FDA Panel Meeting Set on Vancocin Bioequivalence Dispute
FDA has scheduled an 8/4 advisory committee meeting to discuss bioequivalence recommendations
for oral vancomycin hydrochloride capsule drug products, which presumably is intended to resolve an ongoing dispute. In March,
ViroPharma asked FDA to withdraw its 12/08 draft guidance on establishing bioequivalence for generic copies of the company’s
Vancocin (vancomycin HCl capsules). The company says that in 3/06 FDA’s Office of Generic Drugs (OGD) changed its bioequivalence
standard from testing in humans to an in vitro dissolution test because it concluded that Vancocin was a rapidly
dissolving drug product. In 12/08, it says, the Office of Generic Drugs published data directly contradicting that conclusion
but also released a new draft guidance that retains in vitro testing as the means to determine bioequivalence provided
that the generic product has the same inactive ingredients and they are present in the same amounts as in Vancocin. It is
the only FDA-approved product for treating Clostridium difficile-associated pseudomembranous colitis, one of the
most common hospital-acquired infections.
“While we appreciate that FDA has provided a limited level of
public process, we continue to vehemently disagree with an approach that we believe places patient lives in the hands of an
unproven method that is riddled with assumptions, and the result of a profoundly flawed process that could lead to sub-therapeutic
versions of Vancocin,” ViroPharma vice president Thomas Doyle said at the time. “We reiterate our willingness
to assist FDA in any way we can in the development of a rigorous method that will ensure the approval of safe and effective
generic versions of Vancocin.”
Then, earlier this month, ViroPharma said that a recent scientific paper
indicates that OGD was wrong in asserting that the site of action for vancomycin capsules is in the lower GI tract. OGD asserted
that site of action in developing its rationale and justification for waiving in vivo bioequivalence testing for
oral vancomycin capsules and moving to a reliance on in vitro dissolution tests alone. The company submitted a paper
by University of Cincinnati College of Medicine researchers indicating that the infection is no longer limited to the colon
but rather has been expanded with small bowel involvement.
“The omission of this information from OGD’s
guidance clearly demonstrates a lack of understanding of the pathophysiology of Clostridium difficile infection and
poor diligence on OGD’s part in preparing BE determinations for this agent,” it said. “OGD should refrain
from abandoning in vivo bioequivalence testing for generic versions of this drug until such time as experts in the
field agree with OGD that a sufficient understanding of the disease and the associated pathophysiological changes of the gut
exist to develop an in vitro model of drug performance similar to that which is used as the basis for a waiver of
BCS-1 drugs and such experts agree that the same de minimus level of risk is associated with the new diseased-gut
model.”
To read details on the advisory committee meeting, click here.
