At the beginning of last century, American medical supplies in the early years were sold at the back of wagons, which was called the Mobile Medicine Exhibition. At that time, people used a bottled ointment called the magic panacea to treat pain, mucositis, rheumatism and gout. Of course, it is also useful for horses. Fortunately, such days are gone forever.
193s: In 1933, an exhibition entitled American Room of Terror organized by FDA revealed the defects of the 196 Act. This famous exhibition shows dangerous foods, medicines, medical equipment and cosmetics to the public, including a pessary that will puncture the uterus if improperly used, a hair remover that can cause baldness, lotions and ointments that can cause mercury poisoning, hair dyes that can cause poisoning, and eyelash stains that can blind 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 used diethylene glycol (a toxic solvent and chemical analogue of antifreeze) in oral sulfanilamide. Before the problem was discovered, 17 people died, most of them were children. In response to this incident, Congress passed the Federal Food, Drug and Cosmetic Act of 1938. For the first time, manufacturers are required to prove that their products are safe before going on the market.
forties and fifties: in 1941, sulfathiazole tablets produced by an American pharmaceutical company were contaminated with phenobarbital, a sedative sleeping pill, causing nearly 3 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. The Public Health Service Law passed in 1944 covers a considerable scope, including the management of biological products and the control of communicable diseases.
during world war ii, FDA required pharmaceutical companies to batch certify a certain product. Samples taken from each batch of products must be submitted to FDA for testing, and then FDA will approve the sales of products. This regulation was implemented for insulin and penicillin in 1941 and 1945 respectively, and then extended to all antibiotics. Later, this regulation of batch certification of drug production stopped before 1983.
in p>1955, Jonas Salk discovered how to prevent 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 6 people were infected with the virus after being vaccinated with this vaccine, and in addition, 99 family members of these patients were also infected with the virus.
196s: Thalidomide was marketed in Europe as a sleeping pill to treat women's pregnancy vomiting. When the regulatory authorities at that time approved this drug for this indication, they knew nothing about its serious side effects and teratogenicity. The medicine can severely punish the developing fetus. Women who took the medicine in the first three months of pregnancy gave birth to babies with severe hand wall and leg deformities. It is estimated that there are 1 cases of infant malformation in Europe related to the use of this drug. The United States has not approved the drug. At that time, Frances Kelsey, a female scientist, was in charge of reviewing the drug. In 1962, the then US President Kennedy awarded her the Presidential Award for Outstanding Federal Citizen Service, which is the highest honor that a government employee can get as a citizen. The thalidomide incident attracted public attention. Congress passed stricter laws and regulations, requiring pharmaceutical companies not only to ensure the safety of their products, but also to ensure that their products are effective for the indicated indications; The revised regulations require that drugs must be tested on 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; Pharmaceutical manufacturers should inform the subjects whether the drug is used for research purposes, and should obtain the consent of the subjects before conducting the test; Pharmaceutical manufacturers must report unforeseen drug injuries (adverse events); The FDA is authorized to regulate the advertising of prescription drugs.
seventy years is a watershed. GMP for drug production (part 21 and 211 of 21 CFR) and GMP for medical equipment (part 82 of 21 CFR) were finally approved in 1978 to ensure the safety and effectiveness of all these products. These regulations are the lowest good manufacturing practices for methods, equipment or control used in the production, processing, packaging or ensuring the safety of drugs, so that they have the components and efficacy of sound labels and meet the requirements of quality and purity. GLP was formulated in 1979, which is applicable to non-clinical laboratory research for obtaining the approval of the research or marketing application of products regulated by FDA, including food and colored additives, animal food additives, human or animal drugs, medical equipment for human use, biological products and electronic products. These regulations are formulated to ensure the quality and integrity of drug safety data.
The Medical Equipment Amendment signed in p>1976 strengthened the FDA's supervision power over medical equipment. A contraceptive device used by 2 million women caused many serious injuries, which led to the adoption of the amendment. The product was withdrawn from the market in 1975 because it was related to high incidence of pelvic infection, infertility and some deaths. The amendment stipulates that most manufacturers of medical equipment (especially moderately or highly dangerous equipment) must provide the FDA with data on the safety and effectiveness of their products before they go on the market. In addition, it also establishes a set of pre-market and post-market supervision system for drugs, including FDA's supervision over whether pharmaceutical companies comply with GMP, whether they record correctly in product design and production, and maintaining the system according to complaints.
In p>1982, a 12-year-old child named Mary Kellerman took strong acetaminophen capsules (Taylor capsules) because of a cold, and she died a few hours later. Six others also died in the incident, and Johnson & Johnson issued a statement to recall 31 million bottles of Taylor capsules worldwide for destruction. Later research found that the culprit was a sealing strip that was inadvertently opened, causing the capsule to be contaminated with cyanide. The FDA issued a regulation that all over-the-counter drugs for human use must have anti-interference packaging, and wrote this regulation into GMP. Congress passed the Federal Anti-Interference Act in 1983, which made it a crime to destroy packaged consumer products. The Taylor capsule incident had 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 198s, FDA began to publish a series of guidance documents, which played a great role in understanding the current GMP rules. One of them is the "Guide to Inspection of Computer Systems in Drug Processing" published in 1983, which made an early prospect of the functions of computers and may have marked the beginning of computer certification. In 1989, the famous "General Principles and Guidelines in Process Certification" summarized our thoughts and expectations on the process certification of drugs and equipment at present.
active pharmaceutical ingredients used to be called Bulk Pharmaceutical Chemicals. 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 the same is true.
Naturally occurring L- tryptophan and 5- hydroxytryptophan used to be used as food supplements as an adjuvant treatment for insomnia, depression, obesity and attention deficit disorder children. In 1989, an epidemic was discovered, and the onset of eosinophilia-myalgia syndrome was related to food supplements containing L- tryptophan. The US Centers for Disease Control identified more than 1,5 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, it was found in a case related to L- tryptophan in 1991.
7%-8% or more of the medicinal active ingredients used for production in the United States come from overseas manufacturers whose production standards are not high. In view of this, the European Union and the United States recently published a draft document on the production guidance of medicinal active ingredients. Industrial Guidance for the Production, Handling or Holding of Pharmaceutical Active Ingredients was issued in 1989, and GMP(CFR Parts 21 and 211) is also applicable to the production of pharmaceutical active ingredients.
since the 199s, the revision of GMP for drugs and biological products has not been completed, but it really represents the current thinking of FDA. The Final Rules for Electronic Records (21CFR Part 11) requires certain controls to ensure the safety and accuracy of all data and computer systems.
The International Coordination Conference is an association organized by colleagues from Europe, North America and Japan to discuss many documents on quality, safety and effectiveness. Many documents were finally adopted or formulated by the organization and became the industrial management norms of all member States. The E6 guideline on GCP adopted by the International Coordinating Conference in 1996 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 test results, which may soon be adopted and become the current industrial management norms.
In p>1992, the U.S. Congress passed the Compulsory Generic Drugs Act, which prohibited and punished some illegal acts in simplified new drug applications. The bill originated from a bribery and fraud case. The manager of a generic drug company bribed the FDA's new drug reviewers, 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 were forbidden to work in this industry.