“We had to change some things for our practice to stay on top of it,” says Penley, who chairs the Government Relations Committee of the American Society of Clinical Oncology (ASCO). “We assigned a staff member the responsibility of making sure the anticipated needs of each clinic could be met.”

It wasn’t easy. The practice includes more than 50 physicians at multiple sites. “We have places where patients and drugs must come together in a timely manner,” says Penley. The practice’s formulary committee worked out substitution policies where appropriate. When leucovorin and fluorouracil (sold under brand names like Adrucil and Carac) were in shortage, for example, doctors would occasionally substitute capecitabine (Xeloda).

“Xeloda is not a general substitute for leucovorin,” cautions Penley. “Leucovorin and 5-FU [fluorouracil] are often given in combination, and 5-FU was also in short supply. Xeloda was substituted for our colon cancer patients. We also used levoleucovorin [Fusilev], a stereoisomer of leucovorin, which is used primarily in pediatric patients but rarely in adults.” And since levoleucovorin dosing differs from leucovorin dosing, the former could not be substituted in a one-to-one ratio for the latter.

“The dosage calculations for our chemotherapy regimens had to be changed to reflect the different dosing when levoleucovorin was used,” says Penley. “This caused headaches for our IT department, given that all our chemotherapy regimens are in our electronic health records.”

For practices like Penley’s, drug shortages have become a constant thorn. And while shortages have eased in recent months, Tennessee Oncology still keeps a wary eye on the fragile stockpile of medications.

Under the new U.S. Food and Drug Administration Safety and Innovation Act, the FDA will come up with its own early-warning system designed to flag shortages. Drug manufacturers are required to give the feds six-month advance notice when they know one of their drugs will be in short supply. And the agency can use that time to prevent a problem — or at least notify providers that a problem is developing.

“FDA will still be able to use all of the tools we have to prevent and address shortages,” an agency spokesperson said in an e-mail response to a Biotechnology Healthcare query. “However, under the legislation, since companies are now required to notify FDA six months before any discontinuance or interruption of supply of critical medications, we believe we will receive an increased number of notifications of potential shortages from manufacturers. The sooner we receive notices from the manufacturers, the more we are able to do early on, using the tools we have available, to work with the companies to prevent or address the shortage.

“The new legislation will not prevent all shortages,” the FDA spokesperson continued. “Some issues that can lead to shortages may take firms significant time to address, such as sterility problems and other severe problems that have developed during manufacturing.”

Penley and other top officials at ASCO doubt that a notification mandate without penalties for violators will accomplish more than what the FDA has been able to achieve on a voluntary basis over the past year.

“It might as well be voluntary,” says Richard L. Schilsky, MD, chief of the hematology/oncology section at the University of Chicago and Penley’s predecessor as chair of the ASCO Government Relations Committee.

“It’s a huge issue for clinical trials,” says Schilsky. “I used to lead one of the National Cancer Institute-sponsored clinical trial cooperative groups. Over the last two years, that group has issued eight drug shortage notices to participating sites regarding 23 protocols. If you don’t have these drugs, you need to either stop enrolling patients or borrow the drug from someone who does have it. In a couple of cases, the group recommended substitutions.”

The drug shortage issue is far from resolved.

“We get e-mails weekly from pharmacy departments at all the major hospitals in Nashville talking about shortages of one sort or another,” says Penley. “So it’s still a problem.” These days, intravenous narcotics — the kind that are often self-delivered with the push of a button, like hydromorphone (Dilaudid) — are in short supply.

“The big problem is that it’s unpredictable,” says Schilsky. “There’s been no advance warning — that’s really the challenge. Any given week, you never know.” And that leaves an oncologist with three choices: “Omit the drug, delay treatment, or find a different source of the drug.”

“There are still some drugs that we can’t get,” notes Penley. “Doxil [doxorubicin HCl liposome injection], a form of Adriamycin, encapsulated, is still difficult to find. Leucovorin is still in modestly short supply — we’re able to keep a few days’ supply on hand and haven’t had any interruptions for a few months.”

Based on the FDA’s new authority and some actions that he’s seen outside of the FDA, Penley holds out hope that things will get better.

Jeanne Ireland, the FDA’s assistant commissioner for legislation, fired right back, saying that regulatory flexibility — working with manufacturers to speed reviews and recertify plants — helped to prevent 195 shortages last year. When serious safety issues occur at a manufacturer, she noted, the drug maker has to stop production and fix the problem. But shortages have risen steadily over the last few years, she added, even as the flow of FDA warning letters has continued.

At ASCO, no one in charge is taking sides.

“It’s hard to know what led to the improvement,” says Schilsky. “Perhaps the [president’s] order helped spur manufacturers to do better.

“The FDA has given many examples of where its been able to ameliorate drug shortages,” he adds. “There is a variety of things the FDA can do — it depends on what the problem is. If a manufacturing facility is offline and needs to come back online, the FDA can expedite the process to recertify the facility. If raw materials are in short supply, it [FDA] can help manufacturers find new supplies of raw materials. If another manufacturer can produce the product but is waiting to get a generic drug application reviewed, the FDA can expedite the review.”

Penley has heard all the hypotheses, such as the one that says low prices of some generic oncologics have caused manufacturers to walk away from production. Some experts have discounted that argument, he points out. On the other hand, Penley adds, some economic incentives might spur manufacturers to make sure supplies aren’t interrupted.

“There isn’t a comprehensive analysis of the business plan for the production and marketing of generic drugs,” says Schilsky. “There’s a widespread belief that there are few incentives for companies to stay in the game if they encounter significant problems in manufacturing. We have to come up with a business plan for these drug manufacturers that allows them to make enough money to invest in their facilities.”