When is an in vivo bioequivalence study required?

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SFDA: “For dosage forms such as tablets, capsules and oral suspensions, bioequivalence studies are required unless a biowaiver is applicable (see Appendix III).” (SFDA BE v3.1 · Appendix II – Oral immediate release dosage forms with systemic action) “It also sets the relevant criteria under which bioavailability studies need not be required (either waiver for additional strength, see section 3.1.6, a specific type of formulation, see Appendix II or BCS based biowaiver, see Appendix III).” (SFDA BE v3.1 · 2. Scope) “Bioequivalence studies are generally not required if the test product is to be administered as an aqueous intravenous solution containing the same active substance as the currently approved product.” (SFDA BE v3.1 · Appendix II – Parenteral solutions) EU: “For dosage forms such as tablets, capsules and oral suspensions, bioequivalence studies are required unless a biowaiver is applicable (see APPENDIX III).” (EMA BE guideline · Appendix II) “It also sets the relevant criteria under which bioavailability studies need not be required (either waiver for additional strength, see section 4.1.6, a specific type of formulation, see Appendix II or BCS based Biowaiver, see Appendix III).” (EMA BE guideline · 2) “The Biopharmaceutics Classification System (BCS)-based biowaiver may be used to waive in vivo BE studies for certain orally administered IR solid dosage forms as delineated in ICH M9, Biopharmaceutics Classification System-Based Biowaivers.” (ICH M13A · 1.2.1) US FDA: “Any person submitting an abbreviated new drug application to FDA shall include in the application either: (1) Evidence demonstrating that the drug product that is the subject of the abbreviated new drug application is bioequivalent to the reference listed drug (defined in § 314.3(b) of this chapter ).” (21 CFR 320 · § 320.21(b)(1)) “Except as provided in paragraph (f) of this section, FDA shall waive the requirement for the submission of evidence of in vivo bioavailability or bioequivalence if the drug product meets any of the provisions of paragraphs (b), (c), (d), or (e) of this section.” (21 CFR 320 · § 320.22(a)) “For example, an in vivo BE data requirement can be waived for an oral solution if the formulation has the same active ingredient in the same concentration and dosage form as the RLD and does not contain any excipient that significantly affects drug absorption or availability.” (FDA ANDA BE 2026 · IV.A) WHO: “In vivo documentation of equivalence is necessary when there is a risk that possible differences in bioavailability may result in therapeutic inequivalence (2).” (WHO TRS 1052 Annex 8 · 5.1) “(a) oral, immediate-release pharmaceutical products with systemic action, except for the conditions outlined in section 10;” (WHO TRS 1052 Annex 8 · 5.1 (a)) “In the following circumstances, multisource pharmaceutical products are considered to be equivalent without the need for further documentation. (a) When the pharmaceutical product is to be administered parenterally (for example, intravenously, subcutaneously or intramuscularly) as an aqueous solution containing the same API in the same molar concentration as the comparator product and the same or similar excipients in comparable concentrations to those in the comparator product.” (WHO TRS 1052 Annex 8 · 4 (a))

When is an in vivo bioequivalence study required?

SFDA Saudi Food and Drug Authority

EU European Union

US FDA US Food and Drug Administration

WHO World Health Organization

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