Submission of additional bioequivalence study Data for ANDAs - New FDA Requirment

FDA regulations now require report of all bioavailability or bioequivalence studies conducted during drug development. FDA believes it will increase understanding of generic drug development which in turn will promote further development of science-based bioequivalence policies.

FDA regulations now require submission of either a summary report or a complete report of all bioavailability or bioequivalence studies conducted on the same formulations of the drug product submitted for ANDA approval.

The FDA believes that data from any additional bioequivalence studies may be important in determination of whether a product is bioequivalent to the RLD, and aid in the evaluation of generic products.

FDA's Stance:

According to FDA these data will

1. Increase understanding of generic drug development and how changes in components, composition and methods of manufacture may affect formulation performance.
2. Promote further development of science-based bioequivalence policies.

A summary report can be submitted (including in vivo and in vitro testing conducted to demonstrate bioequivalence.), but if the Agency believes that there may be bioequivalence issues or concerns with the drug product, the Agency may request for a complete report.

Format to be used for the Summary Report is the "Model Data Summary Tables" format consistent with the ICH Common Technical Document (CTD)available at the Office of Generic Drugs (OGD) web page.

Same Drug Product Formulation:

As per the amended regulation only data from bioequivalence studies of formulations considered same to the drug product submitted for ANDA approval need to be submitted.

According to FDA same drug product formulation means, the formulation of the drug product submitted for approval and any formulations that have minor differences in composition or method of manufacture from the formulation submitted for approval, but are similar enough to be relevant to the FDA's determination of bioequivalence.

Formulations with differences in composition that are likely to result in a significant difference on formulation quality and performance, are considered non similar and studies need not be submitted.

Immediate Release Formulations and Extended Release Formulations:

Formulations of Immediate Release Formulations and Extended Release Formulations are considered similar if there is a difference in

1. Ingredient intended to affect the colour or flavour of the drug product
2. Ingredient of the printing ink
3. Technical grade and/or specification of an excipient
4. Particle size or polymorphic form of the drug substance or excipients
5. Individual excipient weight between the formulations compared but are Less than or equal to the percentages listed in below Table or cumulative total of all excipient weight differences is less than or equal to 10 percent

Non-Release Controlling Excipient	% Difference in Excipient Weights Between Two Formulations*
Filler
Any Filler	10
Disintegrant
Starch	6
Other	2
Binder
Any Binder	3 / 1 **
Lubricant
Calcium (Ca) or Magnesium (Mg) Stearate	0.5
Other	2
Glidant
Talc	2
Other	0.2
Film Coat
Film Coat	2

* Percentage of difference between another experimental formulation and the formulation proposed for marketing.
** 3 for Immediate Release and 1 for Extended Release formulations.

Formulations of Immediate Release Formulations and Extended Release Formulations are not considered similar if there is a difference in

1. Addition or deletion of an excipient
2. Individual excipient that exceeds the percentages shown in table above or the cumulative total of all excipient weight differences exceeds 10 percent.

Note: Formulations of Extended Release Formulations with a change in release controlling excipients are not considered the same when the differences in the amount of release controlling excipient(s) are greater than 10 percent.

Semisolid Dosage Forms:

Formulations of semisolid dosage form products are considered same if

1. The difference in the amount of an individual excipient is less than or equal to 5 or if the cumulative total of differences in the amount of all excipients is less than or equal to 7 percent.
2. Formulations with differences in particle size distribution of the drug substance

Note: Formulations with differences in technical grade of a structure forming excipient are not considered the same.

A copy of the guidelines for your reference can be found at Submission of Summary Bioequivalence Data for ANDAs draft Guidance.