Table 1.

The FDA's Postmarket Requirement Authorities and Corresponding Enforcement Actions

		Available Enforcement Actions
Statutory Authority	Key Parameters	Civil Monetary Penalties	Misbranding Charges	Withdrawal of Approval
Accelerated approval	• Must target a serious or life‐threatening illness and provide meaningful therapeutic benefit to patients over existing treatments	✓	✓	✓
	• Approval based on a surrogate endpoint that is reasonably likely, based on epidemiologic, therapeutic, pathophysiologic, or other evidence, to predict clinical benefit or on the basis of an effect on a clinical endpoint other than survival or irreversible morbidity
Animal efficacy rule	• Must target serious or life‐threatening conditions caused by exposure to lethal or permanently disabling toxic biological, chemical, radiological, or nuclear substances	X	X	✓
	• Applies only to products for which definitive human efficacy studies cannot be conducted because it would be unethical to deliberately expose healthy human volunteers to a lethal or permanently debilitating toxic biological, chemical, radiological, or nuclear substance, and field trials to study the product's effectiveness after an accidental or hostile exposure have not been feasible
	• Approval only when results of adequate and well‐controlled animal studies are reasonably likely to produce clinical benefit in humans
Pediatric Research Equity Act (PREA)	• Applies when the FDA decides to defer the requirement of submitting safety and efficacy data in respect of a new active ingredient, new indication, new dosage form, new dosing regimen, or new route of administration, until after approval of the drug product for use in adults	✓	✓	Xa
	• Such a deferral may be granted if the drug is ready for approval in adults before studies in pediatric patients are complete or pediatric studies should be delayed until additional safety and effectiveness data have been collected
Food and Drug Administration Amendments Act (FDAAA)	• May be required to assess a known serious risk related to the use of the drug or biologic, to assess signals of serious risk related to the use of the drug, or to identify an unexpected serious risk when available data indicates the potential for a serious risk	✓	✓	? b
	• Can be imposed at the time of, or following, approval

^aWithdrawal of approval is not applicable because in the case of a PMR issued under PREA, at the time of approval, no pediatric indication has been approved. Rather, the approval pertains to an adult indication, which carries a PMR to generate evidence as to whether one or more pediatric indications is also warranted. When the study or studies undertaken to fulfill a PMR under PREA is completed, the FDA evaluates whether the study ‘responds’ to the PMR, which, in turn, informs its decision to grant the pediatric indication(s) and as a result confer an additional period of six months market exclusivity to the sponsor for the approved pediatric indication(s).

^bIn contrast to the accelerated approval pathway and the animal efficacy rule, the FDA lacks the legal authority to withdraw an approval that carries a PMR due to the sponsor's failure to fulfill the PMR. Rather, under FDAAA, s 505(o), the agency can only issue civil monetary penalties or pursue misbranding charges. If, however, a study undertaken pursuant to a PMR attached under FDAAA is completed, and its results yield new safety (or possibly efficacy) issues, then FDA may withdraw the approval under its general power to do so pursuant to s 505(e) of the FFDCA.