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Therapeutic embolisation of blood vessels is a procedure commonly performed to treat a variety of conditions including bleeding problems, arterio-venous malformations (AVM), and benign and malignant hypervascular tumours. A range of degradable and permanent embolisation devices composed of natural and synthetic polymers may be used for such applications. Beads composed of a sulfonate-modified poly(vinyl alcohol) (PVA) hydrogel (DC Bead®) are finding wide-spread use for the occlusion and subsequent local, controlled and sustained delivery of chemotherapeutic agents directly within the vasculature of liver tumours. These so-called drug-eluting beads (DEB) are available in a series of calibrated size ranges for matching vessel size; have appropriate physico-mechanical properties to enable them to be delivered with ease through narrow gauge microcatheters; and have the ability to actively sequester and release positively charged anticancer drugs by an ion-exchange mechanism. This product has become one of the standards of care in the Western World for the treatment of intermediate primary liver cancer.

The purpose of this chapter is to provide the reader with a brief description of drug-device combination products and how they are regulated. As these products contain both a drug and device component, their performance testing necessarily combines elements of the essential requirements for both. Moreover, the combined product itself will possess novel attributes that will require testing to ensure the impact of the one component upon the other is well understood. Understanding such nuances will help product developers streamline their processes and facilitate a faster and smoother route to market by avoiding common mistakes, reducing or eliminating rework and being prepared for the types of questions that will be raised during discussions by regulatory bodies.

Chemoembolisation has been used for many years in the treatment of hypervascularised tumours. Drug eluting beads (DEBs) have been developed in order to affect intra-arterial delivery of chemotherapeutic agents over a sustained period in a controlled manner, whilst occluding the feeding vessels of the tumour. Doxorubicin and irinotecan DEBs have been well characterised in vitro with respect to drug loading and elution kinetics and effects on the physical attributes of the beads related to catheter delivery. These drug–device combinations have been evaluated in a number of preclinical models that demonstrate the concept of high local delivery of the drug combined with lower systemic exposure. These data are supported by encouraging preliminary Phase I/II clinical results in the treatment of both hepatocellular carcinoma and metastatic colorectal cancer of the liver. This chapter summarises the bench-to-bedside development of these drug–device combinations for the treatment of liver cancer.

This chapter considers some of the issues faced and strategies employed when developing drug–device combination products. The rationale for which types of therapeutic and device to combine is discussed. Further, some of the more common drug delivery approaches that are used to enable controlled release from devices are reviewed. This is placed in the context of the combination products discussed in the subsequent chapters of this book. Finally, brief discussion is extended to the difficulties in developing biologic–device combination products.

Two studies evaluating the levels and sources of nitrogen dioxide in approximately 90 employee homes in the Richmond area with continuous sampling during the weeks of August 5, 1980, and February 9, 1981, were performed using samplers in the living room, bedroom, kitchen, and outdoors. Additional data were collected concerning appliance usage, heating/cooling plant, ventilation and cigarette smoking. Results were analyzed using BMDP routines. The largest contributor to NO2 concentration was found to be gas-fired kitchen appliances. The mean kitchen level for homes with gas appliances during the winter study was ∼188 μg/m3. Excluding participants with gas kitchens, incremental influence due to cigarette smoking was detected. The 7-day, 3-room average level of NO2 in the homes of nonsmokers and smokers without gas-fired appliances was 12 and 15 μg/m3, respectively, in the summer. The corresponding winter values were 19 and 22 μg/m3. Furthermore, the individual levels of NO2 in the homes of smokers were generally below both the adjacent outdoor level and the National Ambient Air Quality Standard limit for annual exposure.

Explores the problems of marketing a new material to raise main demand in traditionally stable markets, and examines nine companies in depth in the steel, aluminium and plastics industries. Concerns itself with this critical functional area of the initial market development of new industrial products. Uses only two companies, one in the aluminium and the other in the steel industries, in the study. Concludes that the strong influence of financial considerations in several aspects of market development seem likely to mean only low funds will be needed compared with research and capital investment costs.

Five cases of primary amoebic meningoencephalitis associated with swimming in freshwater lakes have been recorded in Florida over the past 14 years. The present study demonstrated that pathogenic Naegleria, the causative agent, is relatively widespread. Twelve of 26 lakes sampled only once yielded the amoeba. Populations in three of five lakes sampled routinely reached levels of one amoeba per 25 ml of water tested during the hot summer months. Overwintering in freshwater lake bottom sediments was demonstrated, showing that thermal-discharge pollution of waters plays a miniscule, if any, role in the maintenance of pathogenic Naegleria in nature in this semitropical area.

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