Lessons from the Thalidomide Disaster

 

The greatest pharmaceuticals tragedy ever to take place occurred fifty years ago this year, when the sleeping pill and tranquillizer Thalidomide came onto the market. In the years that followed it caused serious deformities in children whose mothers had taken the drug during pregnancy. Many of them died. Both the pharmaceuticals industry and legislators learned lessons from this tragedy. The safety tests that a new drug is required to undergo before it can be administered to humans were made much more stringent.

In 1964, three years after Thalidomide was taken off the market, a testing procedure was discovered that used an animal experiment to identify drugs that might cause deformities. Since then tests for teratogenicity - the medical term for the capacity to cause deformities in embryos and fetuses - have become a fixed component of the pre-clinical trials for every new drug. For that reason no drug has come onto the market since then whose teratogenic effect has failed to be identified.

When the first German pharmaceuticals law was passed in 1978, tests for teratogenicity became a legal requirement for drug approval.

Safety Tests Prior to Administration to Humans

Today, the pre-clinical development of new potential active agents includes tests for the following possible damaging effects:

• Acute toxicity (e.g., for the liver, kidneys or nerves)
  
• Genetic mutations (mutagenicity)
  
• Carcinogenicity
  
• Deformities in embryos or fetuses (teratogenicity)
  
• Infertility

The tests include investigations of how the intake or excretion route of these drugs exacerbates or mitigates these damaging effects.

The tests are conducted primarily in test-tubes, with bacteria cultures or using animals. Chicken eggs and cell cultures are also used for some tests.

The test findings must be submitted to the drug licensing authorities for approval before the new active agent can be administered to humans in clinical studies. Later on, when the development phase has been concluded and an application is submitted for approval of the new drug, the licensing authorities again scrutinize the findings of all the safety tests.

During the development phase, the new drug is tested on both healthy subjects and patients, but not on pregnant women. Women of child-bearing age participating in the studies must use reliable contraceptives.

Drugs and Pregnancy

As a rule the development of a new drug is stopped if it is shown to be teratogenic. If, however, the drug is to be used to treat serious illnesses that have not responded well to existing treatments (such as cancer or rheumatoid arthritis), then development continues even if the active agent has been identified as teratogenic. To ensure that the drug - once it has been approved - is not prescribed to pregnant women by accident, doctors are instructed about its dangers in training sessions, and warnings are included in the instruction leaflet.

But even if an active agent has not been shown to be teratogenic in animal experiments (and is therefore probably safe), a warning must still be included in the patient information leaflet if not enough is known about its effects during pregnancy. Since for ethical reasons studies cannot be conducted on pregnant women this is the only alternative.

Doctors may only prescribe women drugs shown to have a teratogenic effect if pregnancy can be ruled out and if they are using a reliable means of contraception.

During pregnancy (and also while a woman is breast-feeding), drugs should only be taken if there are strong medical reasons in favour of treating the disorder rather than leaving it untreated for some time. Here the risks for mother and child must be weighed up against each other. For example, if a pregnant woman were to suffer from type-1 diabetes neither she nor her unborn child would survive if she stopped injecting herself with insulin, whereas in the case of hay fever or many other ailments it would be better to refrain from treating the condition with drugs so as to rule out any risk for the unborn child.

Caution is in order not only for prescription drugs but also for self-medication. Always a doctor's or pharmacist's advice should be heard before a drug is taken, even if it is just to treat a headache.

Drug Safety in General

In Europe and almost all countries worldwide, drugs may only be sold if they have been thoroughly tested for effectiveness, tolerability and quality during the development phase and approved by a licensing authority following examination of all the study findings.

Once a drug has been approved, the manufacturers are obliged to monitor its safety in close cooperation with the drug authorities and to investigate any indication of problematic side-effects (known in medical jargon as "undesirable drug effects"). In such cases the authorities have the power to instruct doctors and pharmacists at any time to limit the range of conditions for which a drug may be used or to withdraw it from the market.