FDA’s hostility blocks Zika-prevention technology

There have been more than 30,000 Zika infections in U.S. states and territories. The number of locally transmitted cases–-via the bite of the Aedes aegypti mosquito–is continuing to increase, as are the known modes of transmission. Zika infection is known to cause severe birth defects early in pregnancy and subtler ones later, and can also cause a progressive paralysis called Guillain-Barré syndrome. Women of childbearing age are fearful of bearing children with deformities or behavioral abnormalities.

The U.S. Secretary of Health and Human Services declared the outbreak in Puerto Rico a public health emergency on Aug. 12; Gov. Alejandro Garcia Padilla vowed to do “everything in my power to fight the spread” of the disease; and Brenda Rivera Garcia, the commonwealth epidemiologist, told reporters that “Among us scientists, it is scary.”

{mosads}Inexplicably, none of these pronouncements has elicited the use of all the federal legal authority that exists to address the Zika outbreak. Section 564 of the Food, Drug, and Cosmetic Act (FDCA) permits the FDA to issue “Emergency Use Authorizations” (EUAs) for regulated products under certain conditions:

“(a)(1) Emergency Uses. Notwithstanding any provision of this Act (FDCA) and section 351 of the Public Health Service Act and subject to the provisions of this section, the Secretary [of HHS] may authorize the introduction into interstate commerce, during the effective period of a declaration [of a public health emergency] of a drug … intended for use in an actual or potential emergency (…”emergency use”).

“(a)(2) Approval status of product. An authorization under paragraph (1) may authorize an emergency use of a product that (A) is not approved, licensed or cleared for commercial distribution…(“unapproved product”)

One promising unapproved “drug” that could control the vector that spreads Zika, and whose progress has been stymied by regulators, is a genetically engineered Aedes aegypti mosquito product made by Oxitec, a British company. Their scientists have used molecular genetic engineering techniques to create male Aedes aegypti mosquitoes carrying a mutation that causes them to require a certain chemical (the antibiotic tetracycline) to survive. Without it, they die prematurely, as do their offspring.

If these modified males are fed a diet containing tetracycline (to keep them alive long enough to reproduce) and then released into the wild over several months, the result is a marked reduction in the mosquito population. Because male mosquitoes don’t bite, they present no health risk, and because their progeny die before they can reproduce, no genetically engineered mosquitoes persist in the environment. (Moreover, Aedes aegypti is an invasive species in the Americas, so there’s no possibility that reducing their numbers will disrupt natural ecosystems.)

This approach has already been successfully tested abroad. Efficacy trials of the genetically engineered mosquitoes in Malaysia, Brazil, Panama, and the Cayman Islands all resulted in greater than 90 percent suppression of the wild population of Aedes aegypti mosquitoes, with a corresponding decrease in mosquito-transmitted diseases.

As a result, Brazil and the Cayman Islands allow the release of Oxitec mosquitoes as a vector-control approach to check the spread of Zika, dengue and chikungunya viruses.

The U.S. FDA has been hostile toward the Oxitec product. FDA took an unconscionable five years (2011 to August 2016) to authorize a single U.S. field trial (which is being delayed pending the results of a non-binding November public referendum in the geographical area of the field test).

So, while Brazilians and Cayman Islanders are getting protection from Aedes aegypti, U.S. citizens are getting only bureaucratic dithering and delay—and more infections.

As discussed above, the FDA can authorize the emergency use of an unapproved product in a situation that poses a public-health emergency, such as an emerging disease like a new strain of pandemic influenza or a Zika outbreak. There is a detailed protocol to follow for the FDA to issue an Emergency Use Authorization of Medical Products, which begins with the secretary of HHS (or of defense or of homeland security) declaring that a significant health emergency exists. HHS Secretary Sylvia Burwell made that determination months ago, and the FDA has issued ten EUAs for tests to diagnose active or past Zika infections and could do so for other regulated products as well. However, the FDA has resisted, on the grounds that the statutory language permits the emergency use only ofhuman drugs but not animal drugs, and that because the Agency has classified the Oxitec mosquito as an “animal drug,” §564 is not applicable.

The FDA’s legal interpretation is not only incorrect but also fails the common sense test. Section 564(a)(1) allows use of an unapproved “drug” in an emergency, and the FDCA defines the term “drug” as encompassing both human and animal drugs. Section 564(a)(1) says that “notwithstanding any provision of this Act,” the Secretary may authorize an unapproved product even if not approved for humans. The statute requires that four statutory criteria be met — (1) the presence of a serious or life-threatening disease, (2) a “may be effective” standard for effectiveness, (3) a risk-benefit analysis, and (4) the absence of alternatives. All of these apply.

The available evidence suggests that the genetically engineered mosquitoes are a safe, effective and environmentally friendly approach to reducing exposure to the several viral diseases spread by Aedes aegypti. The FDA’s unwillingness to issue an Emergency Use Authorization appears to reflect its years-long antagonism toward the Oxitec genetically engineered mosquitoes.

The CDC estimates that there could be 700,000-875,000 cases of Zika infection in Puerto Rico alone by the end of this calendar year. Puerto Ricans, Floridians and many other Americans are justifiably terrified of the life-altering sequelae of Zika infection. Aren’t they entitled to every protection afforded by U.S. law? Where along the way was the relevant part of FDA’s mission statement–“responsible for advancing the public health by helping to speed innovations that make medicines more effective, safer, and more affordable”—abandoned?

Will Congressional overseers hold FDA officials and their Obama administration political bosses accountable for their callousness and malfeasance?

Henry I. Miller, a physician, is the Robert Wesson Fellow in Scientific Philosophy and Public Policy at Stanford University’s Hoover Institution. He was the founding director of the Office of Biotechnology at the FDA. Drew L. Kershen is the Earl Sneed Centennial Professor of Law (Emeritus), University of Oklahoma College of Law.