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