GMP, inspections, Form 483s and warning letters

Good Manufacturing Practice (GMP) is the body of law and guidance that says how a medicine must be made and tested: in the United States 21 CFR 210 and 211 for drugs, the 600 series for biologics, 1271 for cell and tissue products and 212 for PET drugs; in the EU, EudraLex Volume 4 with its annexes (Annex 1 on sterile products was rewritten in 2022, Annex 2 covers biologicals, Annex 3 radiopharmaceuticals); internationally the ICH Q7 to Q12 guidelines and the PIC/S scheme that lets inspectorates rely on each other. The EU and US operate a mutual recognition agreement for GMP inspections, so each accepts the other's inspections of plants in their territories.

Inspection outcomes follow a ladder. An FDA investigator lists observations on Form FDA 483 at the end of an inspection; the firm has fifteen working days to respond; unresolved or serious findings lead to a Warning Letter, published on the FDA website, and for foreign plants to an Import Alert that stops products at the border; the worst cases end in a consent decree overseen by a court. Data integrity (complete, attributable, original records) has been the most common theme of recent letters to Indian and Chinese API and generic plants, and sterile assurance the most common at injectable plants. The same actions that take a bad plant offline remove its share of supply, which is why almost every recent oncology shortage traces back to an inspection finding at a plant with few competitors, and why the FDA now weighs shortage risk when it acts. OnCo records inspection outcomes only as this class of event and links to the public letters database rather than naming individual findings.