The prescription drug Dopamine is so valuable to Dayton Children’s Hospital that what is left of its dwindling supply is kept in a vault, accessible only by the medical center’s pharmacists.
The drug isn’t the only one proving difficult to keep in stock; it is one of hundreds in short supply nationwide.
“When you start hearing about life-saving medications not being available, that gets really scary,” said Nancy Severt, pharmacy operations manager at Dayton Children’s.
Drug shortages have been commonplace for years, but the problem has grown more serious at hospitals and Emergency Medical Service agencies. According to the U.S. Food and Drug Administration, 56 drug shortages were reported in 2006; by 2011, the number had climbed to 251. The FDA’s list includes drugs that have “the greatest impact on public health.”
The shortages have been felt in Clark County as well, more by first responders than by Springfield Regional Medical Center.
“Ironically, my buyer just put out a list of shortages today, and it is the shortest list I have had since I started here in June 2012,” said Pam Allen, director of Pharmacy Services for Community Mercy Health Partners. “We have not had the problems we have historically had.
“There are still some (problems),” Allen admitted. “I have 18 items on the list. But to have only 18 when I have historically had 30-40 is a welcome situation.”
Reasons for increased shortages include fewer manufacturers as some exit the market; quality-control issues and scrutiny by the FDA, which can shut down production; product recalls; increased demand; and a lack of raw materials.
Allen said thankfully Community Mercy doesn’t currently have a shortage of drugs like Dopamine.
Being smaller can help.
“We are a 254-bed hospital, so you don’t have the volume need that a 1,000-bed hospital has,” said Allen. “It can be helpful, but it can also limit what you can get because you haven’t been purchasing it in the past.”
The vast majority of drugs deemed to be in short supply are produced by generic drug companies. For example, 64 entries were logged on the American Society of Health-System Pharmacists website the week of Dec. 9. Thirty of the hard-to-get drugs were made by drug giant Hospira, a suburban Chicago company that recently pledged to invest $1 billion in its operation.
The ASHP site currently has more than 300 entries listed under “current shortages.” Updated daily, the list includes recognizable names such as heparin, DTaP vaccine, dextrose and caffeine. It also includes exotics such as the black widow anti-venom.
“Do we have a shortage of stuff that matters? Yes, we do. There’s some stuff (on the list) that scares the hell out of me,” said Ernest Boyd, executive director of the Ohio Pharmacists Association.
Dan Gueth, director of pharmacy at Miami Valley Hospital, said he grapples with drug shortages virtually every day.
“It’s been a nightmare over the last two years,” said Gueth, who has been on the job since 1985. “I might have 10 products on my list, but it’s likely I’m going to be told about another back order and we have to scramble.”
Hospitals have buyers who search for additional supplies from drug manufacturers, wholesalers and other medical centers when shortages persist.
But sometimes, as with the dwindling supply of Dopamine at Dayton Children’s, extreme measures are put in place.
“We have vials of it and make up drips specifically for that patient,” Servert said of the drug which sustains blood pressure in critically ill patients. “We’re down to probably five vials of Dopomine. We were able to get the adult version of premix bags, so just to make sure it doesn’t get intermixed with anything else I’ve got it locked up in a vault that only the pharmacists can access.”
The hospital also worries about electrolytes and other injectables used to make formula to feed babies. It faces decisions on what patients get certain pain medications when they are not in abundant supply.
Sometimes, care-givers have to pivot when a drug is discontinued. That was the case in the spring when the supply of the popular sedative chloral hydrate ran out after two drug companies stopped making it in the past five years.
“The doctors liked the way it acted, they liked the way it didn’t linger for hours and hours,” Severt said. “The drug companies were making it, but the demand wasn’t very high so they decided, ‘We’re not selling enough to make any money.’ Our institution was very reliant on it.
“We had to start ordering it as a raw powder, so our doctors had to find alternatives. Now … we do our own testing, compounding and make sure we have a viable shelf life for it.”
Dayton Children’s is part of a network of more than 30 hospitals that work together to monitor shortages and make timely purchases.
“As soon as I know it’s short in Dallas, I start shopping for that product,” said Kevin Myers, the hospital’s pharmacy purchasing manager.
Experts say the so-called “gray market” is one of the factors that is driving up prices. Manufacturers generally sell their products to wholesalers, which then sell to hospitals. But secondary wholesalers also buy drugs and charge higher prices 0n the drugs they buy.
“The gray market, in which companies are charging up to 1,704 percent more for a product than what a facility would have to pay, definitely needs to be monitored and price-gouging eliminated,” said Donna Smith of Arizona-based Avella Specialty Pharmacy.
A bill designed to clamp down on the gray market is pending before a House subcommittee.
Hospitals aren’t the only ones being squeezed by drug shortages. First-responders have fought shortages for years.
Pain-killers such as Morphine and Fentanyl are staples in ambulances and medical helicopters. But there’s no guarantee the drugs will always be available.
“Those shortages do translate into our environment,” said Springfield Fire Rescue Division Chief Nick Heimlich. “The point I would make is we are probably more vulnerable to that … because of our uniqueness of usage.”
Heimlich explained why:
“One is the drug itself is not available. The other is the formula of a particular drug is not available.
“In the hospitals, (getting the drug from) a multi-dose vial is not a problem. In our environment, we use a lot of higher-end, more-refined manufactured products. Things like pre-filled syringes. They are especially beneficial for us, because we don’t have to spend as much time getting the drug to the patient that critically needs it.”
The shortages can be frustrating.
“That’s a function of the business plan of the drug manufacturer,” said Heimlich. “For example, a pre-filled syringe is the most expensive form of the drug. So it has the highest manufacturing cost.”
So manufacturers have to weigh how much to produce with cost-effectiveness.
“You also have to take into account shelf life,” Heimlich added. “They don’t want to produce excess doses that will die on the shelf.
“Most (drug companies), like any other free market enterprise, look at your profit margin and others factors and am I going to be able to survive in this market.”
Shortages at hospitals impact the first responders as well.
“In Clark County, our drugs are restocked by the pharmacies at the hospitals,” he said. “So we rely on them a lot. We work together.”
But the impact has yet to be widespread in Springfield, and patient care has yet to suffer.
“Our guys see it on an individual basis,” said Lt. Brian Leciejewski, training lieutenant for Springfield Fire Rescue Division. “They are aware that there can be an occasional drug that won’t be in the drug bag.
“But I’ve not been made aware of anything that has impacted patient care,” he continued. “We’re always going to have that medication that is going to take care of the problem; it may not be the first choice of provider, but it will take care of the problem.”
It is a scary problem, though.
“Most definitely,” Leciejewski said. “We’re hoping that the powers-that-be make the right decisions so that we can give the best patient care. That is not always guaranteed.”
Dr. Carol Cunningham has served for nearly 10 years as state medical director for the Ohio Department of Public Safety Division — EMS. She constantly worries about running out of injectables used to care for cardiac resuscitation, pain control and the management of seizures.
“It happens every week, there is something short,” she said.
Manufacturers leaving the business reduces the supply of some drugs. The Ben Venue Laboratory in suburban Cleveland ceased production and is shutting down due to quality-control issues. Its closing will not only cost the small town of Bedford more than 1,000 jobs, it will mean one fewer big player in the drug business.
One of the drugs previously made at Ben Venue was Doxil, a popular cancer-fighting injectable. Ben Venue was the only plant in the U.S. that made the drug, but an ongoing shortage was softened when a company in India gained FDA approval earlier this year to produce a brand-name substitute and a generic version of the drug.
Quality-control issues are the most prevalent reason for drug shortages. According to the FDA, manufacturing issues and delays or capacity issues accounted for 77 percent of sterile injectable shortages in 2012. Increased demand triggered 7 percent of shortages, as did discontinuation of products.
“The economic downturn in 2008 precipitated the issue. Manufacturers cut back on spending and some drugs that didn’t make money were discontinued, and as a result the production shortages became exaggerated,” said Robert Weber, Administrator for Pharmacy Services at the Ohio State University Wexner Medical Center and Assistant Dean in the College of Pharmacy.
Generics and savings
Generic drugs save consumers big money — $1.3 trillion in the past decade according to the Generic Pharmaceutical Association. But they also undercut brand-name drugs, which can lead to shortages if the brand-name drug companies cut production.
Drug patents expire after 20 years, but exclusive marketing rights can expire much sooner, leaving a small window for brand-name products to reap big profits to fund research and development. Exclusivity, according to the FDA, was “designed to promote a balance between new drug innovation and generic drug competition.”
“Generic companies — Bedford, American Regent — jump in and start making a product when it comes off patent,” Dayton Children’s Myers said. “That reduces the price, and all the sudden they have problems manufacturing it. It just disappears.”
Generic companies also undercut each other, which leads to lower profit margins. Still, some think they should see past the bottom line.
“I believe that manufacturers have a moral and ethical responsibility to continue making lifesaving drugs or drugs that can medically alleviate a severe disease, and to make them affordable for patients and payers when possible,” Smith said. “However, many times the shortage is out of their control, and any negative economic impacts cannot be dismissed.”
Generic drug-makers contacted for this story would not make executives available to answer questions. A Hospira spokesman said the company is “investing hundreds of millions of dollars to help prevent future shortages,” and is working to increase capacity at existing facilities, build additional capacity (Hospira is adding a plant in India), and strengthen its supply chain.
More production would be good news for Myers, who used to see a couple drug reps every day. Now he sees that many in a week.
“I had a Bedford sales rep that came in every week and she’s gone. American Regent, she’s gone. They have nothing to sell,” he said. “They’re keeping a low profile because they don’t like to get pounded. When they come in here, we’re all over them because we need the product.”
One solution that could ease the drug shortage problem is more lenient expiration dates. The dates are set by the drug companies, but some health districts around the country have extended them on some products. That could only happen in Ohio if all medical agencies agreed.
Proponents of such a policy say there is no harm in using drugs that are nearly full strength.
“I think the industry would be very interested in that,” said Community Mercy’s Allen. “The actual pharmacies would have a interest in that. Most drugs, even if they are expired can be used past an expiration dates. But legally you can’t. It’s a potency issue. There’s a safety cushion.
“It would help the industry and from a financial standpoint.”
There is a program already in place that allows for the use of expired drugs. The U.S. Department of Defense’s Shelf Life Extension Program, launched in 1986, extends the dates on some drugs in the federal stockpile. Those drugs must be tested periodically by the FDA, a cost most public agencies could not stomach.
The Ohio Department of Health distributed a survey this fall to all EMS agencies asking for a list of drugs critical for medical care, with an eye on pushing for more flexible expiration dates.
“The frustrating thing for us as physicians is the manufacturers determine the expiration date, not the FDA,” Cunningham said.
“Even if they’re 95 percent effective, if that’s the only thing out there and if you have one of those conditions — you’re in cardiac arrest or you’re having a seizure or real pain — do you really care if it’s 95 percent, as long as it’s not contaminated?”
Effective drugs taken off shelves when they hit their expiration dateraise medical center costs.
“You can’t flush them down the toilet or throw them in the trash, so we’re paying to get rid of something we’d like to keep that’s still good and useful, and in some places we don’t have a replacement for it,” Gerstner said. “This makes sense how?”
Meanwhile, hospitals and first-responders search for alternatives if their first choice is not an option, at times putting patients in harm’s way.
“I’ve heard in the past few years of surgeries being postponed or cancelled because of certain meds not being available,” Boyd said. “I wouldn’t be scared to ask your hospital in advance if they have the meds you need.”
Drugs in short supply
The American Society of Health-System Pharmacists lists more than 300 drugs on its drug shortage bulletin. Here are some of the drugs on the list, with their uses:
Atropine: Used to stabilize heart rate after heart attack or during surgery.
Caffeine & Ergotamine Tartrate: Caffeine injectable formulation for headache.
Epinephrine injection: Emergency treatment for severe allergic reactions.
Dextrose 50% injection: Pure form of sugar often used to help diabetics.
Glycopyrrolate: Treats peptic ulcers, dries mouth for surgery.
Heparin infusion bags: Blood thinner that prevents clots in blood vessels.
Methylergonovine: Used to stop hemorrhaging post-delivery.
Nicardipine: Used for hypertension and for neuro-critical care patients.
Prochlorperazine: Used for severe headache in ER, although caffeine was original agent of choice.
Propofol: Sedative for surgery and other procedures.