British pharmaceutical company The Distillers Company (Biochemicals) Ltd, a subsidiary of Distillers Co. Ltd. (which became part of Diageo plc in 1997) marketed thalidomide under the brand name Distavel® as a remedy for morning sickness throughout the United Kingdom, Australia and New Zealand. Their advertisement claimed that "Distavel can be given with complete safety to pregnant women and nursing mothers without adverse effect on mother or child...Outstandingly safe Distavel has been prescribed for nearly three years in this country." [5] Around the world, more and more pharmaceutical companies started to produce and market the drug under license from Chemie Grünenthal. By the mid 1950s, 14 pharmaceutical companies were marketing thalidomide in 46 countries under 37 (some reports suggest 51) different trade names.[citation needed]

In the U.S. representatives from Chemie Grünenthal approached Smith-Kline & French with a request to market and distribute the drug in North America. A newly discovered memorandum (found hidden in 2010 the archives of the U.S.Food and Drug Administration (FDA)) shows that, as part of their in-licensing approach, Smith, Kline and French conducted animal tests and ran a clinical trial of the drug in the U.S. involving 875 people, including pregnant women, in 1956–57. In 1956 researchers at SKF involved in clinical trials, noted that even when used in very high doses thalidomide could not induce sleep in mice. And when administered at doses 50 to 650 times larger than that claimed by Chemie Grunenthal to be "sleep inducing" the researchers could still not achieve the hypnotic effect in animals that it had on man. After completion of the trial, and based on reasons kept hidden for decades, SKF declined to commercialize the drug. Later, Chemie Grünenthal, in 1958, reached an agreement with William S Merrell Company of Cincinnati, Ohio to market and distribute thalidomide throughout the United States.[5]

The U.S FDA refused to approve thalidomide for marketing and distribution. However, the drug was distributed in large quantities for testing purposes, after the American distributor and manufacturer Richardson-Merrell had applied for its approval in September, 1960. The official in charge of the FDA, Frances Oldham Kelsey, did not rely on information from the company which did not include any test results. Richardson-Merrell was called on to perform tests and report the results. The company refused and demanded approval six times, and was refused each time. Nevertheless, a total of 17 children with thalidomide-induced malformations were born.[8]

In 1970, DM 100 million were paid by Grünenthal and about DM 320 million by the Federal Government of Germany to the Foundation for Disabled People. Between 1997 and 2008 Grünenthal declined further payments to the thalidomide victims, because at that time the settled payments were exhausted. At the end of 2007, the British entrepreneur Nicholas Dobrik organized a group of victims and began an international campaign to force compensation payments.[9] On 8 May, 2008, Grünenthal announced it would voluntarily pay € 50 million to the Thalidomide Foundation to help to improve the lives of thalidomide victims.[10]

As a result of the thalidomide scandal, the Health Law in Germany was strengthened and new requirements for pharmaceutical testing were created; and the Federal Ministry of Health was established in 1962.

A Long Island, New York family sued the drug maker after their twins were born with deformities in May, 1961. Their son was born without arms, with hands growing from his shoulders, and their daughter suffered from a number of internal deformities. The mother, a German, met her husband in 1959, while studying at the University of Florence. She came to the United States with Contergan tablets she brought from Germany, and a prescription from her physician. The lawsuit alleged that Chemie Grünenthal was negligent in the testing of thalidomide, and that they failed to warn of its effects on unborn children.[11]

In 1968 Grünenthal executives were tried for involuntary manslaughter. By this time the company stated that thalidomide was not recommended for use "during pregnancy as such". The qualifying term obstetrics was employed. It was used in hindsight to strengthen the argument that doctors would interpret the word to mean that thalidomide was safe during the final stage of pregnancy only. This is a fallacious form of reasoning according to the German Medical Association, which defines obstetrics as starting with conception.[12]

In 1964 the Israeli physician Jacob Sheskin discovered the positive effect of thalidomide in the treatment of leprosy. Since the 1970s Grünenthal has delivered thalidomide tablets to leprosy clinics to assist the fight against leprosy. The delivery takes place under strict conditions and by virtue of an agreement with the World Health Organization (WHO).[13] Grünenthal provided more than 1,000 leprosy victims in the United States with thalidomide until a few months before July, 1986. The drug is especially helpful to lepers in treating an extremely painful allergic reaction of the skin. The company discontinued exporting thalidomide because of liability fears. A lack of insurance coverage for those requiring the drug was also a problem.[14]

In August 2012, the company issued its first apology in a half-century saying it regretted the consequences of the drug that led to the births of children without limbs or with shortened limbs during the 1950s and 1960s. Harald Stock, Grunenthal's chief executive, said the company had failed to reach out "from person to person" to the victims and their mothers over the past 50 years.[15]

British issues 2010[edit]

In July 2010, the British Prescription Medicines Code of Practice Authority (PMCPA) received a complaint from a Grünenthal employee, stating that Grünenthal produced and distributed incorrect and misleading data on its own products. After review, it was concluded that Grünenthal produced and distributed Versatis material and data at a congress of healthcare professionals that contained off label information, flawed cost comparison calculations (in favour of its own product), and knowingly concealed the fact that one of the authors was a Grünenthal employee. Hence, the panel concluded that the company’s activities reduced confidence in the pharmaceutical industry and thus ruled a breach of the ABPI Code of Practice for the Pharmaceutical Industry.[16]

In November 2010, the Medicines and Healthcare products Regulatory Agency (MHRA) advised the British authorities that it was concerned that Grünenthal was promoting its unlicensed medicine, tapentadol, to health professionals. Furthermore, these promotional activities included misleading comparisons with competitor pharmaceutical products and the deliberate pressuring of healthcare decision makers to make sure that the new Grünenthal product would be sold after registration. In summary, Grünenthal was found guilty of misleading and unlawful behaviour, and as a result the Appeal Board decided to carry out multiple audits at Grünenthal in 2009 and 2010 to review its practices.[17]

These cases have been preceded by similar cases in 2007, where Grünenthal was found guilty of distributing misleading information on its pharmaceutical products to healthcare professionals.[18]

Further development[edit]

The company has focused on the treatment of pain, and is doing its own research and development in this field. Grünenthal developed the drug Tramadol, which is marketed under the brand name Tramal is one of the best-selling painkillers in the opioid field. Other business units are gynecology, dermatology and anti-infectives.[1] Other current products are the birth control pill Belara and the matrix pain patch Transtec. Unlike Tramadol, which is a Schedule IV(C-IV) medication, the drug Tapentadol HCl, as licensed by Grünenthal, is Schedule II(C-II) in the U.S. (meaning it is a potent agonist, therefore subject to abuse similar to other C-II opioids such as Oxycodone and Morphine).

Initiatives[edit]

Since 2004, Grünenthal GmbH, in cooperation with the EFIC (European Federation of Chapters of the International Association for the Study of Pain), supports young scientists in carrying out innovative and exploratory clinical pain research projects. The EFIC-Grünenthal-Grant, totaling up to 200,000 EUR, is one of the highest research awards for clinical and human experimental research projects on the subject of pain. Research grants are valued at up to €30,000 per project.

References[edit]

  1. ^ a b c Grünenthal GmbH - Facts and Figures, 3. July 2011.
  2. ^ Reversal of Fortune: How a Vilified Drug Became a Life-saving Agent in the "War" Against Cancer - Onco'Zine - The International Oncology Network (November 30, 2013)
  3. ^ Thalidomide's Secret Past: The Link with Nazi Germany - Onco'Zine - The International Oncology Network (November 30, 2013)
  4. ^ Bundesverband Contergangeschädigter e.V. 6. July 2011.
  5. ^ a b c Reversal of Fortune: How a Vilified Drug Became a Life-saving Agent in the "War" Against Cancer - Onco'Zine - The International Cancer Network (November 30, 2013)
  6. ^ VFA: teratogenic effects 6. July 2011.
  7. ^ Contergan info page of Grünethal GmbH 3. July 2011
  8. ^ Report on the website of the U.S. Food and Drug Administration
  9. ^ Medikamentenskandal: Contergan-Firma droht Forderung in Milliardenhöhe Spiegel 10. November 2007.
  10. ^ Grünenthal donates € 50 million to the Foundation
  11. ^ Thalidomide Maker Is Sued by Parents Of Deformed Twins, New York Times, October 19, 1962, pg. 33.
  12. ^ Suffer The Children:The Story of Thalidomide, The Insight Team of the Sunday Times (UK), Viking Press, 1979, pp. 10 - 48.
  13. ^ Pharmazeutische Zeitung concerning Jacob Sheskin 6. July 2011.
  14. ^ Orphan Drugs: Caught In Limbo, New York Times, July 20, 1986, pg. F1.
  15. ^ "Thalidomide maker issues apology". UPI. Retrieved 1 September 2012. 
  16. ^ Prescription Medicines Code of Practice Authority, AUTH/2332/7/10 - Anonymous v Grünenthal http://www.pmcpa.org.uk/?q=node/851
  17. ^ MHRA v Grünenthal, CASE AUTH/2327/6/10 http://www.pmcpa.org.uk/files/2327%2020%20December%20INTERIM.pdf
  18. ^ Prescription Medicines Code of Practice Authority, Overview cases v Grünenthal http://www.pmcpa.org.uk/?q=taxonomy/term/43

External links[edit]