FDA Guidance for Bioequivalence Studies to Support Abbreviated New Drug Applications

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Abbreviated New Drug Applications (ANDAs) present data to the US Food and Drug Administration (FDA) for review and approval of generic drug products only.

These applications only need to “scientifically demonstrate” that the proposed generic drug performance is equivalent to the innovator drug. No efficacy or safety data is required. Hence, they are called abbreviated.

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Equivalent Performance to an Innovator Drug Means:

  •     Similar in its intended use
  •     Same dosage requirements
  •     Same administration route
  •     Same strength
  •     Same quality
  •     Similar performance capacity

Summary Bioequivalence Report Submission for ANDAs: FDA Guidelines 2011

Any ANDA must contain a summary report of the bioequivalence study on the basis of which the agency hopes to gain approval. However, the FDA guidelines stress that the ANDA must also include a report of any additional bioequivalence (BE) study conducted on the drug.

The guidance document also mentions that the FDA may ask for a full bioequivalence report if it deems that necessary on reading the summary reports.

A model for product-specific summary reports offered by the FDA is available here.

What the FDA Means by “Same Drug Formulation”

When the differences in the composition or the manufacturing process are minor enough not to affect the bioavailability and bioequivalence in any way, the FDA regards that as the formulation of the same drug. In such cases, the FDA requires the ANDA to submit the report of all BE studies.

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If the differences in the composition and manufacturing process lead to significant differences, then they do not qualify as the same drug formulation. In such cases, BE study reports are not necessary.

Immediate Release Drug Products that Qualify as Same Drug Formulation

  •     The ingredient difference only affects the color or flavor of the drug
  •     The printing ink uses a different approved product
  •     The percentage difference in an individual excipient needs to be as follows:

○      Filler: ≤ 10

○      Starch as disintegrant: ≤ 6

○      Any other disintegrant: ≤ 2

○      Calcium or magnesium stearate as a lubricant: ≤ 0.5

○      Any other lubricant: ≤ 2

○      Talc as glidant: ≤ 2

○      Any other glidant: ≤ 0.2

○      Film coat: ≤ 2

  •     The difference in the cumulative total of all the excipients needs to be less than or equal to 10%.

The change of one or more excipients would imply that such a drug product for immediate release does not count as the same drug formulation. Differences in the amounts of the same excipients also mean that it is not the same drug formulation.

Other Topics Addressed in this Guidance Document

  •     Extended-Release Drug Products
  •     Semisolid Dosage Forms
  •     Other Complex Dosage Forms

EMA 2010 Guidelines on Investigation of Bioequivalence for Generic Drug Products: A Brief Comparison

This document explains that two drug products using the same active substance must demonstrate that the bioavailability and bioequivalence of that substance are the same in order to be considered as pharmaceutical equivalents.

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The document emphasizes the need to conduct appropriate bioavailability studies to demonstrate that a generic medicinal product and the reference product are bioequivalent. Here the EMA guidelines differ from the FDA guidance document, which does not mention bioavailability studies at all.

The EMA document also mentions that the bioavailability studies recommended in the document may be relevant for demonstrating the bioavailability and bioequivalence of new drug products also.

This document is considerably more detailed than the FDA guidance document.

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