20 August 2007
The US Food & Drug Administration (FDA) has come under significant attack in recent months. Medical device recalls, adverse safety findings and political imbroglios at the agency have contributed to a growing level of scepticism about the FDA's effectiveness.
In the midst of this storm, the agency published a new set of 'Requirements on Content and Format of Labeling for Human Prescription Drug and Biological Products'. The new requirements include a preamble that enunciates the agency's position with respect to the pre-emptive effects of its labeling regulations on potential tort liabilities for manufacturers.
Manufacturers may be tempted to take satisfaction in the public derision directed at the agency. They should not. To function effectively the system requires the respect of the general public as well as a healthy level of respect between the regulator and industry. If the current environment does not improve, industry can expect significant adverse effects: a lessening of the agency's willingness to advocate the preamble's pre-emption positions, as well as increased delays in the handling of applications for approval of new drugs and medical devices.
Two major reports in 2006 advanced particularly pointed criticisms of the FDA - a report from the US Government Accountability Office (GAO) and a report from the Institute of Medicine (IOM).
The GAO report
In its recent report to Congress, the GAO focused on the FDA's ability to monitor postmarket drug safety issues. The report discusses why the GAO deems the FDA's present organisational structure and procedures to be ineffective in handling postmarket drug safety issues, and it analyses recent measures taken by the FDA in an attempt to approve its methods for postmarket decision-making and implementation. The report also makes recommendations to improve the FDA's ability to make and enforce postmarket drug safety decisions.
The GAO discusses the roles of two distinct FDA offices actively engaged in postmarket drug safety monitoring activities. The first is the Office of New Drugs (OND) and the second is the Office of Drug Safety (ODS).
The OND is responsible for approving drugs and monitoring safety issues throughout the lifecycle of approved drug products. It has the authority to address postmarket drug safety issues when they arise and to impose policies and procedures to mitigate safety concerns. The OND devotes approximately 50 per cent of its time to drug safety issues. In contrast, the ODS's sole focus is on postmarket drug safety. The ODS works closely with the OND, but has no authority of its own.
The GAO report blames the FDA's lack of unambiguous critical standards and the agency's poor internal communications for the difficulties the OND and the ODS have had in determining when postmarket drug concerns require FDA intervention and what methods of intervention should be employed. A lack of authority and ineffective means of data collection increase delays in response between the two organisations.
Purportedly, the FDA's reliance on drug sponsors to conduct studies voluntarily and to provide the agency with data and trial results creates difficulties in the FDA's tracking and monitoring of drug safety issues, which forces it to rely upon incomplete or untimely information or results in its own risk-benefit analyses of postmarket products. Moreover, the GAO report implies that the ODS's lack of specific goals and independent authority results in additional delays in the FDA's handling of drug safety issues.
The GAO report suggests that the FDA's newest measures are not enough. The report recommends that the FDA, through the Defense Science Board (DSB), creates a clear and unambiguous dispute resolution process to facilitate decision-making and future communications between the OND and the ODS. Additionally, the GAO maintains that increased funding is necessary to allow the FDA to expand its capabilities to monitor and develop sources for collection of postmarket drug safety data. According to the report, although the FDA has begun to work with the Centers for Medicare and Medicaid Services in an effort to obtain additional drug data, this method could prove to be risky and unreliable for the FDA.
The report concludes that the commissioner of the FDA should take the following actions:
•establish a mechanism for systematically tracking ODS recommendations and subsequent safety actions;
•with input from the DSB and the Process Improvement Teams, revise and implement the draft policy on major postmarket drug safety decisions;
•improve the Center for Drug Evaluation and Research's (CDER) dispute resolution process by revising the pilot programme to increase its independence; and
•clarify the ODS's role on the FDA's scientific advisory committee meetings involving postmarket drug safety issues.
The IOM report
The report by the IOM discusses the present role of the FDA in ensuring drug safety and suggests how the FDA could increase its capabilities.
First, the report discusses the organisational culture of the CDER. According to the IOM, the instabilities and high turnover rates render the agency incapable of operating efficiently and implementing clear, consistent policies and procedures.
The IOM report recommends the creation of an external management advisory board comprising individuals experienced in changing and leading large, complex organisations. It also suggests clear and unambiguous assignments of goals and roles for the ODS and for the Office of Surveillance and Epidemiology (OSE). Additionally, to treat the imbalance of authority that exists between the OND and OSE, the IOM report recommends changes that would result in the OND and the OSE having joint authority in postmarket regulatory actions.
The report states that the FDA's adverse event reporting system is "outdated and inefficient". The IOM suggests that the FDA revamp its technology and its methods for assessing both drug safety and drug efficacy so as to improve its risk-benefits analysis. Moreover, the IOM report suggests that the FDA restructure its organisation by creating additional leadership positions for experts and scientists. Similarly, the report recommends that, by increasing the number of epidemiologists and other such experts it employs, the FDA would increase its credibility and be better prepared to monitor complex scientific drug safety issues.
The IOM views the FDA's role as too much of an advisory or collaborative role. It recommends that Congress require postmarket trials and monitoring programmes and suggests restricted distribution of drugs to facilities, pharmacists or physicians with special training and expertise. Additionally, the report recommends that the FDA be allowed to enforce harsh penalties and sanctions against drug sponsors that fail to comply with drug safety monitoring standards. Finally, the report recommends that drug sponsors be required to accumulate and submit data relating to their products and label new products or new combinations of drugs with a special symbol.
The report finds that the public would benefit from having more information as to how drugs are studied. It recommends that the FDA increase its monitoring and establish stricter controls governing advertising directed at the public and prescribing physicians.
Finally, the report implores Congress to approve increased funding and resources for the agency so that it can conduct independent research and hire more effective leadership and expert personnel.
The findings and recommendations of the GAO and IOM reports are the subject of much debate. It is important for representatives of relevant industries to understand the criticisms of the FDA so they can serve as effective partners to the regulators in making the system work by providing the necessary scientific information to support their applications.
Jim O'Neal is a partner at Faegre & Benson. He was assisted by associate Davina Carson