dissolution profiles

  Dear team,

please advice me on below

If dissolution profiles (f2) does not match with the RLD can we submit ANDA?

Give the reference guideline for this.






Replies to this Topic

Profile Image for Ashok Kumar S. Ashok Kumar
  • Thu, Sep 30, 2010 10:12 AM

Good Morning...

Dear Member, I try to solve your confusion as far as I know.

  • When both test and reference products dissolve 85% or more of the label amount of the drug in ≤15 minutes using all three dissolution media recommended in BCS based Waiver of IR Dosage Form, the profile comparison with an f2 test is unnecessary.
  • FDA recommends that the in vitro comparison be made between the Test vs. Reference Drug. For dissolution, profile comparisons are suggested, FDA also recommends an f2 test be used. An f2 value greater than or equal to 50 suggests a sufficiently similar dissolution profile and no further in vivo studies are needed.
  • For bio-equivalent product, BA-BE Study required on Test vs. Reference Listed Drug (as per USFDA) and, For other/lower strength, we have to perform in-vitro dissolution profile comparison between them.
  • If test is bio-equivalent product (proven by BA-BE Study), then there is no mandatory to match/similar f2 value in between Test & Reference drug.
  • If there is Single Strength, and BA-BE study is passed, then there is f2 test is unnecessary but f2 test is requirement for biowaiver of Multiple Strength (lower/higher). If f2 value is not match with Reference but, should ≥50, it's ok. But, if <50, it may be that Agency (FDA) may ask to perform another Bio Study for multiple strength.
  • Guidance for Industry: Bioavailability and Bioequivalence Studies for Orally Administered Drug Products - General Considerations named guideline showing on pg.16 , ""We recommend that the f2 test be used to compare profiles from the different strengths of the product. An f2 value > 50 indicates a sufficiently similar dissolution profile such that further in vivo studies are not needed. For an f2 value < 50, further discussions with CDER review staff may help to determine whether an in vivo study is appropriate (21 CFR 320.22(d)(2)(ii)). The f2 approach is not suitable for rapidly dissolving drug products (e.g., > 85% dissolved in 15 minutes or less).""
  • I hope you will get your answer. If any one has information, please request you to guide.





and other CFR References, 21CFR  Part 320 Bioavailability and Bioequivalence Requirements...



Edited Thu, Sep 30, 2010 4:23 PM

Dear Ms. Ramadevi,

You can submit the ANDA even your test product does not meet the F2 criteria. When it shows the invivo bio availability when compared to Refernece product (i.e. the log-transformed data in between 85% - 125%).

if you have multiple strengths, lower strengths shold meet the f2 criteria when compared with Biobatch.

Hope this clarifies.



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