Smallpox Vaccine Adverse Event Treatment Will Be Made Under CDC Contract

The Centers for Disease Control & Prevention is in the final stages of negotiating a contract for production of 30,000 vaccinia immune globulin intravenous treatments.

The product, used to treat adverse events from smallpox vaccinations, is expected to be available in 2003. A dollar amount for the contract has not yet been set.

CDC is understood to be considering two products as candidates for the single source contract. One, which has IND studies underway, would use the same source plasma (from vaccinated military recruits) as the intramuscular VIG product manufactured by Baxter in 1994.

CDC originally hoped to have the additional 30,000 VIGIV treatments available by the end of the year, around the time the Acambis/Baxter smallpox vaccine is expected to be delivered.

FDA's Center for Biologics Evaluation & Research is also examining immune globulin IV as an alternative to VIG. After investigating last year whether normal plasma donors have antivaccinia antibodies, CBER tested seven licensed IGIV products and is further investigating two as possible substitutes for VIGIV.

Currently, enough VIG is available under IND protocol to treat adverse events of approximately 675 adults, the number of adverse events that could be expected to result from the smallpox vaccination of 4 mil. to 6 mil. people.

The 30,000 doses would meet CDC's projections for the need for adverse event treatments in the event of a mass U.S. vaccination that did not include pregnant women. If pregnant women were also included, approximately 70,600 VIG doses would be needed.

Were widespread vaccination implemented more selectively, including using HIV, eczema and pregnancy screening, CDC projects 6,000 doses would be needed.

CDC is also considering whether VIG could be used as a prophylaxis for people unable to be vaccinated.

The existing VIG supply is adequate to treat potential adverse events from the 10,000 to 20,000 individuals who would receive smallpox vaccine under recommendations made by CDC's Advisory Committee on Immunization Practices, which met June 19-20 in Atlanta.

Smallpox response teams in states and municipalities should be vaccinated, ACIP said. These teams could include medical team leaders, public health advisors, medical epidemiologists, disease investigators, diagnostic laboratory scientists, nurses, security and law enforcement personnel, and medical personnel who would assist in the evaluation of suspected smallpox cases.

ACIP also recommended vaccination of healthcare personnel at pre-designated hospitals, who "would be pre-designated by appropriate bioterrorism and public health authorities, and personnel within these facilities would be designated by the hospital."

Wyeth's Dryvax is currently being offered for vaccination of response teams, but CDC will likely revisit the issue after the Acambis vaccine becomes available (¹ (Also see "Dryvax Likely Candidate For Smallpox Immunization Of First Responders" - Pink Sheet, 10 Jun, 2002.), p. 24).

"The ACIP recognizes that the implementation of the supplemental recommendations presented in this document requires addressing a number of issues, and that this will take time," the committee wrote.

"The issues include provider and public education, healthcare provider training, availability of vaccine and VIG, developing the appropriate investigational new drug protocols, screening, strategies to minimize vaccine wastage, vaccine adverse event surveillance, and other logistical and administrative issues."

The committee also voted to establish an oversight panel to monitor the use of smallpox vaccine in an effort to maximize safety, efficacy and efficiency. The new panel would act in an advisory role to ensure appropriate vaccine use and collect information on vaccine use as a federal policy on smallpox is developed. The proposal for the advisory group is expected to go to HHS Secretary Tommy Thompson in the next few weeks.

"One approach is to take advantage of experts that already are part of government advisory groups so that we don't have to go through the process of recruiting them and approving them. They already exist, and we can call upon them," said CDC Acting Deputy Director Julie Gerberding, MD, during a June teleconference announcing ACIP's recommendations.

CDC intends to conduct a logistics meeting in early July to plan how the vaccine will be distributed, and hopes to begin vaccinating groups of first responders this fall.

ACIP will review its recommendations "periodically, or more urgently if necessary. These reviews will include new information or developments related to smallpox disease, vaccinia vaccine (including vaccine licensure), risk of smallpox attack, vaccinia vaccine adverse events, and the experience gained in the implementation of the current recommendations."

ACIP will consider smallpox vaccine research issues, including recommendations for pediatric studies, at its Oct. 16-17 meeting.

The National Institutes of Health is looking at protocols for pediatric studies of Dryvax. Acambis does not currently have any plans to do pediatric studies for the cell culture vaccines it is developing, although the company is in discussions with NIH and CDC on whether to do pediatric studies instead of relying on adult data.

The American Academy of Pediatrics' Committee on Infectious Diseases supports pediatric studies with the Acambis product and is concerned that Acambis has not moved forward with the studies.

NIH and Wyeth have been discussing whether the one to five dilution Dryvax vaccine should be used in children, specifically regarding a study with Dryvax in two- to four-year olds. NIH hopes that those studies will provide a framework for studies of the cell culture vaccine.

Fifty-four mil. doses of the Acambis 1000 cell culture vaccinia vaccine are expected to become available for use under an IND in early FY 2003. An additional 155 mil. doses of the Acambis 2000 cell culture vaccinia are expected to become available for use under an IND in October; the vaccine has been produced and is in the vial filling phase.

The Acambis product will be used for pre-exposure immunization after Phase II studies are completed. Acambis is expected to file a BLA for the product in the third quarter 2003 (² (Also see "Acambis Smallpox Vaccine FDA Review Expected In Third Quarter 2003" - Pink Sheet, 3 Dec, 2001.), p. 4).