Center for Drug Evaluation and Research growing crisis around HIV testing and treatment and an inter-agency dispute between officials from the former Bureau of Drugs and officials from the former Bureau of Biologics over whether to approve Genentech's Activase (tissue plasminogen activator) led to the split. In its original form, CDER was composed of six offices: Management, Compliance, Drug Standards, Drug Evaluation I, Drug Evaluation II, Epidemiology and Biostatistics, and Research Resources. The Division of Antiviral Products was added in 1989 under Drug Evaluation II due to the large amount of drugs proposed for treating AIDS. The Office of Generic Drugs was also formed. In 2002,
Center for Drug Evaluation and Research new drugs on healthy volunteers in small groups to determine the maximum safe dosage. Phase II trials involve patients with the condition the drug is intended to treat to test for safety and minimal efficacy in a somewhat larger group of people. Phase III trials involve one to five thousand patients to determine whether the drug is effective in treating the condition it is intended to be used for. After this stage, a new drug application is submitted. If the drug is approved, stage IV trials are conducted after marketing to ensure there are no adverse effects or long term