Drug shortages are putting pharmaceutical companies on the hot seat.

Last week, medical-products giant Johnson & Johnson assured shareholders that it is doing everything possible to resolve a shortage of a chemotherapy drug called Doxil, which is used by patients with ovarian and other sorts of cancer.

Ben Venue Laboratories Inc. manufactures Doxil under contract with Johnson & Johnson, and it was Ben Venue that decided last year to halt production to handle overdue equipment maintenance at an Ohio plant.

Even so, Johnson & Johnson’s CEO was the one sounding contrite last week.

“We’re looking for any type of quality, high-quality source that we can possibly come up with or other ways to get that product to the market,” William Weldon said during a conference call with analysts. “We do realize how critical (Doxil) is for individuals, and it is one of our highest priorities.”

Patients hope that’s the case, but skepticism is growing as the medication shortages persist. Despite arguments to the contrary from manufacturers, questions linger about the role economic decisions are playing in both creating shortages and the failure to get them resolved.

“I have to believe that if we represented a bigger population – that was more of a source of revenue for the drug companies – maybe they would take more action,” said Kathleen Gavin, executive director of the Minnesota Ovarian Cancer Alliance, which has heard from many women affected by the Doxil shortage.

Johnson & Johnson officials said last week that they don’t expect the Doxil shortage to be resolved until very late this year. The company’s Janssen subsidiary issued a statement responding to some of the questions raised about the shortage.

“Some have challenged us, asking if our Doxil shortage is financially motivated in any way,” the company said. “We appreciate this opportunity to tell you that this is absolutely not the case.”

Most drugs don’t experience shortages in the United States. Even so, the number of drug shortages tripled between 2005 and 2010, according to a Food and Drug Administration report on shortages published in the fall.

Nearly half of the shortages stemmed from quality problems at manufacturing facilities, according to FDA. Manufacturing and shipping delays, as well as shortages of active pharmaceutical ingredients, explained another 25 percent of shortages, the agency said. Business decisions by manufacturers to halt production were factors in 8 percent of cases.

In its report, FDA said it has worked with manufacturers to prevent more than 100 shortages in the past two years. The agency said it had frequently asked other firms to increase production or worked with manufacturers to find ways to mitigate the dangers of products with quality problems.

PROBLEM GENERICS

But comprehensive solutions remain difficult to find, in part because so many of the shortages have involved generic, sterile injectable drugs.

“The production capacity of generic manufacturers is expanding only slowly, the infrastructure requirements to produce these drugs safely are significant and updating aging manufacturing facilities will require time and money,” the FDA report stated. “Companies operating at full capacity may not be able to manufacture a drug in shortage without dropping production of another product, potentially producing a secondary shortage.”

Total sales revenue from generic injectable products grew from about $1.5 billion in 2001 to $4.6 billion in 2010, a 251 percent increase after controlling for inflation, according to FDA.

“These data suggest that the overall market for generic injectables is robust, but do not shed light on the profitability of individual drugs,” the FDA report stated. While demand has grown, manufacturing capacity has stayed the same, so existing facilities operate near capacity, the report said.

The drug shortage issue is legitimately called a “crisis,” said Ralph Neas, president of the Generic Pharmaceutical Association, a trade group in Washington, D.C.

But Neas stressed that most shortages are not caused by manufacturer decisions to voluntarily discontinue supplying products. And he insisted that drug companies are not deliberately reducing the supply of medications to drive up prices.

Generic manufacturers believe that FDA could do more to streamline the process by which the agency gives approval for companies to use alternate suppliers of raw materials or alternate manufacturing facilities, Neas said.

“The business of the generics is to produce generic medicines, whether they are sterile injectables or other kinds,” Neas said.

U.S. Sen. Amy Klobuchar, D-Minn, introduced legislation last February that would require more communication from manufacturers in situations that could lead to shortages. President Barack Obama issued an executive order last year that advanced some parts of the bill, but Klobuchar said her legislation is still needed because the issue “appears to be getting worse.”

Among other things, the bill would require all manufacturers to notify the FDA of factors that could lead to shortages. Starting in December, the agency started to require manufacturers that are the only sources of particular drugs to provide early warnings.

Individual manufacturers are stressing their commitment to eliminating shortages.

In response to questions about shortages at Teva Pharmaceuticals, a spokeswoman was quick to point out that Teva had to stop production of most injectable products due to a problem at a manufacturing plant in California.

“In mid-2011, we began slowly ramping up production of these products again, but it is taking a while to resume full manufacturing at the facility,” spokeswoman Denise Bradley wrote in an email.

One of the most prominent shortages last year involved a chemotherapy medication called cytarabine, which is used in many childhood leukemia cases. Hospira Inc., based in suburban Chicago, had trouble producing the drug because of problems with manufacturing it as well as an ingredient shortage.

Hospira identified the root cause of the manufacturing problem and moved to get its version of cytarabine back on the market in March 2011, said Daniel Rosenberg, a company spokesman, in a prepared response to questions.

“Because of our ramp-up of production, Hospira is now supplying a larger portion of the market than we did prior to the shortages,” Rosenberg said. “Hospira is investing hundreds of millions of dollars and taking action to address shortages by increasing capacity at existing facilities, building additional capacity and improving our manufacturing plants.”

SHORTAGES, COSTS

But until that new capacity comes on-line, health-care providers and patients will struggle with shortages. A survey conducted by the American Society of Health System Pharmacists indicated that hospital pharmacists are spending 8 to 12 additional hours per week dealing with shortages, work that costs the health care system about $216 million a year.

At the Minneapolis-based Fairview system, pharmacists have coped with shortages by regularly holding conference calls to discuss how they can shift drug supplies across the clinic system to match supply with demand. Purchasing drugs has become more complicated, too.

“No one wants to purchase so much that they’re causing a strain for other people trying to get the drug,” said Darcy Malard Johnson, the oncology pharmacy program manager with Fairview Pharmacy Services.

At Minnesota Oncology, one of the region’s largest cancer centers, patients have been receiving smaller doses of a drug called leucovorin as part of their chemotherapy. Clinicians at the cancer center have found studies suggesting that the smaller dose still is beneficial, but the situation is not ideal, said Jan Merriman, director of clinical and pharmacy services.

The big issue now, however, is the Doxil shortage. Without the drug, doctors have fewer choices when prescribing a chemotherapy regimen for patients, Merriman said.

For women with ovarian cancer, there are alternative chemotherapy drugs to Doxil, said Gavin of the Minnesota Ovarian Cancer Alliance. But for some women, Doxil has a unique combination of effectiveness and minimal side effects.

“Quality of life is really important,” Gavin said. “If you have a drug that is going to stabilize women, possibly make their tumor regress and they’re possibly going to be able to work or take care of their children or participate in daily living activities – that is really significant.”

Constance Fuller, 63, of White Bear Lake is one ovarian cancer patient having to make do without Doxil. Drug shortages also have made it difficult for Fuller to fill prescriptions for a painkiller as well as the drug Ritalin, which she takes to boost her energy.

“It’s frustrating,” Fuller said. “I guess we are a third-world country now.”

Christopher Snowbeck can be reached at 651-228-5479. Follow him at twitter.com/chrissnowbeck