Immel Resources GMP Timeline

A GMP Timeline

National Archives: FDA pharmacist preparing media (ca 1941-1945)

The following is abstracted from our reprint, A Brief History of the GMPs: The Power of Storytelling. This article was originally published in *BioPharm* Magazine in August 2000, with permission to reprint given by Advanstar Communications.

The U.S. Food and Drug Administration (FDA) has an excellent history page maintained by their History Office. Page includes articles, photographs, and milestones (FDA History Page). Key highlights of GMP history in the United States are shown below.

**A GMP Timeline**

**1902 Biologics Control Act**

Tragedy: At least 12 children die of tetanus contracted from contaminated diphtheria vaccine. Result: Requires inspections and testing of biologics manufacturers’ facilities and products.
**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.
**1938 Federal Food, Drug and Cosmetic Act (FD&C) Act**
Tragedy: Sulfanilamide made with poisonous solvent causes 107 deaths. Result: Requires manufacturers to prove the safety of products before marketing.
**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.
**1944 Public Health Services Act**
Regulates biological products and control of communicable diseases.
**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.

**1963 GMPs for Drugs (28 FR 6385)**

Good manufacturing practices for manufacturing, processing, packing or holding finished pharmaceuticals were first published.

**1975 CGMPs for Blood and Blood Components Final Rule**
Establishes minimum current good manufacturing practices for blood establishments in the collecting, processing, compatibility testing, storing, and distributing of blood and blood components.
**1976 Medical Device Amendments**
Tragedy: the Dalkon Shield IUD seriously injures many patients. Response: New law strengthens FDA authority to oversee medical devices.
**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.
**1979 GLPs (21 CFR 58) Final Rule**
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.
**1980 Infant Formula Act**
Tragedy: 100 children reported seriously ill linked to lack of chloride in soy-based formulas. Result: Congress gives FDA authority to set and enforce nutritional and quality control standards.
**1982 Tamper-Resistant Packaging Regulations Issued for OTC Products**
Tragedy: Acetaminophen-capsule poisoning by cyanide causes 7 deaths. Result: Revision of GMPs to require tamper-resistant packaging for over-the-counter products.
**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.
1987 *Guideline on General Principles of Process Validation*
Agency expectations regarding the need for process validation are outlined.
**1990 Safe Medical Devices Act**
Tragedy: Shiley heart valves and other incidents. Result: FDA given authority to add preproduction design controls and tracking of critical or implantable devices to CGMPs; requires notification of serious device problems by user facilities to FDA. The agency gains ability to order device recalls.
**1992 Generic Drug Enforcement Act**
Precipitated by illegal acts involving abbreviated new drug applications. Result: Creates debarment penalty.
**1996 Two Unrelated Events**
Proposed revision to U.S. CGMPs for Drugs and Biologics (21 CFR 210/211) adds detail for validation, blend uniformity, prevention of cross-contamination, and handling out-of-specification results. *ICH Guidance for Industry: E6, Good Clinical Practice: Consolidated Guidance* from ICH becomes the defacto standard for conducting human clinical trials.
**1997 CGMPs for Medical Devices (Quality System Regulation) Final Rule**
Major revision to current good manufacturing practices for medical devices becomes effective, with design controls in R&D the major change (design controls effective 6/98; rest of rule 6/97).
**1997 Electronic Records Final Rule (21 CFR 11)**
Requires controls that ensure security and integrity of all electronic data.
**1998 Draft Guidances**
Manufacturing, Processing, or Holding Active Pharmaceutical Ingredients and Investigating Out-of-Specification (OOS) Test Results for Pharmaceutical Production.
**1999 QSIT Inspection Handbook**
New FDA technique for inspecting device companies focuses on four major subsystems: corrective and preventive action (CAPA), design controls, management controls, and production and process controls.

2001 ICH Q7A API Guidance

ICH's "Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients (APIs)" is adopted by the United States,
Europe and Japan, and becomes the defacto manufacturing standard for APIs.

2002 Drug Manufacturing Inspections Compliance Manual

New FDA technique for routine drug manufacturing inspections focuses on two or more systems, with mandatory coverage
of the quality system. Other systems are: facilities and equipment, materials, production, packaging and labeling, and
laboratory controls.
Use Information The information on this page is provided free-of-charge for downloading, photocopying, and using in your classes or department meetings. The reprinting, transmission, or distribution for sale or use in a for-fee conference or course of this information is expressly prohibited. If you download the material, please ensure that the following copyright statement appears prominently on the bottom of each page downloaded: Copyright 2010, Immel Resources LLC, Petaluma, CA USA, Phone: (707) 778-7222. Permission to reprint given by publisher, Immel Resources LLC. Disclaimer This information is not all-inclusive nor is it intended to replace the advice of an experienced quality assurance or regulatory compliance professional. Every organization manufacturing pharmaceutical, biological, and medical device products must meet at least the current, applicable current good manufacturing practices (CGMPs).