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OPV Stockpiling in the United States

Trudy V. Murphy, M.D.National Immunization ProgramCenters for Disease Control and

Prevention

February 5, 2003

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Is the US at Risk of an Outbreak of Poliomyelitis?

• US has high vaccination coverage –1995 -1999 National Immunization

Survey, parents of 1.9% - 3.1% of children reported child had no poliovirus vaccine by 19-35 months of age

• Western Hemisphere certified free of indigenous wild poliovirus in 1994

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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

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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

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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

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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

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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 campaignPrevots R. CID 1998;26:419

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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

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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

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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

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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.

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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

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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

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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

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Potential Interim Stockpile Wyeth-Lederle OPV (Expired)

• ~800,000 doses, expired Nov. 2002• Potency test ~quarterly; Sept. 2002• CDC application for IND incomplete• Manufacturer requests no release of

OPV unless Government approves request for indemnification (Public Law 85-804) and contract reflects approval by Secretary of HHS

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First Solicitation for StockpileNon-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

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Second Solicitation for StockpileNon-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

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OPV under IND Covered byNational 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

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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

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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.