Grünenthal is a
pharmaceutical company
The pharmaceutical industry discovers, develops, produces, and markets drugs or pharmaceutical drugs for use as medications to be administered to patients (or self-administered), with the aim to cure them, vaccinate them, or alleviate sympto ...
headquartered in
Aachen
Aachen ( ; ; Aachen dialect: ''Oche'' ; French and traditional English: Aix-la-Chapelle; or ''Aquisgranum''; nl, Aken ; Polish: Akwizgran) is, with around 249,000 inhabitants, the 13th-largest city in North Rhine-Westphalia, and the 28th- ...
in Germany. It was founded in 1946 as Chemie Grünenthal and has been continuously
family-owned
A family business is a commercial organization in which decision-making is influenced by multiple generations of a family, related by blood or marriage or adoption, who has both the ability to influence the vision of the business and the willingn ...
. The company was the first to introduce
penicillin
Penicillins (P, PCN or PEN) are a group of β-lactam antibiotics originally obtained from ''Penicillium'' moulds, principally '' P. chrysogenum'' and '' P. rubens''. Most penicillins in clinical use are synthesised by P. chrysogenum using ...
into the German market in the
postwar period
In Western usage, the phrase post-war era (or postwar era) usually refers to the time since the end of World War II. More broadly, a post-war period (or postwar period) is the interval immediately following the end of a war. A post-war period c ...
, after the
Allied Control Council
The Allied Control Council or Allied Control Authority (german: Alliierter Kontrollrat) and also referred to as the Four Powers (), was the governing body of the Allied Occupation Zones in Germany and Allied-occupied Austria after the end of Wo ...
lifted its ban.
Grünenthal became infamous in the 1950s and 1960s for the development and sale of the
teratogenic
Teratology is the study of abnormalities of physiological development in organisms during their life span. It is a sub-discipline in medical genetics which focuses on the classification of congenital abnormalities in dysmorphology. The related t ...
drug
thalidomide, marketed as the sleeping pill
Contergan
Thalidomide, sold under the brand names Contergan and Thalomid among others, is a medication used to treat a number of cancers (including multiple myeloma), graft-versus-host disease, and a number of skin conditions including complications o ...
and promoted as a
morning sickness
Morning sickness, also called nausea and vomiting of pregnancy (NVP), is a symptom of pregnancy that involves nausea or vomiting. Despite the name, nausea or vomiting can occur at any time during the day. Typically the symptoms occur between th ...
preventive. Thalidomide caused severe birth defects, miscarriages, and other severe health problems. Though these side effects were proven conclusively in 1959, and 1962,
Grünenthal continued marketing the drug well into the 1970s and 1980s.
The company generates more than 50 percent of its income with
pain medication
An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain (that is, analgesia or pain management). It i ...
s such as
Tramadol
Tramadol, sold under the brand name Ultram among others, is an opioid pain medication used to treat moderate to moderately severe pain. When taken by mouth in an immediate-release formulation, the onset of pain relief usually begins within an h ...
. The company has two offices in Germany as well as subsidiaries in Europe, Latin America, the US, and China. In November 2016, the company acquired Thar Pharmaceuticals and in 2018 Averitas Pharma.
History
![Stolberg Grünenthal](https://upload.wikimedia.org/wikipedia/commons/9/95/Stolberg_Gr%C3%BCnenthal.jpg)
Chemie Grünenthal was founded in 1946 by Hermann Wirtz, Sr. A former Nazi party member, as Chemie Grünenthal GmbH in
Stolberg (Rhineland)
Stolberg (, Ripuarian: ) is a town in North Rhine-Westphalia, Germany. It has a long history as an industrial town and belongs to the district Aachen and the lower district court of Eschweiler.
Geography
Stolberg is located approximately 5&nbs ...
. Later, it was renamed Grünenthal GmbH, and its headquarters were moved to
Aachen
Aachen ( ; ; Aachen dialect: ''Oche'' ; French and traditional English: Aix-la-Chapelle; or ''Aquisgranum''; nl, Aken ; Polish: Akwizgran) is, with around 249,000 inhabitants, the 13th-largest city in North Rhine-Westphalia, and the 28th- ...
. The
Allied Control Council
The Allied Control Council or Allied Control Authority (german: Alliierter Kontrollrat) and also referred to as the Four Powers (), was the governing body of the Allied Occupation Zones in Germany and Allied-occupied Austria after the end of Wo ...
had prohibited the research and manufacture of penicillin by German companies. When the ban was lifted, Grünenthal was the first company to introduce penicillin in the postwar period into the German market. This investment achieved a big financial boost for the company.
Thalidomide (Contergan)
![Thalidomide effects](https://upload.wikimedia.org/wikipedia/commons/c/cd/Thalidomide_effects.jpg)
Under its Head of Research
Heinrich Mückter
Heinrich Mückter (14 June 1914 – 22 May 1987) was a German medical doctor, pharmacologist and chemist.
World War II
During the Nazi occupation of Poland, Mückter was deputy director of the Kraków Institute for Typhus and Virus Research. Mà ...
, a former Nazi scientist, Grünenthal synthesised thalidomide in 1954 and acquired a 20-year patent. Soon after obtaining its patent in April 1954, the company started clinical trials, and from November 1956, marketed the drug for the treatment of respiratory infections under the trade name Grippex, a combination drug that contained thalidomide,
quinine
Quinine is a medication used to treat malaria and babesiosis. This includes the treatment of malaria due to ''Plasmodium falciparum'' that is resistant to chloroquine when artesunate is not available. While sometimes used for nocturnal leg cr ...
,
vitamin C
Vitamin C (also known as ascorbic acid and ascorbate) is a water-soluble vitamin found in citrus and other fruits and vegetables, also sold as a dietary supplement and as a topical 'serum' ingredient to treat melasma (dark pigment spots) an ...
,
phenacetin
Phenacetin (acetophenetidin, ''N''-(4-ethoxyphenyl)acetamide) is a pain-relieving and fever-reducing drug, which was widely used following its introduction in 1887. It was withdrawn from medicinal use as dangerous from the 1970s (e.g., withdrawn ...
, and
acetylsalicylic acid. Researchers at Chemie Grünenthal also found that the drug was particularly effective for pregnant women suffering from morning sickness, although no trials were run with pregnant women. In 1957, the company began marketing thalidomide as Contergan.
In 1958, an unusual number of deformities in newborns were reported in Germany. However, scientists first assumed nuclear tests to be the reason for that.
Only in late 1961, researchers found out that Contergan must be the cause. In November 1961, thalidomide was thus taken off the market.
Thalidomide caused severe deformities in the children of women who took the drug during pregnancy. Experts estimate that the drug thalidomide led to the death of about 2,000 children and serious
birth defect
A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can ...
s in more than 10,000 children, about 5,000 of them in
West Germany
West Germany is the colloquial term used to indicate the Federal Republic of Germany (FRG; german: Bundesrepublik Deutschland , BRD) between its formation on 23 May 1949 and the German reunification through the accession of East Germany on 3 O ...
. East German regulatory authorities did not approve thalidomide, and the U.S.
Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
(FDA) also declined to approve the drug.
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. Thalidomide had only been tested on rodents, as was usual practice at the time.
In the UK, the British pharmaceutical company The Distillers Company (Biochemicals) Ltd, a subsidiary of Distillers Co. Ltd. (which became part of
Diageo
Diageo plc () is a Multinational corporation, multinational alcoholic beverage company, with its headquarters in London, England. It operates from 132 sites around the world. It was the world's largest distiller before being overtaken by Kweich ...
plc in 1997) marketed thalidomide under the brand name Distaval as a remedy for morning sickness throughout the United Kingdom, Australia, and New Zealand. Their advertisement claimed, "Distaval can be given with complete safety to pregnant women and nursing mothers without adverse effect on mother or child...Outstandingly safe Distaval has been prescribed for nearly three years in this country."
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.
In the US, representatives from Chemie Grünenthal initially approached
Smith-Kline and French with a request to market and distribute the drug in North America. The U.S. Food and Drug Administration 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
Frances Kathleen Kelsey ( Oldham; July 24, 1914 – August 7, 2015) was a Canadian-American pharmacologist and physician. As a reviewer for the U.S. Food and Drug Administration (FDA), she refused to authorize thalidomide for market because sh ...
, 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 requested approval six times and was refused each time. Nevertheless, a total of 17 children with thalidomide-induced malformations were born.
A
Long Island, New York
Long Island is a densely populated island in the southeastern region of the U.S. state of New York, part of the New York metropolitan area. With over 8 million people, Long Island is the most populous island in the United States and the 18th ...
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 was a German woman who had met her husband in 1959 while studying at the
University of Florence. She came to the United States with Contergan tablets she had 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.
By 1968, the company stated that thalidomide was not recommended for use "during pregnancy as such". The qualifying term
obstetrics
Obstetrics is the field of study concentrated on pregnancy, childbirth and the postpartum period. As a medical specialty, obstetrics is combined with gynecology under the discipline known as obstetrics and gynecology (OB/GYN), which is a surgi ...
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.
As a result of the thalidomide scandal, the
Health Law in West Germany was strengthened and new requirements for pharmaceutical testing were created; the
Federal Ministry of Health was established in 1962.
Criminal trial
In 1968, Grünenthal executives were tried for
involuntary manslaughter
Manslaughter is a common law legal term for homicide considered by law as less culpable than murder. The distinction between murder and manslaughter is sometimes said to have first been made by the ancient Athenian lawmaker Draco in the 7th c ...
. In 1970, the indictment was closed due to the minor guilt of the defendants and insufficient public interest in further proceedings.
Reparations
In 1970, Grünenthal paid
DM 100 million to the , and the German government paid reparations of DM 320 million. Between 1997 and 2008, Grünenthal declined further payments to thalidomide victims. At the end of 2007, the British entrepreneur Nicholas Dobrik organised a group of victims and began an international campaign for further reparations. On 8 May 2008, Grünenthal announced it would voluntarily pay further €50 million to the Thalidomide Foundation to help to improve the lives of thalidomide victims.
Apology
In August 2012, the company issued its first apology in a half-century, saying it regretted the consequences of the drug. 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. The company has refused to compensate the Spanish victims of the drug who have sued the company.
Leprosy treatment
In 1964, Israeli physician Jacob Sheskin discovered the positive effect of thalidomide in the treatment of
leprosy
Leprosy, also known as Hansen's disease (HD), is a long-term infection by the bacteria ''Mycobacterium leprae'' or ''Mycobacterium lepromatosis''. Infection can lead to damage of the nerves, respiratory tract, skin, and eyes. This nerve damag ...
. 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
The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...
. Grünenthal provided thalidomide to more than 1,000 patients with leprosy in the United States until a few months before July, 1986. The drug is especially helpful to patients with leprosy 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.
Versatis and Tapentadol cases
In July 2010, the British Prescription Medicines Code of Practice Authority (PMCPA) received complaints about a poster used by field-based teams at Grünenthal. It promoted the off-label use of Versatis, while the cost comparison analysis was flawed and misleading. The company stated that it had paid for the printing but no editorial control. Nevertheless, the Code of Practice was breached, and an undertaking was received.
In November 2010, the British Medicines and Healthcare products Regulatory Agency (MHRA) received an allegation that Grünenthal promoted its unlicensed product, Tapentadol, to health professionals. Grünenthal conducted an investigation and concluded that the allegation was unsubstantiated.
To date, the PMCPA website lists 16 completed cases involving Grünenthal.
Further drug development
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
Tramadol, sold under the brand name Ultram among others, is an opioid pain medication used to treat moderate to moderately severe pain. When taken by mouth in an immediate-release formulation, the onset of pain relief usually begins within an h ...
, which is marketed under the brand name Tramal, one of the best-selling
opioid
Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid us ...
painkillers
An analgesic drug, also called simply an analgesic (American English), analgaesic (British English), pain reliever, or painkiller, is any member of the group of Pharmaceutical drug, drugs used to achieve relief from pain (that is, analgesia or p ...
. Other business units are
gynecology
Gynaecology or gynecology (see spelling differences) is the area of medicine that involves the treatment of women's diseases, especially those of the reproductive organs. It is often paired with the field of obstetrics, forming the combined are ...
,
dermatology
Dermatology is the branch of medicine dealing with the skin.''Random House Webster's Unabridged Dictionary.'' Random House, Inc. 2001. Page 537. . It is a speciality with both medical and surgical aspects. A dermatologist is a specialist medical ...
, and
anti-infectives
An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dis ...
. Current
products include 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
An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...
, therefore subject to abuse similar to other C-II
opioid
Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid us ...
s, such as
oxycodone and
morphine
Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies (''Papaver somniferum''). It is mainly used as a analgesic, pain medication, and is also commonly used recreational drug, recreationally, or to make ...
).
In 2018, Grünenthal acquired European rights to the pain-related brands Nexium and Vimovo and the US-rights for Qutenza (capsaicin). The company began building a US structure to commercialise the latter asset through Averitas Pharma. Nexium has since been removed from the market due to kidney damage. This drug also did not have sufficient testing before it was brought to market. Later in 2018, Grünenthal obtained global rights for Qutenza.
Social commitment
In 1998, the company launched the
Grünenthal Foundation for Palliative Medicine. With its help, the first academic chair and clinic for
palliative care
Palliative care (derived from the Latin root , or 'to cloak') is an interdisciplinary medical caregiving approach aimed at optimizing quality of life and mitigating suffering among people with serious, complex, and often terminal illnesses. Wit ...
was founded at the
RWTH Aachen University
RWTH Aachen University (), also known as North Rhine-Westphalia Technical University of Aachen, Rhine-Westphalia Technical University of Aachen, Technical University of Aachen, University of Aachen, or ''Rheinisch-Westfälische Technische Hoch ...
in 2010.
Since 2004, Grünenthal supports young scientists through the EFIC-Grünenthal-Grant with €200,000 the world's largest prize in its field. Bursaries of up to €30,000 are awarded per project.
Since 2009, the company has been member of the social initiative . Also, it is founding member of the organization .
References
External links
Official websiteEFIC-Grünenthal Grant
{{DEFAULTSORT:Chemie Grunenthal Of Stolberg-Am-Rhein
Pharmaceutical companies of Germany
Pharmaceutical companies established in 1946
Manufacturing companies based in Aachen
German brands
Scandals in Germany
Medical and health organisations based in North Rhine-Westphalia