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A Risk-Characterization Framework for Decision-Making at the Food and Drug Administration Appendix C Scenarios Provided by the U.S. Food and Drug Administration to the Committee on Ranking FDA Product Categories Based on Health Consequences, Phase II In Phase I of this study, the NAS study Committee completed initial development of a conceptual model and method that has the capability of evaluating FDA-regulated products and/or product categories (excluding tobacco) according to the potential ranges of magnitude of various health consequences to U.S. users of the products at individual and population levels, taking both adverse and beneficial effects into consideration. The purpose of the study is to develop models and methods to inform the public health dimensions of an array of FDA risk-based decisions. (This project does not address regulatory strategies, because those choices will also entail legal and policy judgments that transcend scientific and technologic considerations.) In Phase II, the NAS Committee will, among other things, use concrete examples of risk-based decisions faced by FDA to refine the model. The following scenarios describe different types of decisions that FDA faces every day. Today, FDA uses best available data and information on public health risks and benefits to inform the public health component of these decisions. The agency is asking the NAS to suggest approaches to assessing health consequences in a way that allows public health impacts to be compared within and across broad program areas, and to identify information needs for addressing key uncertainties.
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A Risk-Characterization Framework for Decision-Making at the Food and Drug Administration VACCINES RISK MANAGEMENT – Many vaccines provide critical public health benefits, so that significant disruptions or interruptions in supply may have broad consequences for public health. Suppliers, supplies, and production capacity of some important vaccines are limited. Whenever concerns arise about manufacturing processes, decisions for action must weigh the relative potential consequences for safety versus the potential consequences of decreased availability. Loss of public confidence in these products and any resulting reduction in inoculation rates represents a potentially serious public health hazard. What measures of public health impacts should be taken into account in making decisions about safety interventions and/or risk management strategies, and setting priorities for action? What information is needed to support such decisions? DRUG MANUFACTURING SURVEILLANCE (1) – FDA must decide how to apportion resources between surveillance of manufacturers of normally safe, over-the-counter children’s cough medicine and manufacturers of a narrow therapeutic range, sterile-injectable product. The former has a nonzero risk of economically-motivated adulteration with a potentially lethal sweetener. How can we take all relevant public health impacts into account in making such decisions about surveillance priorities and risk management strategies in this scenario? What data would inform such decisions? DRUG MANUFACTURING SURVEILLANCE (2) – In allocating inspection resources, FDA must choose between engaging in a domestic drug surveillance inspection designated as high-risk by the Center versus a foreign drug inspection. What measures of public health risks and benefits should be taken into account in making decisions about drug inspection priorities, and what analyses could support such decisions? What data would inform such decisions? UNPLANNED EMERGENCY ACTIVITY VERSUS HIGH-PRIORITY PLANNED INSPECTIONS – In order to accomplish two Class 1 (significant health hazard) recalls on firms that required full follow-up, FDA had to pull resources from surveillance of high-risk firms, thus jeopardizing accomplishing the targets set by the Center for surveillance of high-risk firms. Similarly, in the midst of a risk-based assignment for a Center, FDA requested four recalls; we had to marshal our workforce to address this massive undertaking. How should we analyze these situations to better understand the full array of public health impacts of these decisions? What data is needed for such analyses? SETTING PRIORITIES FOR LIMITED INVESTIGATIONAL RESOURCES – An animal producer with multiple drug residue violations appears to have another violation before FDA has finished investigating the previous ones. This occurs in part because other higher priority food borne illness investigations or performance goal work take precedence in tapping the same human resources. What risks and benefits should be considered in analyzing the comparative public health impacts of follow-up violations versus other work, and how might they be compared? What data would inform such analyses?
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A Risk-Characterization Framework for Decision-Making at the Food and Drug Administration COMPARATIVE RISKS/BENEFITS OF FEED SAFETY ACTITIVIES – FDA has committed significant funds for cooperative agreements with the States for work on BSE issues. A number of people have argued that there are more "risky" hazards than BSE. Now that these cooperative agreements are expiring, we have the opportunity to re-allocate these animal feed safety funds to have the biggest public health benefit. We have a number of feed safety programs: feed contaminants (e.g., heavy metals, pesticides, mycotoxins, dioxins/pcbs, pathogens); medicated feed facilities (licensed and unlicensed), drug residues in food animal tissues, and BSE. What measures of public health risks and benefits should we take into account, and how can they be compared? Are there public health measures that factor in feasibility (not just "science-based” factors), so we can get the biggest public health "bang for our buck?" PRIORITY INSPECTION VERSUS CONSUMER COMPLAINT FOLLOW-UP – PDUFA (pre-approval human drug), ADUFA (pre-approval animal drug) and BIMO (clinical trial inspections related to pre-approval) assignments and foreign drug and device manufacturing inspections are designated as priority work by the Centers. However, each FDA field office must also prioritize locally whether an investigator will conduct one of these inspections or follow-up on a consumer complaint. If the complaint involves an illness, what measures of public health impact would inform the decision about whether the consumer complaint should take priority? What data would inform the analysis? CRISIS MANAGEMENT VERSUS CONSUMER COMPLAINT FOLLOW-UP – During the initial melamine contamination investigation, FDA labs were flooded with food products to screen for melamine and melamine byproducts. During that time, several consumer complaint samples were received that were linked to human illnesses. Those complaint samples required use of the same laboratory equipment needed for the melamine analysis. How can we use measures of potential public health impact to inform the decision about prioritizing the use of lab resources? What data is needed for such assessments? CLINICAL TRIAL INSPECTION – FDA must apportion clinical trial inspection resources between trials of two drugs that, by preliminary information, are likely to be equivalently efficacious and safe products. Trial participants for the first product are collected in several large clinical trial research centers. The second product relies on clinical trial information from ~200 separate sites. There are insufficient resources to cover more than 10 sites. How can FDA incorporate public health impacts into its decisions about trial inspection priorities and risk management strategies in this scenario? What data would be needed? BLOOD PRODUCTS RISK MANAGEMENT – There are high public expectations for the safety of most blood products, so that strong efforts to sustain the highest possible degrees of safety are the rule. However, because many blood products are life-saving, there is always a need to consider safety versus availability locally and nationally. In addition, there are few suppliers for some products and, the possibility of local/national shortages due to infectious disease outbreaks, manufacturing problems, or distribution problems. Selected
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A Risk-Characterization Framework for Decision-Making at the Food and Drug Administration types of blood products can present high risks but can also be life-saving/sustaining for specific groups of patients. FDA may also need to consider high profile, potential risks. As a consequence, FDA staff frequently perform ongoing risk assessments to inform actions and help to define data collection needs, safety interventions and/or risk management strategies. What measures of public health risks and benefits should be taken into account in making decisions about safety interventions and/or risk management strategies, and setting priorities for action? What data would inform such decisions? DRUG RECALL – FDA must decide whether to recall a high-demand topical product that has an identified low risk of causing infection only in immunocompromised patients. We could provide consumer alerts with no recall, recall only new shipments, or also recall old product from store shelves if the product is very near expiration. How can FDA take into account the public health impacts of these options, in identifying risk management strategies in this potential recall scenario? What data would inform such decisions? DOMESTIC FOOD INSPECTIONS – FDA must decide how to allocate its domestic field inspection resources between the various categories of foods, for example, between seafood and produce or between low acid canned foods and dairy products. A field work plan is developed that allocates these resources and an attempt is made to link the priorities to risk. Not all firms can be inspected each year, so priority has to be given to some firms at the expense of others and yet even the lowest risk firms should be inspected at some frequency. What are the elements of public health risk and benefit that should be taken into account when allocating these resources? How should these elements be weighted? IMPORT FOOD SAMPLE COLLECTION AND ANALYSIS – FDA must decide how to allocate its import field sample collection and analysis resources between the various categories and countries of origin of foods, for example between spinach from Mexico and canned tuna from Thailand or between spice from India and soft cheese from France. In addition, consideration must be given to the hazard for which the product should be analyzed, for example, E. coli., histamine, Salmonella, and L. monocytogenes. Priorities are set in electronic screening criteria and also refined by the import inspector in the district into which the product is imported. Only a small percentage of products can be collected for analysis, so priority has to be given to some products, shippers, and countries of origin instead of others. What are the elements of public health risk and benefit that should be taken into account when making these decisions? How should these elements be weighted? MEDICAL DEVICE POST-MARKET SURVEILLANCE – FDA reviews medical device adverse event reports to understand post-market device performance and to identify problems. Manufacturers’ understanding of and compliance with adverse event reporting is uneven. What data could be used to determine the public health risks of inaccurate reporting and identify high risk areas? What information could FDA consider in deciding how to focus educa-
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A Risk-Characterization Framework for Decision-Making at the Food and Drug Administration tional resources on improving reporting for specific devices or specific manufacturers? MEDICAL DEVICE RISK WEB PAGES – FDA has a number of web pages to communicate device safety information to the public. There are communications about emerging high risk issues, chronic risk areas and general safety information. What risk factors should be taken into account in setting priorities for which web pages should be updated or created first, to address the most pressing public health issues? MEDICAL DEVICE CONSENSUS STANDARD PRIORITIES – FDA collaborates with standards setting organizations (IEEE, ISO, AAMI, etc) on standards that include specific acceptance criteria for relevant performance characteristics of medical devices; such standards may also include test methods appropriate for evaluating a medical device. These standards influence medical device design and testing decisions. The number of such organizations and meetings is beyond what FDA can reasonably cover. (For example, in 2008, FDA representatives attended more than 60 meetings in the US and abroad in 16 different medical specialty areas; even so, not all medical specialty areas were covered.). How can we consider medical device risk when deciding which standards to collaborate in? What factors are most likely to affect public health?
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