Are Generic Drugs Really Equivilant to the Patented Pharmaceutical? The FDA Wants to Know...

FDA Mulls Tighter Standards for Generics

By Emily P. Walker, Washington Correspondent, MedPage Today Published: July 26, 2011

WASHINGTON -- An FDA advisory committee met Tuesday to discuss the agency's proposed standards for determining when generic drugs can be considered bioequivalent to the brand-name version of the medication. Responding to concerns from industry and physicians, the FDA is proposing imposing stricter standards for bioequivalency on medications known as "critical dose drugs" or "narrow therapeutic index" (NTI) drugs. Small changes in the dose of NTIs could cause serious or life-threatening adverse results, so making sure that each and every pill carries the same dose and works the same is crucial. Generic drugs win FDA approval by showing bioequivalence -- after administration of a standard dosage, blood levels of the generic drug are the same as for the branded original. But although the generic's mean maximal concentration and area under the concentration-time curve are typically within a few percentage points of the original's -- typically about 4% -- the 90% confidence interval for those results means the generics can be as much as 20% below or 25% above the branded drug's mean. That window may be appropriate for, say, a headache drug, but many experts question whether that window is too wide for drugs with very specific action, for instance, drugs to treat epileptics. In 2010, the FDA's Pharmaceutical Science and Clinical Pharmacology Advisory Committee voted 11-2 that current bioequivalence requirements aren't sufficient for NTIs. At the conclusion of that meeting, the committee voted 13-0 that the FDA should develop a list of NTI drugs with clear, specialized criteria for including drugs on the list. These medications include anti-arrhythmics, anticoagulants, and tricyclic antidepressants, among others. The NTI list that FDA developed includes seven drugs: warfarin, levothyroxine, carbamazepine, lithium carbonate, digoxin, phenytoin, and theophylline. Tuesday's advisory committee was slated to discuss whether FDA's definition of an NTI is appropriate and whether the agency's proposed scale for deciding whether an agent is bioequivalent is appropriate. The FDA is proposing that generic drugmakers looking to get approval for an NTI should conduct a replicate design study to quantify the variability of both the generic and the reference product to determine bioequivalence. The issue is especially relevant as use of generic drugs continues to grow. Generic drugs constituted 78% of total prescriptions dispensed in the U.S. in 2010.