title: Proof of concept for a banding scheme to support risk assessments related to multi-product biologics manufacturing.
abstract: A banding scheme theory has been proposed to assess the potency/toxicity of biologics and assist with decisions regarding the introduction of new biologic products into existing manufacturing facilities. The current work was conducted to provide a practical example of how this scheme could be applied. Information was identified for representatives from the following four proposed bands: Band A (lethal toxins); Band B (toxins and apoptosis signals); Band C (cytokines and growth factors); and Band D (antibodies, antibody fragments, scaffold molecules, and insulins). The potency/toxicity of the representative substances was confirmed as follows: Band A, low nanogram quantities exert lethal effects; Band B, repeated administration of microgram quantities is tolerated in humans; Band C, endogenous substances and recombinant versions administered to patients in low (interferons), intermediate (growth factors), and high (interleukins) microgram doses, often on a chronic basis; and Band D, endogenous substances present or produced in the body in milligram quantities per day (insulin, collagen) or protein therapeutics administered in milligram quantities per dose (mAbs). This work confirms that substances in Bands A, B, C, and D represent very high, high, medium, and low concern with regard to risk of cross-contamination in manufacturing facilities, thus supporting the proposed banding scheme.
authors.affiliation: Intertek Scientific & Regulatory Consultancy, Mississauga, ON, Canada. Electronic address: jeffrey.card@intertek.com.
authors.forename: Jeffrey W
authors.initials: JW
authors.lastname: Card
authors.affiliation: Intertek Scientific & Regulatory Consultancy, Mississauga, ON, Canada.
authors.forename: Hana
authors.initials: H
authors.lastname: Fikree
authors.affiliation: Intertek Scientific & Regulatory Consultancy, Mississauga, ON, Canada.
authors.forename: Lois A
authors.initials: LA
authors.lastname: Haighton
authors.affiliation: The Quantic Group, Livingston, NJ, USA.
authors.forename: James
authors.initials: J
authors.lastname: Blackwell
authors.affiliation: Shire, Lexington, MA, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Felice
authors.affiliation: Dimension Therapeutics, Inc., Cambridge, MA, USA.
authors.forename: Teresa L
authors.initials: TL
authors.lastname: Wright
mesh_terms: D001688:Biological Products / Q000592:standards*; D004340:Drug Contamination / Q000517:prevention & control*; D004345:Drug Industry / Q000379:methods / Q000592:standards*; D006801:Humans; D066192:Manufacturing Industry / Q000379:methods / Q000592:standards; D018570:Risk Assessment / Q000379:methods / Q000592:standards
chemical_list: D001688:Biological Products
keywords: Biologics; Cleaning validation; Cross-contamination; Impurities; Manufacturing; Risk assessment