Bracco expects CardioGen shipments to resume next year
October 20, 2011
by Brendon Nafziger
, DOTmed News Associate Editor
Bracco Diagnostics Inc. said it expects to resume shipments of a PET heart agent generator in the first half of next year after it was recalled this summer over fears of giving patients too much radiation. And a seller of used medical equipment said the news could lift PET-CT scanner prices.
In a letter sent to customers Monday, the Princeton, N.J.-based company said it "anticipates a limited and progressive reintroduction of the product to commence in the first or second quarter of next year."
The generator, CardioGen-82, produces rubidium-82 chloride injections, the only commercially available PET agent for myocardial perfusion studies, according to the Society of Nuclear Medicine.
The generator was recalled in July, after two patients set off very sensitive radiation detectors at the U.S. border. The U.S. Dept. of Homeland Security notified the Food and Drug Administration, and eventually the patients -- one of whom was apparently briefly stranded in Canada -- were sent to Oak Ridge National Laboratories in Tennessee, where they underwent full-body scans, according to Bracco.
A third patient also set off alarms, and it turned out the patients had all undergone PET stress tests using the substance several months earlier -- and two actually had their scans at the same Florida heart clinic.
The FDA said the problem that led to the recall, which was voluntarily ordered by Bracco, was likely caused by a "strontium breakthrough," meaning radioactive strontium isotopes used to create the PET agent were inadvertently injected into the patients.
"Our investigation findings, to date, continue to support that the unexpected radiation levels may have been due to user error or strontium breakthrough higher than what is expected with normal generator use or a combination of both," Bracco said in its letter Monday.
Root of the problem
Strontium, the parent isotope of rubidium-82, is "milked" into its daughter isotope by running a saline solution through the central column of the generators, explains Dr. Marcelo F. Di Carli, director of nuclear medicine at Brigham and Women's Hospital in Boston.
The goal is to ensure only rubidium, which has a half-life of 76 seconds, and not strontium, which has a half-life of four weeks, gets into the patient. That's why as part of the FDA's 1995 approval of the product, facilities using it should run daily "strontium breakthrough" checks.
"If you get too many strontium impurities into that solution, the consequence is you could inadvertently deliver higher radiation to patients," Di Carli told DOTmed News.
And that appears to be what happened this summer.
A typical completed stress procedure, with rest and stress scans, with Rb-82 exposes patients to about 3 to 4 mSv, Di Carli said. However, based on models from Los Alamos National Laboratory, where the recalled generators were sent, the FDA estimates the patients received 90 mSv.
Although higher than normal, the FDA said the amount of radiation the patients received was comparable to doses from cumulative exposures of other heart scans. In a follow-up letter to customers Bracco said a patient would need over 1,000 times the dose to have a problem.
"Anything below 100 mSv is still considered low-level radiation," Di Carli said. He also noted that the 90 mSv number mentioned by the FDA is an "ultra-conservative" estimate.
"I don’t know where that comes from. As far as we can tell, there was no specific body measurement," he said.
Ultimate causes still unknown
A September Herald-Tribune article cited officials who suggested that a supply shortage may have been the ultimate cause of the problem. Bracco alerted customers earlier this year that because some cyclotrons -- particle accelerators that make the raw material used in the CardioGen generators -- were down for maintenance, it would have limited supplies from March through July. The newspaper said Bracco extended its 28-day expiration limit for the product to 45 days, before revising it back to 42 days. However, the Florida clinic scanned one of the patients on at least the 44th day, the paper said.
But Di Carli said, although this has been a common suggestion, that his lab tested their generator, which was also bumped up to the six-week cycle, and there was nothing out of the ordinary.
"I think it’s very dangerous to take sides, because the facts are not out there," he said. "It’s premature to say what happened."
Still, in a July announcement about the recall, the FDA faulted CardioGen manufacturing procedures for not being "sufficient to ensure reliable performance of the generator." However, in its most recent letter, Bracco said it has been in "constant communication" with the watchdog agency, and that it has been "revalidating its manufacturing process and reviewing labeling and user training to ensure proper generator use."
The price of a return
The lack of CardioGen may have had an impact on both patients and cardiac PET scanner prices, as the main alternative for PET perfusion studies, 13N-ammonia, has such a short half-life (about 10 minutes) it's generally only usable for the few institutions that have a cyclotron on-site. Di Carli estimates only a handful of the 100 facilities across the country that had been using CardioGen have one.
As a result, patients have been transferred to other modalities, such as SPECT imaging, even though PET offers the preferred "first-line" myocardial perfusion test for certain patient populations, such as the obese, according to SNM.
It also might have had an effect on equipment purchases.
"Prices on used cardiac PET scanners have slid in recent months due to the fact that no new cardiac sites were being built unless you had a cyclotron in your backyard," Josh Nunez wrote Wednesday on the blog of Block Imaging, a medical equipment dealer. "We've seen systems that were selling for around $500,000 slide to around $400,000."
However, Nunez noted that prices are expected to climb back up -- now that CardioGen is likely coming back.
But exactly when that happens, no one's really sure. Di Carli said work is still ongoing to really understand if there's a widespread manufacturing problem or, as seems more likely, just user error. In a week or two, his hospital will invite patients that had the CardioGen scans back for testing, in line with other groups participating in Bracco and the FDA's clinical review.
"It's reasonable to think that these were isolated incidents that were related to essentially human error, not following proper practice," Di Carli said. "But what is unclear is what the FDA will say."