title: Support for the revocation of general safety test regulations in biologics license applications.
abstract: The United States Food and Drug Administration recently removed the requirement for a General Safety Test (GST) for biologics in the Code of Federal Regulations (21 CFR 610.11). The GST, as well as abnormal toxicity (European Pharmacopeia) and innocuity tests (World Health Organization), were designed to test for extraneous toxic contaminants on each product lot intended for human use. Tests require one-week observations for general health and weight following injection of specified volumes of product batches into guinea pigs and mice. At the volumes specified, dose-related toxicity may result when the product is pharmacologically active in rodents. With vaccines, required doses may be > 3 logs higher than intended human dose on a weight-adjusted basis and if an immune modulatory adjuvant is included, systemic immune hyperactivation may cause toxicity. Herein, using the CpG/alum adjuvant combination we evaluated the different test protocols and showed their unsuitability for this adjuvant combination.
authors.affiliation: Pfizer Vaccine Immunotherapeutics, Ottawa Laboratories, Ottawa, ON, Canada.
authors.forename: Dana M
authors.initials: DM
authors.lastname: Evans
authors.affiliation: Pfizer Biotherapeutics Pharmaceutical Sciences, St. Louis, MO, USA.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Thorn
authors.affiliation: Pfizer Worldwide R & D, Peapack, NJ, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Arch-Douglas
authors.affiliation: Pfizer Biotherapeutics Pharmaceutical Sciences, St. Louis, MO, USA.
authors.forename: Justin B
authors.initials: JB
authors.lastname: Sperry
authors.affiliation: Pfizer Biotherapeutics Pharmaceutical Sciences, St. Louis, MO, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Thompson
authors.affiliation: Pfizer Vaccine Immunotherapeutics, Ottawa Laboratories, Ottawa, ON, Canada.
authors.forename: Heather L
authors.initials: HL
authors.lastname: Davis
authors.affiliation: Pfizer Vaccine Immunotherapeutics, Ottawa Laboratories, Ottawa, ON, Canada. Electronic address: michael.mccluskie@pfizer.com.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: McCluskie
mesh_terms: D000818:Animals; D001688:Biological Products / Q000592:standards*; D003257:Consumer Product Safety / Q000331:legislation & jurisprudence* / Q000592:standards*; D017277:Drug Approval / Q000331:legislation & jurisprudence*; D006168:Guinea Pigs; D006801:Humans; D008004:Licensure / Q000331:legislation & jurisprudence*; D051379:Mice; D018675:Toxicity Tests / Q000379:methods; D014481:United States; D014486:United States Food and Drug Administration; D014944:World Health Organization
chemical_list: D001688:Biological Products
keywords: Adjuvant; CpG; Oligodeoxynucleotide; Pharmacology; Safety; Vaccine