๐Ÿ“˜ Concept & Beginner Guide

f2 Similarity Factor โ€” Concept & Beginner Guide

A plain-language walkthrough of the FDA/EMA f2 similarity factor: what it measures, the formula explained step by step, acceptance criteria, and how to use the f2 similarity calculator.

๐Ÿ“ What f2 Measures ๐Ÿ”ข Formula Explained โœ… Acceptance Criteria ๐Ÿ“‹ Regulatory Rules
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f2 Similarity Factor Calculator
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Beginner Guide
Concept, formula & how to use
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๐Ÿ“ f2 Similarity Factor โ€” Quick Concept & Beginner Guide

What is the f2 Similarity Factor?

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The f2 Formula โ€” What It Measures
The f2 (similarity factor) is a logarithmic transformation of the mean squared difference between the Test and Reference dissolution profiles. It was developed by Moore & Flanner (1996) and is now the standard regulatory metric used by FDA, EMA and ICH for comparing dissolution profiles of solid oral dosage forms. A value between 50 and 100 means the two profiles are similar.
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f2 = 50 ร— log [100 / โˆš(1 + ฮฃ(Rt โˆ’ Tt)ยฒ / n)]
Rt = mean % dissolved of Reference product at time point t
Tt = mean % dissolved of Test product at time point t
n = number of time points
When both products dissolve โ‰ฅ 85% at 15 min, f2 may not be required by regulation, but is still provided here.
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When Are Profiles "Similar"?
f2 โ‰ฅ 50: Profiles are similar โ€” the Test product releases at essentially the same rate as the Reference.
f2 < 50: Profiles are NOT similar โ€” the products release at meaningfully different rates.
FDA/EMA require โ‰ฅ 3 time points (excluding 0 min) for a valid regulatory f2 calculation.
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Regulatory Rules to Remember
โ€ข Only one time point should be above 85% dissolution for Test and Reference
โ€ข Minimum 3 time points excluding t=0
โ€ข Use mean % dissolved (not individual unit values) as input
โ€ข If โ‰ฅ 85% at 15 min for both โ€” f2 may be waived per FDA/EMA guidance
โ€ข %CV at each time point โ‰ค 20% (early) or โ‰ค 10% (later) is recommended

What Goes Into the Table

The standalone calculator has one table and nothing else to set up. Each row is one time point, with three boxes: the time in minutes, the mean % dissolved for the Reference product (Rt), and the mean % dissolved for the Test product (Tt). The Reference column comes first and the Test column second, and the (Rt โˆ’ Tt) column is always Reference minus Test.

  • Starting rows. The page opens with the IR template already loaded: 5, 10, 15, 20, 30, 45 and 60 minutes, with the time filled in and the two % columns empty.
  • Templates. The IR button loads those seven rows. The SR button loads six rows at 60, 120, 240, 360, 480 and 720 minutes (1 to 12 hours). Loading a template clears whatever rows were there before.
  • Add Row adds an empty row and the โœ• button removes one. Clear All removes every row and hides the results.
  • Row counter. A line under the table shows how many time points you have, and warns you while there are fewer than 3.
  • Order does not matter. The input table keeps the order you typed. The results table and the chart are sorted by time.

The (Rt โˆ’ Tt) and (Rt โˆ’ Tt)ยฒ columns in the input table stay empty until you calculate, and a sum row appears under the table afterwards.

Pick It First

Above the table is a drop-down labelled Decimal Precision (required before calculating), with options from 0 digits to 5 digits. Nothing is selected when the page opens. If you press calculate without choosing, the calculator stops with a message and moves the cursor to the drop-down. Changing the precision after you have results re-runs the calculation straight away.

The setting changes only what you see. The sum, the square root and the logarithm are worked out with full precision whatever you choose, so f2 does not move when you change the display. See the question about 0 digits in the FAQs below, because at low precision the visible rows may not add up to the visible total.

What Stops the Calculation

SituationWhat happens
No decimal precision chosenA message appears and the drop-down is focused.
The table has no rowsA message asks you to load a template or add a row.
Any box in any row is emptyThe empty boxes are outlined in red, the row number is named in the message, and the cursor jumps to the first one. Fill it or remove the row.
A % value below 0 or above 120The box is outlined and a message names the time point to check. Values up to 120 are allowed because assays can read slightly above 100%.

The calculator does not check that time points are unique. Two rows at the same time are both used in the sum and both counted in n, so keep each time to one row.

Five Time Points, Calculated by Hand

Here are mean results for a Reference and a Test tablet. Choose 2 digits of precision and enter the rows below:

Time (min)Reference (Rt)Test (Tt)Rt โˆ’ Tt(Rt โˆ’ Tt)ยฒ
1031.5029.10+2.405.76
2052.8049.60+3.2010.24
3068.4066.00+2.405.76
4583.7080.90+2.807.84
6092.6090.20+2.405.76

The calculation table under the results then shows these rows, followed by the working rows:

Working rowValue
Sum of (Rt โˆ’ Tt)ยฒ35.36
Sum of (Rt โˆ’ Tt)ยฒ รท n, with n = 57.07
1 + Sum of (Rt โˆ’ Tt)ยฒ รท n8.07
Square root of that2.84
f2 = 50 ร— log [100 รท 2.84]77.33

The medium-calc line under the result card reads f2 = 50 ร— logโ‚โ‚€[100 / 2.84] = 50 ร— 1.55 = 77.33. Because 77.33 is between 50 and 100 and n is 5, the banner reads Dissolution Profiles: SIMILAR, and the result card shows SIMILAR with the note "FDA/EMA criterion (f2 โ‰ฅ 50)".

There is no 15-minute row in this data, so the note under the table says no 15-minute time point was found and the 85% check could not be performed. f2 was calculated from all five rows.

To see the other outcome, replace the Test column with 22.0, 38.5, 52.0, 70.1 and 81.4. The squared differences now add up to 874.10 and f2 drops to 43.87, so the banner turns red and reads NOT SIMILAR.

Three Messages Under the Table

After every calculation the calculator looks for a row at exactly 15 minutes and shows one of three notes:

  • 85% rule satisfied. A 15-minute row exists and both Test and Reference are at or above 85%. The row is highlighted in green in both tables, and the note explains that f2 may not be needed in that case. The f2 value is still calculated.
  • 85% rule not met. A 15-minute row exists, but at least one product is below 85%. The note shows both values.
  • No 15-minute time point. The check cannot be made. This is what the worked example above shows.

None of these notes removes or changes any row. The calculator uses every time point you entered.

Verdicts, Cards, Chart and Math Log

SituationBannerResult card
3 or more rows, f2 from 50 to 100Green, SIMILARSIMILAR
3 or more rows, f2 below 50Red, NOT SIMILARNOT SIMILAR
Fewer than 3 rowsBlue info banner, insufficient time pointsInconclusive
  • Summary cards: the f2 value, the verdict, the number of time points (n) and the total squared difference.
  • Math Log: four numbered steps. Step 1 lists each time point's squared difference and their sum, step 2 divides by n, step 3 adds 1 and takes the square root, and step 4 applies the logarithm and the factor of 50.
  • Chart: time in minutes along the bottom and % result up the side. The Reference is a purple line with square markers and the Test is a blue line with diamond markers. The value is printed under every marker, using your chosen decimals, and a small table beneath the chart repeats the numbers.

Copy Full Report and Print Report

Both buttons need a completed calculation. If you press them before calculating, a message asks you to calculate first.

Copy Full Report copies a text report: a title line, the table (time, Reference, Test, difference, squared difference, separated by tabs so it pastes neatly into Excel), then the f2 value with its tag and the verdict text.

Print Report opens an editable A4 preview that fits on one page. It carries the calculation table with its working rows, the verdict banner with the f2 value and the formula, and the chart as an image. You type these details directly on the sheet before printing: company name, dissolution medium (buffer), Reference brand and batch, Test brand and batch, analysis date, instrument, and the Analyzed by and Checked by lines.

The logo box accepts a PNG, JPG or WebP image of up to 1 MB, between 30 ร— 30 and 512 ร— 512 px on each side. HEIC photos from phones are not accepted. Choose Save as PDF in the print dialog and switch off Headers and footers for the cleanest file. Esc or the Close button leaves the preview.

Mistakes to Avoid

  • Typing one vessel's result instead of the mean. The calculator treats whatever you enter as the mean.
  • Including too many points near full release. Rows after the profile has levelled off pull the differences towards zero and push f2 up. The calculator will not stop you, so follow your guidance on how many points at or above 85% to use.
  • Mixing time units. Everything is in minutes. A 2-hour point is 120, not 2.
  • Entering fractions. Type 92.6, not 0.926. The range check would not catch a fraction because it is between 0 and 120.
  • Leaving a template row empty. The IR template loads seven rows. If you only have five time points, remove the two extra rows, or the calculation stops.
  • Duplicate time rows. They are not rejected, but they are both counted.
  • Relying on 0 digits for hand-checking. Use 2 or more digits when you want the rows and total to match.

Short Answers

Do I enter individual unit values or the mean for each time point?

Enter the mean % dissolved for each product at each time point, for example the average of 6 or 12 units. The standalone calculator does not average anything for you. If you only have unit-level data and want the calculator to work out the means and the %RSD first, use the Comparative Dissolution Profile calculator instead.

Why do I have to choose decimal precision before I can calculate?

The calculate button is always clickable, but if no precision is chosen the calculator stops and shows a message asking you to select 0 to 5 digits. The choice controls how every number is displayed: the table, the sum, the verdict text, the math log, the chart labels, the copied text and the printed report. The calculation itself keeps full precision.

Why do the rows not add up exactly when I choose 0 digits?

Because only the display is rounded. With the example in this guide, the true differences are 2.4, 3.2, 2.4, 2.8 and 2.4, but at 0 digits the rows show 2, 3, 2, 3 and 2, while the sum of squares is still calculated from the real values (35.36, shown as 35). Choose 2 or more digits when you want to check the arithmetic by hand.

Does swapping the Reference and Test columns change f2?

No. The differences change sign, but they are squared before they are added, so f2 is identical. Only the colour and sign shown in the (Rt โˆ’ Tt) column change. It is still worth entering the products in the right columns so the report is correct.

Can f2 be greater than 100?

No. Identical profiles give exactly 100, and every difference between them pulls the value down. If you ever see a number above 100 somewhere else, check the data or the formula used.

What does the calculator do with fewer than 3 time points?

It still calculates f2, but the verdict banner says there are not enough time points for regulatory use, the result card shows Inconclusive, and a note under the table asks you to add more points. The row counter on the data-entry table also reminds you when you have fewer than 3 rows.

Which template should I use for an extended-release product?

The SR template loads six rows at 60, 120, 240, 360, 480 and 720 minutes, which is 1 to 12 hours. Time is always entered in minutes, so convert hours before typing if you build your own rows.

Does the calculator remove time points after 85% dissolution?

No. Every row you enter goes into the calculation. If your guidance allows only one mean at or above 85% for each product, leave out the extra points yourself.

Is the data I type sent anywhere?

The calculation, chart, copy text and print preview all run in your browser, and the calculator script does not send your entries to a server.

Educational use only. This guide explains how the standalone f2 calculator on this site works. It is not a validated system, and it does not replace your SOPs or the guidance your regulator expects you to follow. Please read the disclaimer for how this site should be used.

Ready to Run Your Own f2 Calculation?

๐Ÿ“ Open the f2 Similarity Calculator