Comparing Generic and Innovator Drugs: A Review of 12 Years of Bioequivalence Data from the United States Food and Drug Administration

@article{Davit2009ComparingGA,
  title={Comparing Generic and Innovator Drugs: A Review of 12 Years of Bioequivalence Data from the United States Food and Drug Administration},
  author={B. Davit and P. E. Nwakama and Gary Buehler and D. Conner and S. Haidar and Devvrat T. Patel and Y. Yang and Lawrence X. Yu and J. Woodcock},
  journal={Annals of Pharmacotherapy},
  year={2009},
  volume={43},
  pages={1583 - 1597}
}
Background: In the US, manufacturers seeking approval to market a generic drug product must submit data demonstrating that the generic formulation provides the same rate and extent of absorption as (ie, is bioequivalent to) the innovator drug product. Thus, most orally administered generic drug products in the US are approved based on results of one or more clinical bioequivalence studies. Objective: To evaluate how well the bioequivalence measures of generic drugs approved in the US over a 12… Expand
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References

SHOWING 1-10 OF 106 REFERENCES
Highly Variable Drugs: Observations from Bioequivalence Data Submitted to the FDA for New Generic Drug Applications
TLDR
It was observed that most of the consistent and borderline highly variable drugs underwent extensive first pass metabolism and drug product dissolution variability was high for about half of the inconsistentlyhighly variable drugs. Expand
Generic substitution: issues for problematic drugs.
TLDR
Information and myths persist regarding the adequacy and proven reliability of the FDA's determination of bioequivalence for digoxin and levothyroxine tablets. Expand
Bioequivalence and other unresolved issues in generic drug substitution.
TLDR
Bioequivalence issues are presented together with more general concerns over generic drug substitution, such as consumer perception of risk, differences in product and packaging appearance, and differences in excipients. Expand
What’s the problem with generic antiepileptic drugs?
TLDR
Two pharmacokinetic measures, the area under the drug concentration-time curve (AUC) and maximum concentration (Cmax), are used to determine bioequivalence (and by extension from these surrogate measures, therapeutic equivalence), and two reviews have been conducted by the FDA. Expand
Generic drugs and the prescribing physician.
TLDR
FDA procedures for approving generic drug products are described and the role of the states in generic substitution and the availability of information from the FDA on the therapeutic equivalence of drug products is described. Expand
Drug substitution in transplantation: a National Kidney Foundation White Paper.
TLDR
Changes in the approval process for generics should be accompanied by more consistent substitution practices and patients should be well informed about generic substitutes so that they can participate in treatment choices. Expand
Generic antiepileptic drugs
TLDR
Although generic AEDs are generally safe and effective for most patients, the current bioequivalence standards may not be sufficient for certain patient populations and for certain drugs, requiring vulnerable patients to be monitored very carefully when converting to generic Aeds. Expand
Clinical equivalence of generic and brand-name drugs used in cardiovascular disease: a systematic review and meta-analysis.
TLDR
Clinical evidence does not support the notion that brand-name drugs used in cardiovascular disease are superior to generic drugs, and a substantial number of editorials counsel against the interchangeability of generic drugs. Expand
Understanding the scientific issues embedded in the generic drug approval process.
TLDR
The major scientific issues embedded in the generic drug approval process and the issues surrounding bioequivalence are reviewed to understand why the process works and why many clinicians and consumers remain uninformed. Expand
Absorption Rate Vs. Exposure: Which Is More Useful for Bioequivalence Testing?
TLDR
It was concluded that use of Cmax/AUClqc should be discouraged and that defining bioequivalence in terms of rate and extent of absorption has major problems. Expand
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