title: Stability of live attenuated rotavirus vaccine with selected preservatives and primary containers.
abstract: Rotavirus infection, which can be prevented by vaccination, is responsible for a high burden of acute gastroenteritis disease in children, especially in low-income countries. An appropriate formulation, packaging, and delivery device for oral rotavirus vaccine has the potential to reduce the manufacturing cost of the vaccine and the logistical impact associated with introduction of a new vaccine, simplify the vaccination procedure, and ensure that the vaccine is safely and accurately delivered to children. Single-dose prefilled presentations can be easy to use; however, they are typically more expensive, can be a bottleneck during production, and occupy a greater volume per dose vis-à-vis supply chain storage and medical waste disposal, which is a challenge in low-resource settings. Multi-dose presentations used thus far have other issues, including increased wastage of vaccine and the need for separate delivery devices. In this study, the goals were to evaluate both the technical feasibility of using preservatives to develop a liquid multi-dose formulation and the primary packaging alternatives for orally delivered, liquid rotavirus vaccines. The feasibility evaluation included evaluation of commonly used preservatives for compatibility with rotavirus vaccines and stability testing of rotavirus vaccine in various primary containers, including Lameplast's plastic tubes, BD's oral dispenser version of Uniject™ (Uniject DP), rommelag's blow-fill-seal containers, and MEDInstill's multi-dose vial and pouch. These presentations were compared to a standard glass vial. The results showed that none of the preservatives tested were compatible with a live attenuated rotavirus vaccine because they had a detrimental effect on the viability of the virus. In the presence of preservatives, vaccine virus titers declined to undetectable levels within 1 month. The vaccine formulation without preservatives maintained a stability profile over 12 months in all primary containers that was similar to its profile in standard glass vials. This study demonstrates that there are multiple options for the primary container for rotavirus vaccines intended for oral delivery. Selection of an optimal primary container should take into consideration additional factors, including stability as well as cold chain volume, usability, cost, and manufacturing feasibility.
authors.affiliation: PATH, Seattle, WA, USA. Electronic address: mlal@path.org.
authors.forename: Manjari
authors.initials: M
authors.lastname: Lal
authors.affiliation: PATH, Seattle, WA, USA.
authors.forename: Courtney
authors.initials: C
authors.lastname: Jarrahian
authors.affiliation: PATH, Seattle, WA, USA.
authors.forename: Changcheng
authors.initials: C
authors.lastname: Zhu
authors.affiliation: PATH, Seattle, WA, USA; Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Hosken
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: Chris L
authors.initials: CL
authors.lastname: McClurkan
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA, USA; Department of Laboratory Medicine, University of Washington, Seattle, WA, USA; Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Global Health, University of Washington, Seattle, WA, USA; Benaroya Research Institute, Seattle, WA, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Koelle
authors.affiliation: PATH, Seattle, WA, USA.
authors.forename: Eugene
authors.initials: E
authors.lastname: Saxon
authors.affiliation: PATH, Seattle, WA, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Roehrig
authors.affiliation: PATH, Seattle, WA, USA.
authors.forename: Darin
authors.initials: D
authors.lastname: Zehrung
authors.affiliation: PATH, Seattle, WA, USA.
authors.forename: Dexiang
authors.initials: D
authors.lastname: Chen
mesh_terms: D000284:Administration, Oral; D004349:Drug Packaging; D005240:Feasibility Studies; D005759:Gastroenteritis / Q000517:prevention & control; D005898:Glass; D006801:Humans; D050296:Microbial Viability; D011310:Preservatives, Pharmaceutical; D012401:Rotavirus / Q000502:physiology; D012400:Rotavirus Infections / Q000517:prevention & control; D022243:Rotavirus Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000600:supply & distribution; D014611:Vaccination / Q000379:methods; D064166:Vaccine Potency; D014613:Vaccines, Attenuated / Q000737:chemistry / Q000276:immunology
chemical_list: D011310:Preservatives, Pharmaceutical; D022243:Rotavirus Vaccines; D014613:Vaccines, Attenuated
keywords: Delivery device; Multi-mono-dose; Oral vaccine; Preservatives; Primary container; Rotavirus