OPV Stockpiling in the United States

1
OPV Stockpiling in the United States
Trudy V. Murphy, M.D. National Immunization
Program Centers for Disease Control and
Prevention February 5, 2003
2
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

3
Outbreaks of Poliomyelitis in Countries with
High Vaccine Coverage

• Pockets of under-vaccination -Religious
  communities
• -Vaccine objectors
• -Refugees, immigrants

Patriarca P. JID 1997175S165
4
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 1997175S165
5
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

6
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

7
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 199826419
8
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 198611427 Oostvogel PM. Lancet
1994344665
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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

10
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

11
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.

12
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

13
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

14
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

15
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

17
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

18
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.