Notice & Comment

Zika and Pregnancy-Specific Vaccines’ Regulatory Lacunae

In my next two posts, I will investigate the relationship between regulatory approval of vaccines and the response to the global public health emergency surrounding the spread of the Zika virus. That emergency has resurrected and brought into sharper relief some of the most vexing questions surrounding the regulatory state and pregnancy: the appropriate circumstances, if any, in which fetal tissue research is permissible; when and how the government may sponsor statements shaping reproductive decisions; and how to balance the health and rights of both women and their unborn children when health threats target both. This latter question has come to the fore in the Zika context. Because the virus inflicts its heaviest (known) toll in utero, even knowledge obtained through computer modeling or animal studies will implicate if not require application of that research to pregnant women as human research subjects. The regulatory approach adopted by the U.S. Food and Drug Administration (and mimicked by competent national regulatory authorities elsewhere) toward pregnant women as human research subjects reflects this deep complexity, even fear. Under that approach, FDA effectively allocates maternal immunization regulation to the CDC’s Advisory Committee for Immunization Practices, the World Health Organization’s Strategic Advisory Group of Experts on Immunization, and other national immunization technical advisory groups. Where those organizations recommend immunization of pregnant women, the FDA does not consider the use “off-label”. Otherwise, the approval of vaccines for pregnant women must meet all other regulatory requirements for a vaccine and must include extensive subpopulation data that is never obtained through blinded, placebo controlled clinical trials.

As a result of this system there is no vaccine licensed for use specifically during pregnancy. This regulatory idiosyncrasy is more than just an interesting quirk in the legal landscape for immunization. There is good evidence showing that pregnant women refuse immunizations based on information in package inserts which ranges from statements about there being no information to “safety and effectiveness of [X vaccine] have not been established in pregnant women . . .” The inability of public health authorities to connect statements regarding maternal health with product information deters important interventions that may help both pregnant women and their unborn children.

The Zika public health emergency demonstrates the dilemma posed by the current regulatory approach to maternal vaccines. Technical advisory groups only recommend vaccination for pregnant women after an extraordinarily long safety profile is established from post-immunization adverse event databases (like influenza and Tdap) so even though the subpopulation most likely in need of the vaccine – pregnant women, and, more specifically, their unborn children – they are the least likely to be enrolled in clinical trials for vaccine candidates. As an alternative, it may be more practical to vaccinate girls before they are sexually active, as happens with HPV immunization, although the benefits of that approach would similarly take time to become evident.

In my next post, I’ll discuss the way this regulatory approach burdens global health more broadly and what, if anything, might change in the regulatory landscape to diminish that burden.

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