Nutritional Drug Shortages Take Toll on The Smallest Patients

June 14, 2013— -- Finley Owens will be 3-years-old in July. But he won't be gorging on birthday cake or polishing off a slice of pizza at his party. Finley suffers from a rare condition called hypoganglionosis, where his intestines lack enough nerve endings to fully digest food.

As a result of his condition, Finley subsists almost entirely on intravenous nutrition drugs called total parenteral nutrition, or TPN. At night, his mother, Nicole Gerndt, hooks him up to pump that steadily infuses his blood with a white liquid concoction made of essential fats, vitamins and minerals over 10 hours. The liquid goes straight into Finley's vena cava, the largest vein in his heart.

"Sometimes in the morning he's up and still attached," said Gerndt. "This morning at 5:30 he wanted to get out of bed. "We'll say, 'You have your line [you have to wait].' ... He'll say 'Why?'"

When this system works properly, Finley is able to spend his daylight hours like any other kid. He can play in the dirt with his favorite toy cars and obsess about fire trucks. But when this finely-tuned routine is disrupted, Finley is at risk for suffering a host of nutritional ailments including anemia, calcium deficiency and generally feeling miserable.

Gerndt said that at the end of 2012 she began to get calls from the pharmacy that supplies Finley warning her that core ingredients in Finley's TPN, such as calcium, phosphate and selenium, were becoming scarce. Without these nutrients Finley is at a higher risk for suffering a nutritional deficiency during a key growth period.

There are only a few providers of TPN in the United States. The drugs are difficult to manufacture and if one batch of critical TPN components like phosphorous or calcium goes sour it can send ripple effects through the industry as another supplier tries to pick up the slack by filling the additional orders.

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At the end of last year, one critical supplier of TPN, American Regent/Luitpold, temporarily shut down production to deal with quality control issues, according to the Food and Drug Administration. It is not completely clear that the shutdown of American Regent/Luitpold led to shortages in Finley's medication, but the FDA said the company was the sole provider of many TPN components and that other manufacturers of TPN had difficulty supplying additional orders that were supposed to be produced by American Regent/Luitpold.

Calls to American Regent/Luitpold were not immediately returned.

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Patients reliant on TPN range from adult cancer patients unable to eat solid foods to premature infants lacking fully formed digestive systems. Many patients like Finley have gastrointestinal motility disorders, meaning they can't properly digest food, and rely on TPN to get all or most of their nutrients.

Pharmacists describe the TPN shortages in recent months as extreme. Dr. Steve Plogsted, a pediatric pharmacist at Nationwide Children's Hospital in Columbus, Ohio, works with American Society for Parenteral and Society (A.S.P.E.N.), is concerned that continued shortages will not only put patients in immediate danger but could lead to long-term health effects like bone malformations from calcium deficiency or stunted growth from a lack of zinc.

"People think it's just nutrition so it's no big deal," said Plogsted. "We're trying to allocate what we can. We give newborn babies what we can, because they don't have any stores. ... We don't know the long-term outcome for these little guys

A list of the TPN drugs that have waxed and waned over the last few years can sound like a periodic table pop quiz, with phosphorous, zinc, copper, selenium and chromium all making appearances.

Lose one essential element and you can't just replace it with a Flintstone vitamin. Unlike a meal, there are no extraneous components of TPN and the different components are carefully calibrated to provide people with the exact necessary nutrients to survive.

Phosphate helps muscles contract and is vital for patients on respirators, zinc helps people process specific enzymes, chromium joins up with carbohydrates so you can process sugars in the body. Lipids or fats are particularly critical for premature infants who have no additional nutrient reserves.

According to Gerndt, Finley's TPN has been missing calcium, selenium and phosphate at various times. As a result, Gerndt had to give him supplemental nutrition through his gastronomy tube, a tube in his abdomen that goes directly to his stomach. This means 9 times per day Gerndt has to wrangle Finley and inject a total of six ounces of medication into his stomach. Since Finley's digestive system isn't fully functioning, she worries that he isn't absorbing all the nutrients he receives through the g-tube.

In recent weeks, Gerndt said, Finley has become more lethargic and complains about his stomach becoming tight from the medication.

"We just try to focus on every day. I'm all choked up. It's just hard because it's not like [these drugs] don't exist," said Gerndt. "It is draining because life is challenging enough and this makes it more challenging."

In May the FDA announced it that they would import three additional TPN components from Norway for use in the U.S and expected to import others to alleviate the shortages.

Critical drug shortages have become a growing problem in the U.S. for the last few years. There are currently 238 drug shortages, according to the American Society of Health-System Pharmacists. A 2011 Associated Press review of industry reports found that there had been at least 15 deaths from drug shortages in the prior 15 months.

In June 2012, the FDA came under fire in in a report from the U.S. House of Representatives Committee on Oversight and Government Reform that cited the FDA's actions as a contributing factor in the large number of drug shortages. The report found that the FDA had sent a high number of warning letters to manufacturers, an increase from 474 letters in 2009 to 1,720 letters in 2011, which led to multiple major manufacturers going through remediation at the same time, which severely narrowed supply lines as they shut down manufacturing.

The report also found that the rise in regulation coincided with manufacturers having less financial incentive to make generic, injectable drugs. The report said that was partly caused by hospitals and TPN providers using group purchasing organizations, which could negotiate lower prices from manufacturers, and the implementation of the Medicare Modernization Act in 2003, which lowered the prices Medicare would pay for generic injectable medications.

Daniel Rosenberg of Hospira, a drug manufacturer the FDA cited as helping to provide supplemental drugs after the American Regent/Luitpold shutdown, wrote in a statement that the current shortage was related to the shutdown, "and the difficulty of ramping up production to cover for the unanticipated loss of production from that manufacturer."

Rosenberg did not address any other reasons for continued TPN component shortages.

FDA spokesman Christopher Kelly said that while the FDA can work with companies like American Regent/Luitpold to minimize the effects of the shortage, they do not have the power to demand manufacturers produce certain drugs or the ability to ensure the resulting product is safe for use.

"The reasons for drug shortages are complex and often outside of FDA's control. For example, the majority of drug shortages are caused by a breakdown in quality and manufacturing processes," said Kelly, citing problems with sterility or particulates in drugs as being common problems. "In fact, about 75 percent of drug shortages are caused by manufacturing issues."

As frustrating as the shortages for TPN have been for Finley and his parents, Finley's gastronomy tube, or g-tube, provides his parents with a secondary means of giving him nutrients. For other patients, such as premature infants lacking fully developed digestive systems, there is no back-up plan.

In neonatal and pediatric wards, pharmacists and doctors have had to make difficult decisions about who gets the TPN components and who goes without.

Plogsted said neonatal patients virtually always have the highest priority since they have no additional nutritional stores, but, in theory, this can mean not giving nutrients like zinc, key for growth, to a full-term infant with a heart problem.

Petra Cober, a neonatal pharmacist for the Akron's Children's Hospital, said that, with a lot of planning and extra work, she and her team have been able to stay "a couple of inches ahead of the shortages."

"We're limping by on the skin of our teeth," said Cober. "We have to dedicate a ton of time and resources to maintain that ability when it could be better spent working on other kids."

Cober said she and her team often meet with doctors to decide ahead of time which patients absolutely must have the nutrients and how other nutritional options, such as oral dosages of certain elements, could be used to keep all patients healthy. When a patient is on a lower dosage of a certain nutrient, it often means they have to undergo additional tests to ensure their health isn't compromised.

Additionally, the TPN shortages have been so severe in her region that pharmacists from nearby pediatric hospitals meet periodically to swap shortage stories and, if the shortages are really dire, they swap vials of different nutritional drugs to ensure no hospital is completely lacking an essential nutrient.

At one point after hearing about an impending lipid shortage, Cober purchased special oils, "as the emergency back-up of the emergency back-up," that could be used on some premature infants to provide them with lipids. It's a medical technique that became outdated when TPN was invented and that most of the doctors in the neonatal unit were unfamiliar with. Cober said she has never used the oils and is unlikely to do so, but they're still in her office in case there is an emergency.

"It's definitely been a struggle for [doctors] to understand," said Cober. "They really want to know why all of a sudden this went so south. When [medicine like] phosphorous is the crust of the earth, why don't we have something readily available?"

Cober said that in recent weeks the drug shortages have slightly eased and she is hopeful that the FDA imports from Norway were not a one-time event and that continued imports would help completely alleviate the shortages.

For Finley, Gerndt said she is glad that the FDA had allowed imports, but found no sign that they would significantly help her son.

The week after the FDA announced the Norway imports, Gerndt was told by her home health care pharmacy that there were no trace elements, including zinc and copper, available for Finley's TPN.

"That was one where I was like, 'They got to be kidding me,'" said Gerndt, who talked to her doctors about her concerns. "[I said], I think we're over estimating what Finley can take."