A Practical Approach, Second Edition=Ronald D. Ho.pdf

PRINCIPLES OF RISK ASSESSMENT — FDA PERSPECTIVE 893mother and/or the offspring. Therefore, it is important to measure various immune response parametersthat may be induced by the vaccine. At a minimum, serum samples collected from pregnantanimals should be assessed for antibody production at designated time points. In addition, cordblood as well as blood samples from newborn animals should be evaluated for the presence ofantibodies (i.e., antibody transfer from the mother to the fetus or neonate). If adverse effects onembryo-fetal development are observed, additional studies, including studies for assessments ofpotential immunotoxicity (i.e., lymphocyte subset tests, immune function tests) may be necessaryto further evaluate the mechanism for the toxicity.For certain vaccines, there may be concerns that immunization of pregnant females may interferewith the ability of the offspring to mount an active immune response to either the same or a relatedvaccine antigen. Such concerns may need to be addressed on a case-by-case basis in clinicalimmunogenicity studies in infants born to mothers that have been immunized with the vaccineduring pregnancy.D. Summary RemarksCBER has formulated guidance for developmental toxicity studies for preventive vaccines in a draftguidance document for industry Considerations for Reproductive Toxicity Studies for PreventiveVaccines for Infectious Disease Indications. 52 However, regulatory policy with regard to reproductiveand developmental toxicity assessment of preventive vaccines will need to be viewed in thecontext of the evolving field of biotechnology and may change as new test systems and informationbecome available. It is important, therefore, to initiate a dialogue with CBER to discuss proposedprotocol designs for preclinical reproductive toxicity studies well in advance of implementation.Preclinical protocols for these products should follow general principles set forth in the CBERdraft guidance document, applicable ICH documents, and other available guidance. However, themost useful approach for reproductive and developmental toxicity testing of preventive vaccinesshould be based on rational science.A. PerspectiveIV. DRUG SAFETYCDER is currently involved in an attempt to change the way animal data are translated into riskassessment for humans. The primary focus is on molecular entities new to the market that havebeen tested in a relatively small series of clinical trials, sometimes 100 patients or less. When adrug first goes to market, it is likely that there will be very little information about its effects onmother or offspring when given during pregnancy, unless it is very specifically intended to be usedduring pregnancy. The most common situation with drugs at the FDA is that the molecular entityis new, animal data is available, and essentially no human experience data is available to predictwhat will happen to the general population. This is a very different situation from one in which aproduct has been on the market for several years, and product registries, behaviors, etc., exist forit. In a study, the use of a drug is tightly controlled, whereas drugs in the general population canbe taken in combination with other prescription medications, over-the-counter medications, andherbal and food supplements.B. Product LabelsAt the present time, the FDA uses established pregnancy labeling categories for drugs, but manycomplaints have been made against the use of the categories. The categories are defined by theavailability of human data (positive or negative), the availability of animal reproductive toxicity© 2006 by Taylor & Francis Group, LLC