A Risk-Characterization Framework for Decision-Making at the Food and Drug Administration (2011) / Chapter Skim
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6 Case Study of a Targeting Decision That Spans Food and Drug Administration Centers
6 Case Study of a Targeting Decision That Spans Food and Drug Administration Centers
Pages 111-138
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From page 111... ...
The committee did not conduct exhaustive literature searches or reviews, and all information is illustrative. The case study simply provides an illustration of how the committee's framework might be used for a targeting decision that spans FDA centers.
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From page 112... ...
Despite its low toxicity in laboratory animals, melamine has been associated with several outbreaks of toxicity in humans and companion animals. In animals, the consumption of feed that contains melamine and cyanuric acid has been shown to cause nephrolithiasis (kidney stones)
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From page 113... ...
Therefore, investigations of other feed ingredients, both imported and domestic, were appropriate to ensure the safety of pet foods and food-animal feeds that could be manufactured with such ingredients. In September 2008, news from China indicated foodborne toxicosis in young children caused by melamine contamination of infant formula.
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From page 114... ...
actions the agency will take to reduce or mitigate the identified risks, and, in the longer term, strategic-investment decisions, in which FDA decides whether to invest resources in improved testing methods, increased surveillance, or similar efforts devoted to understanding the identified risks. The case study examines the first type of decision (a targeting decision)
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From page 115... ...
Infant Formula Exposed Population About 4 million children are born in the United States each year, and most of them consume at least some formula during the first year of life. Those younger than 6 months old are at greatest risk from contaminated formula because their primary dietary sources are exclusively baby formula or baby formula and breast milk.1 After 6 months, most children begin to reduce formula consumption as their diet shifts to cereals and other solid foods; after 1 year, most children have transitioned away from formula.
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From page 116... ...
Number per year experiencing 5.5 0 adverse health effects that affect (0-3,500) only quality of life Personal Degree to which a person can Before any determination that melamine Before any determination that melamine controllability eliminate or reduce his or her own might be present in infant formula, might be present in pork products, risks through voluntary actions parents have no ability to control risks consumers have no ability to control those to their infants; once aware of the risks; once aware of the potential problem, potential problems, 90-95% of parents 80-90% of consumers could avoid could avoid potentially contaminated potentially contaminated food products.
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From page 117... ...
Ability to detect Ability to detect unexpected Adverse health effect rates would have Not detectable adverse health population-level adverse effects to be 10-100 times higher than expected effects to be detected and correctly attributed. Ability to mitigate Probability that an informed 90-100% 10-50% of effects associated with adverse health institution will be able to reduce contaminated pork products could be effects or mitigate any adverse health mitigated before the contamination source effects associated with the product is identified; 90-100% of future problems being evaluated if such a problem could be mitigated once the contamination is known to exist source is known.
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From page 118... ...
d0 2 Studies released after the timeframe for this hypothetical case study clearly identified the importance of the presence of cyanuric acid with melamine for manifestation of the toxic effects observed. However, the committee assumed that the strength of that relationship was still uncertain at the time of this case study.
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From page 119... ...
Dose Estimates Estimating the number of children who receive various doses of melamine through contaminated formula requires estimates of each of the following: Total number of infants who consume potentially contaminated infant formula (Nd as shown above)
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From page 120... ...
Table 6-3 shows, for example, that a 1-week-old consuming formula contaminated at 100 ppm in the dry formula will most likely ingest melamine at 1.5 mg/kg per day, but it could be as high as 2.6 or as low as 0.5 mg/kg per day depending on eating habits and infant weight. After the time that this hypothetical study would have been conducted, WHO set the tolerable daily intake (TDI)
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From page 121... ...
Dose-Response Relationship At the time this study would have been conducted, little was known about the dose-response relationship of the effects observed in infants and melamine consumption. In China, where melamine concentrations ranged from less than 1 ppm to over 1,000 ppm, Gossner et al.
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From page 122... ...
and range (black vertical line) of estimated melamine dose for an exposed infant of various ages given uncertainties in melamine concentration in formula, infant weight, and formula consumption.
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From page 123... ...
250,000 various melamine doses 200,000 150,000 100,000 50,000 0.00 0.20 0.40 0.60 0.80 1.00 1.20 1.40 1.60 1.80 2.00 mg/kg per day FIGURE 6-3 Distribution of the number of infants exposed to various melamine doses. Red line shows the median estimate of the number of infants who receive at least the indicated dose.
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From page 124... ...
At the high end, it is possible that thousands of cases of renal disease requiring medical attention would occur; deaths would still be very rare. TABLE 6-4 Estimates of Mortality and Morbidity from Melamine Contamination in Infant Formula for the Hypothesized Dose-Response Relationship Incorporating Uncertainty in Exposure and Dose Type of Effect Low Median High Affecting quality of life only 0 5.5 3,500 Less severe adverse effects 0 4.5 2,900 Severe adverse effects 0 1.0 630 6 x 10-5 Death 0 0.04
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From page 125... ...
Once aware of the potential health consequences, parents could take steps to avoid potentially contaminated formula relatively easily. If the problem were isolated to a small number of identified formula manufacturers, the availability of formula from other manufacturers would allow virtually all parents to select uncontaminated formula.
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From page 126... ...
pet food as an inexpensive addition to their diets. Because melamine contamination of pet food was known to have occurred, the exposure pathway considered most likely and evaluated here is from contaminated pet foods being fed to hogs raised for human consumption.
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From page 127... ...
hog supply is fed excess pet food, the only hypothesized route to melamine contamination.
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From page 128... ...
So, for example, a hog consuming 35% of its diet as pet food that is contaminated at 1,000 ppm would have a net concentration of 350 ppm melamine in its diet. The committee combined the uncertainties in diet composition and melamine concentrations in the feed with uncertainty in the number of hogs consuming any contaminated pet food in a simple Monte Carlo simulation model to estimate a distribution of the number of hogs consuming feed with different net concentrations of melamine.
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From page 129... ...
Combining the conservative factor of 0.001 with the estimated distribution of the number of hogs consuming foods with various concentrations shown in Figure 6-5 results in estimates of the numbers of hogs with various melamine concentrations in their tissues. Figure 6-6 illustrates the results of the calculation.
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From page 130... ...
FIGURE 6-5 Distribution of hogs consuming feed with various melamine concentrations. Tissue concentrations (ppb)
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From page 131... ...
Personal Controllability As in the case with infant formula, the first element necessary for personal controllability -- knowledge that a potential risk exists -- is lacking in the case of melamine contamination in pork products. There is no way for a consumer to detect directly that contamination exists, so individual knowledge of a potential problem is possible only after institutions detect and announce that such a problem is possible.
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From page 132... ...
Ability to Mitigate Adverse Health Effects Once a problem is detected, steps can be taken to ensure that contaminated ingredients are no longer used in animal feed. The use of pet food as a supplement is not widespread, and the producers that do use the supplement could be readily identified and notified, so mitigating risks by preventing future use of contaminated animal feed would be relatively easy.
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From page 133... ...
Fewer people are likely to suffer adverse health effects from melamine contamination of animal feeds than from contaminated infant formula, but the ability to detect and mitigate such problems is lower for animal feeds than for infant formula. The risk characterization described is an illustration of the evaluation that could be used to rank potential risks: it compares the effects of potential contamination in various products by using a consistent set of metrics.
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From page 134... ...
For example, pulling large quantities of baby formula from market shelves will greatly increase anxiety and lead to changes in how babies are fed. The publichealth consequences of potential contamination of animal feed have already been evaluated in the sections described above, and the public-health consequences of having no contamination in infant formula can be assumed to be zero.
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From page 135... ...
FIGURE 6-8 Potential outcomes of a decision to test infant formula but not animal feed, assuming a test without error, and interventions if the test result is positive.
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From page 136... ...
2007. 104 Deaths Reported in Pet Food Recall.
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From page 137... ...
2007. FDA Warns Tembec About Violations at Animal Feed Plant.
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From page 138... ...
Hog Industry. Na tional Agricultural Statistics Service, Agricultural Statistics Board, United States Department of Agriculture [online]
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