For the past 10 years, the US Food and Drug Administration has campaigned for a more efficient, risk-based approach to monitoring
drug-manufacturing activities. The agency's goal has been to encourage consistent production of high-quality products while
providing less routine oversight. Yet, a series of serious manufacturing breakdowns in recent months has led to plant closures
and massive product recalls, raising questions about industry investment in and commitment to modern production systems able
to meet established regulatory standards.
In April, the McNeil unit of Johnson & Johnson (J&J, New Brunswick, NJ) shut its flagship facility in Fort Washington, Pennsylvania,
and recalled millions of bottles of children's cold medicines due to repeated failures to meet manufacturing standards and
comply with regulations. The problems, observed FDA Principal Deputy Commissioner Joshua Sharfstein at a Congressional hearing
in May, appear related to the company's "pattern of noncompliance" with quality control requirements. J&J now faces potentially
serious legal issues, as Congressional leaders have raised charges of stonewalling, and FDA is examining whether the firm
knowingly misled the regulators.
Meanwhile, Genzyme (Cambridge, MA) continued its struggle to restore production capacity after contamination problems prompted
the closure of its Allston Landing, Massachusetts, facility in June 2009. The company paid a hefty fine and invested millions
in plant cleaning and renovation. Manufacturing issues also compelled KV Pharmaceutical (St. Louis, MO) to shut down operations
and recall multiple generic products and vitamin therapies. And several vaccine manufacturers are working hard to eliminate
extraneous viruses from cell banks and to correct manufacturing issues identified by FDA inspectors.
These situations raise questions about whether drug and biological manufacturers are cutting corners in their quality systems
needed to comply with current good manufacturing practices (CGMPs). In 2002, FDA launched the Pharmaceutical CGMPs for the 21st Century initiative to modernize the regulation of drug manufacturing and to spur industry efforts to ensure product quality. After
issuing several new policies and guidances to encourage a risk-based approach to quality control, FDA had to move the effort
to the back burner as other issues, including these compliance crises, began to dominate the agency's agenda.
The current surge in manufacturing problems has placed drug quality and GMP compliance back in the spotlight at FDA. In a
major speech last August (2009), FDA Commissioner Margaret Hamburg emphasized the importance of industry adherence to regulatory
standards (see the October 2009 edition of Washington Report in Pharmaceutical Technology). Hamburg outlined initiatives to accelerate the correction of manufacturing violations identified during plant inspections
and to streamline the process for issuing Warning Letters to companies that fail to address violations expeditiously.
Those policies appear to be taking hold. FDA has increased the frequency and timeliness of its "untitled" and Warning Letters
that cite ongoing manufacturing problems. This approach is a reversal of the Bush administration's targeted enforcement strategy,
which was based on the idea that manufacturers would take a limited number of Warning Letters more seriously. FDA enforcement
efforts may gain more clout if Congress enacts long-sought legislation to strengthen the agency's legal powers, namely by
providing FDA with the ability to mandate recalls, expand civil monetary penalties, and gain easier access to company records.
There's more talk of FDA injunctions and consent orders, and the pharmaceutical legal community is watching closely to see
whether the government brings charges against J&J and McNeil executives for not doing more to prevent company violations of
food and drug laws.
In Washington this month