Understanding the scientific issues embedded in the generic drug approval process

OBJECTIVE: To review the major scientific issues embedded in the generic drug approval process. DATA SOURCES: Articles indexed initially under terms such as generic medications, generic drugs, bioequivalence, and bioinequivalence. These terms were used to search indexing services such as MEDLINE, International Pharmaceutical Abstracts, CINAHL (a database of nursing and allied health literature), and Science Citation Index. Additional data sources included the Code of Federal Regulations and regulatory guidances from the Food and Drug Administration (FDA) Center for Drug Evaluation and Research. STUDY SELECTION: Performed by the authors. DATA EXTRACTION: Not applicable. DATA SYNTHESIS: Despite the fact that regulations regarding bioequivalence have been in place for more than 20 years, controversies over bioequivalence continue to arise. Consensus on many of these issues is driving the development of new FDA guidances regarding bioequivalence. Still, despite the issuance of new guidance and consensus building among scientists, many clinicians and consumers remain uninformed regarding the scientific basis for establishing bioequivalence and the generic drug approval process in general. Although some have suggested that the generic drug approval process is flawed, overall, it appears that the process works. CONCLUSION: Understanding the generic drug approval process and the issues surrounding bioequivalence is of paramount importance to both clinicians and scientists.