title: Duration of chronic toxicity studies for biotechnology-derived pharmaceuticals: is 6 months still appropriate?
abstract: For chronic use biotechnology-derived pharmaceuticals, toxicity studies of 6 months have generally been accepted for regulatory approval. This review assessed the data for 23 approved biotechnology-derived pharmaceuticals to determine whether the studies conducted were predictive of human safety and whether there is new data from approved products indicating that longer than 6 months is necessary. This assessment involved three approaches; whether new toxicities were identified at >6 months, similarity of findings between 6 months and shorter studies and predictivity of clinical adverse events. In two cases there were apparently new findings in studies >6 months. On examination however, one of these cases was a well established risk with foreign protein administration to animals (adalimumab). For insulin aspart, the 12 month study identified tumors not seen in shorter term studies, however, determination of carcinogenic potential is not a goal of chronic toxicity studies and is addressed by separate studies. In most cases the toxicology studies were predictive of common clinical adverse reactions, but were poorly predictive of rare clinical events or some serious adverse reactions. Although specific circumstances may require a longer study, this review indicates no new data is available to refute the utility of 6 month studies to support chronic clinical dosing with biotechnology-derived pharmaceuticals.
authors.affiliation: Biogen Idec Inc., Fourteen Cambridge Center, Cambridge, MA 02141, USA. janet.clarke@biogenidec.com
authors.forename: Janet
authors.initials: J
authors.lastname: Clarke
authors.forename: Christopher
authors.initials: C
authors.lastname: Hurst
authors.forename: Pauline
authors.initials: P
authors.lastname: Martin
authors.forename: John
authors.initials: J
authors.lastname: Vahle
authors.forename: Rafael
authors.initials: R
authors.lastname: Ponce
authors.forename: Barbara
authors.initials: B
authors.lastname: Mounho
authors.forename: Shawn
authors.initials: S
authors.lastname: Heidel
authors.forename: Laura
authors.initials: L
authors.lastname: Andrews
authors.forename: Theresa
authors.initials: T
authors.lastname: Reynolds
authors.forename: Joy
authors.initials: J
authors.lastname: Cavagnaro
mesh_terms: D000818:Animals; D001709:Biotechnology; D004353:Drug Evaluation, Preclinical; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D004364:Pharmaceutical Preparations; D036401:Toxicity Tests, Chronic
chemical_list: D004364:Pharmaceutical Preparations