[Original brands and generic preparations].

Area of Science:

• Pharmacokinetics and Drug Development
• Regulatory Science
• Pharmaceutical Quality Assurance

Context:

• Modern drug approval processes assume therapeutic equivalence between original and generic drugs based on bioequivalence.
• Current guidelines focus on pharmaceutical equivalence and limited bioavailability deviations, with fewer drastic changes than in the past.

Purpose:

• To evaluate the adequacy of current drug approval guidelines in ensuring therapeutic equivalence.
• To highlight potential discrepancies between approved drugs not covered by existing regulatory procedures.

Summary:

• Drug approval studies often use limited volunteer populations (young, healthy males) and may not assess meal effects on bioavailability.
• Post-approval monitoring of quality maintenance is not consistently enforced.
• Tolerated bioavailability deviations can be significant, potentially leading to sub-therapeutic or toxic effects, as seen with carbamazepine, phenytoin, levothyroxin, verapamil, and aspirin.

Impact:

• Current drug approval rules are insufficient to cover all potential issues, particularly for drugs with a narrow therapeutic range.
• Scrutiny of drug documentation and manufacturer reliability (scientific support, product history) is essential for product selection.
• The internet is an increasingly important resource for drug information beyond official documentation.