ATLANTA — Interim guidelines for use of rabies vaccine have been drafted by an ad hoc working group of the Centers for Disease Control and Prevention to address contingency plans in the event that the current “less than ideal” vaccine supply situation becomes an actual shortage.
At the summer meeting of the CDC's Advisory Committee on Immunization Practices (ACIP), CDC Rabies Program chief Charles E. Rupprecht, VMD, characterized the current rabies vaccine supply situation as being in a “yellow” phase, with “green” being the ability to meet all ACIP recommendations for both pre-exposure and postexposure prophylaxis and red being “critical,” where even those in greatest need would not be able to receive the vaccine (MMWR 2008;57[RR03]:1-26).
“Supplies of biologicals used in human rabies prophylaxis are expected to remain less than ideal over the next several years,” he said, adding that the CDC, along with the Food and Drug Administration, the Department of Health and Human Services, and national stakeholders “continue to work together toward productive solutions to mitigate current human rabies supply issues.”
In June 2007, Sanofi Pasteur Inc. began a planned renovation of its Imovax Rabies vaccine production facility in France to maintain compliance with both FDA and French regulatory requirements. The facility is scheduled to be approved and operational by mid- to late 2009. Prior to suspending production at that facility, the company had established an inventory based on historical levels of sales and projected market demand, Sanofi Pasteur's Dr. David Johnson informed the committee.
After the renovations began, Novartis, the only other supplier of rabies vaccine for the United States (RabAvert), experienced manufacturing problems that prevented them from meeting rabies vaccine supply projections. In early 2008, Novartis announced that it would supply RabAvert for postexposure prophylaxis (PEP) use only. Consequently, in May 2008, Sanofi Pasteur was forced to do the same, as the increase in demand for Imovax began outpacing the company's historical levels of supply.
Those developments, combined with a slight increase in rabies cases—a 5% increase in 2007 over the 6,940 cases reported in 2006—have resulted in the current uneasy situation. “It's been a series of unfortunate concomitant events,” Dr. Rupprecht remarked.
A bit of relief is expected in the next few weeks, as Novartis had just received approval for a shipment of a small amount of vaccine prior to the ACIP meeting in late June. The company plans to make a small amount of that supply available for high-priority pre-exposure use, Novartis' Dr. Rajiv De Silva said.
Moreover, Novartis has just broken ground on a new vaccine production facility in Marburg, Germany, which will supply the U.S. market. It is expected to be operational by 2011. In the meantime, “we are working closely with the FDA to implement some interim steps to ensure sufficient production in our existing facility to supply the U.S. market for 2009 and 2010. … Our situation has improved, but we're not out of the woods yet,” Dr. De Silva said.
Aside from restricting the vaccine to PEP, other principles outlined in the draft document include centralization of national-state communications, mandatory consultation with knowledgeable public health officials prior to use of the vaccine, and renewed education and outreach for key medical providers regarding what constitutes a true exposure.
In general, PEP should be postponed until animal control can locate and capture the suspect animal for rabies testing and until diagnostic tests are completed, and should be withheld after bites from animals where adequate surveillance exists and there is no documented terrestrial rabies reservoir. Of course, PEP is always instituted if there is a high suspicion of rabies, based in part on animal species, local epidemiology, and the nature of the exposure. Most states have guidelines for the length of time to survey an area and to start diagnostic testing in high-risk situations, Dr. Rupprecht said in a follow-up interview.
If rabies vaccination must be given, options to lessen use during a shortage situation include administering only one booster dose to people previously vaccinated, dropping the fifth (final) dose of the series in a vaccine-naive individual, using alternative schedules, use of an intradermal route, and consideration of using other biologicals.
In general, in the event of any shortage situation, people traveling abroad would be “deprioritized” for pre-exposure vaccine and educated in “bite avoidance.” Individuals who will be living overseas can obtain vaccination abroad where safe injection practices are used with an approved cell culture vaccine, Dr. Rupprecht said.
When pre-exposure vaccine becomes available, prioritization will involve “first responders” such as animal control workers, diagnosticians, and veterinary staff.