Grünenthal
Encyclopedia
Grünenthal GmbH is a German
pharmaceutical company
in Stolberg (Rhineland) near Aachen
, which holds the patent to Ultram (Tramadol
), and its much stronger derivative Nucynta (Tapentadol
), both used as analgesic
s (painkillers) with Norepinephrine Reuptake Inhibition. Unlike Ultram, which is not a scheduled medication, Tapentadol HCI is Schedule II(C-II) in the U.S. (meaning it is a potent agonist, therefore subject to abuse similar to other C-II opioid
s such as Oxycodone
and Levorphanol
). The firm was a branch of a soaps, toiletries, and cosmetics business which was formed a short time after World War II
.
(Contergan or Softenon) in the 1950s. The drug was responsible for teratogenic deformities in children born after their mothers used it during pregnancies, prior to the third trimester.
Recent research however, originating from different sources, suggest that the history of Thalidomide
might stretch past 1953 to the World War II
. It has been claimed that Thalidomide
was actually first developed as a possible antidote to nerve toxins, such as sarin
, by Otto Ambros
, a Nazi scientist who joined Grünenthal after the war. Correspondence between various drug companies, French firm Rhône-Poulenc, which was under Nazi control during the war years, Astra, which held the Swedish licence to distribute Thalidomide
, and IG Farben
, the German pharmaceutical firm, seem to confirm the alternative past of the product. Furthermore, a relation has been suggested between testing Thalidomide
and the Nazi death camps.
Grünenthal has reacted to these claims by stating: “To our knowledge there was no collaboration between Grünenthal and Rhône-Poulenc for the development of Contergan/thalidomide. Three Grünenthal employees discovered thalidomide and Grünenthal is the sole inventor on the patent.”
According to Grünenthal, Dr. Heinrich Mückter was one of those responsible for inventing Thalidomide
. Other sources mark Dr Mückter as a fledgling pharmacologist who carried out wartime experiments on Polish prisoners to find a cure for typhus. He caused the death of hundreds in the process.
Beginning with the production of antibiotics, the company entered the field of synthetic drug development by the mid-1950s. To do this the business vacated a section of its packing plant and hired a research staff numbering a half dozen scientists and technicians. The employees were placed under the direction of Dr. Mückter, who joined Chemie Grünenthal in 1946.
An early member of the Mückter's research team was Wilhelm Kunz, who became a pharmacist in World War II. His job involved synthesizing organic compounds with the goal of finding new compounds which Chemie Grünenthal might use.
Grünenthal contended that Thalidomide was suitable for both pregnant women and nursing mothers. In reply to a query from a Heilbrunn physician, the corporation maintained that there was no evidence that the drug would pass through the placental membrane after entering a pregnant mother's blood.
Grünenthal withdrew Thalidomide and all compounds containing it from the market on November 26, 1961. A study published in August 1962 revealed the instances of phocomelia
and use of the drug. In fifty case histories all but five women had taken Thalidomide between the thirtieth and fiftieth day after their last menstrual period. The five exceptions took the sedative between the fiftieth and sixtieth day after. In the twenty-one instances in which a date of conception could be ascertained, the mother had taken the drug between the twenty-eighth and forty-second day after conception.
. 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 not testing the Thalidomide preparation, and failing to warn of its effects on unborn children.
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
.
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 on their skins. The company discontinued exporting Thalidomide because of liability fears. A lack of insurance coverage for those requiring the drug was also a problem.
In addition, Grünenthal has been under investigation and reprimanded frequently by Regulatory Authorities for unlawful, and regulation breaching practices.
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/ data on a congress to healthcare professionals that contained off label promotion, 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 considered 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.
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 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.
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.
Germany
Germany , officially the Federal Republic of Germany , is a federal parliamentary republic in Europe. The country consists of 16 states while the capital and largest city is Berlin. Germany covers an area of 357,021 km2 and has a largely temperate seasonal climate...
pharmaceutical company
Pharmaceutical company
The pharmaceutical industry develops, produces, and markets drugs licensed for use as medications. Pharmaceutical companies are allowed to deal in generic and/or brand medications and medical devices...
in Stolberg (Rhineland) near Aachen
Aachen
Aachen has historically been a spa town in North Rhine-Westphalia, Germany. Aachen was a favoured residence of Charlemagne, and the place of coronation of the Kings of Germany. Geographically, Aachen is the westernmost town of Germany, located along its borders with Belgium and the Netherlands, ...
, which holds the patent to Ultram (Tramadol
Tramadol
Tramadol hydrochloride is a centrally acting synthetic opioid analgesic used in treating moderate pain. The drug has a wide range of applications, including treatment for restless legs syndrome and fibromyalgia...
), and its much stronger derivative Nucynta (Tapentadol
Tapentadol
Tapentadol is a centrally acting analgesic with a dual mode of action as an agonist at the μ-opioid receptor and as a norepinephrine reuptake inhibitor. While its analgesic actions have been compared to tramadol and oxycodone, its general potency is somewhere between tramadol and morphine in...
), both used as analgesic
Analgesic
An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....
s (painkillers) with Norepinephrine Reuptake Inhibition. Unlike Ultram, which is not a scheduled medication, Tapentadol HCI is Schedule II(C-II) in the U.S. (meaning it is a potent agonist, therefore subject to abuse similar to other C-II opioid
Opioid
An opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract...
s such as Oxycodone
Oxycodone
Oxycodone is an opioid analgesic medication synthesized from opium-derived thebaine. It was developed in 1916 in Germany, as one of several new semi-synthetic opioids in an attempt to improve on the existing opioids: morphine, diacetylmorphine , and codeine.Oxycodone oral medications are generally...
and Levorphanol
Levorphanol
Levorphanol is an opioid medication used to treat severe pain. It is the levorotatory stereoisomer of the synthetic morphinan and a pure opioid agonist, first described in Germany in 1948 as an orally active morphine-like analgesic...
). The firm was a branch of a soaps, toiletries, and cosmetics business which was formed a short time after World War II
World War II
World War II, or the Second World War , was a global conflict lasting from 1939 to 1945, involving most of the world's nations—including all of the great powers—eventually forming two opposing military alliances: the Allies and the Axis...
.
Initiatives
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, totalling 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.Thalidomide
According to Grünenthal, the company invented and marketed ThalidomideThalidomide
Thalidomide was introduced as a sedative drug in the late 1950s that was typically used to cure morning sickness. In 1961, it was withdrawn due to teratogenicity and neuropathy. There is now a growing clinical interest in thalidomide, and it is introduced as an immunomodulatory agent used...
(Contergan or Softenon) in the 1950s. The drug was responsible for teratogenic deformities in children born after their mothers used it during pregnancies, prior to the third trimester.
Recent research however, originating from different sources, suggest that the history of Thalidomide
Thalidomide
Thalidomide was introduced as a sedative drug in the late 1950s that was typically used to cure morning sickness. In 1961, it was withdrawn due to teratogenicity and neuropathy. There is now a growing clinical interest in thalidomide, and it is introduced as an immunomodulatory agent used...
might stretch past 1953 to the World War II
World War II
World War II, or the Second World War , was a global conflict lasting from 1939 to 1945, involving most of the world's nations—including all of the great powers—eventually forming two opposing military alliances: the Allies and the Axis...
. It has been claimed that Thalidomide
Thalidomide
Thalidomide was introduced as a sedative drug in the late 1950s that was typically used to cure morning sickness. In 1961, it was withdrawn due to teratogenicity and neuropathy. There is now a growing clinical interest in thalidomide, and it is introduced as an immunomodulatory agent used...
was actually first developed as a possible antidote to nerve toxins, such as sarin
Sarin
Sarin, or GB, is an organophosphorus compound with the formula [2CHO]CH3PF. It is a colorless, odorless liquid, which is used as a chemical weapon. It has been classified as a weapon of mass destruction in UN Resolution 687...
, by Otto Ambros
Otto Ambros
Otto Ambros was a German chemist, notably involved with the research of chemical nerve agents.-Early life:He was the son of a university professor. He went to school and passed his Abitur exam in Munich. In 1920 he went to the University of Munich to study chemistry and agricultural science...
, a Nazi scientist who joined Grünenthal after the war. Correspondence between various drug companies, French firm Rhône-Poulenc, which was under Nazi control during the war years, Astra, which held the Swedish licence to distribute Thalidomide
Thalidomide
Thalidomide was introduced as a sedative drug in the late 1950s that was typically used to cure morning sickness. In 1961, it was withdrawn due to teratogenicity and neuropathy. There is now a growing clinical interest in thalidomide, and it is introduced as an immunomodulatory agent used...
, and IG Farben
IG Farben
I.G. Farbenindustrie AG was a German chemical industry conglomerate. Its name is taken from Interessen-Gemeinschaft Farbenindustrie AG . The company was formed in 1925 from a number of major companies that had been working together closely since World War I...
, the German pharmaceutical firm, seem to confirm the alternative past of the product. Furthermore, a relation has been suggested between testing Thalidomide
Thalidomide
Thalidomide was introduced as a sedative drug in the late 1950s that was typically used to cure morning sickness. In 1961, it was withdrawn due to teratogenicity and neuropathy. There is now a growing clinical interest in thalidomide, and it is introduced as an immunomodulatory agent used...
and the Nazi death camps.
Grünenthal has reacted to these claims by stating: “To our knowledge there was no collaboration between Grünenthal and Rhône-Poulenc for the development of Contergan/thalidomide. Three Grünenthal employees discovered thalidomide and Grünenthal is the sole inventor on the patent.”
According to Grünenthal, Dr. Heinrich Mückter was one of those responsible for inventing Thalidomide
Thalidomide
Thalidomide was introduced as a sedative drug in the late 1950s that was typically used to cure morning sickness. In 1961, it was withdrawn due to teratogenicity and neuropathy. There is now a growing clinical interest in thalidomide, and it is introduced as an immunomodulatory agent used...
. Other sources mark Dr Mückter as a fledgling pharmacologist who carried out wartime experiments on Polish prisoners to find a cure for typhus. He caused the death of hundreds in the process.
Beginning with the production of antibiotics, the company entered the field of synthetic drug development by the mid-1950s. To do this the business vacated a section of its packing plant and hired a research staff numbering a half dozen scientists and technicians. The employees were placed under the direction of Dr. Mückter, who joined Chemie Grünenthal in 1946.
An early member of the Mückter's research team was Wilhelm Kunz, who became a pharmacist in World War II. His job involved synthesizing organic compounds with the goal of finding new compounds which Chemie Grünenthal might use.
Grünenthal contended that Thalidomide was suitable for both pregnant women and nursing mothers. In reply to a query from a Heilbrunn physician, the corporation maintained that there was no evidence that the drug would pass through the placental membrane after entering a pregnant mother's blood.
Grünenthal withdrew Thalidomide and all compounds containing it from the market on November 26, 1961. A study published in August 1962 revealed the instances of phocomelia
Phocomelia
Phocomelia is an extremely rare congenital disorder involving the limbs . Étienne Geoffroy Saint-Hilaire coined the term in 1836....
and use of the drug. In fifty case histories all but five women had taken Thalidomide between the thirtieth and fiftieth day after their last menstrual period. The five exceptions took the sedative between the fiftieth and sixtieth day after. In the twenty-one instances in which a date of conception could be ascertained, the mother had taken the drug between the twenty-eighth and forty-second day after conception.
Litigation
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 FlorenceUniversity of Florence
The University of Florence is a higher study institute in Florence, central Italy. One of the largest and oldest universities in the country, it consists of 12 faculties...
. She came to the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
with Contergan tablets she brought from Germany
Germany
Germany , officially the Federal Republic of Germany , is a federal parliamentary republic in Europe. The country consists of 16 states while the capital and largest city is Berlin. Germany covers an area of 357,021 km2 and has a largely temperate seasonal climate...
, and a prescription from her physician. The lawsuit alleged that Chemie Grünenthal was negligent in not testing the Thalidomide preparation, and failing to warn of its effects on unborn children.
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
Obstetrics
Obstetrics is the medical specialty dealing with the care of all women's reproductive tracts and their children during pregnancy , childbirth and the postnatal period...
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
Fertilisation
Fertilisation is the fusion of gametes to produce a new organism. In animals, the process involves the fusion of an ovum with a sperm, which eventually leads to the development of an embryo...
.
Grünenthal provided more than 1,000 leprosy
Leprosy
Leprosy or Hansen's disease is a chronic disease caused by the bacteria Mycobacterium leprae and Mycobacterium lepromatosis. Named after physician Gerhard Armauer Hansen, leprosy is primarily a granulomatous disease of the peripheral nerves and mucosa of the upper respiratory tract; skin lesions...
victims in the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
with Thalidomide until a few months before July 1986.
The drug is especially helpful to lepers in treating an extremely painful allergic reaction on their skins. The company discontinued exporting Thalidomide because of liability fears. A lack of insurance coverage for those requiring the drug was also a problem.
In addition, Grünenthal has been under investigation and reprimanded frequently by Regulatory Authorities for unlawful, and regulation breaching practices.
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/ data on a congress to healthcare professionals that contained off label promotion, 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 considered 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.
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 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.
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.