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The Food and Drug Administration (FDA) regulates pharmaceutical drug products to ensure a continuous supply of high-quality drugs in the USA. Continuous processing has a great deal of potential to address issues of agility, flexibility, cost, and robustness in the development of pharmaceutical manufacturing processes. Over the past decade, there have been significant advancements in science and engineering to support the implementation of continuous pharmaceutical manufacturing. These investments along with the adoption of the quality-by-design (QbD) paradigm for pharmaceutical development and the advancement of process analytical technology (PAT) for designing, analyzing, and controlling manufacturing have progressed the scientific and regulatory readiness for continuous manufacturing. The FDA supports the implementation of continuous manufacturing using science-and risk-based approaches.

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Recent research in our group has shown that mixture-casting Nafion with quaternary ammonium bromides can increase the electrochemical flux of redox couples through the membrane and allow for larger redox species to diffuse to the electrode surface. The research has also suggested that when these salts are cast with Nafion micellar pore size is changing. Therefore, it was proposed that the quaternary ammonium salts could be employed to tailor the structure of the Nafion membrane for immobilizing enzymes in the polymer. For cations with a high affinity for the sulfonic acid groups of Nafion, the modified structure of Nafion can also help to stabilize the enzyme and increase activity by providing a protective outer shell and an ideal chemical environment that resists a decrease in pH within the pore structure. This research examines the ability to immobilize dehydrogenase enzymes in Nafion that has been modified with quaternary ammonium bromides. Fluorescence assays, fluorescence microscopy, and cyclic voltammetric studies were employed to analyze the ability to immobilize an enzyme within the membrane, to determine the activity of the immobilized enzyme and to examine the transport of coenzyme within the membrane. Dehydrogenase enzymes immobilized in tetrabutylammonium bromide/Nafion membranes have shown high catalytic activity and enzyme active lifetimes of greater than 45 days. A variety of dehydrogenase enzymes have been successfully immobilized in the membrane, including: alcohol dehydrogenase, aldehyde dehydrogenase, glucose dehydrogenase, and lactic dehydrogenase.

Amy Berning served as the project's Contracting Officer's Technical Representative. The National Institute on Alcohol Abuse and Alcoholism (NIAAA) provided funding and support for the assessment of alcohol use disorders. The National Institute on Drug Abuse (NIDA) provided funding for the collection of additional blood samples and the administration of the drug use disorders assessment. The National Institute of Justice (NIJ) provided support for querying participants about interaction with the criminal justice system. AbstractThis report presents the first national prevalence estimates for drug-involved driving derived from the recently completed 2007 National Roadside Survey (NRS). The NRS is a national field survey of alcohol-and drug-involved driving conducted primarily among nighttime weekend drivers, but also daytime Friday drivers. The survey involved randomly stopping drivers at 300 locations across the continental United States; sites were selected through a stratified random sampling procedure. This included data that we collected during a two-hour Friday daytime session at 60 locations and during four 2-hour nighttime periods (10 p.m. to midnight and 1 a.m. to 3 a.m. on both Friday and Saturday) at 240 locations. Both self-report and biological measures were taken. Biological measures included breath alcohol measurements on 9,413 respondents, oral fluid from 7,719 respondents, and blood samples from 3,276 respondents. Oral fluid and blood samples were subjected to laboratory screening and LC/MS-MS and GC/MS confirmation for 75 drugs and metabolites, including illegal, prescription, and over-the-counter drugs. These data were analyzed to develop the first national prevalence estimate of alcohol-and drug-involved driving. Two prior reports on the 2007 NRS described: (1) the sampling plan and data collection methodology, summarizing the response patterns to the various stages of the multi-part survey; and (2) the prevalence estimates for alcohol-involved driving derived from the study, and comparing them with the three previous National Roadside Surveys (NRS). iii AcknowledgementsThe authors received extensive assistance from State and local officials in the conduct of this project. Our data collection procedures were not routine. The willingness of officials to help us identify cooperating local law enforcement agencies and the willingness of agencies to participate in the project were essential to our success. To all those who helped in conducting this study, the authors express their sincere gratitude. ) which presents the prevalence estimates for alcohol-involved driving derived from the study, and compares those estimates with data from the three previous National Roadside Surveys. MethodologyThree prior national roadside surveys of drivers to estimate prevalence of drinking and driving and determine changes over time have been conducted in the United States. These surveys, which included a brief interview and a breath sample to determine blood alcohol concentration (BAC), were conducted on a s...