Transcript FDA Regulation of Biologics

Why Smallpox Bioterrorism?
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Stable aerosol Virus
Easy to Produce
Infectious at low doses
Human to human
transmission
10 to 12 day incubation
period
High mortality rate (30%)
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CDC Materials
•Small Pox Vaccine History
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1000 AD - China, deliberate inoculation of smallpox
into skin or nares resulting in less severe smallpox
infection. Vaccinees could still transmit smallpox
1796 - Edward Jenner demonstrated that skin
inoculation of cowpox virus provided protection
against smallpox infection
1805 - Italy, first use of smallpox vaccine
manufactured on calf flank
1864 - Widespread recognition of utility of calf
flank smallpox vaccine
1940’s - Development of commercial process
for freeze-dried vaccine production (Collier)
Herd Immunity
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Smallpox Spreads to the Non-immune
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Immunization Slows the Spread
Dramatically
Epidemics Die Out Naturally
Herd Immunity Protects the
Unimmunized
Smallpox Vaccine
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Live Virus Vaccine (Vaccinia Virus)
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Crude Preparation We Have Now
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Not Cowpox, Might be Extinct Horsepox
Must be Infected to be Immune
Prepared from the skin of infected calves
Filtered, Cleaned (some), and Freeze-dried
New Vaccine is Clean, but still Live
Complications of Vaccination
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Local Lesion
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Progressive
(Disseminated)
Vaccina
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Can be Spread on the
Body and to Others
Deadly Like Smallpox,
but Less Contagious
Encephalitis
Heart Disease?
Historic Probability of Injury
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Small Risk from Bacterial and Viral
Contaminants
Small Risk of Allergic Reaction
35 Years Ago
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5.6M New and 8.6M Revaccinations a Year
9 deaths, 12 encephalitis/30-40% permanent
Death or Severe Permanent Injury 1/1,000,000
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Mostly among immunsupressed persons
Global Eradication Program
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1950 - Pan American Sanitary Organization
initiated hemisphere-wide eradication
program
1967 - Following USSR proposal (1958) WHO
initiated Global Eradication Program
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Based on Ring Immunization
Vaccinate All Contacts and their Contacts
Isolate Contacts for Incubation Period
Involuntary - Ignore Revisionist History
1977 - Oct. 26, 1977 last known naturally
occurring smallpox case recorded in Somalia
1980 - WHO announced world-wide eradication
Eradication Ended
Vaccinations
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Cost Benefit Analysis
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Vaccine was Very Cheap
Program Administration was Expensive
Risks of Vaccine Were Seen as
Outweighing Benefits
Stopped in the 1970s
Immunity Declines with Time
Universal Vulnerability
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Agriculture and Smallpox
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Isolated Communities
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Stays Endemic or Dies Out Forever
Most Communities had Significant
Immunity
Synchronous Infection
Break Down of Social Order
Now the Whole World is Susceptible
How Have Risks Changed?
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Immunosuppressed Persons Cannot
Fight the Virus and Develop Progressive
Vaccinia
Immunosuppression Was Rare in 1970
Immunosuppression is More Common
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HIV, Cancer Chemotherapy, Arthritis Drugs,
Organ Transplants
Role of Medical Care
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Smallpox
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Can Reduce Mortality with Medical Care
Huge Risk of Spreading Infection to Others
Very Sick Patients - Lots of Resources
Cannot Treat Mass Casualties
Vaccinia
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VIG - more will have to be made
Less sick patients - longer time
Complications Last time - 1947
New York Outbreak
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Case from Mexico
6,300,000 Vaccinated in a Month
3 Deaths from the Smallpox
6 Deaths from the Vaccine
Would Have Been Much Higher Without
Vaccination?
What would happen now?
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Assume 1,000,000 Vaccinated in Mass
Campaign with No Screening
Assume 1.0% Immunosuppressed
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10,000 Immunosuppressed Persons
Probably Low, Could be 2%+
Potentially 1-2,000+ Deaths and More
With Severe Illness