Drug Administration Code Research Articles

Population Dynamics of Listeria monocytogenes, Escherichia coli O157:H7, and Native Microflora During Manufacture and Aging of Gouda Cheese Made with Unpasteurized Milk

Cheeses made with unpasteurized milk are a safety concern due to possible contamination with foodborne pathogens. Listeria monocytogenes and Escherichia coli O157:H7 have been implicated in several outbreaks and recalls linked to Gouda cheese made with unpasteurized milk. The U.S. Food and Drug Administration Code of Federal Regulations requires cheeses made with unpasteurized milk to be aged at a minimum of 1.7°C for at least 60 days before entering interstate commerce. The goal of this study was (i) to assess the population dynamics of L. monocytogenes and E. coli O157:H7 during aging of Gouda cheese when the pathogens were inoculated into the unpasteurized milk used for manufacture and (ii) to compare the native microbial populations throughout manufacture and aging. Unpasteurized milk was inoculated with L. monocytogenes at 1 or 3 log CFU/mL or with E. coli O157:H7 at 1 log CFU/mL, and Gouda cheese was manufactured in laboratory-scale or pilot plant-scale settings. Cheeses were stored at 10°C for at least 90 days, and some cheeses were stored up to 163 days. Initial native microflora populations in unpasteurized milk did not differ significantly for laboratory-scale or pilot plant-scale trials, and population dynamics trended similarly throughout cheese manufacture and aging. During manufacture, approximately 81% of the total L. monocytogenes and E. coli O157:H7 populations was found in the curd samples. At an inoculation level of 1 log CFU/mL, L. monocytogenes survived in the cheese beyond 60 days in four of five trials. In contrast, E. coli O157:H7 was detected beyond 60 days in only one trial. At the higher 3-log inoculation level, the population of L. monocytogenes increased significantly from 3.96 ± 0.07 log CFU/g at the beginning of aging to 6.00 ± 0.73 log CFU/g after 150 days, corresponding to a growth rate of 0.04 ± 0.02 log CFU/g/day. The types of native microflora assessed included Enterobacteriaceae, lactic acid bacteria, mesophilic bacteria, and yeasts and molds. Generally, lactic acid and mesophilic bacterial populations remained consistent at approximately 8 to 9 log CFU/g during aging, whereas yeast and mold populations steadily increased. The data from this study will contribute to knowledge about survival of these pathogens during Gouda cheese production and will help researchers assess the risks of illness from consumption of Gouda cheese made with unpasteurized milk.

Radiation Dosimetry and Biodistribution of the TSPO Ligand11C-DPA-713 in Humans

Whole-body PET/CT was used to characterize the radiation dosimetry of (11)C-DPA-713, a specific PET ligand for the assessment of translocator protein. Six healthy control subjects, 3 men and 3 women, underwent whole-body dynamic PET scans after bolus injection of (11)C-DPA-713. Subjects were scanned from head to mid thigh with 7 passes performed, with a total PET acquisition of approximately 100 min. Time-activity curves were generated in organs with visible tracer uptake, and tissue residence times were calculated. Whole-body dosimetry was calculated using OLINDA 1.1 software, assuming no voiding. The absorbed dose is highest in the lungs, spleen, kidney, and pancreas. The lungs were determined to be the dose-limiting organ, with an average absorbed dose of 2.01 × 10(-2) mSv/MBq (7.43 × 10(-2) rem/mCi). On the basis of exposure limits outlined in the U.S. Food and Drug Administration Code of Federal Regulations (21CFR361.1), the single-dose limit for (11)C-DPA-713 radiotracer injection is 2,487.6 MBq (67.3 mCi). (11)C-DPA-713 has an uptake pattern that is consistent with the biodistribution of translocator protein and yields a dose burden that is comparable to that of other (11)C-labeled PET tracers.

Demographic differences in estimated blood donor eligibility prevalence in the United States

The prevalence of blood donor eligibility factors has a major impact on the availability of blood donors and thus the blood supply in the United States. The prevalence of these factors may differ between demographic groups and thus help explain the differences in blood donation rates. The study population (18-69 years old who were African American [AA], white, or Hispanic) was 185,073,489. Forty eligibility factors determined by US Food and Drug Administration's Code of Federal Regulations and AABB Standards for Blood Banks and Transfusion Services were used to calculate whole blood donation eligibility rates. Eligibility data were obtained from the 2007 to 2008 National Health and Nutrition Examination Survey, National Ambulatory Medical Care Survey, US Census Bureau, and Centers for Disease Control and Prevention. Eligibility rates were determined by race/ethnicity, sex, and age groups (18-39 and 40-69 years). In 2007 to 2008, 122 million Americans (65.9% of the study population and 41.0% of the total US population) were estimated to be eligible to donate blood in the United States. Significant differences in eligibility rates by demographic characterizers were determined (p < 0.001): AAs (36.5%), whites (46.4%), and Hispanics (40.7%); males (45.4%) and females (42.7%); individuals 18 to 39 years old (35.8%); and individuals 40 to 69 years old (32.9%). AAs were significantly less eligible to donate blood than whites and Hispanics. Disparities in donor eligibility exist by race/ethnicity, sex, and age groups.

Extraction Efficiencies of Heavy Metals in Hydroethanolic Solvent from Herbs of Commerce

Heavy metal contamination of herbal products is a major concern in the herbal and dietary supplement industry. Heavy metal exposure is well-documented to cause a variety of adverse human health effects and to negatively impact our environment. The Final Rule for Dietary Supplements for current good manufacturing practice regulation, 21 U.S. Food and Drug Administration Code of Federal Regulations 111, requires dietary supplement manufacturers to establish herbal purity limits for heavy metal contaminants considered safe for human consumption. Heavy metals may enter into the herbal manufacturing process via bioaccumulation from the harvest site or during postharvest processing phases, such as drying and/or liquid extraction. Traditionally, herbalists have used hydroethanolic solvents to extract herbal biomasses in pure food-grade ethanol-water combinations with solvent polarities capable of removing a wide range of hydrophilic and lipophilic constituents. The presented data demonstrate that hydroethanolic solvents are not completely efficient in the extraction of heavy metal accumulations from plant matrixes; and can act as an effective decontamination step in herbal product processing.

Modified Wheat Starches Increase Bread Yield

The yield of bread (amount of bread produced from a given weight of flour) is important to the commercial bread baker. Adding more water into the dough formula is an effective method of increasing bread yield with essentially no increase in processing costs. Thus, increased dough absorption is important from an economic point of view. According to the United States Food and Drug Administration Code of Federal Regulations (http://www.cfsan.fda.gov), standardized white bread produced in the United States can contain up to 38% water (USDA 2003). With most flours, it is not possible to add sufficient water in the formula to obtain bread with a final moisture content of 38%. Dough that contains excess water becomes wet and sticky and cannot be processed. In general, the amount of water lost during baking is controlled by a number of factors. These include oven temperature, baking time, surface area of the bread, and water absorption of the dough. Increased water absorption leads to higher moisture in the resulting bread and increased bread yield (Tipples and Kilborn 1968; Czuchajowska et al 1989; Puhr and D’Appolonia 1992). Dough size and shape, oven temperature, and baking time are essentially fixed in a commercial bakery. Therefore, increasing water absorption is the most practical way to increase bread yield. The water absorption of flour is determined by a number of factors including the levels of protein, arabinoxylans, and damaged starch present in the flour. Tipples and Kilborn (1968) reported that increased starch damage level and the accompanying increase in dough water absorption led to an increase in bread yield. Damaged starch imbibes water and swells at room temperature. Thus, a low level (≈5% fwb) of damaged starch has a positive effect on dough by increasing water absorption. However, at high levels (>8% fwb), the damaged starch granules interact with the gluten and change the rheological properties of the dough. The dough becomes strong but loses its elastic character. The dough is unable to expand normally during proofing and oven spring, resulting in loaves with reduced loaf volume and poor crumb grain. Added αamylase can overcome this problem by degrading the damaged starch to decrease the interaction and improve oven spring. This is the major advantage of adding α-amylase to bread flour. The degradation of the damaged starch by α-amylase also releases some of the water held by the damaged granules. Therefore, if the damaged starch level is too high, the dough becomes wet and sticky during fermentation and may produce bread with a sticky crumb. Starch can be chemically or physically modified to alter its physical properties and make it more useful in certain applications. Modifications that are commonly performed and the properties of the resulting modified starches are discussed by BeMiller (2007) and Miyazaki et al (2006). Certain of the modified starches, including pregelatinized starches, imbibe water and swell at room temperature in a manner similar to that found with damaged starch. The majority of the modified starches available are produced from corn starch. Corn starch is not compatible with gluten in breadmaking; however, wheat, rye, and barley starches are compatible with gluten (Hoseney et al 1971). Thus, modified wheat starch would be preferred in breadmaking. It is possible that certain modified wheat starches and, particularly, pregelatinized modified wheat starches might increase dough absorption in a manner similar to damaged starch but without the drawbacks described above. The modified starch may be less reactive with the gluten protein and, thus, have less effect on dough rheology. It is also possible that the modified starch would be a poorer substrate for α-amylase and not be as severely degraded during fermentation. Another approach to increasing dough absorption would be the use of the enzyme glucose oxidase which has been reported to increase dough absorption (Vemulapalli et al 1998). The objectives of this study were to determine whether bread yield could be increased by adding modified wheat starch or pregelatinized modified wheat starch to the bread formula. In addition, the effect of glucose oxidase added in combination with pregelatinized modified starch was studied.

Concurrent Infusions.

Clarification of the appropriate use of the concurrent drug administration code.

Economic cost for implementation of the U.S. Food and Drug Administration's Code of Federal Regulations Title 21, Part 1271 in an egg donor program

To assess the economic cost of implementing the U.S. Food and Drug Administration's Code of Federal Regulations Title 21, Part 1271 for infectious screening of egg donors in our practice during the first year. Physicians and employees of our practice were surveyed to ascertain the scope of duties and the number of hours spent to implement the regulations. The economic cost to the practice and the cost of additional laboratories were calculated. Private practice. Egg donors and recipient couples who underwent treatment in our center from May 25, 2005 (the day regulations became effective) to May 25, 2006; and physicians, administrators, and staff who were employed by the practice during this time frame. Using a questionnaire, structured interviews were conducted for all physicians and employees of our practice. The information regarding number of hours was provided to our chief financial officer, who calculated the cost to the practice. The cost that recipient couples paid for laboratory tests that would not otherwise be required to meet American Society for Reproductive Medicine guidelines and the cost of an external audit were also added to the overall practice costs to determine a total cost associated with the regulations in the first year. List of activities associated with implementation of the regulations, personnel hours involved to implement the regulations, and economic cost to the practice and to recipient couples. The total number of personnel hours spent by our practice in preparation for implementation of the regulations was 623.3 hours. In the first year, 675.2 additional hours were required to implement the regulations for 40 donors who cycled during this time. The economic cost to the practice for both preparation and implementation of the regulations was $219, 838, and the cost of additional laboratory work borne by the recipient couples was $15,880. Thus, the total cost was calculated to be $235,718 at 1 year after implementation of the regulations. Implementation of the FDA 21 CFR, Part 1271 was associated with a very high economic cost, even if the costs incurred by the government to develop and implement the regulation are excluded.