2006). It is clear that FDA authority to require postmarketing studies (in cases other than accelerated approval, etc.) is at best unclear, and statutory change is needed to enable FDA to require such studies when necessary and appropriate.

Authority to Unilaterally Impose Risk-Reducing Remedies, Such as Label Changes and Distribution Restrictions

During the drug development process and up to the point of approval, FDA has a great deal of power. Its communications with sponsors at meetings and in written exchanges (including approval and other letters issued while an NDA is under review) carry enormous weight; sponsors are highly motivated to accede to FDA’s requests and demands during this time to avoid any delay in the approval of their product. After approval, however, unless a case meets the statutory definition of fraud or misbranding or the high threshold for proving imminent hazard to the health of the public, FDA’s regulatory and enforcement options generally lie at the ends of the spectrum of regulatory actions: do nothing or precipitate the voluntary withdrawal of the drug.1 FDA relies on firms to withdraw drugs from the market voluntarily when safety issues are revealed. Doing nothing implies not acting on potential threats to the health of the public, and precipitating withdrawal implies taking the drug from patients who need it, so neither is a satisfactory option. Currently, most actions involve softer remedies negotiated with a drug sponsor; FDA cannot unilaterally compel label changes, addition of boxed warnings, or fulfillment of postmarketing study commitments. Nor can it unilaterally restrict marketing, change the content of a package insert (including Medication Guides2), or change the content of other documents intended for the public. The process of negotiation works well in many cases, but for some products the process can be long and have potentially adverse repercussions for safety. The diminished FDA authority after approval is of concern because knowledge of a drug’s risk-benefit profile is never complete at the time of approval.

FDA takes several approaches to monitoring postmarketing safety. CDER staff members review Adverse Event Reporting System (AERS) reports using data mining techniques for automated monitoring of the AERS database, conduct retrospective and observational studies using external administrative databases, and track the status of phase 4 studies. CDER


Withdrawals are almost always voluntary rather than mandated by FDA. According to its statute, FDA can institute recalls only for devices and baby formula (Adams et al., 1997).


Medication Guides, or MedGuides, are patient-specific labeling for prescription drug products determined by FDA to have “serious and significant public health concern requiring distribution of FDA-approved patient information” (21 CFR 208.1, 4-1-05 Edition, p. 114) (CDER, 2006).

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