Shortage of Yellow Fever Vaccine Has CDC and FDA Scrambling

April 28, 2017

A shortage of yellow fever vaccine approved in this country has the Centers for Disease Control and Prevention (CDC) and the US Food and Drug Administration (FDA) scrambling to make do at a time when the mosquito-borne disease poses more of a threat.

The federal solution is to import a yellow fever vaccine not approved by the FDA and drastically reduce the number of clinics where it can be administered, according to an article published online today in the CDC's Morbidity and Mortality Weekly Report.

The yellow fever vaccine now approved by the FDA (YF-VAX) is manufactured by Sanofi Pasteur. Roughly half a million doses are distributed to military and civilian travellers each year, with two thirds of the doses going to some 4000 authorized nonmilitary clinics.

Sanofi Pasteur estimates that its supply of YF-VAX will run out in mid-2017 because of manufacturing problems last year that occurred while it switched production from an existing plant to a new one. In the process, a large number of doses were lost.

To meet demand until the new plant is up and running in 2018, the FDA is allowing the manufacturer to import its yellow fever vaccine called Stamaril, which is made by a subsidiary and licensed in 70 other countries. Approved as an "expanded access" investigational new drug (IND), Stamaril contains the same vaccine substrain used in YF-VAX and resembles it in terms of safety and efficacy.

For clinicians administering Stamaril instead of YF-VAX, one big change will be filling out the paperwork associated with an IND, said Amesh Adalja, MD, a spokesperson for the Infectious Diseases Society of America, in an interview with Medscape Medical News.

"It will be more complicated," said Dr Adalja, a senior associate at the Johns Hopkins Center for Health Security in Baltimore, Maryland. "Hopefully it won't be too onerous."

How Sanofi Will Distribute the Substitute Vaccine

Temporary reliance on Stamaril will change how the vaccine is distributed.

Right now, yellow fever vaccinations are limited to roughly 4000 clinical facilities certified for that purpose by state health departments. They include independent and chain drug stores, municipal and county public health departments, independent medical practices, and hospital systems. The CDC maintains a directory of them in its US Yellow Fever Vaccination Center Registry.

Sanofi Pasteur will distribute Stamaril to only 250 of these vaccination centers, however, to better manage the job of training staff to satisfy IND protocols and FDA guidance. The drug company worked with the CDC to design a two-tier selection process: Tier 1 sites will consist of 193 centers that ordered at least 250 doses of YF-VAX in 2016; smaller-volume centers to ensure coverage in all 50 states, the District of Columbia, and US territories; and centers that serve nonmilitary US government employees. Another 59 sites in tier 2 will belong to multisite clinical organizations, such as a hospital system, that ordered an aggregate 250 doses of YF-VAX last year.

The drug manufacturer is now recruiting the 250-odd vaccination centers, with IND training by webinar to extend through May.

Dr Adalja said it will be important for US residents traveling to yellow fever zones to locate one of the select vaccination centers well ahead of their trip. The CDC said it will eventually post a complete list of the centers on its website.

New Version of the Zika Story?

Efforts to bolster the nation's supply of yellow fever vaccine have an anxiety-producing backstory: Recent outbreaks of the disease that threaten to come ashore to the US mainland.

According to the article, the CDC, the FDA, the US Department of Defense, and Sanofi Pasteur began talking about vaccine supply adequacy in the spring of 2016, after yellow fever began ravaging Angola and the Democratic Republic of Congo in late 2015. Now Brazil is experiencing a major outbreak, and the United States could be next, according to an article coauthored by Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, that appeared online in the New England Journal of Medicine last month.

The path of yellow fever could follow the same path as Zika has. Both are transmitted by the Aedes aegypti mosquito, which is native to South and Central America as well as parts of the United States. US travelers to Brazil could get bitten by an infected mosquito and, when back home, pass on the virus to another mosquito that takes a bite.

To stretch the stockpile of yellow fever vaccine, the World Health Organization has recommended using a fifth of the standard dose. Although immunity may last only 12 months instead of a lifetime, the partial dose can effectively stem the spread of yellow fever. The article does not mention fractionating Stamaril, a move Dr Adalja called unnecessary at this point.

He credits the CDC and FDA with taking early steps to prevent a vaccine shortage.

"This reflects proactive management of the problem," Dr Adalja said.

Follow Robert Lowes on Twitter @LowesRobert

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