History of gmp

brief history of GMP

1. 1906 Pure Food and Drug Act Creates one of the first government regulatory agencies (now known as FDA); the culmination of 25 years of lobbying, this act makes it illegal to sell “ adulterated”or “ misbranded”food or drugs.

2. The First Regulations 1906 Pure Food and Drug Act: Illegal to sell adulterated (contaminated) food or drugs Labeling must be truthful Dangerous ingredients must be listed Predecessor to FDA is created Bureau of Chemistry Authority to seize illegal food and drugs Twenty five years of lobbying to get this act passed

3. Human Tragedy 1935 Diethylene glycol (antifreeze) accidentally used in oral “elixir of sulfanilamide” resulting in 107 deaths, many of them children

4. 1938 Federal Food, Drug and Cosmetic (FD&C) Act Tragedy: Sulfanilamide made with poisonous solvent causes 107 deaths . Result : Requires manufacturers to prove the safety of products before marketing.

5. Additional Regulations 1938 Food, Drug and Cosmetic Act: Companies required to prove safety of their products FDA is formalized and given additional authority Authority to prevent companies from making products (Injunctions) Authority to inspect companies Criminal prosecutions Define manufacturing and quality control requirements

6. 1941 Two unrelated events Insulin Amendment requires FDA to test and certify purity and potency of insulin. Tragedy: nearly 300 deaths and injuries from distribution of sulfathiazole tablets tainted with phenobarbital.Result : FDA revises manufacturing and quality controls drastically, the beginning of what will later be called GMPs.

7. More Human Tragedy 1941 Sulfathiazole cross-contaminated with Phenobarbital resulting in nearly 300 deaths 1960 Thalidomide used to treat morning sickness in pregnant women. Lack of testing results in 10,000 children born with serious deformities ( phocomelia )

8. 1962 Kefauver-Harris Drug Amendments Tragedy:Thalidomide causes birth defects in thousands of European babies.Result:Manufacturers must prove efficacy of products before marketing them and ensure stricter control over drug testing.

9. 1978 CGMPs Final rules for drugs and devices (21 CFR 210–211 and 820) Establishes minimum current good manufacturing practices for manufacturing,processing , packing, or holding drug products and medical devices.

10. Industry Guidelines - GMPs 1978 FDA establishes regulations known as Good Manufacturing Practices ( cGMPs ) for Finished Pharmaceuticals. Contain minimum requirements to ensure purity, safety and efficacy of products. The “c” in cGMP means current . Holds everyone accountable for the quality and safety of products .

11. 1979 GLPs Final Rule (21 CFR 58) Establishes good laboratory practices for conducting nonclinical laboratory studies that support applications for research or marketing permits for human and animal drugs, medical devices for human use, and biological products .

12. 1982 Tamper-resistant packaging regulations issued for OTC products Tragedy:Acetaminophen-capsule poisoning by cyanide causes seven deaths . Result : revision of GMPs to require tamper-resistant packaging.

13. 1983 Two unrelated regulatory events The Guide to the Inspection of Computerized Systems in Drug Processing initiates tighter controls on computers and computer validation.Federal Anti-Tampering Act makes it a federal crime to tamper with packaged consumer products.

14. 1987 Guideline on General Principles of Process Validation Agency expectations regarding the need for process validation are outlined.

15. 1992 Generic Drug Enforcement Act Precipitated by illegal acts involving abbreviated new drug applications.Result : Creates debarment penalty.

16. 1996 Proposed Revision to US CGMPs for Drugs and Biologics (21 CFR 21–211) Adds detail for validation, blend uniformity, prevention of cross-contamination, and handling out- ofspecification results .

17. 1997 Electronic Records Final Rule (21 CFR 11) Requires controls that ensure security and integrity of all electronic data.

18. 1998 Draft guidances Manufacturing,Processing , or Holding Active Pharmaceutical Ingredients and Investigating Out-of-Specification ( OOS) Test Results for Pharmaceutical Production.

19. Why GMPs? No more human tragedy! GMPs help prevent mix-ups and contamination GMPs are general and contain only minimum requirements Pharmaceutical Industry needs to go beyond the minimum requirements Standard Operating Procedures (SOPs) Internal documents written by the company management You must read, understand and follow SOPs