Tuesday, May 18, 2010

FDA Pronounces Rotavirus Vaccine Safe After All: Will FDA Leadership be More Cautious Next Time?

It’s official: FDA has given the all clear to resume use of GlaxoSmithKline’s Rotarix despite evidence of contamination with porcine circovirus. (Read the official announcement here.)

That outcome was something of a foregone conclusion after an advisory committee discussion of the issues last week—and especially after the discovery that Merck’s RotaTeq may be similarly contaminated. After all, it is one thing to suspend use of a vaccine when there is a readily available alternative; it is another to suspend vaccination for a disease altogether. (Read our coverage in “The Pink Sheet” here.)

There are interesting and important implications for manufacturers here, especially as you think about standards for cell-culture based flu vaccines in the future. More generally, any biological product is vulnerable to advances in analytic technology that make possible detection of the previously undetectable.

But we wonder what if any implications this will have on FDA’s newly installed leadership team. We doubt there will be much call to revisit this episode from Congress—as there would have been, if, say, Andrew von Eschenbach were still the commissioner and this were 2007. As you may recall, that was a time when seemingly every decision made by FDA came in for scrutiny on the Hill.

Now, FDA’s leadership has some breathing room: a Democratically controlled Congress has no reason to undercut a Democratically appointed FDA commissioner.

Still, there may be some internal lessons learned that will have implications for how the Hamburg team operates from here on out. There is an old maxim routinely cited by career staff at FDA: “absence of evidence is not evidence of absence.” The leadership team’s response to the circovirus contamination issue appears to be open to some significant second-guessing on that score.

Here is how FDA Commissioner Margaret Hamburg explained the suspension during an address at the Food & Drug Law Institute annual meeting April 22. She cited Rotarix as a classic public health dilemma facing the agency. On the one hand, there was an unexpected contaminant in a vaccine, one that is not known to pose safety risk but still clearly not an acceptable finding. On the other hand, the vaccine is for a disease that is generally mild in the US, but a significant public health threat globally.

Hamburg cited FDA’s actions as an example of “creativity” in applying legal tools in the context of emerging issues where there is no black-and-white answer.

“Our decision was based in part on the fact that an alternative rotavirus vaccine without the extraneous viral material is widely available in this country. But we did not recall the Rotarix vaccine or state that it is unsafe. We also made it clear that other countries could and should make different judgments based on their local assessment of benefit versus risk. Our recommendation was based on an effort to balance science and data with a certain level of uncertainty and also a recognition that this was really the first example of an application of new technologies that allowed us to learn more about a vaccine product.”

Sounds reasonable enough. But read that first part again: “Our decision was based in part on the fact that an alternative rotavirus vaccine without the extraneous viral material is widely available in this country.”

That turns out not to be a “fact” after all, since Merck’s product ultimately showed signs of viral DNA (albeit apparently not the virus itself.) It is one thing to “suspend” use of a product due to an uncertain risk and encourage patients to choose a product free of that risk. But it turns out that FDA, in effect, encouraged doctors and parents to use Merck’s product even though it has a similar risk.

It isn’t just Hamburg who highlighted Rotarix as emblematic of the agency’s new “public health approach to the law.” Chief Counsel Ralph Tyler cited Rotarix as an example of how the Chief Counsel can and should enable FDA’s leadership to meet its public health objective (as we noted here).

Tyler took on New York Times reporter Gardiner Harris, quoting his March 23 article on Rotarix and taking issue with the assertion that FDA’s action “demonstrates that lawyers have lost considerable power at the FDA” since “neither statutes nor agency rules allow the commissioner to ask doctors to pause in their use of a medical product because the agency does not regulate the practice of medicine.”

“This breathtakingly incorrect view of the proper role of the agency’s lawyers is exactly backwards,” Tyler declared. “Contrary to the view expressed by Mr. Harris, empowering a client to act empowers, rather than diminishes, the lawyer.”

“The frequency with which a lawyer says ‘no’ is most assuredly not the measure of a lawyer’s power,” Tyler concluded.

Those remarks were addressed rhetorically to Harris, but the real target was the past approach of the Chief Counsel’s office under the Bush Administration, and most notably under former Chief Counsel Dan Troy. Troy was the first official appointed at FDA during the Bush Presidency, and set a tone of limiting FDA’s actions to those he viewed as soundly based in explicit legal authority. Troy argued that FDA was in danger of losing credibility with the courts, which would potentially eliminate its ability to protect the public health altogether.

Troy, incidentally, happens to be chief counsel for GSK.

So did FDA try a little too hard to find an opportunity to declare a new doctrine for protecting the public health? Should the agency have waited for more data before, in effect, giving the rotavirus vaccine market to Merck?

Those questions are all too easy to answer with the benefit of hindsight. As Hamburg said at FDLI: “We had to operate within shades of gray and I think managed to do so. And the law supported us.”

The real question is whether Hamburg may decide to be more cautious next time …
image from flickr user ~K~ used under a creative commons license

No comments: