2. Requirements for Vaccines Intended for Use During Pregnancy
Additional requirements apply to vaccines developed for use during
pregnancy. Animal testing and clinical testing must be specified to address
the potential reproductive risk of the product before pregnant women
participate in clinical trials.
48 Phase I clinical trials must begin with non-
pregnant women of childbearing age.
49 If results of the proposed vaccination
are positive, studies of the vaccine may be advanced into early studies of
pregnant women classified as low-risk (healthy mothers who experience few
or no complications).
50 If adequate data from phase I clinical trials of
pregnant women is observed, phase II may begin to identify a pilot evaluation
of efficacy (i.e. a test to examine the feasibility of an approach that is intended
to be used in a larger scale study).
51 Phase III trials for vaccine candidates
intended for use during pregnancy use a randomized, blinded, well-controlled
study, wherein the control arm receives placebo and the primary endpoint is
prevention of clinical disease in a larger population of pregnant women.
After clinical development stages, the vaccination would advance to the
licensing application where FDA reviewers would evaluate the information
necessary for a risk/benefit analysis and issue a recommendation regarding
approval of the vaccine.
Evaluations of safety are crucial during each phase of clinic trials, and
continue after the approval of the vaccine.
54 Until a vaccine is given to the
general population, all potential adverse reactions are unknown.
many vaccines are subjected to post-marketing surveillance, known as
“Phase IV” studies once on the market.
56 A key criterion during phase IV
studies is to determine if there is a “reasonable possibility that the drug (or
biologic) caused the event and whether the event (or a pattern of events) is
57 During general population use of the vaccine, it may be
necessary to develop a pregnancy registry, in order to explore potential
48. See Roberts & Gruber, supra note 4, at 968.
52. See Roberts & Gruber, supra note 4, at 968.
53. 42 U.S. C. A. § 262 (k) (2015); see also Vaccine Product Approval Process, supra
54. See Roberts & Gruber, supra note 4, at 967; see also Alberto E. Tozzi et al.,
Assessment of Causality of Individual Adverse Events Following Immunization (AEFI): A
WHO Tool for Global Use, 31 VACCINE 5041, 5043 (2013),