生物等效性研究中使用替代参考标准的案例研究-Jiang.pdf

1、Case Studies of Using Alternate Reference Standard in Bioequivalence StudiesXiaojian Jiang,Ph.D.Division of Bioequivalence II,Office of BioequivalenceOffice of Generic Drugs,CDER/FDA SBIA Generic Drug Forum April 10,20252DisclaimerThe opinions and information in this presentation are those of this p

2、resenter and does not necessarily represent views and/or policies of the U.S.Food and Drug Administration3Topics for DiscussionBackground informationDefinition of Reference Listed Drug(RLD)and Reference Standard(RS)General Considerations in Selecting RSAlternative RS due to the Unavailability or Lim

3、ited Market Distribution of the Current RS and Other SituationsCase Studies Summary4What is RLD and RS?FDA identifies listed drugs in the Orange Book that are eligible to be designated as a Reference Listed Drug(RLD)and/or Reference Standard(RS).RLD is the listed drug to which the Abbreviated New Dr

4、ug(ANDA)applicant must show its proposed generic drug is the same with respect to active ingredient(s),dosage form,route of administration,strength,labeling,and conditions of use,among other characteristics.RS is the specific drug product selected by FDA that the ANDA applicant must use in conductin

5、g any in vivo bioequivalence testing required to support approval of its ANDA.FDA also recommends use of the RS for the in vitro testing.FDA Guidance Document:Referencing Approved Drug Products in ANDA Submissions Guidance for Industry.October 20205Selection of the RS(1)Ordinarily,FDA selects the RL

6、D(highest strength)When FDA cannot select the RLD,FDA will generally select a previously approved ANDA,which is therapeutically equivalent to the RLD and is the generic market leaderRLD is no longer marketedPrevent a shortageQuantity of the RLD in the distribution is not sufficient for the testingAd