미국의 의약품 약효동등성 관리

Regulation and Management of Generic Drugs to Assure Therapeutic Equivalence in the United States

Since Jul $1^{st}$ 2000, generic substitution has been allowed in Korea with the beginning of 'separation of drug dispensing from prescription'. The management and regulation of generic drugs in order to assure the therapeutic equivalence to the brand-name drug is very important in terms of patient safety. In the United States, there is a hierarchy of regulations and many guidances for this purpose. The 'Federal Drug, Food and Cosmetic Act' and 'Food and Drug Administration Modernization Act(1997)' is in the highest position on the regulation of drugs. Sections 21CFR314 and 21CFR320 of 'Code of Federal Regulation Title 21 Food and Drugs' are quite concrete regarding 'New Drug Application/Abbreviated New Drug Application' and 'Bioequivalence'. The guidelines and guidances issued by the FDA CDER are the easiest to understand. Each state has its own regulations for generic substitution and the US FDA has standard operating procedures (SOP), called 'Manual of Policies and Procedures (MAPP)' for the management of drugs. The US FDA requires that a generic drug have the same standard quality as the brand-name drug. Generic drugs should meet the 'Good Manufacturing Practice' standards and show therapeutic equivalence to the 'reference listed drug (brand-name drug)'. A bioequivalence study should be conducted like an ordinary clinical trial, after the approval of IRB. FDA also inspects the bioequivalence study site and manufacturing facilities. After the approval, the applicant of generic drug should report on qualtity and safety periodically. If this were unmet, FDA would cancel the approval. Therapeutic equivalence is usually proven by bioequivalence, with some exceptions. FDA has clear and strict guidances for the exemption of in vivo bioequivalence study. FDA is trying to be both concrete and flexible for many kinds of drug action modes.