Potential transmission of BSE via medicinal productsBMJ 1996; 312 doi: https://doi.org/10.1136/bmj.312.7037.988 (Published 20 April 1996) Cite this as: BMJ 1996;312:988
Patients can be reassured that measures are in place to reduce risk
The identification of 10 cases of Creutzfeldt-Jakob disease, which seem to represent a new variant,1 and the announcement by the Spongiform Encephalopathy Advisory Committee (SEAC) on 20 March that these cases could be linked to exposure to bovine spongiform encephalopathy, have caused great concern. Patients are worried about the risks of developing Creutzfeldt-Jakob disease not only from eating beef but also from medicinal products of bovine origin and are looking to doctors, pharmacists, and pharmaceutical companies for reassurance.
The risk of transmission of bovine spongiform encephalopathy via medicinal products depends on whether the infective agent is a human pathogen and on the level of exposure to the agent. To date, no epidemiological link has been made between any spongiform encephalopathy that is transmissible in animals and human disease, despite exposure of humans to the scrapie agent for at least 200 years. This suggests that the risk of transmission to humans is small.2
Measures aimed at minimising exposure to transmissible spongiform encephalopathies via medicinal products were introduced soon after the report of the Southwood Committee in 1988, in guidelines for manufacturers issued by Britain's Committee on Safety of Medicines in 1989, and essentially adopted by the European Committee for Proprietary Medicinal Products in 1992.3 Materials were to be sourced from cattle aged under 6 months from countries free of bovine spongiform encephalopathy or from countries where a low number of cases had been reported, provided the disease was notifiable in that country and the carcases of affected animals were destroyed and their progeny not used.
The guidelines included a classification of various tissues and body fluids according to potential risk of infectivity, based on experimental data from studies of scrapie in sheep and goats.2 3 Brain and spinal cord were ranked most highly infective, lymphoreticular tissue less so, and most other tissues and body fluids as of low or no detectable infectivity. More recent studies of cattle with proved bovine spongiform encephalopathy have to date detected infectivity only in the brain and spinal cord with none detectable in other tissues or fluids, including gut and lung (from which some heparins are sourced); pancreas (the source for bovine insulin); bone, bone marrow, skin, and cartilage (the raw materials for gelatin); milk (from which lactose and lactulose are derived); and serum (used in vaccine production).2 4
The guidelines also recommended purification procedures known to remove or inactivate agents causing transmissible spongiform encephalopathies, autoclaving or treatment with sodium hydroxide or sodium hypochlorite being considered more effective than extraction by organic solvents, protein removal, or filtration, although no procedure guarantees complete inactivation of these agents.3 5 Bioassay can now be used to test the efficacy of purification methods in removing scrapie or bovine spongiform encephalopathy agent.
In response to the recent crisis in Britain, pharmaceutical companies have made available information on the sourcing and processing of their products, together with risk assessments based on this information. In statements issued by the manufacturers of bovine insulins available in Britain, the risk to patients is assessed as negligible. With regard to gelatin, the Spongiform Encephalopathy Advisory Committee concluded in its statement of 24 March that it was safe for use in pharmaceutical and medical devices. The Association of the British Pharmaceutical Industry has provided assurance that there is no threat from medicines that have been manufactured in Britain since 1989 to the same standards as became obligatory elsewhere in the European Union in 1992.
Whether or not patients exposed to products of bovine origin before the respective measures were implemented could be incubating disease will depend in the first place on whether or not bovine spongiform encephalopathy proves to be transmissible to humans, as well as the sources and purification processes used at the time and the extent of exposure to the products in question. For some products it can be demonstrated in the laboratory that the purification or extraction procedures in use since well before the advent of bovine spongiform encephalopathy were sufficient to eliminate disease activity. The route of dosing would also be a factor, a higher dose being required to cause infection (in animal models) orally than parenterally, and subcutaneously than intravenously.2 In reality, with the current state of knowledge, the risks in some cases are as unquantifiable as those of having eaten beef in the mid-1980s.
For patients currently receiving medication of bovine origin, which will have been sourced and manufactured according to the guidelines, there is a need to keep the perceived risks of continuing such medication in perspective. Doctors and patients will need to weigh these unknown and possibly non-existent risks against the known risks of discontinuing or changing medication; for example, restabilising diabetic patients on porcine or human insulins may prove difficult because they have a different action profile from bovine insulin. In discussing the potential risks with patients, doctors can refer to the measures described above, which have now been in place in Britain for some seven years (longer than elsewhere in Europe), and to the fact that the Spongiform Encephalopathy Advisory Committee believed that they were “sufficient with current knowledge to satisfactorily protect…human health.”2
Conflict of interest Medical adviser to CP Pharmaceuticals Limited, a manufacturer of bovine insulin.
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