Drug Shortages Create Crisis for Manufacturers, Regulators - Clamor mounts over compromised care and rising costs due to lack of crucial therapies. - BioPharm International

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Drug Shortages Create Crisis for Manufacturers, Regulators
Clamor mounts over compromised care and rising costs due to lack of crucial therapies.


BioPharm International
Volume 24, Issue 11, pp. 12-14

ADDRESSING PRODUCTION PROBLEMS

Manufacturers now support stronger early notification requirements, largely to reduce complaints about industry responsibility for most shortages. FDA reports that most supply problems arise from GMP and product quality failings, along with difficulties obtaining active ingredients or problems at a manufacturing site. Industry consolidation has reduced the number of generic-drug firms making sterile injectables, Cox observed at the FDA workshop, and it takes time for another manufacture to establish a facility to produce these more complex and costly medicines.

Reliance on contract manufacturers also has led to shortages for both brand and generic drugs. Johnson & Johnson faces serious supply problems for cancer and AIDS treatment Doxil (liposomal doxorubicin) because its contract producer, Boehringer Ingelheim's Ben Venue Laboratories, decided to exit the CMO business.

The strong link between manufacturing issues and shortages raises questions about pharma's commitment to quality production. FDA wants manufacturers to prevent shortages by developing continuity of supply plans, with backup suppliers and alternative production strategies for critical products. Industry has a responsibility, FDA officials assert, to proactively identify and promptly resolve manufacturing problems and to implement quality-by-design strategies to prevent failures.

An alternative view is that FDA creates shortages through overly aggressive enforcement of manufacturing rules. Agency officials maintain that they don't halt production for minor violations, but only for significant problems with drug sterility and contamination. Before requesting a drug recall or seizure, they check to make sure such action won't precipitate a shortage. But strong action is needed when inspectors find glass and metal particles in vials and new impurities and degradants. In some cases, companies have been cited multiple times for violations and still fail to correct manufacturing deficiencies until threatened with total shutdown.

FDA officials also emphasize that they can act fast to help bring online a new producer or new supplier when needed. "We can turn things around in a matter of weeks," Kweder insisted at the House hearing, in response to manufacturer claims that FDA requires two-to-three years to approve a new manufacturing site. "This is not business as usual," she stated.

But stakeholders feel there is more that FDA and other government agencies can do to prevent critical shortages. FDA should revise how it calculates risks and benefits from regulatory action to give greater weight to patient safety issues that arise with shortages. The federal government should establish stockpiles for medically necessary drugs, as done for treatments against bioterrorist attacks and pandemics. And antitrust officials should scrutinize proposed pharma company mergers to assess how the combination would affect limited drug supplies.

At the same time, there's interest in providing more incentives for manufacturers to enter depleted markets. Tax credits or rebates could spur manufacturers to update facilities or launch production of low-profit drugs. Some kind of exclusivity could be offered for new production of a drug in short supply. Or, generic-drug makers might be eligible for reduced user fees on applications to produce hard-to-obtain medicines.

Shortages in controlled substances, such as long-acting painkillers and drugs to treat children with attention deficit hyperactivity disorder, are generating calls for the Drug Enforcement Agency (DEA) to work more closely with FDA and industry to modify limits on active ingredients. Manufacturers receive DEA annual quotas on controlled drug substances, but would like a way to transfer allotments when one company ceases production.

There's also support for more resources for FDA to deal effectively with shortages. FDA formed the drug-shortage program in 1999 to manage anticipated supply disruptions from the Y2K shift to the new millennium. But with only five staffers and limited legal authority, FDA is hamstrung in preventing supply disruptions.

BALANCE NEEDED

Parallel to the shortage crisis, FDA has been campaigning for more authority to control counterfeiters and manage an increasingly global pharma supply chain. A number of bills before Congress would empower FDA to deal more forcefully with illegal imports and to address drug manufacturing problems. The challenge is to ensure that efforts to strengthen FDA clout does not aggravate drug shortages.

At a hearing Sept. 14, before the Senate Health, Education, Labor, and Pensions (HELP) Committee, Deborah Autor, recently named FDA deputy commissioner for global regulatory operations and policy, presented a long list of desired policy changes to promote drug safety and level the playing field between domestic and foreign manufacturers. Autor wants mandatory recall authority for drugs, power to detain and destroy violative imports at the border, and much stiffer penalties for noncompliance. Drug manufacturers and importers would have to register and list manufacturing facilities using identifier numbers, and importers would have to demonstrate that they meet quality standards, instead of FDA proving that they do not. Autor also seeks more authority to enforce track-and-trace standards, which would help hospitals and physicians know whether drugs from unknown or unusual sources are legitimate.

Industry supports many of these changes, but is wary that continued shortages will spur calls for even greater government intervention in the market. The danger is that added rules could make low-profit drug markets less attractive to manufacturers. Yet, patients are waiting: Short supplies of drugs to treat children with leukemia in the US is "shameful," lamented oncologist Len Lichtenfield at the FDA workshop. "Maybe we need more government intervention."

Jill Wechsler is BioPharm International's Washington editor, Chevy Chase, MD, 301.656.4634,
.


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