FDA Says Use of Rotarix Should Resume

Roxanne Nelson

May 14, 2010

May 14, 2010 (UPDATED May 18, 2010) — The US Food and Drug Administration (FDA) announced today that it is revising its recommendations for rotavirus vaccines. The agency says that based on a careful evaluation of a variety of scientific information, it has determined that it is appropriate for clinicians and healthcare professionals to resume the use of Rotarix (GlaxoSmithKline) and to continue the use of RotaTeq (Merck).

The agency reached its decision based on an evaluation of laboratory data drawn from the manufacturers and its own laboratories. In addition, the Vaccines and Related Biological Products Advisory Committee of the FDA convened on May 7 to discuss the findings of porcine circovirus 1 (PCV1) DNA in Rotarix, and both PCV1 and PCV2 DNA in RotaTeq.

Based on a thorough assessment of the information, a review of the scientific literature, and input from scientific and public health experts, the FDA has decided to reverse its recommendation to temporarily suspend the use of Rotarix.

In making its decision, the FDA took into consideration that both rotavirus vaccines have strong safety records. To date, millions of children have safely received the vaccines, and clinical trials that involved tens of thousands of patients also demonstrated a strong safety record.

Another factor is that there is no evidence that either PCV1 or PCV2 poses a safety risk; neither has been known to cause infection or illness in humans. In addition, the FDA has considered the fact that the benefits incurred by the vaccines are substantial and outweigh the risk, which is theoretical at this point.

Background on the Recommendation

Components of PCV1 in the Rotarix vaccine were detected when an independent research team applied a new technology for detecting viral genetic material to the vaccine. DNA fragments of PCV1 were identified in 2 lots of Rotarix, and GlaxoSmithKline was notified of the findings on February 9, 2010.

The manufacturer then initiated extensive experiments to confirm the results and investigate further, and the FDA was notified of these findings on March 15, 2010. At that point, the FDA began to review the evidence, begin their own testing, and consult with experts.

PCV1 and PCV2 are both small viruses composed of a single strand of circular DNA and are common in pigs. However, although they may cause illness in pigs, neither is known to infect or cause symptoms in humans. Because these viruses are not known to cause human illness, the FDA has not required routine testing for them in vaccines.

However, even though there was no known safety risk, on March 22 the FDA recommended that healthcare practitioners temporarily suspend the use of the Rotarix until the agency was able to further evaluate the situation.

At a press conference when the recommendations were first announced, FDA Commissioner Margaret Hamburg, MD, said, "We do not believe there is a clinical risk.

"However, as with all vaccines, we recommend that clinicians watch for any serious adverse events and report them," she added.

Although preliminary testing of the RotaTeq vaccine did not reveal any contamination, and clinicians were advised to continue using it, DNA fragments of both PCV1 and PCV2 were eventually identified in this vaccine as well. However, the FDA did not make any recommendations to suspend its use.

The reason for this was that the advisory committee was meeting the day after the FDA learned of the contamination in the RotaTeq vaccine, explained FDA spokesperson Shelly Burgess.

"Since the meeting was the next day, they just decided to wait before taking any action," she told Medscape Medical News. "The advisory committee recommended resuming the use of Rotarix and not taking any action with RotaTeq.

"The FDA will continue to monitor both vaccines for continued problems with contamination," she added.

Wrong Course of Action?

However, Paul Offit, MD, questioned the initial recommendation to suspend Rotarix. "I don't think that it should have been suspended in the first place," said Dr. Offit, who is chief of the Division of Infectious Diseases and the director of the Vaccine Education Center at the Children's Hospital of Philadelphia, Pennsylvania.

"We had the following facts at hand, and all available information says porcine circovirus doesn't infect mammals," he explained. "The vaccine has a very strong safety record — it's been on the market for several years, and millions of doses have been administered safely."

The FDA faced a difficult communications issue. "Obviously, we don't want porcine circovirus in the vaccine, as it serves no useful purpose," Dr. Offit said. "But it's always a matter of judging risk vs benefit, and clearly, there's nothing theoretical about rotovirus."

By removing Rotarix from the market, the FDA elevated a theoretical and virtually nonexistent risk — the risk of PCV1 — above the known risk of rotovirus, he pointed out.

He acknowledged that it was a difficult decision for the FDA to make: Not telling the public would make it seem like "a cover-up," but announcing the contamination would generate worry among the public, even though the risk involved was only theoretical.

Dr. Offit is the coinventor and patent holder of the RotaTeq vaccine, and he noted that the FDA probably did not recommend halting its use when they discovered it was contaminated because they had already had a chance to review the data.

"They were able to look at the situation closely, review the tremendous safety experience, and then came to the right decision to put Rotarix back on the market and leave RotaTeq on the market," said Dr. Offit.

Continue Monitoring of PCV1/PCV2

At the advisory meeting held on May 7, the majority of participants supported the continued use of the rotavirus vaccines, and they argued that the benefits far outweigh the theoretical risks of the contaminant. Some committee members remained apprehensive about contamination, although GlaxoSmithKline told the advisory committee that the company is committed to removing PCV from the vaccine.

"The introduction of the rotavirus vaccines offers the promise of preventing large numbers of infections, hospitalizations, and deaths, both in the United States and throughout the world," said William Jarvis, MD, former chief of various branches and divisions within the National Center for Infectious Diseases at the US Centers for Disease Control and Prevention, Atlanta, Georgia. Dr. Jarvis is currently an advisor for Medscape Infectious Diseases.

Obviously, no contaminant should be present in any of our vaccines, Dr. Jarvis told Medscape Medical News. "The fact that this vaccine is administered orally rather than by injection perhaps makes the issue of a DNA contamination less critical, as the normal human stomach acidity would degrade such DNA," he said. "In addition, the large number of doses of this vaccine administered since its introduction without any evidence of adverse impact of this potentially contaminating DNA supports the FDA decision to allow its use."

Dr. Jarvis noted that he is certain that the FDA has looked at their own adverse event system and at the Centers for Disease Control and Prevention's vaccine adverse event system to see whether they can find any adverse event associated with this contamination. "Nevertheless, the company should be doing everything in its power to identify the source of this contamination and eliminating it," he added.

More information is available on the FDA's Web site.

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