TM OPV Stockpiling in the United States Trudy V. Murphy, M.D. National Immunization Program Centers for Disease Control and Prevention February 5, 2003

TM Is the US at Risk of an Outbreak of Poliomyelitis? US has high vaccination coverage – National Immunization Survey, parents of 1.9% - 3.1% of children reported child had no poliovirus vaccine by months of age Western Hemisphere certified free of indigenous wild poliovirus in 1994

TM Outbreaks of Poliomyelitis in Countries with High Vaccine Coverage Pockets of under-vaccination -Religious communities -Vaccine objectors -Refugees, immigrants Patriarca P. JID 1997;175;S165

TM Potential Sources of Neurovirulent Polioviruses Eradication of polioviruses incomplete –Endemic areas –Vaccine-derived strains –Laboratory containment The U.S. remains at risk of an outbreak of poliomyelitis Patriarca P. JID 1997;175;S165

TM Emergency Response to an Outbreak of Poliomyelitis in U.S. Inactivated (IPV) and live attenuated oral (OPV) poliovirus vaccines induce similar levels of individual protection after three doses IPV and OPV differ in their risks and effectiveness when used to control an outbreak of poliomyelitis

TM OPV Vaccine of Choice in Outbreak Settings Public health goal is to eradicate outbreak strain Extensive experience using mass campaigns demonstrates OPV interrupts transmission polioviruses Interferes with or reduces replication of outbreak strain at mucosal level

TM OPV Halts Circulation of Poliovirus OPV used in Albania, 1996: –80% population vaccinated in mass campaign –90% decrease in cases within 2 weeks –No case poliomyelitis after second mass campaign Prevots R. CID 1998;26:419

TM IPV and Outbreaks of Poliomyelitis No example of successful control of an outbreak using IPV Countries that use all-IPV for routine vaccination, used OPV for control of outbreaks (Netherlands, Finland) Hovi T, Lancet 1986;1:1427; Oostvogel PM. Lancet 1994;344:665

TM Challenges of Response to an Outbreak of Poliomyelitis Vaccine acceptance among objectors may not be optimal regardless of type Risk of VAPP after OPV is established, but less than the risk of poliomyelitis in an outbreak

TM Challenges of Response to an Outbreak of Poliomyelitis IPV is vaccine of choice for –immediate vaccination –the immunodeficient and their contacts –adults (usually) –persons refusing OPV

TM U.S. Uses IPV for Routine Poliovirus Vaccination In January 2000, the ACIP recommended IPV for routine vaccination against poliomyelitis to avoid the rare but established risk of vaccine associated paralytic poliomyelitis (VAPP) OPV no longer is manufactured in U.S.

TM Options for Obtaining OPV Administer remaining U.S. licensed, expired OPV as investigational new drug (IND), given adequate potency, sufficient supply Establish stockpile of non-U.S. OPV Administer under IND Administer as U.S. licensed product

TM Desirable Characteristics of OPV Product for U.S. Stockpile Trivalent OPV Extensive (global) use, meets U.S. or WHO standards for safety, potency ~ 4,000,000 doses; available on staggered timeline Rotation with OPV in active market to avoid replacing expired vaccine

TM Status of U.S. OPV Stockpile Interim stockpile of licensed, expired Wyeth-Lederle OPV (IND) First solicitation for non-U.S. made OPV Planned second solicitation for non- U.S. made OPV Hurdles to establish U.S. OPV stockpile

TM Potential Interim Stockpile Wyeth-Lederle OPV (Expired) ~800,000 doses, expired Nov Potency test ~quarterly; Sept CDC application for IND incomplete Manufacturer requests no release of OPV unless Government approves request for indemnification (Public Law ) and contract reflects approval by Secretary of HHS

TM First Solicitation for Stockpile Non-U.S. Made OPV Initiated June 1999; preference for product licensed in U.S. One respondent Product required IND Lacked desirable characteristics Liability issues unresolved Negotiations ended February 2002

TM Second Solicitation for Stockpile Non-U.S. Made OPV CDC intends to issue in near future 4,000,000 doses, trivalent OPV IND use (U.S. license preferred) One year; option 9 additional years Liability issues remain

TM OPV under IND Covered by National Childhood Vaccine Injury Act OPV listed in Vaccine Injury Table Vaccine taxed on use No distinction made between investigational and approved vaccines for purposes of injury compensation Final determination resides with court August 2001

TM Hurdles to Establish OPV Stockpile for Emergency Use in the U.S. Manufacturer interest –Future demand for OPV uncertain –Requirements to obtain IND (U.S. license) perceived as onerous, expensive –Assurance of full indemnification CDC to hold IND –Protocol, IRB

TM Conclusion All groups recommend OPV to control an outbreak of poliomyelitis; use of OPV is supported by experience and scientific evidence A stockpile of OPV meeting FDA requirements for use is the foundation for preparedness in the event of an outbreak of poliomyelitis in the U.S.