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Over 400 British children whose mothers took the drug during pregnancy will benefit from the payout by Distillers Company, which marketed the German-manufactured drug in Britain.
The company will pay £6 million in direct claims and will also set up a £14 million trust fund to look after the children's future.
The court hearing follows a high-profile campaign in the media calling for more compensation for thalidomide families.
Amid mounting pressure from politicians and the public, including its own shareholders and workers, the company agreed a settlement representing about 40% of what each child might have received had his or her family sued Distillers individually.
The families have undertaken to withdraw all allegations of negligence in return.
Thalidomide became notorious in the 1960s when it was prescribed to pregnant women to ease morning sickness.
It was found to cause severe birth defects, and thousands of children across the world were born limbless or with severely shortened limbs.
More cases have come to light as a result of the publicity, with another 32 coming forward in the last six months alone.
The deal follows a long-standing challenge to Distillers over the amount of damages it offered in its original settlement in 1968.
Francis Purchas QC, the lawyer representing the children, paid tribute to the "courageous stand" taken by parents in disputing the amount offered by Distillers.
David Mason, whose daughter Louise was born without limbs after his wife took the thalidomide drug in early pregnancy, has led the campaign for greater compensation for victims.
Outside the court today he said, "I am happy at the result and the ending to this saga."
The lawyer for Distillers, John Wilmers QC, said the lengthy court proceedings had prevented the company from putting right what he called false allegations made against them over the years.
"My clients have always denied and continue to deny that either they or any of the scientists and medical men who advised them were in any way negligent," he said.
The families will receive cheques for £5,000 within the next few weeks as the first part of the settlement, but it may take more than a year to assess how much each child will receive from the £6 million lump sum and from the trust fund.
There was further heartache for the thalidomide parents as they had to wait several months, and in some cases years, before assessments of individual cases could be made and payments released.
In addition, a so-called "Y-list" of thalidomide victims emerged - 98 children who were suspected of suffering deformities due to the drug, but who could not prove it and so were unable to claim compensation.
In 2005 Distillers, now part of Diageo, agreed an extra one-off payment worth 70% of the annual payments made to children from the trust fund.
The payment was intended to meet unforeseen costs incurred by thalidomide survivors as they became older.
There is also pressure for further compensation after thalidomide survivors began giving birth to children suffering similar physical deformities.
Thalidomide was available in the UK from 1958 and taken off the market in late 1961.
It is now being made available again after evidence that it could slow down a wasting disease suffered by patients with cancer.
It is also licensed in the US for treating a complication of leprosy.
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