History of GMP
Good Manufacturing Practice resulted from a long history of the need for consumer protection. GMPs are regulations issued by authority of the Federal Food, Drug, and Cosmetic Act. To understand why they are the way they are, it is useful to look back at the history of FDA legislation and consumer protection issues.
The Pure Food and Drug Act of 1906
At the beginning of the 20th century, there were no federal regulations to protect the public from dangerous products, and technology was primitive. The move from an agricultural to an industrial society meant that people were getting their food from sources further away. Conditions in food and drug industries would be unthinkable today. Ice was the main means of refrigeration, milk was unpasteurized. Chemical preservatives and toxic colors were uncontrolled. Medicines containing opium, morphine, heroin, and cocaine were sold without restriction and labeling did not indicate their presence.
In 1903, Harvey W. Wiley, a chemist with the US
In 1906, Upton Sinclair published The Jungle, a graphic exposure of the meatpacking industry. Public outcry resulting from filthy conditions described in this book pushed Congress to pass the Pure Food and Drug Act of 1906. This act prohibited the interstate transport of unlawful food and drugs under penalty of seizure of the products and/or prosecution of the responsible parties. The basis of the law rested on the regulation of product labeling rather than pre-market approval. Drugs could not be sold in any other condition unless the specific variations from USP and National Formulary standards were plainly stated on the label. The food law prohibited the addition of any ingredients that would substitute for the food, conceal damage, pose a health hazard, or constitute a filthy or decomposed substance. If the manufacturer opted to list the weight or measure of a food, this had to be done accurately. Also, the food or drug label could not be false or misleading in any particular, and the presence and amount of eleven dangerous ingredients, including alcohol, heroin, and cocaine, had to be listed.
While this law was a great step forward, it nonetheless left gaps in consumer protection. It allowed the government to take non-compliant companies to court, but did not allow for proactive compliance requirements. Labels were not required to state weight or measure - it was only required that a contents statement, if used be truthful. Even after amendments to the law outlawing false therapeutic claims, a defendant only needed to show that he personally believed in his fake remedy to escape legal consequences. Congress, however, refused to take action until a tragedy that took the lives of over 100 people (mostly children) occurred.
Sulfanilamide is a drug used to treat streptococcal infections, and was produced in powder and tablet form. Because children often needed to take the drug for sore throats, the S.E. Massengill Company developed a liquid form of this drug. They tested it for flavor, appearance, and fragrance, and found it acceptable. They sent out 633 shipments in September of 1937. They soon found out that many people who took this drug were dying terrible deaths of kidney failure and experiencing stoppage of urine, severe abdominal pain, nausea, vomiting, stupor, and convulsions. Many of the victims were children.
The chemists at Massengill had used a toxic chemical to dissolve the solid sulfanilamide into a liquid. They used diethylene glycol, a chemical normally used as an anti-freeze. At the time, there were no requirements that drugs be tested for safety. Massengill was only charged with a minor labeling infraction, calling the medicine an "elixir" when it had no alcohol in it. Massengill refused to take responsibility for the deaths, but the head chemist who developed the drug committed suicide.
The Federal Food, Drug, and Cosmetic Act
In 1937 when this tragedy occurred, the Senate had introduced a bill to overhaul the 1906 law, but congressional action had stalled. As a response to the tragedy, the Federal Food, Drug, and Cosmetic Act was passed in 1938. It required that drug manufacturers show that a drug is safe before marketing it. Other provisions of this act include that cosmetics and therapeutic devices were regulated for the first time; proof of fraud was no longer required to stop false claims for drugs; poisonous substances in foods became regulated; authority was granted to FDA to inspect factories; and federal court injunctions were added as an allowable legal remedy.
In the years leading up to the thalidomide incident, Senator Estes Kefauver held hearings on drug costs, the state of science supporting drug effectiveness, and claims made in advertising and labeling. Despite disturbing findings, Congress once again did not pass legislation until a near tragedy struck. This time tragedy was avoided due to the diligence of a woman by the name of Frances Oldham Kelsey. She was a PhD in pharmacology working for FDA. While she was a faculty member at the University of Chicago she had worked on finding a cure for malaria, and during her studies had learned that some drugs pass through the placenta during pregnancy. One of her first assignments at FDA was to review an application from Richardson Merrill for the the tranquilizer and painkiller thalidomide. It was also used in pregnant women for morning sickness. Despite the fact that thalidomide was approved in Canada and many countries in Europe and Africa, Kelsey withheld approval and requested additional studies because she was concerned about the drug's impact on the nervous system. Around the same time, many babies starting being born with severe deformities in Europe and other places. When these deformities were eventually traced to the use of thalidomide during pregnancy, Kelsey became a hero for keeping thalidomide of the US market.
The Drug Amendments of 1962
Because of the high profile nature of the thalidomide incident, public opinion pushed Congress to unanimously pass the Drug Amendments of 1962. These Amendments tightened control over prescription drugs, new drugs and investigational drugs. Effectiveness now had to be shown before a drug would be approved, drug firms were required to send adverse reaction reports to FDA, and drug advertising in medical journals was required to provide complete information to doctors (risks as well as benefits.) And most significantly for this article, The Drug Amendments of 1962 formalized Good Manufacturing Practices.
In the years since 1962 many laws have been passed which impact GMP and how FDA carries out its mission. Stricter labeling requirements came in 1966 when the Fair Packaging and Labeling Act required all consumer products in interstate commerce to be honestly and informatively labeled, with FDA enforcing this for food, drugs, cosmetics, and medical devices. Anti-tampering regulations came about in 1983 after seven people in Chicago died after taking Tylenol laced with cyanide.
The GMP regulations grew out of legislation passed because terrible tragedies either killed many people, or almost did. GMP ensures that the medical products we use are safe, pure, and effective. Everyone who works in the life science industry is responsible to ensure that their organization's products do not harm the customer, and that they do what they are supposed to do. If you were using your own product, wouldn't you want it to be manufactured according to the strictest of standards?
Copyright © 2002-2011 Artisan
Consulting Group. All rights reserved.