Drugs in short supply: Change and challenge among all stakeholders

Unprecedented levels of drug shortages, especially those drugs for which there are no substitutes, has prompted legislators to take action. Since the inception of the FDA Drug Shortage Program (DSP) in 2000, the agency has been tracking the nation’s prescription pharmaceuticals and publishing a list of drugs in short supply. The current FDA list reports 178 drug shortages, twice the number reported 5 years ago. The Preserving Access to Life-Saving Medicines Act, introduced February 7, 2011, and sponsored by US Senators Amy Klobuchar (D-Minn.) and Bob Casey (D-Pa.), would increase the authority of FDA to address and mitigate this problem affecting prescription drugs.

Why supplies fail

According to FDA spokesperson Christopher Kelly, the agency has been carefully tracking the causes of shortage, especially those in sterile injectables used in anesthesia and oncology therapy. In fact, sterile injectables now account for 77% of all drug shortages, according to the National Cancer Institute (NCI).

“Over the past several years we continually see quality issues, as well as discontinuations and manufacturing delays, as the major reasons for shortages,” Kelly explained.

Sterile injectables such as propofol and cisplatin, are both unique. “They have a complex manufacturing process compared to other dosage forms,” Kelly said, and the production capacity for manufacturers is limited. These drugs typically have a long manufacturing lead time, and if one of the few firms making these products experiences a problem at any point in the process, a shortage almost always occurs. But shortages also can occur when firms shut down to upgrade processes, and/or cease making older agents to begin production of newer, more profitable drugs.

Using market research data, FDA can quantify drug shortages and forecast how much product will be needed to supply the market each month, Kelly said. Yet FDA has limitations.

The agency does not require notification when companies elect to discontinue a product, unless it meets the agency’s definition of “medically necessary,” as a sole source product without substitute. And when firms encounter difficulty in acquiring raw materials or have packaging or other manufacturing problems, they are not required to inform FDA of a potential shortage. The proposed Klobuchar-Casey bill would authorize FDA to require notification from manufacturers of problems, or plans to withdraw a product. However, Valerie Jensen, RPh, associate director of the DSP in FDA’s Center for Drug Evaluation and Research (CDER), said that manufacturers who voluntarily reported problems last year, “helped avert at least 38 drug shortages.”

Filling empty shelves from abroad

The 2010 propofol shortage was solved by going beyond US borders, according to Jensen.

“When we see that the US-approved manufacturers are not able to meet demand and a shortage is developing with no resolution, then we will help supply US patients with an overseas product. When we do that, we evaluate safety and efficacy very carefully, using our regulatory discretion.”

The temporary importation of Fresenius Propoven 1% from Germany was so successful in solving the propofol shortage that Jensen said, “We are now seeking overseas firms to supply the United States with other drugs in short supply.”

Giving less than the best

At the core of shortages is the affect on provider decisions and patient care. Georgia-based clinical oncologist, Fred Schnell, MD, remembered the serious shortage of commonly used chemotherapy drugs that began several years ago and worsened in 2010. “All of a sudden, it was mysterious, a shortage of oncology drugs at all the pharmacies,” Dr Schnell said. “They were completely unavailable and we couldn’t buy drugs anywhere.”

Some of the drugs, “such as mitomycin C have no substitute, and it becomes a dreadful thing to tell a patient we can’t get one of the key drugs,” he said. “Shortages in oncology become a huge patient safety issue,” and when unavailability prompts the treatment to necessarily deviate from standard of care, Dr Schnell said, “we’re giving patients less than the best, less than they deserve.”

ASHP call to action

The American Society of Health-System Pharmacists (ASHP) and 3 other organizations led the effort to help the healthcare community manage issues related to drug shortages. ASHP, the American Society of Anesthesiologists, the American Society of Clinical Oncology, and the Institute for Safe Medication Practices, participated in a summit in November 2010 that brought together stakeholders to develop recommendations for new approaches to prevent patient harm and minimize disruptions in care caused by drug shortages. The summit report is available at www.ashp.org/drugshortages/summitreport. Representatives from ASHP and these other organizations met with aides to Sen. Klobuchar (D-Minn.) to discuss key points from the groups’ November Drug Shortages Summit that should be included in federal legislation.

“Legislation introduced by Sens. Amy Klobuchar (D-Minn.) and Robert Casey (D-Pa.) is a critical first step towards addressing the serious public health threat posed by drug shortages,” according to officials at the ASHP in a press release.

The “Preserving Access to Live Saving Medications Act” (S 296), gives FDA new tools to help prevent drug shortages.

“Drug shortages present a significant challenge to our health care system and interfere with the quality of care that patients receive in our nation’s hospitals,” said ASHP Executive Vice President and CEO Henri R. Manasse, Jr., PhD, ScD. “We are pleased to see a legislative proposal offered to address this critical issue and will advocate strongly for its passage.”

ASHP is calling on its members to lobby for passage of this act.

Early warning system

In a public statement Sen. Klobuchar commented that The Preserving Access to Life-Saving Medicines Act, “will help set up an early warning system so pharmacists and physicians can prepare in advance and ensure that patients continue to receive the best care possible.”

In the meantime, FDA’s Jensen urged pharmacists to help. “We would definitely ask pharmacists to watch our website and if that doesn’t agree with what they are experiencing to let us know. Sometimes the first we ever hear of shortages comes from pharmacists. Early notification of any circumstance that could lead to shortage is essential.”

The FDA Manual of Policies and Procedures 6003.1 (MaPP) describes how the CDER DSP works with internal and external stakeholders to prevent, alleviate, and resolve shortage situations. Resources for practitioners who face shortages can be found at www.ashp.org/drugshortages/summitreport.