How is dissolution profile similarity (f2) assessed?

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SFDA: “The results of in vitro dissolution tests at three different buffers (normally pH 1.2, 4.5 and 6.8) and the media intended for drug product release (QC media), obtained with the batches of test and reference products that were used in the bioequivalence study should be reported.” (SFDA BE v3.1 · 3.2.1 In vitro dissolution tests complementary to bioequivalence studies) “Where more than 85% of the drug is dissolved within 15 minutes, dissolution profiles may be accepted as similar without further mathematical evaluation.” (SFDA BE v3.1 · Appendix I – 2. Similarity of dissolution profiles) “An f2 value between 50 and 100 suggests that the two dissolution profiles are similar.” (SFDA BE v3.1 · Appendix I – 2. Similarity of dissolution profiles) EU: “An f2 value between 50 and 100 suggests that the two dissolution profiles are similar.” (EMA BE guideline · Appendix I, 2) “Where more than 85% of the drug is dissolved within 15 minutes, dissolution profiles may be accepted as similar without further mathematical evaluation.” (EMA BE guideline · Appendix I, 2) “The results of in vitro dissolution tests at three different buffers (normally pH 1.2, 4.5 and 6.8) and the media intended for drug product release (QC media), obtained with the batches of test and reference products that were used in the bioequivalence study should be reported.” (EMA BE guideline · 4.2.1) US FDA: “Two dissolution profiles are considered similar when the f2 value is ≥50.  When both test and reference products demonstrate that ≥85% of the labeled amount of the drug is dissolved in 15 minutes, comparison with an f2 test is unnecessary, and the dissolution profiles are considered similar.” (FDA M9 · 3.2) “Three buffers: pH 1.2, pH 4.5, and pH 6.8.  Pharmacopoeial buffers should be employed.  Additional investigation may be required at the pH of minimum solubility (if different from the buffers above).” (FDA M9 · 3.2) “To allow the use of mean data, the coefficient of variation should not be more than 20% at early time-points (up to 10 minutes) and should not be more than 10% at other time points.” (FDA M9 · 3.2) WHO: “Studies should be performed in at least three media covering the physiological range, including pH 1.2 hydrochloric acid, pH 4.5 buffer and pH 6.8 buffer.” (WHO TRS 1052 Annex 8 · Appendix 1) “If both the test and reference (comparator) products show more than 85% dissolution in 15 minutes, the profiles are considered similar (no calculations required).” (WHO TRS 1052 Annex 8 · Appendix 1) “An f2 value between 50 and 100 suggests that the two dissolution profiles are similar.” (WHO TRS 1052 Annex 8 · Appendix 1)

How is dissolution profile similarity (f2) assessed?

SFDA Saudi Food and Drug Authority

EU European Union

US FDA US Food and Drug Administration

WHO World Health Organization

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