title: Regulatory aspects of oncology drug safety evaluation: past practice, current issues, and the challenge of new drugs.
abstract: The drug development of new anti-cancer agents is streamlined in response to the urgency of bringing effective drugs to market for patients with limited life expectancy. FDA's regulation of oncology drugs has evolved from the practices set forth in Arnold Lehman's seminal work published in the 1950s through the current drafting of a new International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) safety guidance for anti-cancer drug nonclinical evaluations. The ICH combines the efforts of the regulatory authorities of Europe, Japan, and the United States and the pharmaceutical industry from these three regions to streamline the scientific and technical aspects of drug development. The recent development of new oncology drug classes with novel mechanisms of action has improved survival rates for some cancers but also brings new challenges for safety evaluation. Here we present the legacy of Lehman and colleagues in the context of past and present oncology drug development practices and focus on some of the current issues at the center of an evolving harmonization process that will generate a new safety guidance for oncology drugs, ICH S9. The purpose of this new guidance will be to facilitate oncology drug development on a global scale by standardizing regional safety requirements.
authors.affiliation: Division of Drug Oncology Products, Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring MD, 20993, USA. hans.rosenfeldt@fda.hhs.gov <hans.rosenfeldt@fda.hhs.gov>
authors.forename: Hans
authors.initials: H
authors.lastname: Rosenfeldt
authors.forename: Timothy
authors.initials: T
authors.lastname: Kropp
authors.forename: Kimberly
authors.initials: K
authors.lastname: Benson
authors.forename: M Stacey
authors.initials: MS
authors.lastname: Ricci
authors.forename: W David
authors.initials: WD
authors.lastname: McGuinn
authors.forename: S Leigh
authors.initials: SL
authors.lastname: Verbois
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000633:toxicity*; D055808:Drug Discovery; D015507:Drugs, Investigational / Q000009:adverse effects; D017408:Guidelines as Topic; D006801:Humans; D007880:Legislation, Drug / Q000639:trends*; D009369:Neoplasms / Q000188:drug therapy; D012098:Reproduction / Q000187:drug effects; D012449:Safety; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000970:Antineoplastic Agents; D015507:Drugs, Investigational