Causes of shortage
In response to the increasing frequency and severity of drug shortages in recent years, the FDA conducted a review, the results of which they published in October.2 The leading causes of drug shortages were quality problems—glass shards, fungi, or other contaminants—at a drug manufacturing facility (43%); delays in manufacturing or shipping (15%); and a shortage of the active pharmaceutical ingredient (10%).
Other causes included increases in demand, business choices, and other companies discontinuing the product lines.2 On the basis of 127 drug shortages between January 1, 2010, and August 26, 2011, the FDA review found that injectable medications accounted for 102 (80%) of the drugs in short supply.2
One of the companies with manufacturing problems is the injectable drugs manufacturer Ben Venue Laboratories, which has 4 factories in Bedford, Ohio. The Boehringer Ingelheim–owned company manufactures valproate(Drug information on valproate) sodium injection, haloperidol(Drug information on haloperidol) lactate injection, and buprenorphine(Drug information on buprenorphine) injection, among other injectable drugs. Last year, Ben Venue voluntarily suspended manufacturing “to permit implementation of lasting corrective actions to address manufacturing-related issues as noted in FDA and other global regulatory agency inspections,” said spokesperson Jason Kurtz. He added that in the past 3 years, the company has invested more than $250 million to upgrade its facilities. A public statement posted on its Web site stated, “. . . no products manufactured in the North facility will be available to patients and healthcare professionals before the fourth quarter of 2012.3
In some cases, only one company manufactures a particular drug. For example, Hospira, the sole supplier of diazepam(Drug information on diazepam) injection used to treat anxiety disorders (short-term) and alcohol(Drug information on alcohol) withdrawal symptoms (among other disorders), is experiencing manufacturing delays. But according to the company spokesperson, Daniel Rosenberg, the company expects a full recovery by summer.
Obtaining active pharmaceutical ingredients for the manufacturing of controlled substances has been particularly challenging, according to manufacturers and others. In testimony before the House Committee on Energy and Commerce Subcommittee on Health last year, Jonathan Kafer, Vice President of Sales and Marketing for Teva Pharmaceuticals, described the dilemma as follows4:
From our work with the DEA [Drug Enforcement Agency] and FDA, we know that it is a difficult balancing act to ensure availability of controlled substances to patients in need while also striving to curb abuse and diversion. In an effort to control the supply of these medicines, the DEA makes yearly allocations of controlled drugs to the respective manufacturers of these products. In many instances, however, the use of a drug product changes over the year due to increased usage or shifting of markets. This can result in a shortage of these products, because without access to more of the controlled active ingredient, manufacturers are unable to increase supply. Currently, there are a number of controlled drugs on the American Society of Health-System Pharmacists shortage list.
Robb pointed to the DEA’s quota system for the shortages in ADHD medication as well as to demand outstripping supply: “Diagnosis and treatment with medication for ADHD in both pediatric and adult fields have increased in the last 5 years, so there is a larger demand for the products. But at the same time, the supply of ready materials to make the medications has not increased through the DEA.”
Jeffrey Scott, a DEA agent and spokesperson, said the quota for amphetamine salts has been “bumped up” for 2012 and that the quota can be revised mid-year. “Part of our mission is to ensure uninterrupted supply to meet legitimate medical and scientific needs, but we are only part of a chain that gets the medications to the public—the part that determines the quota of amphetamine salts used in ADHD medications. We develop the quota based on established medical need, retail consumption, manufacturers’ estimates, past quota history, etc. It is our best educated guess.”
Manufacturing companies that make decisions on how best to use their quota allocation, such as for brand-name versus generic forms of the drugs, are the next link in the chain, he added.
On October 31, 2011, President Obama issued an Executive Order that directed the FDA, as well as the Department of Justice, to take action to reduce and prevent drug shortages through expedited reviews and to identify market participants who are stockpiling medications or pricing drugs exorbitantly.5 On the congressional front, the Committee on Energy and Commerce, Subcommittee on Health last fall examined drug shortages.
Several health care professional organizations (eg, AACAP, the American Psychiatric Association, and the American Academy of Pediatrics) along with several ADHD groups have formed an ADHD drug short-age coalition. The coalition has arranged visits to key congressional leaders and FDA officials, called for more transparency in the DEA quota-setting process, and recommended an interagency agreement between the FDA and DEA so that when a controlled-medication shortage is identified, the agencies can work together on an action plan.
[Editor's note: For further information, see FDA warns consumers about counterfeit version of Teva’s Adderall, published subsequent to this article.]