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  1. Science and Research | Drugs

Impact Story: Overcoming Challenges to Evaluating Bioequivalence in Complex Drugs

Regulatory Science Impact Story

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FDA-initiated research is facilitating the availability of high-quality, affordable generic drug products.

FDA plays an important role in helping to ensure that new brand name medicines are safe and effective before they are sold. Over time, when pharmaceutical companies develop ways to make a duplicate version of the brand name drug product, FDA helps ensure that these generic drug products are as safe and effective as the brand name medicine.

Generic Drug Requirements
  • Same active ingredient(s)
  • Same route of administration
  • Same dosage form
  • Same strength
  • Same conditions of use
  • Inactive ingredients already approved in a similar New Drug Application

Learn about Generic Drugs Science & Research and Approvals & Reports

Developing generic drug products can be more efficient than developing brand name drug products, largely because the safety and efficacy of the brand name drug product has already been established, so that work does not need to be repeated for the generic drug product. Instead, the developer of the generic drug product must demonstrate that they have made a pharmaceutically equivalent version of the brand name product. This means the generic drug product must be in the same dosage form (tablet, solution, cream, etc.), contain the same active drug(s) at the same strength, and have the same route of administration (by mouth, injection, skin application, etc.) as the brand name drug product. In addition, the generic drug product must demonstrate bioequivalence, delivering the same amount of the same drug to wherever it is needed in the body (the site[s] of action) at the same rate and to the same extent of absorption as the brand name drug product.

One of the most accurate, sensitive, reproducible, and efficient ways to demonstrate bioequivalence is to compare the prospective generic drug product and the brand name product in a pharmacokinetic study, which assesses the rate and extent to which the drug becomes available in the body (e.g., in the blood) at various points after dose application. Once the study has demonstrated bioequivalence and matters related to product quality, performance, and other regulatory considerations have been addressed, FDA approves the generic drug product as being as safe and effective as the brand name drug product.

This approach works well for drug products intended to deliver drugs to the blood (the systemic circulation). However, demonstrating bioequivalence is not always straightforward and efficient, particularly for drug products that are complex. Complex drugs include those that are intended to deliver medication to local sites of action, such as the lung (e.g., an inhaled medication for asthma) or the skin (such as a cream or ointment for eczema), where measuring how much drug is present at different times—known as the rate of absorption—can be difficult. The scientific challenges associated with demonstrating bioequivalence with these types of medications are among the reasons that generic drug products are not available for many complex brand name drug products.

FDA is working to overcome these challenges by advancing research to help develop efficient, scientifically rigorous new tools to characterize product qualities and evaluate bioequivalence for complex drug products. This research helps support the FDA in creating guidance for industry on viable approaches to developing specific generic drug products. It also helps the FDA to verify through clinical studies that the generic drug is as safe and effective as the brand-name version. Patients and caregivers can be confident about switching to generic drug products and benefit from the associated substantial cost savings.

Read about FDA's work in the development and evaluation of dermal open-flow microperfusion, an innovative bioequivalence methodology for topical drugs.

For more information, please visit the Office of Generic Drugs.

Learn about the Generic Drugs Program

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