he pill in Japan: will approval ever come?
Recall of Tripedia vaccine.
On January 27, 1999, the Food and Drug Administration initiated a voluntary recall of Tripedia diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP), lot number 0916490, manufactured by Pasteur Merieux Connaught USA. Routine post-release stability testing completed in January 1999 indicated that the potency of the diphtheria toxoid component of this lot was below specification. The potency of the tetanus and pertussis components of this lot was acceptable. (+info)
Does over-the-counter nicotine replacement therapy improve smokers' life expectancy?
OBJECTIVE: To determine the public health benefits of making nicotine replacement therapy available without prescription, in terms of number of quitters and life expectancy. DESIGN: A decision-analytic model was developed to compare the policy of over-the-counter (OTC) availability of nicotine replacement therapy with that of prescription ([symbol: see text]) availability for the adult smoking population in the United States. MAIN OUTCOME MEASURES: Long-term (six-month) quit rates, life expectancy, and smoking attributable mortality (SAM) rates. RESULTS: OTC availability of nicotine replacement therapy would result in 91,151 additional successful quitters over a six-month period, and a cumulative total of approximately 1.7 million additional quitters over 25 years. All-cause SAM would decrease by 348 deaths per year and 2940 deaths per year at six months and five years, respectively. Relative to [symbol: see text] nicotine replacement therapy availability, OTC availability would result in an average gain in life expectancy across the entire adult smoking population of 0.196 years per smoker. In sensitivity analyses, the benefits of OTC availability were evident across a wide range of changes in baseline parameters. CONCLUSIONS: Compared with [symbol: see text] availability of nicotine replacement therapy, OTC availability would result in more successful quitters, fewer smoking-attributable deaths, and increased life expectancy for current smokers. (+info)
Recent developments in maintenance prescribing and monitoring in the United Kingdom.
After a brief historical review of British drug legislation and public and governmental attitudes, this paper describes the wide range of policies and practices that have appeared since the explosion of illicit drug abuse in the 1960s. The spectrum goes from a reluctance to prescribe at all to maintenance on injectable opiates. Comparisons are made with differing attitudes to the availability of abortion in public health services. Compared with 5 years ago, about three times more methadone is being prescribed. There is a steady increase in prescriptions for injectable methadone but heroin maintenance is still rare. The "British System" permits great flexibility in the choice of opiates for maintenance. Some amphetamine-prescribing programmes also exist. Hair analysis for drugs to monitor levels of both prescribed and unprescribed drugs is a welcome and promising alternative to undignified and often misleading urine tests. (+info)
Harm reduction in Bern: from outreach to heroin maintenance.
In Switzerland, harm-reduction programs have the support of the national government and many localities, in congruence with much of the rest of Europe and in contrast with the United States, and take place in public settings. The threat of AIDS is recognized as the greater harm. This paper describes the overall national program and highlights the experience from one city; the program is noteworthy because it is aimed at gathering comparative data from controlled trials. (+info)
Regulatory decision strategy for entry of a novel biological therapeutic with a clinically unmonitorable toxicity into clinical trials: pre-IND meetings and a case example.
The following material was derived from a synthesis of case histories taken from investigational new drug (IND) applications and drug sponsors' experiences, utilizing fictionalized data to avoid any resemblance to any proprietary information; any such resemblance is accidental. These examples are used as an instructional scenario to illustrate appropriate handling of a difficult toxicology issue. In this scenario, a drug caused a toxicity in animals that was detected only by histopathologic analysis; if it were to develop in patients, no conventional clinical methods could be identified to monitor for it. It is not unusual for a firm to cancel clinical development plans for a lead drug candidate that causes such a toxicity, especially if such a drug is intended for use as a chronic therapeutic in a population of patients with a chronic disease. This case synthesis was inspired by a Food and Drug Administration (FDA) agreement to allow such a product to proceed into clinical trials after substantive pre-IND discussions and agreement on well-considered toxicology program designs. The scientists most closely involved in the strategy development included the sponsor's toxicologist, veterinary toxicologic pathologist, and pharmacokineticist, as well as the FDA's reviewing pharmacologist. The basis of this decision was thorough toxicity characterization (1-month studies in 2 species); correlating toxicities with a particular cumulative area under the curve (AUC) in both species; identification of the most sensitive species (the species that showed the lower AUC correlating with toxicity); allometric assessment of clearance of the drug in 3 nonhuman species; construction of a model of human kinetics (based on extrapolation from animal kinetics); and finally, estimation of clinical safety factors (ratios of the human estimated cumulative AUC at the proposed clinical doses, over the animal cumulative AUC that correlated with the no adverse effect levels). Industry and FDA scientists negotiated a joint assessment of risk and benefit in patients, resulting in the FDA permitting such a compound to enter into clinical trials for a serious autoimmune disease. Such constructive, early communication starts with the pre-IND meeting, and the conduct and planning for this meeting can be very important in establishing smooth scientific and regulatory groundwork for the future of a drug under IND investigation. (+info)
Safety assessment of biotechnology-derived pharmaceuticals: ICH and beyond.
Many scientific discussions, especially in the past 8 yr, have focused on definition of criteria for the optimal assessment of the preclinical toxicity of pharmaceuticals. With the current overlap of responsibility among centers within the Food and Drug Administration (FDA), uniformity of testing standards, when appropriate, would be desirable. These discussions have extended beyond the boundaries of the FDA and have culminated in the acceptance of formalized, internationally recognized guidances. The work of the International Committee on Harmonisation (ICH) and the initiatives developed by the FDA are important because they (a) represent a consensus scientific opinion, (b) promote consistency, (c) improve the quality of the studies performed, (d) assist the public sector in determining what may be generally acceptable to prepare product development plans, and (e) provide guidance for the sponsors in the design of preclinical toxicity studies. Disadvantages associated with such initiatives include (a) the establishment of a historical database that is difficult to relinquish, (b) the promotion of a check-the-box approach, i.e., a tendancy to perform only the minimum evaluation required by the guidelines, (c) the creation of a disincentive for industry to develop and validate new models, and (d) the creation of state-of-the-art guidances that may not allow for appropriate evaluation of novel therapies. The introduction of biotechnology-derived pharmaceuticals for clinical use has often required the application of unique approaches to assessing their safety in preclinical studies. There is much diversity among these products, which include the gene and cellular therapies, monoclonal antibodies, human-derived recombinant regulatory proteins, blood products, and vaccines. For many of the biological therapies, there will be unique product issues that may require specific modifications to protocol design and may raise additional safety concerns (e.g., immunogenicity). Guidances concerning the design of preclinical studies for such therapies are generally based on the clinical indication. Risk versus benefit decisions are made with an understanding of the nature of the patient population, the severity of disease, and the availability of alternative therapies. Key components of protocol design for preclinical studies addressing the risks of these agents include (a) a safe starting dose in humans, (b) identification of potential target organs, (c) identification of clinical parameters that should be monitored in humans, and (d) identification of at-risk populations. One of the distinct aspects of the safety evaluation of biotechnology-derived pharmaceuticals is the use of relevant and often nontraditional species and the use of animal models of disease in preclinical safety evaluation. Extensive contributions were made by the Center for Biologics Evaluation and Research to the ICH document on the safety of biotherapeutics, which is intended to provide worldwide guidance for a framework approach to the design and review of preclinical programs. Rational, scientifically sound study design and early identification of the potential safety concerns that may be anticipated in the clinical trial can result in preclinical data that facilitate use of these novel therapies for use in humans without duplication of effort or the unnecessary use of animals. (+info)