(1) Reasons for Proposal
Recent events saw the discovery of carcinogens unintentionally mixed with drugs, causing major concern and sparking public demand for the strengthening of drug safety. Accordingly, this Amendment tightens the acceptance criteria for biological equivalence tests to levels used by the United States, Europe, and other leading nations, and tightens the criteria for selecting comparators, etc. for revised approvals, thereby aiming to ensure the reliability of drug quality while also addressing and improving weaknesses in the current provisions.
(2) Major Provisions
A. Require biological equivalence tests to be conducted using specified comparators (Article 3-2, paragraph 4)
Strengthen safety control of revised marketing approvals (notifications) by requiring biological equivalence tests to be conducted using the specified comparators when a revised marketing approval (notification) for a drug involves the modification of biological equivalence test standards,
B. Strengthen requirements for exemption from biological equivalence testing of preparations with a content that differs from products whose biological equivalence has been verified (Article 7, paragraph 2; attached Table 2-2)
Strengthen drug safety control and reliability by modifying exemption criteria prescribing that where the same manufacturer intends to obtain approval for a product with a content that differs from that of a product whose biological equivalence has been verified, an exemption shall be made from biological equivalence testing, which shall be substituted with comparative dissolution profiles
C. Delete exceptions concerning acceptance criteria for biological equivalence testing (Article 17, paragraph 3)
Harmonize regulations to match international standards by deleting provisions stipulating that even if a biological equivalence test results in a 90% confidence interval outside log 0.8 to log 1.25, equivalence shall be recognized by exception if the mean difference between the test drug and comparator is between log 0.9 and log 1.1, if there are at least 24 test subjects, or if the comparative dissolution test meets the criteria for equivalence
