The committee has examined five areas of regulation in which it believes that FDA’s authority requires strengthening. The committee reasserts the importance of a regulatory system that is dynamic and flexible; a key aspect is that most NDAs and approvals pose few issues of concern and little or no need for unusual postapproval monitoring and risk management. For most drugs, the existing interaction between regulator and sponsor is adequate—incoming safety information does not reveal extremely serious unlabeled adverse events (AEs), and regulatory re-examination (for new indications and labeling changes) is more or less routine. The committee’s recommendations for regulatory change apply mainly to what may be a smaller proportion of drugs—which cannot always be identified beforehand—that have complex risk-benefit assessments and both lingering and emergent safety concerns. Possible examples may be found among drugs that are similar to those with a poor safety record, NMEs with unique modes of action, drugs for which preclinical testing revealed a potential for clinical safety problems, and so on. First, clarification or strengthening of existing authority for use postapproval is needed to take important regulatory action out of the realm of negotiation and the bully pulpit. Second, FDA needs a new way to address DTC advertising that has provoked great interest and debate in recent years. Third, FDA needs sufficient enforcement tools to ensure that regulatory requirements imposed at or after approval are fulfilled. Fourth, FDA needs to develop a major strategy to improve public and health care provider awareness that approval is not the end of uncertainty and that as new drugs enter the market, more information about their benefits and risks is likely to become available. Fifth, regulation of drugs in the United States would be greatly strengthened by requiring a milestone in each drug’s lifecycle that triggers a comprehensive review of consolidated safety and efficacy data and of the status of postmarketing conditions and commitments.
The committee has found that FDA has some ability to ask for and negotiate with sponsors about various risk management and other actions. For example, marketing of isotretinoin is conditioned on a four-step RiskMAP (iPLEDGE) that consists of: registration of and an educational program for patients, pharmacies, prescribers, and distributors; implementation of an education program for the four groups just listed; implementation of a reporting and data collection system for serious AEs in compliance with statutory requirements and as pertaining to the sale and dispensing of isotretinoin outside the iPLEDGE program; and implementation of a