Analysis of the Generic Drugs Approved by the US FDA between 1980 and 2009

OBJECTIVES: Generic market competition reduces drug prices and increases access to pharmaceuticals after expiration of patents and market exclusivity periods. This study assessed the characteristics of generic approvals and the time from originator drug approval to first generic entry for drugs approved by the FDA in the period 1980-2009. METHODS: The study included all new molecular entities (NMEs) and therapeutic biologic applications (BLAs) approved by the FDA in the study period. Data derived from the FDA and were updated through 12/31/2009. Differences between group means and between proportions were assessed using t-test and chi-square test, respectively. Significant level was set at 0.05. RESULTS: The FDA approved 739 NMEs and 75 BLAs during the study period. After excluding drugs discontinuations, the analysis included 625 marketed NMEs. The FDA approved at least one abbreviated new drug application (ANDA) for 39.4% of marketed NMEs. There were ANDA approvals for 3 discontinued drugs. BLAs had not generic competition because a process for approval of generic BLAs has not been passed by Congress. There were 175 Paragraph IV patent certifications (required for ANDAs for originator products with unexpired patents listed in the FDA Orange Book-OB) for the NMEs approved after the Hatch-Waxman Act (1984). Paragraph IV certifications were filed for 50.0% of the 180 ANDAs for marketed NMEs approved after the Hatch-Waxman Act implementation. The patent and market exclusivity of 28.5% of the NMEs with generic competition had not expired at the moment of ANDA approval. There were 130 marketed NMEs without patents and market exclusivity listed in the OB that did not have ANDA approval. Orphan drugs had a higher percentage of NMEs without patent and market exclusivity and without ANDA approvals (61.5%) than non-orphan drugs (40.8%) (p<.01). No significant differences were found in ANDA approvals between priority and standard review drugs. Time from NDA approval to generic entry was on average 11.9±4.2 years (n=249), and varied by therapeutic class from 9.4±3.4 years for musculo-skeletal ANDAs (n=17) to 16.5±4.1 for dermatological ANDAs (n=12)(p<0.001). The top classes by number of ANDA approvals were cardiovascular (n=54, 11.4±3.5 yrs), nervous system (n=50; 10.2±3.2 yrs) and antiinfectives (n=30; 14.0±4.3 yrs). CONCLUSIONS: A large percentage of ANDA approvals had Paragraph IV certifications for patents listed in the OB that were not valid or enforceable. Orphan drugs had less generic competition than drugs for larger patient populations. There is a need for establishing a regulatory system for biologic generic approval.