Status of safety pharmacology in the pharmaceutical industry, 1993

General pharmacology and safety pharmacology studies are of considerable value in drug discovery and safety assessment. The knowledge gained from these studies adds mechanistic perspectives and functional dimensions to contemporary animal pharmacology and toxicology studies. If conducted prior to initiation of drug development activities, general pharmacology and safety pharmacology studies can assist in the selection of drug classes and specific candidates for drug development, and contribute to selection of rational high doses for chronic toxicity studies. If conducted prior to initiation of clinical safety studies, these studies can influence the design of clinical protocols so that appropriate strategies are put in place to ensure appropriate patient management and care. Finally, general pharmacology and safety pharmacology studies can provide an important communication pathway between the non-clinical and clinical segments of a drug development program.     

Investigating mitochondrial dysfunction to increase drug safety in the pharmaceutical industry

Drug-induced mitochondrial dysfunction is a contributor to both late-stage compound attrition and post-market drug withdrawals. This review outlines the mechanisms which lead to drug-induced mitochondrial dysfunction and discusses the tremendous advances that have been made in the development of in vitro methods to identify mitochondrial impairment. Potentially useful animal models and in vivo methods to detect drug-induced mitochondrial impairment are also discussed.     

Globalization of the pharmaceutical industry: the physician's role in evaluating drug safety

The trend toward uniformity of drug registration procedures due to imminent European Economic Community globalization has encouraged pharmaceutical companies to conduct studies on a worldwide basis. This standardization of methods will facilitate the "poolability" of efficacy and safety data generated by these international studies into a common database. With the internationalization of the pharmaceutical marketplace, physicians in industry may be required to collect and interpret such reports from all over the globe. The globalization of the pharmaceutical industry will thus broaden the opportunities for physician involvement in safety detection.     

Nanotechnology in the pharmaceutical industry

Nanotechnology is being employed in the pharmaceutical field for many reasons, but perhaps the leading goals are to improve drug solubility/bio-availability and/or delivery to various sites of action. Nanotechnology is also being employed to develop new and improved therapeutic devices. Published patent applications in the area have increased at a near exponential rate over the past 10years and it is expected that companies will continue to study this area actively for many years to come.     

Biobusiness in the pharmaceutical industry

Although conventional biotechnology used for the synthesis of antibiotics, vitamins, amino acids, nucleotides, enzyme inhibitors and immunomodulating compounds has still a major impact in the production of pharmaceutical compounds, the importance of the new biotechnology is increasing. Whereas in conventional biotechnology naturally occurring strains are screened for production of pharmacologically active compounds, in new biotechnology known organisms are programmed by genetic engineering to produce a distinct protein or glycoprotein of human origin for substitution therapy. Such complex compounds from new biotechnology can be divided into products which might replace compounds which are already on the market by safer recombinant products such as human insulin, human growth hormone, urokinase, factor VIII and products which are new on the market such as interferons, lymphokines, tissue plasminogen activator, oligonucleotide probes, monoclonal antibodies and subunit vaccines. However, only a few of these recombinant products have reached the market such as human insulin, interferon alpha, interferon beta, human growth hormone and recombivax HB. In most cases, depending on the difficulties in demonstrating clinical efficacy, the investigated drugs have reached the marketing phase much faster than conventional chemical drugs. Return on investment of biotechnical produced pharmaceutics mainly depends on the issues of whether the product has to compete with chemically synthesized drugs, whether it is totally new but competes with other bioproducts, whether it is exceptional but the proof of clinical efficacy is difficult, or whether it is totally new and clinical studies are promising.(ABSTRACT TRUNCATED AT 250 WORDS)     

Epidemiology in the pharmaceutical industry

A survey assessing the practice of epidemiology in the pharmaceutical industry was sent to all member companies and research affiliates of the Pharmaceutical Research and Manufacturers of America (PhRMA) and to six non‐member companies. Eighty‐three companies were surveyed. Screening questions established whether or not a company employed epidemiologists, had an epidemiology department, or contracted work to epidemiologists outside the company. The survey included questions about organizational structure, functional role of epidemiologists, epidemiology department activities within the company, and collaboration with external partners. The response rate was 90.4%. Of the responding companies, 40% employed epidemiologists, 20% had epidemiology departments, and 36% utilized epidemiologists contracted outside the company. Eighty per cent of companies that employed epidemiologists also contracted epidemiology services outside of the company, while 6.7% of companies that did not employ epidemiologists utilized outside epidemiology services. Among all companies 42.7% employed or utilized epidemiologists. Differences were found in the extent to which large, medium and small pharmaceutical companies employ and utilize epidemiologists. The survey demonstrates that epidemiologists perform many roles within the pharmaceutical industry; that there are many potential opportunities for epidemiologists in this industry and that increased emphasis on safety will require more epidemiology training and recruitment efforts. Copyright © 2000 John Wiley & Sons, Ltd.     

The changing relationship between health care professionals and the pharmaceutical industry

Although UCLA had established policies and procedures for visiting pharmaceutical representatives, changes in both the pharmaceutical business environment and in UCLA's physical environment mandated an update. To deal with the changes, a multidisciplinary team comprised of various departmental staff members met to develop a new vendor representative visitation policy that included the practice of drug sample distribution. More stringent registration requirements and shared responsibility for policy enforcement are the key elements of the new policy.     

LD50 - its value for the pharmaceutical industry in safety evaluation of drugs.

Abstract Does the pharmaceutical industry perform LD₅₀-determinations in animals just because it is required by the authorities or are there any scientific benefits from counting dead animals and calculating and index of lethal toxicity? This is an important question when discussing LD₅₀ and possible alternatives. We will try to answer this question by presenting data and some views collected during almost ten years at a Swedish pharmaceutical company. We will describe how we have made use of the LD₅₀-values in the safety evaluation process. We will compare LD₅₀-values with the dose levels used in longterm toxicity both after single or repeated administration and with therapeutical dose levels in man for different classes of drugs. These data will enable us to demonstrate the value of the LD₅₀-determinations. As we are of the opinion that the LD₅₀-value itself has a limited value for the total safety evaluation of drugs we will look into the possibility of replacing the LD₅₀-determination with something else as an indication of lethal toxicity. In order to minimize the number of animals used and the number of animals dying because of dosing in studies on lethal toxicity we will try to support a proposal to use the maximal nonlethal dose (MNLD) as an indication of lethal toxicity in small animals.     

Action of the pharmaceutical industry

The presence of drugs in the environment, principally in water, can be detected analytically. Although concentrations detected are very low, their presence raises the issue of the impact on the natural medium and human health. In the first part of this review, we attempt to answer some of the most frequently asked questions: why are drugs found in the environment? where do they come from? is there a health hazard? In the second part, we describe measures taken by the pharmaceutical industry to protect the environment. Action is taken to control waste from production sites but also to coordinate the efforts of the pharmaceutical profession via CYCLAMED. Collection and reuse of unused drugs is also discussed.