Regulatory Guidelines (regulatory + guideline)

Distribution by Scientific Domains


Selected Abstracts


Prescribed stimulant use by Western Australians with Attention Deficit Hyperactivity Disorder (ADHD): does amount dispensed exceed the expected authorised use?

AUSTRALIAN AND NEW ZEALAND JOURNAL OF PUBLIC HEALTH, Issue 6 2007
Janine Calver
Abstract Objective: To investigate to what extent Western Australian (WA) patients with Attention Deficit Hyperactivity Disorder (ADHD) received prescribed stimulants in excess of their notified dose from WA pharmacies in 2004 (termed ,discrepancy'). Design and data sources: Analysis of administrative data about all people aged two years and older who were prescribed stimulants for the treatment of ADHD in WA, and had at least one stimulant prescription dispensed from a WA pharmacy during the period 1 January to 31 December 2004. Outcome measures: Discrepancies were identified using minimum and maximum estimation methods (MinDE, MaxDE). We calculated for both methods the discrepancy prevalence by age and sex and annual surplus of stimulant accrued by age. Results: Of the 15,190 ADHD patients who comprised the study population, 5.4% to 19.0% received stimulants surplus to requirement in 2004, with peak prevalences in 6-8 year-olds (MaxDE 20.1%) and 25-34 year-olds (MaxDE 27.6%; MinDE 10.5%). The amount of stimulant dispensed surplus to requirement was highly skewed, with median annual values that ranged from one to 4.1 standard bottles (100 tablets) of dexamphetamine 5 mg for the MinDE and MaxDE methods, respectively. Conclusion: It is difficult to definitively estimate to what extent WA ADHD patients accrued excess stimulant medication using routine administrative data. Improvements to the WA Stimulant Regulatory Guidelines are recommended in the interests of patient safety, public transparency, methodological rigour and encouraging good prescribing practices. [source]


Influence of single versus multiple actuations on the particle size distribution of beclometasone dipropionate metered-dose inhalers

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 8 2003
M. R. Feddah
The particle size distributions of beclometasone dipropionate delivered from Becotide and Respocort inhalers after single and multiple actuations were investigated using the Andersen Mark II Cascade impactor and the drug was quantified using high performance liquid chromatography. The fine particle mass and the mass median aerodynamic diameter were calculated. An apparent increase in mass median aerodynamic diameter was observed when the number of actuations increased. In addition, the fine particle mass decreased as the number of actuations increased. When performing and analysing cascade impaction study data differences between single versus multiple actuations must be considered. Regulatory guidelines should be amended to stipulate the number of actuations to be loaded into devices used to evaluate the particle size distribution of inhaled aerosol products. [source]


S32.3: Regulatory guidelines and their statistical impact on respiratory trials

BIOMETRICAL JOURNAL, Issue S1 2004
Dieter Hauschke
No abstract is available for this article. [source]


The role of banned substance residue analysis in the control of dietary supplement contamination

DRUG TESTING AND ANALYSIS, Issue 9 2010
Dr Catherine MG Judkins
Abstract The potential for contaminated dietary supplements to result in a failed doping test remains a concern for athletes, trainers, and sporting authorities despite improvements to regulatory guidelines. Previous surveys of readily available supplements confirm that many are contaminated with steroids and stimulants prohibited for use in elite sport. Suggested responses to this issue include the complete avoidance of all supplements. Many athletes, however, use nutritional supplements to achieve effective training and also to ensure that daily nutritional requirements are met (e.g. recommended levels of vitamins and minerals). This ensures that the use of supplements is and will remain the norm for a range of sports. As a result, an alternative approach of rigorous testing of materials destined for use by elite athletes has been introduced in several countries. While the testing of final product for banned substances may help mitigate the problem, it will not help to remove the underlying issue of contamination. In this article we describe an alternative approach that uses appropriate quality assurance procedures backed up by testing to remove sources of contamination. The decrease in the incidence of contamination amongst supplement companies adopting such a system is explained, and contrasted with the relatively high incidences of contamination found in products that are not part of a quality system. These findings are of key importance to both supplement manufacturers and those involved in advising athletes about supplement use. Copyright © 2010 John Wiley & Sons, Ltd. [source]


Salt-water recycling for brine production at road-salt-storage facilities

ENVIRONMENTAL PROGRESS & SUSTAINABLE ENERGY, Issue 4 2009
G. Michael Fitch
Abstract This research investigates the storm-water quality at road-salt-storage facilities located at Virginia Department of Transportation (VDOT) winter maintenance locations and investigates the feasibility of a sustainable solution to better manage the salt-contaminated storm-water runoff. Collection ponds are currently used at most salt-storage sites to contain highly saline runoff and prevent its release into the environment. During a synoptic, winter-time sampling, chloride-ion concentrations in these ponds were found to be significantly greater than state and federal regulatory guidelines for surface-water-quality criteria, with individual values exceeding 2000 mg/L. The pond water is currently treated as a waste product by VDOT, resulting in significant costs for disposal. However, this saline pond water can potentially be recycled to produce concentrated brine solutions, which can then be used by VDOT for either prewetting dry salt during application to roadways or for direct brine application. Laboratory and field tests have been performed using a bench-scale brine generation system to quantify the effects of hydraulic retention time, temperature, and influent-water quality on system performance. Results of these studies have found that the storm-water runoff captured in collection ponds requires no pretreatment before entering the brine generation system and can effectively produce brine at the target salt concentration. Results of a cost-benefit analysis indicate that it is possible under multiple scenarios to recover the investment capital of implementing brine generation at all VDOT winter maintenance locations, typically within a 4-year horizon. © 2009 American Institute of Chemical Engineers Environ Prog, 2009 [source]


Parallel transmit and receive technology in high-field magnetic resonance neuroimaging

INTERNATIONAL JOURNAL OF IMAGING SYSTEMS AND TECHNOLOGY, Issue 1 2010
Andrew G. Webb
Abstract The major radiofrequency engineering challenges of high-field MR neuroimaging are as follows: (1) to produce a strong, homogeneous transmit B1 field, while remaining within regulatory guidelines for tissue power deposition and (2) to receive the signal with the maximum signal-to-noise and the greatest flexibility in terms of utilizing the benefits of parallel imaging. Borrowing from developments in electromagnetic hyperthermia, the first challenge has been met by the use of transmit arrays, in which the input power to each element of the array can be varied in terms of magnitude and phase. Optimization of these parameters, as well as the form of the applied RF pulse, leads to very homogeneous B1 fields throughout the brain. The design of large receive arrays, using impedance-mismatched preamplifiers and geometrical overlap for interelement isolation, has resulted in significant sensitivity improvements as well as large acceleration factors in parallel imaging. © 2010 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 20, 2,13, 2010 [source]


Near infrared spectroscopy in the development of solid dosage forms

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 2 2007
Eetu Räsänen
The use of near infrared (NIR) spectroscopy has rapidly grown partly due to demands of process analytical applications in the pharmaceutical industry. Furthermore, newest regulatory guidelines have advanced the increase of the use of NIR technologies. The non-destructive and non-invasive nature of measurements makes NIR a powerful tool in characterization of pharmaceutical solids. These benefits among others often make NIR advantageous over traditional analytical methods. However, in addition to NIR, a wide variety of other tools are naturally also available for analysis in pharmaceutical development and manufacturing, and those can often be more suitable for a given application. The versatility and rapidness of NIR will ensure its contribution to increased process understanding, better process control and improved quality of drug products. This review concentrates on the use of NIR spectroscopy from a process research perspective and highlights recent applications in the field. [source]


RT08 Population PK and PK/PD investigations and Monte Carlo simulations for a rational dosage regimen

JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 2006
P. L. TOUTAIN
Objective There are several means whereby dosage schedules for clinical use may be set, some more appropriate and scientific than others! The challenge of the 21st century must be for colleagues in the pharmaceutical industry, those serving registration bodies and academic colleagues to pool their expertise with the objective of designing dosage schedules for clinical use, which are based on the application of sound scientific principles appropriate for each drug class. In this Roundtable Session colleagues of international standing will review (a) pharmacological and other sources of variability in the responses to drugs; (b) the advantages and limitations of pre-clinical studies for dose selection; (c) the roles of population PK and population PK/PD together with Monte Carlo simulations in dosage regimen selection; (d) Bayesian approaches to dosage selection and (e) regulatory guidelines on the type and extent of studies required for selecting dosages. There is no unanimity amongst stakeholders on either the principles or the methods underlying dosage schedule design. Dose titration studies have long been the principal means of fixing doses but PK-PD and population PK-PD studies are now challenging more traditional approaches. The papers and discussion in this Roundtable Session will provide a critical basis for future advances in this crucial area of therapeutic drug usage. Getting the doses right means that the patient will receive maximum benefit, in terms of optimal efficacy with minimal toxicity, and hence correct dosing will contribute enormously to animal welfare. [source]


RT09 Bayesian approaches in dosage selection

JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 2006
D. CONCORDET
Objective There are several means whereby dosage schedules for clinical use may be set, some more appropriate and scientific than others! The challenge of the 21st century must be for colleagues in the pharmaceutical industry, those serving registration bodies and academic colleagues to pool their expertise with the objective of designing dosage schedules for clinical use, which are based on the application of sound scientific principles appropriate for each drug class. In this Roundtable Session colleagues of international standing will review (a) pharmacological and other sources of variability in the responses to drugs; (b) the advantages and limitations of pre-clinical studies for dose selection; (c) the roles of population PK and population PK/PD together with Monte Carlo simulations in dosage regimen selection; (d) Bayesian approaches to dosage selection and (e) regulatory guidelines on the type and extent of studies required for selecting dosages. There is no unanimity amongst stakeholders on either the principles or the methods underlying dosage schedule design. Dose titration studies have long been the principal means of fixing doses but PK-PD and population PK-PD studies are now challenging more traditional approaches. The papers and discussion in this Roundtable Session will provide a critical basis for future advances in this crucial area of therapeutic drug usage. Getting the doses right means that the patient will receive maximum benefit, in terms of optimal efficacy with minimal toxicity, and hence correct dosing will contribute enormously to animal welfare. [source]


Skeletal health: primate model of postmenopausal osteoporosis

AMERICAN JOURNAL OF PRIMATOLOGY, Issue 9 2009
S.Y. Smith
Abstract Currently, the nonhuman primate is the most widely used large animal model to evaluate the safety and efficacy of new drug entities to treat or prevent estrogen-deficiency-induced bone loss and osteoporosis. Surgical ovariectomy (OVX) induces a state of high bone turnover and rapid bone loss establishing a new steady-state bone mass within 8,9 months. Many systems in the monkey are similar to humans, including skeletal and reproductive physiology and the immune system, making this a plausible model suitable to evaluate the effects of new bone drugs. The long-term sequelae following OVX and withdrawal of monthly exposure to cyclic reproductive hormones in older female monkeys (cynomolgus and rhesus) mimics estrogen depletion and postmenopausal bone loss occurring in women. Characterization of the primate model revealed an apparent limitation to the extent of bone loss. Animals lose bone mass after OVX, but the extent of the bone loss cannot be described as osteoporotic. The small differences between OVX and sham-operated controls in many important bone measurements is overcome by including 15,20 animals per group to provide adequate statistical power. The long-term, at least 16 month, bone safety studies performed to satisfy regulatory guidelines provide an opportunity to study treatment effects for an extended period not covered in shorter-term safety studies. In vivo end-points such as densitometry and biochemical markers translate easily to clinical use, while biomechanical end-points that cannot be measured clinically can be used to predict fracture prevention. To date, the monkey OVX model has been used to support submissions for many new drugs including anabolics, bisphosphonates and selective estrogen receptor modulators. Despite its limitations, the OVX monkey model remains the best characterized of the large animal models of osteopenia and has become integral to osteoporosis drug development. Am. J. Primatol. 71:752,765, 2009. © 2009 Wiley-Liss, Inc. [source]


An inventory of shedding data from clinical gene therapy trials

THE JOURNAL OF GENE MEDICINE, Issue 10 2007
Ellen A. M. Schenk-Braat
Abstract Viruses are the most commonly used vectors for clinical gene therapy. The risk of dissemination of a viral vector into the environment via excreta from the treated patient, a phenomenon called shedding, is a major safety concern for the environment. Despite the significant number of clinical gene therapy trials that have been conducted worldwide, there is currently no overview of actual shedding data available. In this article, an inventory of shedding data obtained from a total of 100 publications on clinical gene therapy trials using retroviral, adenoviral, adeno-associated viral and pox viral vectors is presented. In addition, the experimental set-up for shedding analysis including the assays used and biological materials tested is summarized. The collected data based on the analysis of 1619 patients in total demonstrate that shedding of these vectors occurs in practice, mainly determined by the type of vector and the route of vector administration. Due to the use of non-quantitative assays, the lack of information on assay sensitivity in most publications, and the fact that assay sensitivity is expressed in various ways, general conclusions cannot be made as to the level of vector shedding. The evaluation of the potential impact and consequences of the observations is complicated by the high degree of variety in the experimental design of shedding analysis between trials. This inventory can be supportive to clinical gene therapy investigators for the establishment of an evidence-based risk assessment to be included in a clinical protocol application, as well as to national regulatory authorities for the ongoing development of regulatory guidelines regarding gene therapy. Copyright © 2007 John Wiley & Sons, Ltd. [source]


Clinical responses to tumor necrosis factor , antagonists do not show a bimodal distribution: Data from the Stockholm Tumor Necrosis Factor , Followup Registry

ARTHRITIS & RHEUMATISM, Issue 6 2003
Ronald F. van Vollenhoven
Objective To study the distribution of clinical responses to treatment with the tumor necrosis factor , (TNF,) antagonists etanercept and infliximab, and in particular, to determine whether there is a biologically meaningful distinction between responders and nonresponders. Methods Among patients in the Stockholm TNF, Followup Registry, we analyzed the clinical responses to etanercept and infliximab, using the American College of Rheumatology (ACR) core set of outcome measures. For each parameter, the absolute change (value at baseline , current value) and the percentage change ([absolute change]/[value at baseline] × 100) from baseline were calculated. The results were plotted as histograms and inspected visually, and the distributions were statistically compared with computer-generated normal distributions. Results Absolute and relative changes in outcomes on the ACR core set of measures in 406 patients receiving etanercept or infliximab were studied. All but a few of these analyses yielded normal or somewhat skewed distributions. The statistical analyses did not detect any non-normal distributions, and visually, the distributions did not appear to be bimodal. Conclusion The clinical response to TNF, blockade displays a normal or skewed, but not bimodal, distribution. The frequently encountered perception that a clear distinction can be made between responders and nonresponders is not borne out. These relatively straightforward findings imply that the biologic mechanisms determining responsiveness to TNF, blockade are multifactorial and may also have important implications for regulatory guidelines pertaining to treatment with these biologic agents. [source]