The assessment of real hazards and appropriate counter‐measures: The clinician's view

Biologicals whether or not produced by biotechnological techniques comprise a heterogeneous collection of substances which are derived from natural organisms or cells, or equivalent substances produced by synthesis, which are assayed by biological methods. These substances are used for various purposes in medicine and may be divided into three principal groups; vaccines, sera (including immunoglobulins and monoclonal antibodies) and biologically active proteins. General concerns specific to the safety of biological products relate to possible adverse immunological interactions and the presence of contaminants: particularly viruses and bacteria, nucleic acids, and ‘additives’. Additives include impurities derived from the manufacturing and purification processes and materials deliberately added as preservatives or adjuvants. Each biological product demands individual review but in making assessments special consideration is needed of the extent of batch to batch variability and whether studies to confirm the absence of any increased frequency of neoplasia as a consequence of nucleic acid contamination should be pursued. In the future more biologically active proteins will be produced including some which differ from natural proteins in being more specific in activity, of greater potency or with a different pattern of distribution metabolism and excretion. These and new monoclonal antibodies may interact immunologically with host tissues in unexpected and undesirable ways and demand the application of new specific preclinical and clinical screens. The need for post marketing surveillance studies of an appropriate scale is no less for biologicals than for defined chemical entities.