T36 - Symposium
Risk Assessment at FDA: Applications for Informing Science-based DecisionsSapphire 3:30-5:00 pm
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| Chair(s): S. Anderson
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The U.S. Food and Drug Administration (FDA) has regulatory authority over a broad range of products ranging from foods, drugs, veterinary products, biologic products, medical devices and other medical products. Over the past several years, FDA has used risk assessment as a tool to support and inform decisions in food safety – on issues such as Listeria monocytogenes in foods, Salmonella in eggs, and others. Historically applications of the risk assessment paradigm have focused on environmental, chemical, toxicological, and more recently, on food safety issues. However, the paradigm is finding utility in evaluating potential public health risks addressed by or that may arise from FDA-regulated products such as drugs, vaccines, blood products and other medical products – and potentially as a means for evaluating and optimizing the effectiveness of interventions to further reduce risks. The goal of the session is to present and examine the broad range of applications and challenges of using risk assessment as a risk management decision tool to address public health risks for a variety of FDA-regulated products. The session brings together speakers from four different FDA Centers to discuss some of the risk assessments that have been developed and some of the critical methodological, policy and risk management issues they address. As part of the overall theme of the meeting presenters will discuss the methods and applications of their work and possibly delve into the current and future directions for risk assessment in their product-related area.
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T36.1 Evaluation of the Public Health Impact of Vibrio parahaemolyticus in Raw Oysters. Miliotis M.D.*, Bowers J.C., Walderhaug M.O., DePaola A., Dennis S.D.; U.S. Food and Drug Administration mmilioti@cfsan.fda.gov
Abstract: The risk assessment on the public health impact of Vibrio parahaemolyticus in raw oysters was initiated by FDA in response to widespread outbreaks that occurred in the U.S. in 1997 and 1998. The 2001 draft risk assessment report was revised in response to public comments, newly available data, and modeling techniques. The risk assessment had two main objectives:
• determine the factors that contribute to the risk of becoming ill from the consumption of pathogenic V. parahaemolyticus in raw oysters and
• evaluate the likely public health impact of different control measures, including the efficacy of current and alternative microbiological standards.
The risk assessment demonstrated that incidence of illness is impacted by region, season, harvest method, and storage times and temperatures. Levels of V. parahaemolyticus at harvest were found to be the most significant factor that impacted the incidence of illness. Another highly influential factor affecting the predicted risk of illness is the percentage of V. parahaemolyticus that are pathogenic. Control measures and mitigation strategies that reduce levels of V. parahaemolyticus in raw oysters or prevent the growth of the microorganism were shown to be effective in reducing the risk of V. parahaemolyticus-related infections.
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T36.2 Risk Management for Pharmaceutical Quality: A Perspective on Change and Adaptation in Science-Based Decision Making . Claycamp H. G.; US Food and Drug Administration gregg.claycamp@fda.hhs.gov
Abstract: The FDA and its regulated industries are defining applications of risk analysis and quality systems for a variety of public health risks falling within the agency’s regulatory scope. The objective of this presentation is to review quality risk management’s successes, challenges and ultimate potential from a risk analysis perspective. Risk and quality are broadly based concepts—terms not precise enough for formal analysis until they are defined for a specific context. These concepts merge and sometimes collide in the emerging application of “quality risk management” for pharmaceuticals. Pharmaceutical quality has been used a conceptual surrogate for public health; and, in this regard, pharmaceutical quality has at least three components: a consistent delivery of label performance, lack of contamination, and product availability. Each broad component bounds a complex array of specific adverse consequences and the associated variables for estimating risk. Similarly, if the FDA and pharmaceutical industry are to leverage the risk analysis experience in other public health areas, then they face a diversity of risk analysis paradigms, definitions and concepts, all purporting to be the optimal way to identify, assess and manage risk. The principal motivations for these programs have been FDA’s need to “match its level of effort against the magnitude of risk” given resource constraints and industry’s need to innovate without onerous regulatory scrutiny. For the FDA’s goals, general risk ranking and similar prioritization approaches are likely to be helpful. For industry, adoption of risk analytical tools at several levels of quantitative formality might demonstrate that risk management can control or eliminate risks to pharmaceutical quality. Overall, risk management and quality systems are viewed as the principal means by which the public health can continue to be protected in an era of increasing demands on performance by both government and industry.
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T36.3 Methods for Assessing Potential Risk of variant Creutzfeldt-Jakob Disease (vCJD) through Blood Coagulation Factors used to treat Hemophilia and other Bleeding Disorders. Yang H, Anderson S; Office of Biostatistics and Epidemiology, Center for Biologics Evaluation and Research , US Food and Drug Administration yangh@cber.fda.gov
Abstract: Two recent probable transfusion transmitted cases of human variant Creutzfeldt-Jakob disease (vCJD) via blood in the United Kingdom have raised concern that coagulation factors, used to treat certain bleeding disorders, and other plasma derived products might also pose a risk. It is possible that some US blood plasma donors may have been exposed to the bovine spongiform encephalopathy (BSE) agent and potentially infected with vCJD during extended periods of travel to the UK and Europe since 1980. We developed a risk assessment methodology to estimate the possible number of US donors that may be affected by vCJD and the potential exposure of recipients of plasma derived products to the vCJD agent. Potential exposure in product recipients was modeled using statistical distributions to reflect the uncertainty of the data and input variables. The key input factors in the model were frequency and duration of travel, size of plasma pool, effectiveness of donor deferral, concentration of vCJD agent in blood, vCJD clearance during manufacture, and amount of product used by recipients. Outputs of the model included the potential percentage of contaminated plasma pools, concentration of vCJD agent in pools, amount of vCJD infectivity per unit of product, and level of patient exposure to infectivity on an annual basis. The risk assessment model predicted that there was a low potential risk of vCJD transmission through plasma derivatives. In general, products with limited clearance and reduction of the vCJD agent during the manufacturing process and used in larger quantities would be predicted to have a higher potential risk than other plasma derived products.
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T36.4 Combining Chemical and Microbial Risks. Turturro A., Hass B.; DBRA/NCTR/FDA/PHS/DHHS aturturro@nctr.fda.gov
Abstract: As part of an Interagency collaborative project with the Environmental Protection Agency, we are studying the influence of immunosuppressive chemicals on induction and progress of infection with Cryptosporidium parvum, a parasite that can be found in unpasturerized foods, to better understand the impact of exposure to these chemicals on epidemics caused by the parasite. A common treatment for a number of conditions, glucocorticoids, are immunosuppressive and sensitize animals to infection. Using a fairly broad glucocorticoid dose-response regime and a fixed parasite dose (approximating the ID50 of the C. parvum dose in untreated humans), we have evaluated the consequences of use of these drugs on C. parvum infectivity. Also, using standard methodology, e.g., such as those developed for initiation-promotion paradigms, we have indicated the impact these agents in doses usually prescribed may have in humans both during an outbreak and under normal C. parvum exposures. Suggestions are made on how to combine these risks, the relevance to other areas such as risk assessment for immunotoxicity, and for precautions to take to decrease the risk of becoming infected from the combined effects of chemical and microbial agents.
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T36.5 Risk-Ranking and the Animal Feed Safety System. Hooberman B.*, Ekelman K., Okelo P., Kamara I., Ekperigin H.; Center for Veterinary Medicine, U.S. Food and Drug Administration bhooberm@cvm.fda.gov
Abstract: The FDA Center for Veterinary Medicine is developing a comprehensive, risk-based, preventive animal feed safety system (AFSS) that will enable the Agency to minimize, reduce, or eliminate the risks posed to animal and human health by contaminants present in animal feeds. The AFSS will incorporate a risk-ranking approach to inform decision-making as to which feed-related activities pose the greatest risk to public health and to aid in the determination of the best methods to address those risks. To implement the risk-ranking approach, a comprehensive list of chemical, biological and physical hazards has been identified. For each of the hazards, the potential health effects are being characterized with respect to both animal and human health. Assessing the exposure scenarios for these hazards is a particularly challenging aspect of this effort, given the enormous complexity and diversity of feed manufacturing and processing in the U.S. This presentation will provide the latest iteration of our risk-ranking model and discuss its usefulness and limitations.
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