Revised Comparative Dissolution Test Guideline for Pharmaceutical Equivalence | Ministry of Food and Drug Safety

The second outcome of the Pharmaceutical Review and Communications Group… information on the method of determining equivalence and considerations, etc.

The Ministry of Food and Drug Safety (Minister Oh Yoo-gyeong) revised the ‘Comparative Dissolution Test Guideline’ on the 18th to guide in detail the considerations required when evaluating the equivalence of pharmaceuticals by comparative dissolution test.

Comparative dissolution test refers to an in vitro test to predict the similarity of pharmacokinetics in vivo by comparing the dissolution patterns of the reference drug and the test drug.

The pharmaceutical equivalence test standard (MFDS ​​notice) was revised in November of last year to evaluate the results of comparative dissolution tests using similarity factors* at all time points measured instead of comparing dissolution rates only at specific time points in the past.

Accordingly, in this revised guideline, △ the equivalence determination method using the similarity factor and considerations △ the change in the dissolution rate measurement time point △ the statistical method that can be applied when the dissolution rate deviation is large is provided in detail.

The similarity factor (f2) is the difference between the two dissolution curves calculated using the dissolution rate (%), and the formula is f2 = 50·log[1+(1/n)∑nt=1(Rt – Tt)2]-0.5ㆍ100. n-number of comparison time points, Rt-average dissolution rate of control drug, Tt-average dissolution rate of test drug. Dissolution rate comparison time points include at least three time points excluding hour 0.

In particular, a bootstrap method for evaluating equivalence with a confidence interval using a similarity factor was presented in detail when the dissolution rate variance was large. Bootstrap is a statistical technique to find out the distribution of a given sample using a sample extracted from the obtained measured values.

The Ministry of Food and Drug Safety announced that it reviewed the contents of the guideline revision in depth by utilizing the equivalence review division of the ‘Drug Review Communication Group (CHORUS)’, which was launched in March to provide practical help to companies preparing for comparative dissolution tests.

CHORUS (CHannel On RegUlation Submission & Review) is a channel through which the Ministry of Food and Drug Safety discovers regulatory improvement tasks in the field of drug review and provides two-way communication with the pharmaceutical industry to come up with solutions. △clinical trial review △approval/review support It is composed of five divisions: △Life cycle change management △Advanced quality review △Equivalent review.

The Ministry of Food and Drug Safety said, “We expect that the revision of this guideline will help smooth performance of the comparative dissolution test and increase the predictability of the review. We will do our best to support the rapid development of new products.”

The revised ‘Comparative Dissolution Test Guideline’ can be found on the official website of the Ministry of Food and Drug Safety (www.mfds.go.kr) > Legal Data > Data Room > Guide/Guideline.

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