Pharmaceutical Industry

The pharmaceutical industry is engaged in the discovery and development of new therapeutic agents and processes. This is a large, multidisciplinary exercise that involves very large teams of scientists and support staff in prolonged programmes that cost many millions of pounds a year. At any stage of the process, problems can arise that jeopardise the survival of the project, whether it involves preclinical toxicity, lack of efficacy in clinical trials or a lack of economic viability. The number of compounds that reach the market is low and failed projects contribute to the expense of new drugs. The market is highly competitive and there are pressures of time and expense as well as the need for high quality work and confidentiality.

The 'preclinical' phase of the development process involves the selection of suitable candidates for drug development and their testing for efficacy and safety during the early phases of clinical development. The testing procedures for safety and assessment of toxicity are legal requirements that are well defined worldwide. Much of the testing involves the use of laboratory animals as surrogates for human exposure and reports on the effects of new compounds must be reported to regulatory agencies for approval to test the agent in man. A pivotal part of many of these reports is the assessment of the pathological effects of a new compound in toxicity studies. The veterinary pathologist is a vital element in the selection process for new compounds and the evaluation of toxicity in regulatory studies.

Drug discovery pathology

In recent years the pathologist has taken a more prominent role in the process of selecting candidates for inclusion in development programmes. The drug discovery process includes a seriers of assays designed to identify disease targets, typically a membrane receptor or a critical part of a molecular chain involved in cellular homeostasis. Agonists and antagonists for identified targets are synthesised and screened for efficacy using in vitro systems and animal models. Pathoilogists advise on disease mechanisms, develop methods to localise targets in human and animal tissues evaluate efficacy in animal models and develop new models often using transgenic animals.

Project team support

The Project team for a new compound comprises representatives of all departments involved in the multidisciplinary task of bringing a drug to the market. The medicinal chemist through formulation, pharmacology, metabolism, toxicokinetics, toxicology and pathology are the core of the preclinical phase with the clinical trials unit, the chemists scaling up to bulk production, patents and regulatory affairs providing other essential functions. The veterinary pathologist has a wide range of background knowledge that enables him/her to understand many of the functions of the preclinical team and many have found a career away from the microscope in this field.

Regulatory studies

In order to obtain permission from national governments for clinical trials, and ultimately to license a compound for sale, pharmaceutical companies must submit exhaustive files of data generated in a range of studies and experiments. Many of the studies are necessary for particular phases of the clinical trials in man and often follow a similar pattern. Although animal experiments are kept to a minimum, there is still a requirement for a large number to be performed each year. The pathology is a key element in many studies and well qualified and experienced staff are needed to carry them out. Much of the work involves light microscopy and forms about 50% of the average work load for pathologists. In the past decade, pharmaceutical companies have concentrated on studies in the early phases of development (often up to 30 days of drug administration) and have contracted out longer studies to CRO. This means that first-hand experience of evaluating long-term studies is not part of the weekly routine.

Investigative pathology

When problems are encountered in toxicology studies, it is important to establish the mechanism that underlies it in order to proceed towards approval from regulatory agencies. A range of investigative techniques may be employed and this aspect of the job provides some of the most interesting and demanding work. In some companies, groups of pathologists specialise in investigative studies and may be allowed to publish some of their findings.

Good laboratory practice (GLP)

Most of the work undertaken must be conducted to high standards of quality as governed by the guidelines for GLP. This creates a rigorous and demanding working environment that is appropriate for issues related to safety of products to be used in man.