title: Adventitious agents in viral vaccines: lessons learned from 4 case studies.
abstract: Since the earliest days of biological product manufacture, there have been a number of instances where laboratory studies provided evidence for the presence of adventitious agents in a marketed product. Lessons learned from such events can be used to strengthen regulatory preparedness for the future. We have therefore selected four instances where an adventitious agent, or a signal suggesting the presence of an agent, was found in a viral vaccine, and have developed a case study for each. The four cases are: a) SV40 in polio vaccines; b) bacteriophage in measles and polio vaccines; c) reverse transcriptase in measles and mumps vaccines; and d) porcine circovirus and porcine circovirus DNA sequences in rotavirus vaccines. The lessons learned from each event are discussed. Based in part on those experiences, certain scientific principles have been identified by WHO that should be considered in regulatory risk evaluation if an adventitious agent is found in a marketed vaccine in the future.
authors.affiliation: IABS, POB 1925, Palm Springs, CA 92263, USA. Electronic address: petriccianiIABS@aol.com.
authors.forename: John
authors.initials: J
authors.lastname: Petricciani
authors.affiliation: Grimalkin Partners, 13401 Norden Drive, Silver Spring, MD 20906, USA. Electronic address: rsheets@grimalkinpartners.com.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Sheets
authors.affiliation: 3 The Farthings, Kingston Upon Thames, Surrey KT2 7PT, UK. Electronic address: elwyn.griffiths2011@btinternet.com.
authors.forename: Elwyn
authors.initials: E
authors.lastname: Griffiths
authors.affiliation: Group Lead, Norms and Standards for Biologicals, Department of Essential Medicines and Health Products (EMP) Health Systems and Innovation (HIS) Cluster, WHO L276, Avenue Appia 20, 1211 Geneva 27, Switzerland. Electronic address: knezevici@who.int.
authors.forename: Ivana
authors.initials: I
authors.lastname: Knezevic
mesh_terms: D000818:Animals; D001435:Bacteriophages / Q000302:isolation & purification; D001688:Biological Products / Q000009:adverse effects / Q000592:standards; D017925:Circovirus / Q000235:genetics / Q000302:isolation & purification; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D004340:Drug Contamination / Q000517:prevention & control; D006801:Humans; D022542:Measles-Mumps-Rubella Vaccine / Q000009:adverse effects; D009108:Mumps Vaccine / Q000009:adverse effects; D023321:Poliovirus Vaccines / Q000009:adverse effects; D011634:Public Health; D012194:RNA-Directed DNA Polymerase / Q000302:isolation & purification; D022243:Rotavirus Vaccines / Q000009:adverse effects; D013539:Simian virus 40 / Q000302:isolation & purification; D014765:Viral Vaccines / Q000009:adverse effects* / Q000302:isolation & purification / Q000592:standards*; D014944:World Health Organization
chemical_list: D001688:Biological Products; D004279:DNA, Viral; D022542:Measles-Mumps-Rubella Vaccine; D009108:Mumps Vaccine; D023321:Poliovirus Vaccines; D022243:Rotavirus Vaccines; D014765:Viral Vaccines; D012194:RNA-Directed DNA Polymerase
keywords: Adventitious agents; Regulatory preparedness; Vaccines; Viral contamination