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During the week of April 21, 2008, Australian health official authorized a recall of several batches of a common blood-thinning drug that has been contaminated. Heparin is widely used to prevent blood clotting in patients undergoing surgery, who have suffered a heart attack, or who are bedridden.

But at the moment, there are some serious concerns about the safety of some Heparin products that are contaminated. The latest product is Clexane. The recall by the Therapeutic Goods Administration (TGA) follows reports from overseas of severe allergic reactions, and in some cases death from an intravenous form of the same drug.

TGA director Dr Rohan Hammett told AM five batches of the drug have been recalled.

“In March of this year, the TGA instituted requirements that all Heparin-containing products needed to be tested for evidence of a contaminant that’s been associated with adverse events overseas,” he said.

“At this stage the Clexane product, or five batches of it, have tested positive for that contaminant, and we are recalling those batches of Clexane.

“It’s important to note that to date there have been no reports of adverse events or untoward reactions to Clexane in Australia. This is purely precautionary at this stage.”

He says all forms of intravenous Heparin in Australia have been tested for the contaminant and are free of the contaminant.

Dr Hammett would not confirm reports that the contaminated Heparin was linked to China.

“There are different theories about how the contamination in the Heparin products may have occurred,” he said.

“The TGA is actively investigating where the contamination may have occurred along the manufacturing supply chain.”

The president of the Australian Medical Association, Rosanna Capolingua, has praised the recall.

“This is a very serious situation,” she said. “There have been a number of recorded deaths due to anaphylaxis, which is a severe allergic reaction to Heparin products, to Clexane, for instance in the United States, and the AMA fully supports the TGA’s decision to recall Clexane in the interests of public health and safety.”

The contamination scandal has led to fears of a worldwide Heparin shortage.

Dr Capolingua says the product should now be rationed.

“Hospitals will need to think very carefully about rationing unaffected batches of Clexane and also doctors will have to think about using alternatives to Clexane to protect their patients from thrombosis,” she said.

Health experts suggested on April 21, 2008, that children with Attention Deficit Hyperactivity Disorder (ADHD) should have their hearts checked out prior to starting treatment with Ritalin or other stimulant drugs.

The American Heart Association called for these children to undergo an electrocardiogram, a test that detects and records the heart’s electrical activity, before taking such drugs. The group said it is not clear that these medications increase a child’s risk of sudden cardiac death, but issued the new recommendations out of an abundance of caution.

“There’s been concern that these drugs might be associated in a very small number of individuals’ sudden cardiac arrest or sudden cardiac death,” said Dr. Victoria Vetter of the University of Pennsylvania School of Medicine in Philadelphia, who led the panel that drafted the recommendations.

“There’s no registry in the country to determine how many young people are dying from sudden cardiac arrest and what they might have causing that and similarly how many of those who die might be on these medications. So there’s no causal information,” Vetter added in a telephone interview.

Ritalin, Novartis AG’s brand name for the generic drug methylphenidate, is a central nervous system stimulant prescribed to calm and focus children with ADHD, a condition marked by inattention, hyperactivity and impulsive behavior.

ADHD appears to be more common in children with heart conditions, the American Heart Association said in the recommendations, published in its journal Circulation.

The group said U.S. Food and Drug Association data showed that between 1999 and 2004, 19 children taking ADHD drugs died suddenly and 26 children had cardiovascular events such as strokes, cardiac arrests and heart palpitations.

Millions Treated

Millions of U.S. children are taking ADHD drugs.

Research has indicated that stimulants like Ritalin can raise the heart rate and blood pressure. While these side effects are unimportant for most children with ADHD, they can be relevant for those with a heart condition, the American Heart Association said.

Some heart conditions can raise the risk for sudden cardiac death, which can happen when heart rhythm becomes erratic.

The association’s recommendations call for a child to get an electrocardiogram before starting ADHD stimulant medications because the test may identify conditions like heart rhythm abnormalities that can trigger sudden cardiac death.

“It won’t pick up every one. There will be some false positives. But it’s a relatively inexpensive and simple test that doesn’t hurt the children in any way and it will let us identify some of these children and know that they have heart conditions,” Vetter said.

“We particularly don’t want to scare people or to alarm them,” Vetter said.

The group also urged doctors to evaluate the heart health of children already taking ADHD medications if they were not evaluated before they began treatment. If the electrocardiogram turns up trouble, that does not necessarily mean the child should not get ADHD medications, Vetter said.

“We would monitor those children more carefully, start them on lower doses of drugs and see how they do,” she said.

Two U.S. health agencies said last year they were launching a two-year assessment of potential heart risks from ADHD drugs.

The FDA, on April 22, 2008, was scolded by House members for not being proactive and performing more inspections of foreign drug makers in the wake of a litany of problems with the blood thinner Heparin and other products.

“Last year, this nation’s regulatory failures resulted in dead dogs and cats. This year, it has tragically led to the deaths of people,” said Rep. Bart Stupak, D-Mich. “If we don’t make some rapid progress on fixing the foreign drug inspection program, the next melamine or heparin tragedy will soon be upon us.”

FDA Commissioner Andrew von Eschenbach told a House subcommittee that he has asked the administration for more money to conduct inspections, but he did not specify how much. He agreed that more inspections are needed, but not to the lengths Democrats suggested, which is to inspect every foreign firm every two to three years.

“I don’t believe that’s the solution to the problem,” von Eschenbach said. “It’s much more complex, and the solution needs to be much more comprehensive than simply inspecting a facility.”

Rep. John Dingell, D-Mich., said he’s tired of hearing from FDA commissioners about conducting business in new, innovative ways in place of additional financial resources. He said commissioners have talked about the need for the agency to be leaner and meaner. But, it’s turned out that it’s leaner, weaker and less capable of doing its job, Dingell said.

Von Eschenbach said the FDA needs to make greater use of independent companies or foreign regulators to certify that drug firms have good manufacturing systems.

Republican members of the subcommittee were in agreement with Democrats that the lack of foreign inspections is a big problem.

“We have already heard the numbers that show the imbalance in risk priorities, with most domestic firms inspected about every two years, but literally hundreds of foreign firms that have not seen an inspection, if at all, in a decade,” said Rep. John Shimkus, R-Ill. “Clearly these priorities need to be brought closer into balance.”

The Government Accountability Office testified that the FDA was making progress in conducting more inspections of foreign drug manufacturers, but still inspects relatively few facilities.

The agency conducted 30 such inspections in the last fiscal year and plans to conduct at least 50 this year, according to government auditors.

That’s not nearly enough for members of Congress, who point out that there are more than 3,200 foreign drug firms listed by the FDA.

An estimated $10 million has been dedicated for foreign inspections this year.

Concerns about the inspection program were recently highlighted when the FDA learned that contaminated doses of the blood thinner Heparin had probably come through a Chinese plant that the agency had never inspected.

The GAO’s auditors said that it’s just too early to determine the effectiveness of the FDA’s plans for improved oversight of foreign facilities. For example, the agency has said it’s exploring the creation of a cadre of investigators who would conduct foreign inspections, but it has not provided any additional details or time frames.

Also, the agency plans to establish foreign offices in three Chinese locations: Beijing, Shanghai and Guangzhou. Later, it will consider setting up locations in India, the Middle East, Latin America and Europe.

Von Eschenbach said 13 employees would be assigned to China to staff the three offices. Eight would come from the U.S. Five would be local residents more familiar with the country’s customs, language and business practices.

The commissioner said the U.S. program has received support from several different Chinese agencies, but was still waiting final approval from a foreign affairs office.

Rep. Joe Barton, R-Texas, said ballpark estimates from Republican aides indicated that the FDA would need an additional 500 inspectors to get to the point where foreign firms were inspected with the same regularity as domestic firms. The GAO said the cost of such regular inspections would be about seven times the current budget, or about $70 million annually.