BETHESDA, MD 30 August 2010—Two thirds of the way into the year, 2010 shows signs of being the worst 12-month period ever in which the demand for certain drug products has outstripped supply.
"Already, in 2010, we`re seeing higher-than-normal levels," Valerie Jensen, associate director of FDA`s drug shortages program, said in early August. "We are working on a really large number of shortages right now."
Pharmacists likewise report trouble obtaining many products.
"It`s a huge problem right now," said Wayne Russell, senior director of pharmacy for North Carolina-based group purchasing organization Premier Inc. "We`ve been barraged with requests from our hospitals on a variety of products that either they are unable to obtain at all or cannot obtain adequate quantities."
Russell said some of the most serious recent shortages include emergency-use injectable forms of calcium chloride, dextrose, epinephrine, furosemide, and sodium bicarbonate.
James Stevenson, director of pharmacy services at University of Michigan Health System, also cited shortages of emergency-use prefilled syringes as a growing problem. He said supply problems with 50% dextrose injection have been a major headache for the pharmacy.
"These things are in emergency boxes all over the place," Stevenson said. "And if we have to draw up dextrose in syringes ourselves, they have very short dating on them—usually only about 30 hours. So if you`ve got to distribute these to hundreds of different locations, and they`re only going to be good for 30 hours, now you`re into a practical situation that you just can`t really manage."
FDA`s efforts. Jensen said FDA has tracked drug shortages for the past several years and usually records hundreds of critical product shortages annually. The drug-shortage group`s full-time staff of three works with other divisions in the agency to monitor and help resolve supply issues for products FDA considers to be medically necessary.
Jensen said her group answers questions from practitioners and others about shortages and takes reports about supply problems.
"We`re really happy to receive the notifications," Jensen said. "Sometimes manufacturers don`t report shortages to us, and those notifications are the first reports we receive."
When one or more manufacturers stop making a critical drug product, FDA can contact other makers of the drug and encourage them to increase their production capacity to meet the market`s needs. Jensen said the agency will expedite any necessary facility inspections or reviews so that more product can be manufactured.
"If they need any FDA assistance, we`re willing to supply that for these products," Jensen said. "We`re constantly doing it."
Even better, she said, is for a manufacturer to contact FDA about impending issues that necessitate the use of additional manufacturing sites to avoid disruptions in supply. When that occurs, Jensen said, FDA "can work proactively to get the additional site on board before there`s a shortage."
But Jensen said FDA`s authority over drug shortages is limited and not always understood by the public.
"We do hear that people think that we can require a firm to continue to make a product, or that we could require a firm to increase production if there`s a limited capacity," she said. "Those are two things we can`t do. Another thing we can`t do is require firms to report shortages to us. We really want that information, but we can`t require it. So information that we receive is always voluntary."
Manufacturers who are the sole source of a medically necessary approved drug product are required to notify FDA six months before discontinuing that product. But the agency cannot compel the manufacturer to keep the product on the market after that time.
Safety concerns. Shortages of high-risk medicines like emergency drugs, pain medications, and anesthetic agents are a potential safety problem because of the resultant need to use unfamiliar product presentations and strengths, Stevenson said.
He recalled when premixed i.v. heparin bags were unavailable because of problems with raw materials. The hospital obtained an alternative product—a commercial i.v. additive system that requires activation before infusion.
"Because we didn`t have the regular product, a nurse took one of these, didn`t activate the heparin, and hung the bag. And so for a period of time a patient got no heparin," Stevenson said.
He said this patient wasn`t harmed but could conceivably have died as a result of the mishap.
The Institute for Safe Medication Practices in late July highlighted similar shortage-related problems and called them "a key patient safety concern in healthcare today."
Bona Benjamin, ASHP`s director of medication-use quality improvement, said in mid-August that ASHP and FDA staff were scheduled to meet later that month to discuss patient care issues precipitated by drug shortages and find ways to anticipate and manage shortages in cooperation with the agency.
Work-force repercussions. Stevenson said managing shortages became so time-consuming for the pharmacy staff that the hospital hired a full-time pharmacy technician this year to take on the task. But other staff members continue to be affected by shortages.
"It`s taking a tremendous amount of time of my drug information staff, my contract and purchasing people, and the pharmacists and technicians who run what we call our medication-use systems, which is basically our automation," Stevenson said.
In the health system`s highly automated environment, he said, changing products because of a shortage requires separately updating the computerized prescriber-order-entry system, bar-code-assisted medication administration system, and inventory system.
"Each one has its own database. You have to go in and adjust each one of them, make sure they`re all in sync. So it`s a huge challenge," Stevenson said.
Russell said Premier`s staff similarly spends an increasing amount of time dealing with product shortages and finding alternative product sources. He said when production was halted at Teva`s Irvine, California, manufacturing site in 2009 because of quality issues with propofol, supply disruptions occurred for other drug products made at the factory.
Russell said Premier had to find and contract with an alternate supplier for each affected product and ensure that the suppliers could meet market demands for the products.
Teva did not respond to requests to discuss production issues at the Irvine plant for this story.
Causes. Jensen said manufacturers` decisions to discontinue older products, especially injectable medications, are a major reason for drug shortages. She said the other main cause is manufacturing problems, like the "particulate issues and sterility issues" that led to the propofol shortage.
Jensen said FDA`s goal for resolving such quality-related shortages is "to minimize any risks that are involved with the products so that they can be returned to the market as quickly as possible."
Although Teva no longer makes propofol, Hospira in August began releasing small amounts of the drug, and APP Pharmaceuticals is no longer the sole manufacturer of propofol products for the United States, according to ASHP`s drug shortages resource center.
"Hopefully, we`re going to see increased supplies of propofol now that we have two manufacturers back on the market," Jensen said.
