1930s: 1933 The exhibition entitled "American House of Terror" organized by FDA exposed the defects of 1906. This famous exhibition shows dangerous foods, medicines, medical equipment and cosmetics to the public, including pessary, depilatory drugs that may lead to baldness, emulsions and ointments that may lead to mercury poisoning, hair dyes that may lead to poisoning, and eyelash stains that may lead to blindness in women. Later, these exhibits were taken to the White House, demanding that the government provide stronger protection for consumers. Sulfonamides were discovered after 1935, when many manufacturers began to produce this antibacterial agent. A company uses diethylene glycol (a chemical analogue of toxic solvent and antifreeze) in oral sulfanilamide. Before the problem was discovered, 107 people died, most of them were children. In response to this incident, Congress passed the 1938 Federal Food, Drug and Cosmetics Act. For the first time, manufacturers are required to prove that their products are safe before they go on the market.
In the 1940s and 1950s: 194 1 year, sulfathiazole tablets produced by an American pharmaceutical company were contaminated by phenobarbital, causing nearly 300 deaths or injuries. This incident prompted the FDA to completely revise the regulations on drug production and quality control, and later evolved into GMP today. 1944 The Public Health Service Law covers a considerable scope, including the management of biological products and the control of infectious diseases.
During the Second World War, FDA required pharmaceutical companies to carry out batch certification of certain products. Samples taken from each batch of products must be submitted to the FDA for testing, and then the FDA will approve the sale of products. This regulation was implemented for insulin and penicillin in 194 1 and 1945 respectively, and then extended to all antibiotics. Later, the regulation of batch certification of drug production stopped before 1983.
1955, jonas salk discovered the method of preventing polio by vaccination. Many manufacturers began to produce their own vaccines. Because a company failed to completely inactivate the virus in a batch of its products, about 60 people were infected with the virus after vaccination, and 99 family members of these patients were also infected with the virus.
1960s: Thalidomide was marketed in Europe as a sleeping pill to treat vomiting during pregnancy. At that time, when the regulatory authorities approved this drug for this indication, they knew nothing about its serious side effects and teratogenic effects. This medicine will seriously damage the developing fetus. Babies born to women who took the drug in the first three months of pregnancy had severe hand wall and leg deformities. It is estimated that 1000 cases of infant malformation in Europe are related to the use of this drug. The United States has not approved this drug. At that time, Frances Chersi, a female scientist, was in charge of reviewing the drug. 1962, then US President Kennedy awarded her the Presidential Award for Outstanding Federal Citizen Service, which is the highest honor a government employee can get as a citizen. The thalidomide incident has aroused public concern. Congress passed stricter laws and regulations, requiring pharmaceutical companies not only to ensure the safety of products, but also to ensure that products are effective for indicated indications; The revised regulations require that drugs must be tested in animals before being used in humans, and at the same time stipulate the management of clinical trials, so that researchers are responsible for supervising the drugs studied; The pharmaceutical production enterprise shall inform the subjects whether the drug is used for research purposes, and shall obtain the consent of the subjects before conducting the experiment; Drug manufacturers must report unforeseen drug injuries (adverse events); The FDA is authorized to supervise the advertising of prescription drugs.
Seventy years is a watershed. GMP for drug production (210 and 2 1 CFR) and GMP for medical devices (820 of 21CFR) were finally approved at 1978 to ensure the safety and effectiveness of all these products. This specification is the minimum good manufacturing practice for the methods, equipment or controls used in drug production, processing, packaging or ensuring drug safety, so that it has the ingredients and efficacy of a sound label and meets the requirements of quality and purity. GLP is formulated in 1979, which is suitable for non-clinical laboratory research to obtain the approval of FDA-regulated products, including food and colored additives, animal food additives, human or animal drugs, medical devices for human use, biological products and electronic products. In order to ensure the quality and integrity of drug safety data, these provisions are formulated.
The medical device amendment signed in 1976 strengthened the FDA's supervision power over medical devices. Contraceptive devices used by 2 million women caused many serious injuries, which led to the adoption of the amendment. This product was withdrawn from the market on 1975 due to the high incidence of pelvic infection, infertility and partial death. The amendment stipulates that most manufacturers of medical equipment (especially moderately or highly dangerous equipment) must provide FDA with data on the safety and effectiveness of their products before they go on the market. In addition, a set of pre-marketing and post-marketing supervision system has been established, including FDA's supervision on whether pharmaceutical companies comply with GMP, whether they record correctly in product design and production, and maintaining the system according to complaints.
1982, a child named Mary Kellerman 12 years old took strong acetaminophen capsules (Taylor capsules) because of a cold, and she died a few hours later; Six other people also died in the incident, and Johnson & Johnson issued a statement to recall 31100,000 bottles of Taylor capsules worldwide for destruction. Later research found that the culprit was the sealing strip that was inadvertently opened, which led to the capsule being contaminated by cyanide. The FDA issued a regulation that all over-the-counter drugs used by people must have anti-interference packaging, and this regulation was written into GMP. Congress passed the federal anti-interference bill in 1983, making it a crime to destroy packaged consumer goods. Taylor capsule incident has a great impact on the pharmaceutical industry. It reminds us not only that we need to constantly train our employees in GMP, but also that our products may become killers that endanger public safety.
In 1980s, FDA began to issue a series of guidance documents, which played a great role in understanding the current GMP rules. One of them is "Inspection Guide of Computer System for Pharmaceutical Processing" published by 1983, which makes an early prospect of the functions of computers and may mark the beginning of computer certification. In 1989, the famous "General Principles and Guidelines for Process Certification" summarized our thoughts and expectations on the current process certification of drugs and devices.
Active pharmaceutical ingredients used to be called raw materials. This recent change in terminology reflects the fact that some active ingredients are produced by biological methods rather than chemical methods. The term new chemical entity is often expressed as new molecular entity now, and so is it.
In the past, naturally occurring L- tryptophan and 5- hydroxytryptophan were often used as food supplements as adjuvant treatments for children with insomnia, depression, obesity and attention deficit disorder. 65438-0989 found the epidemic situation, and the onset of eosinophilia-myalgia syndrome was related to food supplements containing L- tryptophan. The US Centers for Disease Control identified more than 65,438+0,500 cases, including at least 38 deaths, and finally determined that the disease was related to L- tryptophan. Experiments conducted by FDA and Mayo Clinic show that some L- tryptophan products on the market contain impurities, one of which is called X-peak. Although the meaning of this substance is unknown at present, it was found in the cases related to L- tryptophan in 199 1.
70%-80% or even more of the medicinal active ingredients used for production in the United States come from overseas manufacturers with low production standards. In view of this, the European Union and the United States recently published a draft document on the production guidelines for medicinal active ingredients. 1989 issued an industrial guide on the production, handling or possession of pharmaceutical active ingredients, and drug GMP(CFR parts 2 10 and 2 1 1) is also applicable to the production of pharmaceutical active ingredients.
Since 1990s, the revision of GMP for drugs and biological products has not been completed, but it truly represents the current thinking of FDA. The final rule of electronic records (21CFR part11) requires certain control measures to ensure the safety and accuracy of all data and computer systems.
The International Coordination Meeting is an association organized by colleagues from Europe, North America and Japan, which discusses many documents about quality, safety and effectiveness. Many documents were finally adopted or formulated by the organization and became the industry management norms of all member countries. 1996 The GCP E6 guideline adopted by the international coordination meeting has now become the de facto standard for clinical trials. Recently, many other guidance documents have been issued, including a draft guidance on handling abnormal detection results, which may soon be adopted and become the current industry management norms.
1992, the U.S. Congress passed the Generic Drug Enforcement Act, which prohibited and punished some illegal acts in simplifying the application for new drugs. The bill originated from a bribery and fraud case. The manager of a generic drug company bribed the FDA's new drug reviewer, and the information submitted to the FDA was not the test results of his own products, but the test results of brand-name drugs. The people involved were finally removed from the pharmaceutical industry and prohibited from engaging in this industry.