BSE/TSE Risks BSE/TSE Risks Brian Matthews reviews the situation for active
pharmaceutical ingredients and starting materials in Europe
and discusses the global implications for healthcare
manufacturers BSE is one of a family of TSEs which have been identified over the years. These include: •   scrapie: a TSE affecting sheep (first described in 1732) and goats but it is indicated in      one of the documents prepared in the BSE Inquiry that a case of ‘bovine scrapie’ was
     reported in France in 1881¹, with clinical signs of ataxia and pruritus;
•   chronic wasting disease (CWD) (described in 1967 and affecting certain animals of the      deer/elk family in northern Colorado and southeastern Wyoming, and later in South
     Dakota,  Nebraska,  Oklahoma,  Montana  and  Saskatchewan),  with  clinical  signs  of
     altered behaviour, excessive salivation, wasting, florid amyloid plaques;
•   transmissible mink encephalopathy (TME) (described in 1965 but with outbreaks dating      to at least 1947), with clinical signs of ataxia, somnolence and seizures;
•   feline spongiform encephalopathy (FSE) (first described in 1990), with altered behaviour      and ataxia;
•   bovine   spongiform   encephalopathy   (BSE)   (first   recognised   in   November   1986   but      possibly present in a cow in December 1984);
•   Creutzfeldt-Jakob disease (CJD)² in man (described in the early 1920s): –   sporadic form (the commonest, with an apparent natural incidence of the order of      one  person  per  million  population)  with  typical  clinical  features  of  dementia,
     myoclonus,  variable  ataxia,  spongiform  changes  and  amyloid  plaques  in  about
     15% of cases;
–   a more rare familial form (described in 1924) with the same clinical features with      an autosomal-dominant pattern of expression, longer survival and more common
     amyloid plaques;
–   (new)   variant   CJD   (described   1996)   with   young   onset   of   action,   psychiatric presentation, dysesthesias, ataxia, PRNP codon 129 methionine homozygous, no
periodic  electroencephalogram  (EEG)  complexes,  bilateral  increased  thalamic
densities on magnetic resonance (MR) imaging, fluid amyloid plaques; •   fatal familial insomnia (described in 1986), an autosomal-dominant inheritance, with      a  mutation  at  the  PRNP  codon  179  linked  to  128  methionine  and  symptoms  of
     insomnia,  dysautonomia,  ataxia,  myoclonus,  late  mild  dementia,  with  minimal
     vacuolation, no plaques, and PrPSc difficult to detect;
•   sporadic  familial  insomnia  (described  in  1999)  with  a  similar  pattern  to  fatal  familial      insomnia but a negative family history and no mutation identified in either PRNP gene;
•   Gertzsmann-Sträussler-Scheinker (GSS) syndrome (a rare condition affecting two to five      persons  per  100  000  000  population)  identified  in  1936,  with  a  familial  autosomal-
     dominant pattern with ataxia and dementia with universal amyloid plaques;
•   kuru  –  a  human  form,  associated  with  ritual  cannibalism  in  a  tribe  the  eastern highlands of New Guinea, first described in 1957 (and later shown to be transmissible
to chimpanzees by intracerebral injection) with clinical signs of ataxia, tremor, cranial
nerve abnormalities, common amyloid plaques. TSEs related to BSE have been shown to affect kudu, gemsbok, nyala, oryx, eland, domestic
cat, cheetah, puma, tiger, ocelot, bison, Ankole cow and lions. The causative agent of TSEs Two theories of what is responsible for TSEs have been put forward³: Sigurdsson (in 1954)
suggested that there was a viral cause, using the term ‘slow unconventional virus’. Griffith
put forward the concept of a self-replicating protein in 1967 and this was developed into the
prion protein theory by Prusiner in 1982. The latter has wider acceptance today. Brian R Matthews, B Pharm, PhD, MRPharmS, MBIRA is Senior Director, EC Registration, Alcon Laboratories (UK) Ltd, Hemel Hempstead,  UK.  This  paper  formed  the  basis  of  a  presentation  at  the  Parenteral  Drug Association  meeting  entitled:  Good
Pharmaceutical Manufacturing and Quality Strategies, held in Taormina, Italy, 5–6 April 2001. Further information on materials
of animal origin used in medical devices can be found in The Regulatory Affairs Journal (Devices), 1998, 6(1), 14 and 6(2), 93.