An ongoing disruption in the availability of widely-used prescription drugs has garnered the attention of lawmakers, among them Sen. Barbara Mikulski (D-Md.), who are now involved in trying to improve the situation and avert a widespread crisis.
In December, Mikulski called for reform to alleviate prescription drug shortages as part of the reauthorization of the Prescription Drug User Fee Act (PDUFA).
Mikulski is a senior member of the Senate Health, Education, Labor and Pensions (HELP) Committee, which is studying drug shortages and their effects.
“I have heard from Maryland hospitals, doctors, nurses and patients that drug shortages are a serious problem with serious consequences,” Mikulski said in recent testimony before the HELP committee. “Maryland hospitals are seeing shortages of over 100 drugs … [d]octors and nurses are forced to either delay care or prescribe drugs that they aren’t familiar with, which oftentimes are less effective, have unknown side effects and can lead to medical errors.”
Mikulski pledged to work toward building a legislative framework with proper enforcement to ensure access to prescription drugs for the nation’s patients and health care providers.
In its most recent online update, the U.S. Food and Drug Administration (FDA) lists current shortages of 108 different drugs. Among them are products including ticlopidine tablets, used to reduce the risk of stroke; tetracycline tablets, which fight bacterial infections and pneumonia; morphine sulfate, used for pain management; and a host of electrolytes necessary to nourish patients who must be fed intravenously.
The next delivery of many of these drugs is expected sometime in April, while others aren’t expected until after July or have been suspended indefinitely. In the case of tetracycline, two manufacturers cannot estimate a release date at this time.
Among the primary reasons listed for drug shortages are manufacturing delays, material shortages, supply issues and increased demand. But economics and even regulatory obligations have also contributed to shortages.
“The FDA has been aggressive in making sure manufacturers follow manufacturing guidelines,” said Masoomeh Khamesian, pharmacy director at Howard County General Hospital (HGCH). “If not, the FDA asks them to stop making the drug, and there’s not much time to give us advance notice when that happens.”
It can be months before a cited manufacturer can correct problems and resume production — if it resumes at all.
“Manufacturers aren’t making a lot of money on older drugs and may decide to stop making them altogether when something like this happens,” Khamesian said.
Another factor is the so-called “grey market,” the influence of which pharmacists say has been growing during the past five years. It involves secondary wholesalers who buy products as soon as they hear rumors of shortages, then resell them at steep markups.
“If I can’t purchase something in the morning, I might get 10 phone calls from wholesalers in the afternoon,” Khamesian said. “If a unit costs 20 cents, they will sell it for $20.”
But James Caldwell, pharmacy director for the Anne Arundel Medical Center (AAMC), said there is a legitimate side to the wholesale industry.
“I don’t know where you draw the line between free market and grey market,” Caldwell said. “We’re sometimes happy to have access to wholesalers because we just can’t find products anywhere else.”
Only three states — Kentucky, Maine and Texas — have enacted price gouging laws specifically addressing secondary wholesalers.
Blame can also go to the pusher.
“With the abuse of prescription drugs becoming a national health problem, the Drug Enforcement Administration has limited the production of controlled dangerous substances used to treat ADHD and severe pain,” said Howard Schiff, executive director of the Maryland Pharmacists Association.
Additionally, the elimination of certain propellants in inhaled drugs has caused an increase in demand for substitutes, Schiff said.
What’s the Alternative?
Drug shortages aren’t predictable and can occur for any type of drug with no rhyme or reason, although the most chronic problems have been seen in the narcotics field.
“If there’s a trend, it’s mostly injectables, older drugs, generics and basic electrolytes, such as sodium, potassium and magnesium,” said Caldwell.
Patients and pharmacies have developed their own workaround solutions, but these are seldom ideal situations. “The drug shortage has caused changes in practice particularly in the acute settings,” said Schiff. “Pharmacies have been scrambling to find suitable substitutes for cancer patients and others with life-threatening diseases.”
In order to avoid panic, he said, many hospitals do make public what drugs are unavailable and what secondary choices have to be made.
According to Mikulski’s testimony, the University of Maryland and The Johns Hopkins University are working with the Veterans Administration to open up their pharmacies to each other to manage shortages.
At HCGH, standard practice is to have a three-day inventory on hand, but sometimes it’s impossible to know what’s unavailable until the day a delivery is expected, Khamesian said.
Hospitals use single-dose injectable vials for safety reasons, but are sometimes forced to draw a supply of single-dose syringes from a multiple dose vial and parcel them out. “It’s a huge burden on the staff, and we only have 24 hours to use it,” Khamesian said. “What’s not used is wasted.”
Progress and Reform
To date, the Senate HELP committee has made progress in working through most of the issues before it.
On Jan. 13, Sens. Tom Harkin (D-Iowa) and Mike Enzi (R-Wyo.), the chairman and ranking committee members, announced an FDA agreement with the prescription drug, generic drug and biosimilar industries on user fees that helps speed the FDA’s review of medicines in order to make them available.
“Moving forward, we expect the FDA and the medical device industry to continue to work together to resolve any outstanding issues quickly so our committee can move forward … to authorize all four user fee agreements in a timely manner,” Harkin and Enzi wrote. “An agreement between FDA and the industry is critical to fostering greater innovation while ensuring that the review process for new medical devices is predictable, consistent and transparent.”
Improved regulatory measures would also be helpful, pharmacists argue.
“I’m in favor of stronger regulations, especially against price gouging,” Khamesian said. “Manufacturers should not just stop making products and not tell anyone; they should work with other manufacturers to make sure the supply continues.”
When it comes to production lines that have been shut down for guideline violations, the FDA could be more helpful in getting production resumed quickly, Caldwell said, adding that abbreviated new drug applications that take less effort to accomplish could also help.
For Maryland specifically, reform is a tough issue to address, Schiff said. “There are few manufacturing plants in the state and only one major distributor at this time.”
Another part of the problem is that production of medications is done in a free market, while dispensing is done in a closed market where pricing is set by insurers, both private and government, he observed.
“Outside of the use of manufacturing incentives,” Schiff said, “the ‘bully pulpit’ is probably the best bet.”