- Keywords > biological products
- Keywords > blood products and related biologicals - quality assurance and safety
- Keywords > blood transfusion
- Keywords > Bovine Spongiform Encephalopathy (BSE)
- Keywords > Creutzfeldt-Jakob syndrome – diagnosis
- Keywords > Creutzfeldt-Jakob syndrome – pathogenicity
- Keywords > pharmaceutical preparations
- Keywords > Prion diseases
- Keywords > transmission of BSE
(2006; 59 pages)
A variant form of Creutzfeldt-Jakob Disease (vCJD), a fatal brain disease of humans, first appeared in the mid-1990s, as a result of the bovine spongiform encephalopathy (BSE or “mad-cow” disease) epidemic in the United Kingdom. Since first reported in 1996, up to June 2006, 161 cases of vCJD have occurred in the United Kingdom, 17 in France, four in Ireland, two cases in USA and the Netherlands and single cases in Canada, Italy, Japan, Portugal, Saudi Arabia and Spain. Cases of BSE and vCJD have been decreasing in the United Kingdom in recent years, but both diseases have appeared in other countries.
Until recently, all vCJD cases were attributed to consumption of beef products contaminated with the infectious agent of BSE. Since December 2003, three individuals have been identified with vCJD infections probably acquired from blood transfusions – two with typical vCJD symptoms and the other with pre-clinical vCJD involving spleen and lymph nodes but not brain. The fact that the three vCJD infections followed transfusions from clinically healthy persons who became ill more than a year after donating blood implies that other blood donors who might currently be incubating the disease would also be potential sources of infection for recipients. The possible extent of future blood-borne spread of vCJD infections is still unknown. The identification of these cases has intensified the concern about possible unmapped ways in which the disease might spread. Except for the three transfusion-transmitted infections, no cases of vCJD have been linked to any medicinal product to date, and guidelines have been developed by the World Health Organization (WHO) and other authorities to minimize the risk.
A Consultation held at the WHO in September 2005 brought together experts and regulators from around the world to revise existing WHO Guidelines on Transmissible Spongiform Encephalopathies (TSEs) in relation to Biological and Pharmaceutical Products (2003) which recommended ways to prevent potential transmission of vCJD through human blood and blood products, as well as through medicinal products prepared with bovine derived materials. The primary aim of the Consultation was to provide evidence-based information to national regulatory authorities of WHO Member States – especially to those where BSE has not yet been reported and where surveillance systems for BSE and vCJD may not be in place. The information is intended to assist them in conducting risk assessments and selecting measures to reduce the risk of transmitting vCJD by human blood and blood products and other medicinal products of biological origin, collectively called biologicals.
The WHO Guidelines of 2003 encouraged authorities to consider introducing precautionary measures to minimize the then-theoretical risk of transmitting vCJD by blood and blood products while not compromising an adequate supply. While acknowledging that transfusion transmitted vCJD is no longer just a theoretical possibility, experts in the 2005 WHO Consultation again advised authorities to assess the vCJD risk in the context of their own national situations, weighing the potential benefits of adopting precautionary policies to reduce that risk against the impact that those policies might have on the supply of blood.
Earlier WHO Consultations repeatedly stressed that, when feasible, tissues or body fluids of ruminant origin should be avoided in the preparation of biological and pharmaceutical products. When bovine materials must be used, they should be obtained from sources assessed to have negligible risk from the infectious agent of BSE. Most bovine tissues, including bovine muscle, used to manufacture biologicals, if carefully selected by taking into account the geographical distribution of BSE and collected according to guidelines, have little risk of contamination with BSE agent. Recent findings of disease-associated proteins in muscles of sheep with scrapie (a disease similar to BSE but not known to infect humans) and the recognition of BSE itself in a goat, reinforce the need for manufacturers of biologicals to maintain the precautionary safety measures recommended in the previous WHO guidelines. Ruminant blood and blood derivatives, such as fetal calf serum in cell cultures media and bovine serum albumin stabilizers, are also used to prepare biologicals.
Bovine blood has not been identified as a source of infection, and properly collected fetal bovine serum has a negligible risk. However, the blood of sheep with experimental BSE or natural scrapie can be infectious and, because scrapie and BSE agents behave similarly in sheep and goats, the blood of small ruminants should either be avoided in preparing biologicals or selected very carefully from sources known to be free of TSEs.
There is a continuing need to ensure that all national regulatory authorities with limited resources have ready access to reliable and up-to-date information when assessing TSE risks and evaluating product safety. That information includes guidance to help minimize or eliminate the risk for transmitting BSE and vCJD to humans via biologicals and other medicinal products.