Will FDA tighten standards for generic drugs? According to CDER Director, Dr. Janet Woodcock – the answer is “yes.” Good call.
At a meeting of the Generic Pharmaceutical Association in Bethesda, Maryland, Janet said the agency is discussing tightening the limits "so there is less variability.”
Less variability equals better predictability.
Dr. Woodcock commented that patients have complained about generic anti- seizure medications not working as well as brand-name counterparts.
This strikes a very personal note for me. One of my sons has Juvenile Myoclonic Epilepsy. His condition is wonderfully controlled via his meds – and I’d like it to stay that way.
Woodcock said that industry executives have approached her with concerns that some generic drugs have spurred quality concerns that went unnoticed in the approval process because clinical testing includes too few patients.
“They say, ‘I know there are products out there that aren’t equivalent,’ and typically they’re manufacturing folks,” Woodcock said in her speech. “I’ve heard it enough times from enough people to believe that there are a few products that aren’t meeting quality standards.”
Woodcock said she didn’t know when the agency would come to any conclusions about generic standards of equivalence. The standards assure the generic is absorbed at the same rate and extent as the brand-name version.
The absorption problems aren’t necessarily harmful, Woodcock said. FDA permits generic drugs to absorb at a 25 percent different rate and extent than the originals they copy.
In April, a group of outside FDA advisers, the Pharmaceutical Science and Clinical Pharmacology Advisory Committee, voted 11-2 that the agency’s equivalence requirements aren’ sufficient for certain medicines. They didn’t offer an alternative, and suggested the FDA list “critical dose drugs,” or drugs where a small difference in concentration can change patients’ reaction, that may need new standards.
The Pharmaceutical Science and Clinical Pharmacology Advisory Committee voted unanimously, with one abstention, that critical dose drugs do constitute a distinct group and voted unanimously that FDA should develop a formal list of those drugs - although the terminology of "narrow therapeutic index" may be more appropriate. And in an 11-2 vote, the committee concluded that current bioequivalence standards are not sufficient for drugs in the narrow therapeutic index group.
Critical dose drugs have a narrow therapeutic index, meaning that "small changes in blood concentration have the potential to result in serious therapeutic failures and/or serious adverse drug reactions." FDA is consulting the committee on the need to establish separate bioequivalence criteria for these drugs given continuing debate about whether critical-dose drugs require special consideration, the agency explained.
Currently, the "sameness" of a brand product and a generic version is evaluated based on two-treatment crossover study to prove bioequivalence, the aim being to show that the 90 percent confidence intervals of the geometric mean test/reference ratios for both maximum plasma concentration and the area under the plasma concentration-time curve fall within a range of 80 percent to 125 percent.
It’s good news that the FDA is taking a strong stance in favor of the public health – because there will be many who seek to undermine this important initiative.
