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Stiffer enforcement of quality standards aims to restore public confidence in agency actions.
The new leadership at the US Food and Drug Administration is wasting little time in taking steps to make the agency more efficient and effective. The FDA is announcing new rules and policies almost daily and strengthening enforcement of manufacturing and marketing requirements to show the industry it means business.
FDA Commissioner Margaret Hamburg began by reorganizing her immediate office to emphasize the importance of food safety and scientific integrity and to encourage speedy compliance with rules. An expanded office of external affairs will improve communications with the media, health professionals, and special interest groups. Several crosscutting activities—bioresearch monitoring, combination products, orphan drugs, and pediatrics—will be managed by a new Office of Special Medical Programs.
Budget development will shift to the policy office to better explain to Congress how the FDA spends its resources and why it may need additional funding. Hamburg is benefiting from a record $3 billion budget for the coming year (including some $600 million in user fees) but will be hard-pressed to further expand resources.
A prominent addition is the Center for Tobacco Products, authorized by Congress in June and launched by the FDA in record time. The Center will be headed by Lawrence Deyton, an MD with experience in academia, public health, and Congress, and successful in revitalizing smoking cessation programs as a top health official at the Department of Veterans Affairs. The tobacco legislation charges the FDA with enforcing marketing restrictions on tobacco products, regulating product ingredients, and taking action to reduce youth smoking. Leeway for the FDA to promote smoking cessation could stimulate development of new nicotine replacement products.
Hamburg is intent on positioning the FDA as a science-based regulatory agency where politics don't override medical judgment in making regulatory decisions. The agency hopes to deal effectively with internal disputes over product safety and approval actions and to avoid public controversies, such as the one that delayed approval of an over-the-counter version of the Plan B emergency contraception pill.
At the August meeting of the FDA's Science Advisory Board, Hamburg highlighted the need to strengthen regulatory science as a field, noting that it has atrophied compared to the surge in biomedical research investment by the National Institutes of Health. She emphasized the importance of "revitalizing and re-energizing" support for the Critical Path Initiative and acknowledged concerns about the slim pipeline for new drugs and medical products. An increased focus on regulatory science and efforts to make the FDA review process as efficient as possible can benefit innovation, she commented, while the current lack of transparency about the FDA review process can be "very stifling to innovation." Here Hamburg echoed opinions expressed by biotech companies and venture capitalists at a recent meeting organized by the FDA and the White House's Office of Science and Technology Policy to address innovation and transparency.
Under the Hamburg regime, FDA Chief Scientist Jesse Goodman will spur innovation as head the Office of Science and Innovation. He also heads up a new office of scientific integrity that will resolve scientific disputes within the agency, coordinate responses to outside charges of inappropriate actions, resolve appeals, and oversee advisory committees. And Goodman will oversee counterterrorism and emerging threats, which involves coordinating the FDA's response to the current influenza pandemic, facilitating access to effective medical countermeasures, and authorizing emergency use of needed therapies.
In addition to these organizational changes, the FDA has proposed new rules designed to expand patient access to investigational medicines, finalizing proposals made in 2006 and long sought by patient advocates. The policy makes it easier for seriously ill individuals to obtain unapproved drugs and clarifies for manufacturers when they may be able to charge patients for an experimental drug outside a clinical trial.
The FDA also has issued a proposed rule requiring electronic submission of postapproval adverse event (AE) reports for drugs, biologics, and medical devices. Most (80%) of drug AEs already are submitted to the agency online or in digital media, and the new policy aims to prompt small biotech firms and device makers to follow suit. The FDA is establishing a new web portal that it says will be easier for small companies and individuals to use for AE reporting. There are no changes in the scope and timing of AE filings, which should make it fairly easy for manufacturers to comply. However, the FDA estimates it will save $2.4 million a year and, more importantly, will gain access to safety information much more quickly.
Hamburg's most high profile initiative is to streamline the process for issuing warning letters and for taking enforcement actions against manufacturers that violate good manufacturing practices (GMPs) and other agency rules. Many serious violations "have gone unaddressed for far too long," including manufacturing problems, product adulteration, and false and misleading labeling and advertising, Hamburg commented at an August meeting sponsored by the Food and Drug Law Institute. The commissioner wants to limit all the back-and-forth wrangling with regulated companies that delays compliance and says the FDA will implement recalls or seizures if serious health and safety issues are not corrected promptly.
Under the new program, a manufacturer has 15 working days after receiving a 483 inspection report to head off a warning letter or other regulatory action by providing information on how it will address cited violations. The FDA also aims to issue warning letters more promptly by ending the extra internal legal review of such documents before they are sent out. The Bush administration requirement that the FDA chief counsel examine all proposed warning letters, "created very cumbersome practices without a lot of benefit," observed Hamburg. Now the chief counsel will review only those proposed warning letters that raise "novel, complex, and sensitive issues," such as an activity involved in a lawsuit or recently established by legislation.
On its part, the FDA hopes to encourage fast industry corrective action by promptly reinspecting or re-evaluating a company's remedial efforts. So that manufacturers are not left wondering if a corrective action is adequate, the FDA will issue a formal close-out letter and post it on its web site, providing manufacturers with an official statement to show investors and customers that they're back in the FDA's good graces, and that a facility or product is no longer tainted by quality or safety issues. But if reinspection reveals that cited problems are not corrected, FDA says it won't just issue another warning letter, but may initiate seizures, closures, or take other regulatory action.
Even before announcing these changes, FDA officials were stepping up GMP enforcement and publicizing warning letters. In June, Genzyme had to shut down its facility in Allston Landing, MA because of viral contamination, leading to serious shortages of enzyme replacement therapies such as Cerezyme (imiglucerase). A threat to revoke Immucor's biologics license for poor quality control of blood diagnostic products prompted fast development of a corporate remediation plan and quality process improvements.
Hamburg expects an increase in warning letters initially, but anticipates that the volume will level off as industry recognizes that a strong compliance program is good for business and for consumers. The FDA's success in spurring compliance "should be measured not by the number of warning letters or injunctions or seizures," she said, but by "our impact on the health and welfare of the public." Failure to meet FDA standards means that a company is "putting the public at risk" and also "jeopardizing the public's confidence in your industry." Alternatively, speedy corrective efforts by companies and broader compliance throughout the industry will increase public confidence in the FDA and better educate consumers about potential risks in medical products.
Jill Wechsler is BioPharm International's Washington editor, Chevy Chase, MD, 301.656.4634, email@example.com