International Conference on Harmonisation; guidance on Q9 Quality Risk Management; availability. Notice

The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled "Q9 Quality Risk Management."' The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The guidance provides principles and examples of tools for quality risk management that can be applied to all aspects of pharmaceutical quality throughout the lifecycle of drug substances, drug products, and biological and biotechnological products. The guidance is intended to enable regulators and industry to make more effective and consistent risk-based decisions.     

The Compensation Culture: Cliché or Cause for Concern?

The ‘compensation culture’ has featured frequently in the popular press over the last decade. There have, however, been comparatively few academic studies and such studies as there have been have largely focused on personal injury claims. A compensation culture, if it exists, could extend much wider than that. This article compares the exponential increase in the use of the term ‘compensation culture’ in the national printed media since 1995 with available statistics relating to the Queen's Bench, County Courts, and employment tribunals. Far from spiralling upwards, these statistics show a broad decline across a range of claims with the exception of claims before the employment tribunals, where the government has created a slew of new heads of claim. In order to counter the misconceptions founded by the popular media, and to allow for greater scrutiny, more attention should be paid to the collection and dissemination of judicial and claims statistics.     

Urinary excretion profiles of 11-nor-9-carboxy-Delta9-tetrahydrocannabinol. Study III. A Delta9-THC-COOH to creatinine ratio study

Huestis and Cone reported in [J. Anal. Toxicol. 22 (1998) 445] that serial monitoring of Delta9-THC-COOH/creatinine ratios in paired urine specimens collected at least 24h apart could differentiate new drug use from residual Delta(9)-THC-COOH excretion following acute marijuana use in a controlled setting. The best accuracy (85.4%) for predicting new marijuana use was for a Delta(9)-THC-COOH/creatinine ratio > or = 0.5 (dividing the Delta9-THC-COOH/creatinine ratio of specimen no. 2 by the specimen no. 1 ratio). In previous studies in this laboratory [J. Anal. Toxicol. 23 (1999) 531 and Forensic Sci. Int. 133 (2003) 26], urine specimens were collected from chronic marijuana users > or = 24 h or > = 48 h apart in an uncontrolled setting. Subjects with a history of chronic marijuana use were screened for cannabinoids with the EMIT II Plus cannabinoids assay (cut-off 50 ng/ml) followed by confirmation for Delta9-THC-COOH by GC-MS (cut-off 15 ng/ml). Creatinine was analyzed as an index of dilution. The objective of the present study was to evaluate whether creatinine corrected specimens could differentiate new marijuana or hashish use from the excretion of residual Delta(9)-THC-COOH in chronic marijuana users based on the Huestis 0.5 ratio. Urine specimens (N=376) were collected from 29 individuals > or = 96 h between urine collections. The mean urinary Delta9-THC-COOH concentration was 464.4 ng/ml, mean Delta9-THC-COOH/creatinine ratio (ng/(ml Delta9-THC-COOH mmoll creatinine)) was 36.8 and the overall mean Delta9-THC-COOH/creatinine ratio of specimen 2/mean Delta9-THC-COOH/creatinine ratio of specimen 1 was 1.37. The Huestis ratio calculation indicated new drug use in 83% of all sequentially paired urine specimens. The data were sub-divided into three groups (Groups A-C) based on mean Delta9-THC-COOH/creatinine values. Interindividual mean Delta9-THC-COOH/creatinine values ranged from 4.7 to 13.4 in Group A where 80% of paired specimens indicated new drug use (N=10) and 20.4-39.6 in Group B where 83.6% of paired specimens indicated new drug use (N=7). Individual mean Delta9-THC-COOH/creatinine values ranged from 44.2 to 120.2 in Group C where 84.5% of paired urine specimens indicated new marijuana use (N=12). Correcting Delta9-THC-COOH excretion for urinary dilution and comparing Delta9-THC-COOH/creatinine concentration ratios of sequentially paired specimens (collected > or = 96 h apart) may provide an objective indicator of ongoing marijuana or hashish use in this population.     

Distribution of ∆9‐Tetrahydrocannabinol and 11‐Nor‐9‐Carboxy‐∆9‐Tetrahydrocannabinol Acid in Postmortem Biological Fluids and Tissues From Pilots Fatally Injured in Aviation Accidents

Little is known of the postmortem distribution of ?⁹‐tetrahydrocannabinol (THC) and its major metabolite, 11‐nor‐9‐carboxy‐?⁹‐tetrahydrocannabinol (THCCOOH). Data from 55 pilots involved in fatal aviation accidents are presented in this study. Gas chromatography/mass spectrometry analysis obtained mean THC concentrations in blood from multiple sites, liver, lung, and kidney of 15.6 ng/mL, 92.4 ng/g, 766.0 ng/g, 44.1 ng/g and mean THCCOOH concentrations of 35.9 ng/mL, 322.4 ng/g, 42.6 ng/g, 138.5 ng/g, respectively. Heart THC concentrations (two cases) were 184.4 and 759.3 ng/g, and corresponding THCCOOH measured 11.0 and 95.9 ng/g, respectively. Muscle concentrations for THC (two cases) were 16.6 and 2.5 ng/g; corresponding THCCOOH, “confirmed positive” and 1.4 ng/g. The only brain tested in this study showed no THC detected and 2.9 ng/g THCCOOH, low concentrations that correlated with low values in other specimens from this case. This research emphasizes the need for postmortem cannabinoid testing and demonstrates the usefulness of a number of tissues, most notably lung, for these analyses.     

Over-the-counter vaginal contraceptive and spermicide drug products containing nonoxynol 9; required labeling. Final rule

The Food and Drug Administration (FDA) is issuing a final rule establishing new warning statements and other labeling information for all over-the-counter (OTC) vaginal contraceptive drug products (also known as spermicides, hereinafter referred to as vaginal contraceptives or vaginal contraceptives/spermicides) containing nonoxynol 9 (N9). These warning statements will advise consumers that vaginal contraceptives/spermicides containing N9 do not protect against infection from the human immunodeficiency virus (HIV), the virus that causes acquired immunodeficiency syndrome (AIDS), or against getting other sexually transmitted diseases (STDs). The warnings and labeling information will also advise consumers that use of vaginal contraceptives and spermicides containing N9 can irritate the vagina and rectum and may increase the risk of getting the AIDS virus (HIV) from an infected partner. This final rule is part of FDA's ongoing review of OTC drug products. FDA is issuing this final rule after considering public comments on its proposed regulation, and all relevant data and information on N9 that have come to our attention.