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��Contains Nonbinding RecommendationsDraft t for ImplementationDraft Guidance on EstradiolAugust 2021��Recommended Aug This draft guidance, when finalized, will represent the current thinking of the Food and Dr u g Administration (FDA, or the Agency) on this topic. It does not establish any rights for any person and Office of Generic Drugs. This guidance, which interprets the Agency’s regulations on bioequivalence at 21 CFR part 320provides productspecific recommendations on, among other things, the design of bioequivalence ��RecommendeAug2021in a negative plasma concentration value, the value should be set equal to 0 before calculating the baselinecorrected area under the curve (AUC).Applicants may consider using a referencscaled average bioequivalence approach for estradiol. If using this approach, the applicant should provide evidence of high variability in the bioequivalence parameters (i.e., withinsubjectvariability 30%) for the reference product. For general information on this approach refer to productspecific guidance for progesterone oral capsules entitled Guidance on Progesteronefor additional information regard

ing highly variable drugs. Analyteto measureEstradiolin plasma Bioequivalence based on (Estradiol, using baselinecorrected dataPharmacokinetic and statistical analysis should be performed on both uncorrected and corrected data. Determination of bioequivalenceshould be based on the baselinecorrected data.Waiver request of in vivotesting:Not applicableDissolution test method and sampling times:Not applicable dditional InformationDevice:Prospective applicants should refer to FDA’s guidance for industry entitled parativeAnalyses and Related Comparative Use Human Factors Studiesfor a DrugDevice CombinationProduct Submitted in an ANDA, which, when finalized, will provide the Agency’s currentthinking on the identification and assessment of any differences in thdesign of the userinterface for a proposed generic drugdevice combination product when compared to its reference productFDA recommends that prospective applicants consider the following characteristics of the reference product when designing the tesproduct:ber of doses in the reference productExternal operating principles and external critical design attributes of the reference productUniqueAgency IdentifierPSG