Medication shortages threaten cancer care
The oncology community and the FDA tackle ongoing drug shortage problem
Multiple groups are attempting to alleviate the nation's drug shortage problem, but experts predict it is not going to be solved any time soon. As a result, cancer patients and those who care for them will face continuing challenges in obtaining medications vital to their treatment.
“The number of drugs in shortage is increasing substantially every year,”says Len Liehtenfeld, MD, deputy chief medical officer of the American Cancer Society (ACS). “We're at the beginning of a journey—we're nowhere near the end.”
As the shortage problem continued to escalate over the past year, the issue received increasing attention from President Barack Obama, Congress, and the US Food and Drug Administration (FDA). In October 2011, the FDA released a report, A Review of FDA's Approach to Medical Product Shortages,which highlighted some key statistics:
The number of drug shortages has tripled from 61 in 2005 to 178 in 2010.
Sterile injectables accounted for the majority (80%) of the 127 studied drug shortages in 2010 and 2011. The major therapeutic drug classes that experienced shortages included oncology drugs (28%), antibiotics (13%), and electrolyte/nutrition drugs (11%).
The leading primary reasons for the shortages were problems at the manufacturing facility (43%), delays in manufacturing or shipping (15%), and active pharmaceutical ingredient shortages (10%).
Manufacturing quality problems that have resulted in shortages have included serious issues such as findings of glass shards, metal filings, and fungal or other contamination in injectable products.
In the shortages studied, the FDA's most common actions were asking other firms to increase production, working with manufacturers to mitigate quality issues, expediting review of regulatory submissions, and exercising regulatory discretion in controlled importation of similar products approved abroad but not in the United States.
Oncology Medication Shortages
Because oncology drugs (primarily older injectables) have been so highly affected by shortages, organizations such as the ACS and American Society of Clinical Oncology (ASCO) have taken an active interest in addressing the problem. ASCO, for example, was one of the cosponsors of a 2010 Drug Shortages Summit, which also involved the American Society of Health–Systems Pharmacists, the American Society ofAnesthesiologists, and the Institute for Safe Medication Practices. Some of the recommendations that came out of the summit have since been incorporated into legislation being considered by Congress that aims to tackle elements of the shortage problem. Meanwhile, the summit sponsors have continued to call attention to the issue in the media and among government leaders.
“For cancer patients, the problem is there often is no ‘work-around’ drug, meaning for some there literally are no substitutes,” says Michael Link, MD, president of ASCO. “The worst-case scenario—the one we fear the most—is being in the unconscionable position of having to triage which of your patients gets a certain drug, and we do have documented eases of that happening.”
Among the drugs that have faced critical shortages since the problem began are cytosine arabinoside (Cytarabine), used mainly in the treatment of cancers of white blood cells, such as acute myeloid leukemia, in children and adults. The FDA stepped in to get more supplies of the drug to help alleviate the problem in the short term, but shortages continue.
That shortage was particularly frustrating for Dr. Link, a pediatric oncologist. “We can cure about 80% of our patients,” he says, “but when virtually all of these curative drugs are in short supply, it's horrible knowing you can't begin the best treatment”
The oncology drug shortages also have led to delays in starting or continuing therapy, substitutions of less effective or potentially more toxic regimens, patients having to switch physicians or locations in order to get a particular drug, and disruptions or changes to clinical trials, which ultimately affects research progress. In addition, many observers have noted that “gray markets” for particular drugs have emerged, leading to price gouging.
“When people are told, ‘If you don't get the drug, you're going to die,’ they're paying the penalty get the drug,” says Dr. Lichtenfeld.
According to the FDA, the ranking member of the House Committee on Oversight and Government Reforms announced an investigation into potential gray markets, citing a report that a leukemia drug with a typical contract price of US $12 per vial was being sold at US $990 per vial. Meanwhile, a Premier healthcare alliance report released in August 2011 estimated that the typical gray market vendor marks up prices by an average of 650%.
Federal Groups Take Action
As the situation worsened, Congress, the FDA, and President Obama all took steps to address the problem. The FDA, for example, held a September 26, 2011, public workshop on the matter, bringing together multiple groups to discuss key issues and potential solutions. On October 31, President Obama issued an executive order that directed the FDA to broaden reporting of potential shortages of certain prescription drugs and to farther expedite regulatory reviews that can help prevent or respond to shortages. The order also called for the FDA to work with the Department of Justice to examine whether potential shortages have led to illegal price gouging or stockpiling of life-saving medicines.
The executive order directs the FDA to take additional steps to require manufacturers to provide adequate advance notice of manufacturing discontinuances or other actions that could lead to critical shortages. It also requires the FDA to expand its efforts to expedite review of new manufacturing sites, drug suppliers, and manufacturing changes to help prevent shortages. In addition, the Obama Administration:
Sent a letter to drug manufacturers reminding them of their legal responsibility to report to the FDA the discontinuation of certain drugs and to voluntarily notify the FDA about potential prescription drug shortages in cases where notification is not currently required.
Increased staffing resources to the FDA's Drug Shortage Program to enhance the agency's ability to prevent and mitigate drug shortages as a result of increased early notification by manufacturers.
Expressed support for bipartisan legislation in the Senate (5 296) and House of Representatives (HR 2245) that would require all prescription drug shortages to be disclosed and give the FDA new authority to enforce those requirements.
Released 2 reports: the one previously mentioned from the FDA on its role in monitoring, preventing, and responding to shortages as well as another from the Department of Health and Human Services Office of the Assistant Secretary for Planning and Evaluation that assesses the underlying factors leading to drug shortages.
“The executive order is a step in the right direction, but will it solve the problem? I don't think so,” Dr. Lichtenfeld says. “Ultimately, we need more manufacturers involved and committed to the transparency of information that's available:'
Coming Up Short
These oncology drugs have experienced shortages in recent months.
Carboplatin Solution for Injection
Daunorubicin HCI Injection
Doxorubicin Liposomal Injection (Doxil)
Leucovorin Calcium Injection
Thyrotro pin Alfa
Source: - Amencan Society of Health–Systems Pharmacists
Experts agree that the reasons for the drug shortages are numerous and complex and will take time to fix. Some theorize that consolidation and low prices in the generic drug manufacturing industry have made it difficult for these companies to make a profit; therefore, they have little incentive to manufacture the drugs or address any manufacturing problems.
“What strikes me is that the causes of over half the shortages are quality-based,” adds Dr. Lichtenfeld. “If we can address quality issues in other industries, we should be able to address them in drug manufacturing.”
At the same time, with fewer firms making older, sterile injectable drugs, there are fewer production lines available. The raw material supplies also are limited due to capacity issues at their facilities. The limited production capacity for these drugs, combined with the long lead times and complexity required for their manufacture, makes them vulnerable to shortage, according to FDA spokesperson Shelly Burgess.
“When one company has a problem or discontinues, it is difficult for the remaining firms to increase production quickly,” she says.
Other reasons cited for the shortages include:
Growth in demand while manufacturing capacity has remained stable;
Production delays at the manufacturer and delays in receiving raw materials and components from suppliers; and
Discontinuation of older drugs in favor of newer, more profitable drugs.
FDA officials further note that the reasons stem from economic, legal, regulatory, policy, and clinical decisions and that the solutions will involve a collaborative effort among all stakeholders. Numerous solutions continue to be discussed and explored among Congress, health care providers, manufacturers, and various government entities.
“We're optimistic that now that light has been shed on the problem and it is receiving attention from the highest levels of government, there will be research that will get at the causes and solutions that will help;' Dr Link says.
Meanwhile, patients and physicians likely will have to contend with these shortages for the foreseeable future.
“One hope is that we can get the type of responses we deserve,” says Dr Lichtenfeld. “If not, then I guess it will come down to legislation to determine what our options are.”