Drug Safety and Shortages Challenge Manufacturers - Pharmaceutical Technology

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Drug Safety and Shortages Challenge Manufacturers
As drug shortages make headlines, FDA tests the Sentinel safety system and its efect on healthcare.


Pharmaceutical Technology
Volume 35, Issue 3, pp. 32-40

Scarce supplies

Although early information about adverse drug events can curb prescribing of unsafe drugs, early warnings also can help prevent serious shortages of important medicines, which have been on the rise in recent years. The University of Utah Drug Information Service recorded 211 drug shortages in 2010, up from 166 in 2009 and 70 in 2006. The most dire shortages are affecting anesthetics and treatments for cancer, pain, and serious infections. FDA notes that sterile injectable drugs accounted for almost half of all drug shortages in 2009 because fewer companies are able to make these more complex products, and any interruptions in production lines can affect multiple products and cause lengthy production delays.

The situation has led to complaints from hospitals and physicians about having to use less familiar and sometimes inappropriate alternative products that can cause dosing errors and compromise patient safety. The Institute for Safe Medication Practices (ISMP) reported an increase in medication mishaps related to switches to alternate medications to replace unavailable products. Changes in opioid pain killers, for example, generated confusion about correct dosage, as has the need to use sedation agents with various strengths and patient monitoring protocols.

The issue has made front-page news as state correction departments seek out substitutes for sodium thiopental, the drug commonly used for lethal injections. It no longer is made in the US, following the exit of Hospira (Lake Forest, IL) from the market in January. States have run into trouble trying to import the drug from the United Kingdom and other countries that oppose capital punishment, and Ohio recently faced demands by Lundbeck, the maker of the barbiturate pentobarbital, not to use its product for lethal injection. Further complicating the issue, lawyers for a group of prisoners on death row have filed suit against FDA for permitting the import of thiopental supplies and similar products that are registered overseas, but not by FDA safe and effective.

The shortages stem from a number of factors. Many of these products are low-margin generic drugs that are not sufficiently profitable to support a production upgrade when FDA inspectors uncover manufacturing violations. Quality problems with the anesthetic propofol in 2009 prompted recalls by Hospira and Teva Pharmaceuticals that created severe shortages. And after receiving multiple warning letters from FDA, Teva closed its Irvine, California, manufacturing facility for injectibles, and it seems far from being able to reopen it.

Pharmacists and physicians discussed remedies to the shortage crisis at a meeting last November organized by ISMP and the American Society of Health-System Pharmacists. The group's report acknowledges that manufacturers generally run production lines at full capacity, making it difficult to respond quickly to increased market demand. Limited sources of active ingredients can cause disruptions, while just-in-time inventory practices make it hard for manufacturers to deal with sudden shortages.

Some established sterile products are not as profitable to companies as new therapies and may be dropped, especially when continued production requires an overhaul of facilities. This observation appears particularly true for those decades-old products that have been marketed without formal FDA approval but have been the target of an enforcement crackdown in recent years. While a rise in FDA inspections of injectable drug manufacturing processes has created problems for several companies, no one wants contaminated products on the market.

Although many of these situations are unavoidable, health professionals believe that more early warnings from manufacturers about emerging shortages will help them deal with serious short supply situations. Pharmacists and physicians want Congress to require companies to notify FDA earlier and more quickly about looming supply problems for a broader range of "medically necessary" products, including drugs with a single active ingredient source. Such a proposal has been introduced into the Senate, and further remedies may be offered.

In addition to waving the stick, FDA could encourage the production of short-supply drugs by speeding through new applications and offering tax credits to manufacturers that expand production or upgrade manufacturing facilities for needed products. A process for extending stability for products in short supply also might help. Without some way to lessen shortages, manufacturers will appear to be putting profits above patients and leaving the public to cope with ineffective, and even unsafe, alternative therapies.

Additional information on the Sentinel Initiative is available at http://www.fda.gov/Safety/FDAsSentinelIntiative/ucm2007250.htm.

Jill Wechsler is Pharmaceutical Technology's Washington editor, 7715 Rocton Ave., Chevy Chase, MD 20815, tel. 301.656.4634,
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Survey
FDASIA was signed into law two years ago. Where has the most progress been made in implementation?
Reducing drug shortages
Breakthrough designations
Protecting the supply chain
Expedited reviews of drug submissions
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Reducing drug shortages
32%
Breakthrough designations
8%
Protecting the supply chain
40%
Expedited reviews of drug submissions
8%
More stakeholder involvement
12%
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