Drug applications—including NDAs, BLAs, and efficacy supplements— are reviewed primarily by FDA’s Center for Drug Evaluation and Research (CDER), with a smaller proportion reviewed by the Center for Prior to submission of an Biologics Evaluation and Research (CBER). When we refer to consumer advocacy groups, we are referring to groups that advocate on behalf of consumers and patients. application, sponsors may choose to seek accelerated approval status if the drug is intended to treat a serious or life-threatening illness (such as cancer) and has the potential to provide meaningful therapeutic benefit to patients over existing treatments. Sponsors of a drug with accelerated approval status may be granted approval on the basis of clinical trials conducted using a surrogate endpoint—such as a laboratory measurement or physical sign—as an indirect or substitute measurement for a clinically meaningful outcome such as survival. According to FDA, the agency generally also speeds its review of drug applications with accelerated approval status by granting them priority review, although priority review can also be granted to an application without accelerated approval status. FDA grants priority review for applications that it expects, if approved, would provide significant therapeutic benefits, compared to available drugs, in the treatment, diagnosis, or prevention of a disease. Applications for which there are no perceived significant therapeutic benefits beyond those for available drugs are granted standard review. See 21 U.S.C. § 355(d); 42 U.S.C. § 262(j). prevent FDA from approving the application. In response, sponsors can submit additional information to FDA in the form of amendments to the application. Certain applications are also subject to review by an independent advisory committee. FDA convenes advisory committees to provide independent expertise and technical assistance to help the agency make decisions about drug products. Additionally, FDA might require the sponsor to submit a Risk Evaluation and Mitigation Strategy (REMS) for the drug under review to ensure that the benefits of the drug outweigh its risks. FDA review time for an original application is calculated as the time elapsed from the date FDA receives the application and associated user fee to the date it issues an action letter; it is calculated using only the first review cycle and therefore does not include any time that may elapse while FDA is waiting for a sponsor to respond to FDA’s first-cycle action letter or any review time that elapses during subsequent review cycles. In order to close the review cycle for NDAs, BLAs, and efficacy supplements, FDA must complete its review and issue an approval letter, a denial letter, or a “complete response” letter (i.e., a letter delineating any problems FDA identified in the application that prevented it from being approved). The review cycle will also be closed if the application is withdrawn by the sponsor. The date on which one of these actions occurs is used to determine whether the review was completed within the PDUFA goal time frame. If FDA issues a complete response letter, the sponsor may choose to submit a revised application to FDA. These are known as resubmissions and their review is covered under the user fee paid with the original submission. Resubmissions are classified as Class 1 or Class 2 according to the complexity of the information they contain, with Class 2 being the most complex. Although the prescription drug performance goals have continued to evolve with each reauthorization of the prescription drug user fee program, the goals for NDAs, BLAs, and efficacy supplements have remained fairly stable for recent cohorts—a cohort being comprised of all the submissions of a certain type filed in the same fiscal year (see table 1). For standard NDAs, BLAs, and efficacy supplements, the current goal was phased in until it reached the current level (90 percent of reviews completed within 10 months) in FY 2002. Similarly, the goal for Class 1 NDA and BLA resubmissions was phased in, reaching its current level of 90 percent of reviews completed within 2 months in FY 2001. FDA can extend the review time frame for NDAs, BLAs, or Class 2 resubmissions by 3 months if it receives a major amendment to the application from the sponsor within 3 months of the goal date. FDA met most of its performance goals for priority and standard original NDA and BLA submissions for the FYs 2000 through 2010 cohorts. However, the average FDA review time increased slightly during this period for both priority and standard NDAs and BLAs. The percentage of FDA first-cycle approvals for both priority and standard NDAs and BLAs generally increased from FY 2000 through FY 2010; however, the percentage of first-cycle approvals has decreased for priority NDAs and BLAs since FY 2007. FDA met most of its performance goals for priority and standard original NDA and BLA submissions during our analysis period by issuing the proportion of action letters specified in the performance goals within the goal time frames. Specifically, for priority original NDAs and BLAs, FDA met the performance goals for 10 of the 11 completed cohorts we examined (see fig. 1). FDA also met the performance goals for 10 of the 11 completed standard NDA and BLA cohorts we examined. However, FDA did not meet the goals (i.e., issue the specified proportion of action letters within the goal time frames) for priority or standard NDAs and BLAs in the FY 2008 cohort. FDA and industry stakeholders we interviewed suggested that the reason FDA did not meet the goals for this cohort was that extra time was required for implementation of REMS requirements, which were introduced as part of the implementation of FDAAA. Although the FY 2011 cohort was still incomplete at the time we received FDA’s data, FDA was meeting the goals for both priority and standard original NDAs and BLAs on which it had taken action. For the subset of priority NDAs and BLAs that were for innovative drugs, FDA met the performance goals for 9 of the 11 completed cohorts—all cohorts except FYs 2008 and 2009. For the subset of standard NDAs and BLAs that were for innovative drugs, FDA also met the performance goals for 9 of the 11 completed cohorts—all cohorts except FYs 2007 and 2008. For the incomplete FY 2011 cohort, FDA was meeting the goals for the subsets of both priority and standard NDAs and BLAs that were for innovative drugs. If FDA issues a complete response letter to the sponsor noting deficiencies with the original submission, the sponsor can resubmit the application with the deficiencies addressed. For Class I NDA and BLA resubmissions, FDA met the performance goals for 8 of the 11 completed cohorts we examined. For Class 2 NDA and BLA resubmissions, FDA met the performance goals for 10 of the 11 completed cohorts we examined. Although the FY 2011 cohort was still incomplete at the time we received FDA’s data, FDA was meeting the goals for both the Class 1 resubmissions and the Class 2 resubmissions on which it had taken action. Overall, average FDA review time—the time elapsed from when FDA received a submission until it issued an action letter—increased slightly from FY 2000 through FY 2010 for both priority and standard NDAs and BLAs. There was a larger increase in average review time for both types of applications beginning in FY 2006. However, average review time began decreasing after FY 2007 for standard applications and after FY 2008 for priority applications, bringing the review times back near the FY 2000 levels (see fig. 2). As mentioned previously, FDA and industry stakeholder groups noted the implementation of REMS requirements as a contributing factor to increased review times for the FY 2008 cohort. Although the FY 2011 cohort was still incomplete at the time we received FDA’s data, average FDA review time for applications on which FDA had taken action was 186 days for priority NDAs and BLAs and 308 days for standard NDAs and BLAs. Trends in average FDA review time for the subset of NDAs and BLAs that were for innovative drugs were similar to trends for all priority or standard NDAs and BLAs. For the subset of priority NDAs and BLAs that were for innovative drugs, average FDA review times were sometimes longer and sometimes shorter than those for all priority NDAs and BLAs; review times for the subset of standard NDAs and BLAs that were for innovative drugs were generally slightly longer than review times for all standard NDAs and BLAs. We were unable to calculate the average time to final decision for original NDAs and BLAs—that is, the average time elapsed between submission of an application and the sponsor’s withdrawal of the application or FDA’s issuance of an approval or denial action letter in the last completed review cycle. Time to final decision includes FDA review time as well as time that elapsed between review cycles while FDA was waiting for the sponsor to resubmit the application. We were unable to complete this calculation because most cohorts were still open for these purposes (i.e., fewer than 90 percent of submissions had received a final action such as approval, denial, or withdrawal). Specifically, for priority NDAs and BLAs, only four cohorts (FYs 2001, 2002, 2005, and 2006) had at least 90 percent of submissions closed, and for standard NDAs and BLAs, only one cohort (FY 2002) had at least 90 percent of submissions closed. (See app. I, table 4 for details.) As a result, there were too few completed cohorts available to calculate the time to final decision in a meaningful way. FDA may opt to consider an application withdrawn (and thus closed) if the sponsor fails to resubmit the application within 1 year after FDA issues a complete response letter. When we examined the open applications using this criterion, we identified 194 open NDAs and BLAs in FYs 2000 through 2010 for which FDA had issued a complete response letter in the most recent review cycle but had not yet received a resubmission from the sponsor. FDA had issued the complete response letter more than 1 year earlier for 162 (84 percent) of these applications.