While some FDA offices seek to accelerate access to vital medicines made abroad, agency field inspectors are struggling to
monitor a surge in imports of food and medical products. FDA has been working for more than five years to install an automated
Predictive Risk-Based Evaluation for Dynamic Import Compliance Targeting computer system, known as PREDICT, to replace its
outdated import screening process, which cannot handle the approximately 24 million shipments expected to arrive at US ports
of entry this year. The import volume includes up to 40% of drug products and 80% of active pharmaceutical ingredients.
The new system aims to prevent future Heparin crises by shifting from inspecting imports at point of entry to an approach
that reaches "back further to where products are manufactured" to ensure that drugs meet quality standards beginning where
they are produced, explained FDA Commissioner Margaret Hamburg at an April 2011 hearing before the House Energy and Commerce
Committee. FDA critics complained, however, that PREDICT is deployed in only 4 of 20 FDA district offices and pressed Hamburg
to do a better job. The commissioner blamed delays on software problems and noted that PREDICT was being expanded from California,
Seattle, and New York to field offices in Florida and San Juan, Puerto Rico, bringing coverage up to 50% of all imports this
The agency would gain more tools for managing imports, moreover, from proposed drug-safety legislation that authorizes FDA
to detain and destroy violative imports, to impose stiffer criminal and civil penalties on rule-breaking suppliers, and to
refuse admission to products from plants that block FDA inspections. The bill, sponsored by Rep. John Dingell (D-MI), also
would give FDA authority to issue subpoenas related to drugs, as with recently approved food-safety legislation, and would
authorize more FDA overseas inspections, recalls of tainted products, and the collection of more manufacturing information.
Crack down on opioids
In the US, the most alarming drug-safety issue involves overuse, misuse, and abuse of extended-release opioid drugs. FDA and
manufacturers have been struggling to devise a Risk Evaluation and Mitigation Strategy (REMS) since 2009 to promote safe use
of these medications. The task is complicated, however, by the use of these powerful painkillers by millions of individuals
suffering acute pain, which generates opposition from patient advocates and physicians to any policies likely to limit access
to these important therapies.
Yet, prescription drug abuse has become the nation's deadliest drug problem. FDA estimates that more than 33 million Americans
misused extended-release or long-acting opioids in 2007, up from 29 million five years earlier. The Centers for Disease Control
and Prevention (CDC) documents a rise in deaths and emergency-room visits related to prescription drug use, and unintentional
overdose deaths involving opioids nearly quadrupled from about 3000 in 1999 to more than 11,000 in 2007.
Drug-treatment programs are seeing more young patients coming in either addicted to opioid prescription drugs or in the first
years of heroin use that started with opioids, explains Deni Carise, chief clinical officer at Phoenix House, the leading
national drug-abuse treatment provider. "People think that taking a prescription drug is okay, and the habits quickly get
very expensive," she pointed out.
FDA unveiled its opioid REMS in April 2011 as a central component to a federal campaign to reduce prescription-drug diversion
and abuse by 15% in five years. The REMS requires manufacturers to develop educational materials that will make physicians
and consumers more aware of the dangers of opioids, as well as their appropriate use in treating pain. The broader program,
which is led by White House Office of National Drug Control director Gil Kerlikowske, also calls for more extensive monitoring
of drug use by the CDC, and for the Drug Enforcement Agency (DEA) to crack down on "pill mills" and clinics offering easy
access to pain medication. Because many adolescents initially obtain these drugs from family medicine cabinets or from friends,
more federal and state "take-back" events will promote proper disposal of unused or expired medications. Also, the plan supports
state prescription drug monitoring programs with databases to track prescriptions for certain drugs and inform physicians
and pharmacies of excessive patient drug use.
To better educate prescribers in the appropriate use of these medications and to alert patients to dangers of drug misuse,
FDA wants generic and brand opioid manufacturers to collectively design training materials for use by continuing medical educational
(CME) programs, which agency officials will scrutinize to ensure objectivity, accuracy, and absence of promotional bias (see
sidebar, "Pharma's influence on CME"). The industry group also will develop common elements for Medication Guides that pharmacists
will give patients.
Pharma‘s influence on continuing medical education (CME)
Elements to Assure Safe Use (ETASU) in the REMS will involve a collective strategy for evaluating the effectiveness of educational
and monitoring efforts in six months, 12 months, and annually thereafter. The assessment will report on how many prescribers
complete educational programs and if the REMS has any impact on patient access to opioids—for both appropriate and inappropriate
uses. FDA has required similar REMS for two recently approved pain-relief products (Covidien's Exalgo and Purdue Pharma's
OxyContin), and these would be incorporated into the new class-wide REMS.