Summary of Questions and Recommendations
FDA Food Advisory Committee Meeting
December 16-17, 2014

Full Report (PDF - 73.3 KB)

Topic:

Susceptible Populations

Charge:

The Foods Program requests guidance from its Food Advisory Committee on how to integrate scientific considerations for susceptible populations into its risk assessment procedures and methodologies, including under what conditions a separate risk assessment should be conducted.

Question 1:

When conducting a risk assessment:

• What are the most important susceptibility factors to consider when determining whether a certain segment of a population could be considered more (or less) susceptible to the effects of a chemical?
• What data and level of confidence in the data are needed to initiate the development of a separate risk assessment for the subpopulation(s) determined to be susceptible?
• Is an epidemiologic study or animal bioassay that reports quantitative results showing an association between exposure and effects for susceptible individuals sufficient?
• What additional types of data should be considered?
• How should data that cannot be quantified be considered and weighted?
• Should different types of data be weighted differently?

Question 2a:

Are these appropriate questions to be considered in the problem formulation, planning, and scoping phases?

• Are there specific subpopulations or life stages of particular concern?
• Are some exposure routes or durations of particular concern to specific populations?
• How will exposures of the populations of interest be estimated?
• What are the quality and quantity of data available to identify whether or not subpopulations are disproportionately susceptible?
• How can the assessment be used to support decisions regarding susceptible populations?
• What additional questions should be considered?

Question 2b:

What additional areas of expertise should be considered?

Question 3:

What are the mechanisms to ensure that relevant outcomes are identified, considered, and prioritized for different susceptible populations?

Question 4:

How do differences in outcome latency and outcome development influence consideration of susceptibility factors in assessing whether a particular subpopulation is differentially susceptible? What types of studies are needed to address such differences?

Question 5:

For potential departures from use of the established intraspecies factor of 10 in risk assessments, what criteria need to be considered?

Summary of Food Advisory Committee recommendations to the Office of Food and Veterinary Medicine

• In the problem formulation, planning, and scoping phases of a risk assessment, FDA needs to determine the susceptible population, the exposure, including routes, duration, and frequency, which cause risk. Biological and exposure factors need to be considered when defining susceptible populations.
• While epidemiological evidence that is supported by animal evidence would be ideal for the development of separate risk assessments for the vulnerable group, this should not be considered necessary. Prioritization of value of individual data collections will rank first that generated from human exposures, i.e., from epidemiology studies. Prospective cohort studies will be valued most highly with design features that indicate high quality, e.g., large numbers of subjects that complete the planned time frame and inclusion of numerous subpopulations with well-defined criteria for inclusion. Thereafter, data of other epidemiological designs should be highly valued followed by comprehensive studies in experimental animals that include human-relevant exposure levels and duration.
• Latency is a difficult scientific issue that requires special tools. They need to be applied on a case-by-case basis to improve the risk assessment process. The FAC encouraged FDA to create a white paper that summarizes what is known about specific chemicals and latency to produce toxic effects from early life exposures, examples including carcinogens endocrine activators and agents that may be acting through epigenetic or other relevant modes of action.
• In general, the intraspecies factor of 10 most likely captures much of increased susceptibility of specific human subpopulations; however, the use of this default value without scientific backing for its numerical size is difficult to justify. The may be a need under certain circumstances for an additional UF for vulnerability.
• When considering life stage susceptibility, different subpopulations are often defined in terms of age. Although age as a delimiter is convenient and consistent with available data, the rationale for age delimitation is to capture various physiological and behavior changes that impact on susceptibility to adverse response to chemicals. The Committee proposed a slight modification to the pediatric lifestage age brackets that were proposed by the FDA in 2000, in order to capture: (1) prenatal life stages; and (2) substages that have particular significance for the FDA’s food and cosmetics programs.