(including imatinib). The sample included 275 therapeutic products and 4 drugs used as diagnostic agents. The FDA-defined regulatory classification of orphan-designated products could be identified for 208 products. Among that group, there were 133 products (64 percent) classified as NMEs.18 Information about review status was assessed for drugs approved after 1992, when the priority review classification was created; among orphan products, 144 (70 percent) were listed as Priority drugs, whereas 61 (30 percent) were classified as Standard.

Among the 279 products, small molecules (183, 65 percent) outnumbered biologic-based orphan products (96, 35 percent), although the ratio has changed in recent years as the number of new biologic products overall has increased. From 1990 to 1999, 27 orphan products were approved under a BLA (21 percent) and 101 were approved under an NDA (79 percent), while from 2000 to 2009, 32 products were approved under a BLA (29 percent) and 78 were approved under an NDA (71 percent). In the full product group, there were 214 (77 percent) products approved under an NDA and 65 (23 percent) approved under a BLA.19 Among the biologic-based drugs were 24 hormones, 18 clotting factors, 12 enzymes, 11 monoclonal antibodies, 9 antibodies, 9 protein conjugates, 7 cytokines, 4 proteins, and 2 biological mixtures.

The greatest number of the 279 orphan products was approved primarily for use in oncology-related conditions (79, 28 percent), predominantly chemotherapy, but also management of cancer-related conditions such as electrolyte disturbances and adverse effects of drug management. In the second-largest group, 43 products (15 percent) were approved for various infectious diseases, including HIV/AIDS-related conditions. The next largest clinical indications were neurological or psychiatric conditions (31, 11 percent) and enzyme deficiencies (28, 10 percent).20 Renal, cardiovascular, rheumatologic, dermatological, gastroenterological, and pulmonary conditions each made up less than 10 percent of the approvals. Thirty-six (13 percent) different products had indications specifically for pediatric


By way of comparison, FDA officials report that the overall number of NMEs and significant new BLAs for the period 1983 to 2009 was 178 or 64 percent of the total NDAs and BLAs.


These numbers differ somewhat from the numbers of small molecules and biologic-based orphan products because not all biologic-based drugs are reviewed via a BLA. For historical reasons, some biologic-based products, including monoclonal antibodies and hormones, have been regulated under the NDA process.


Enzyme deficiencies include all replacement products (clotting factors, etc.) as well as other therapies aimed at treating patients with congenital enzyme deficiencies through exogenous administration of the enzyme itself (e.g., pegademase bovine [Adagen] for ADA [adenosine deaminase] deficiency in patients with severe combined immunodeficiency). By contrast, hormone replacement therapies such as somatropin were defined as being endocrine products.

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