The Pharmaceutical Journal
Vol 269 No 7214 p337
7 September 2002

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World Congress of Pharmacy and Pharmaceutical Sciences 2002 summary

International perspective on safety issues

Awareness of problems in relation to the safety of medicines is increasing. The challenge to pharmacists is to increase their knowledge of processes known to reduce medication errors and to contribute to interdisciplinary methods of preventing and solving these errors. Four speakers at a board of pharmaceutical practice symposium on 2 September looked at the safety of medicines from the patient and the regulatory perspective and described the challenges of ensuring the safety of two specific types of products — herbal medicines and biotechnology products.

In explaining the patient's view, Dr Kevin Moody (Health Action International, The Netherlands) said that consumers have a right to safe medicines, but for them, safety means more than preventing and managing medication errors. Patients welcome attention to adverse reactions, but safety also means receiving the right diagnosis, a treatment that works and the health outcome that is hoped for.

Demands on patients to accept financial and moral responsibility for their health are growing, he said. In return they expect (and have a right) to be actively involved in their care, and reporting of medication errors should be part of this involvement. In any case, patient reports could add information to health professional reports. Health professionals report relatively few adverse events, partly because they consider the event to be insignificant (eg, a headache) or well known, or they fear being blamed.

Involving patients

Involving patients in reporting helps to validate their role in assuming the risks associated with taking medicines. It is also of benefit to health care professionals in that they are not solely responsible for reporting and it has the potential to reduce their workload. By adding information to databases, patient reporting could also enhance rational drug use. Moreover, the quality of reporting is richer and also first-hand.

However, there are potential problems with patient reporting. First, there is a need to distinguish between regular side effects and errors. Secondly, health professionals may not trust patients to interpret their own complaints. Thirdly, not all countries have a highly literate population and the availability of appropriate information, Dr Moody said.

He went on to say that the structure for patient reporting needs careful consideration. Ideally, the responsible body should be independent (neither government nor industry), the reporting procedure should be simple, available on the internet and provide a channel for feedback. Collected data should be shared both within and among countries in case "action" was needed. Patient reporting systems are most effective within an existing "official" reporting system to verify causality and should be seen as part of a pharmacovigilance system, he concluded.

Vaiyapuri Subramaniam (Food and Drug Administration, United States) provided a regulatory perspective and described how pharmacists contribute to patient safety through the FDA's drug quality reporting system (DQRS). With this system, which began in 1988, safety information on medicines is voluntarily disseminated through MedWatch. Reports are related to the appearance of the medicine and classified into three groups: imminent or serious health hazard (priority 1), potentially significant (priority 2) and routine follow-up (priority 3).

Pharmacists are the main source of reports, he said. In 2001, hospital pharmacists contributed 42 per cent of reports and community pharmacists 18 per cent. The remainder came from patients (8 per cent) doctors (7 per cent), nurses (3 per cent), pharmacy technicians (1 per cent) and others (21 per cent). The main problems reported in 2001 were due to packaging (33 per cent), labelling (12 per cent) and lack of effect of the drug (12 per cent) with the rest made up of defects such as physical change to the medicine, reconstitution difficulties, tampering with the packaging and general deterioration. In other words, these were "textbook complaints", Mr Subramaniam concluded, and pharmacists had demonstrated that they could contribute to product safety by participating in this system.

Markus Veit (German Central Institute for Pharmaceutical Research) discussed some of the problems in ensuring the safety of herbal products. Several safety issues have come under the spotlight recently, including toxicity (eg, hepatotoxicity of kava), adverse effects (eg, anaphylactic reactions with chamomile) and interactions (eg, St John's wort, garlic).

The safety of herbal products is closely tied to product uniformity and batch-to-batch consistency. Consistency has to be achieved with all the constituents of a herbal product, including the active principles, active markers, accompanying constituents (eg, inorganic salts, carbohydrates, amino acids) and constituents with potential negative impact (eg, allergens, toxins).

To achieve such consistency requires control and standardisation of the preparation process. This means characterising and defining the plant material used, together with all the chemicals used in the production process. Each step of the process — from cultivation, harvesting and drying through to extraction, production of the finished product, packaging and storage — has to be standardised. Specification limits and ranges for impurities have to be set.

Mr Veit went on to say that safety and uniformity for herbal products should be harmonised globally. At the European Union level, a directive is currently under discussion in which there are three categories of herbal medicinal products: traditional use, well-established use and new entities. Traditional use means use of 30 years within the EU or 15 years in the EU and 15 years elsewhere, and a list of ingredients, doses and permitted claims for this category will be defined.

According to the directive, traditional use products (because they are predefined) will have to satisfy only standards of quality — not efficacy or safety. Products in the well-established use category and new entities will have to satisfy standards of quality, efficacy and safety. However, for well-established use products, evidence for efficacy and safety could be derived from bibliographic material (eg, post-marketing studies, epidemiological studies, studies conducted with similar products) and not just clinical trials. Widely accepted scientific monographs such as those from the Europe Scientific Co-operative on Phytotherapy and the World Health Organization for herbal drugs could be used as a basis for the safety of products with well established medicinal use, he said.

Biotechnology products

Silvio Garattini (Mario Negri Pharmacology Research Institute, Milan, Italy) discussed the safety and efficacy of biotechnology products. Biotechnology products represent an advancement because they add a new dimension to the therapeutic armamentarium. Of the 202 products reviewed by the European Medicines Evaluation Agency between 1995 and 2001, 67 were biotechnology products.

Most of these fell into four therapeutic categories — gastrointestinal, blood, anti-infectives and antineoplastics and immunomodulating agents. "It is remarkable, that no biotechnology products have yet been developed for the management of disorders of the cardiovascular system, the central nervous system and the respiratory system," he said.

Interest in biotechnology products has grown on the basis that they are more specific, less toxic and less expensive than conventional products. However, this has not proved to be true. Epoetin-beta and darbo-epoetin-beta, for example, are essentially "me-too" drugs with adverse reactions no different from erythropoetin. Tenecteplase and reteplase are no more efficacious than streptokinase. Desirudin and lepirudin have a safety profile similar to heparin. No difference in mortality from breast cancer has been demonstrated from a combination of trastuzumab and paclitaxel compared with paclitaxel alone.

Biotechnology products have not been adequately compared with other products. "This makes any sound evaluation of both safety and efficacy difficult, and there is a need to establish an independent European fund for clinical trials," he concluded.
— Contributed by Pamela Mason.