Bovine spongiform encephalopathy manufacturing

The regenerative medicine consists of three components cell, nutrient, and scaffold. The combinatory usage of these components is important. For the scaffold manufacturing, bioactive natural organic materials originated from marine products are indispensable because the severe inflection problems such as bovine spongiform encephalopathy, avian and swine influenzas, and tooth-and-mouth disease in bovine, pig, and buffalo occur all over the world. 

Excipients used in injectable formulations have to meet several stringent requirements. A positive identification test uniquely applicable to the excipients is required (e.g., infrared spectrophotometry and chromatography). It is important that manufacturers identify and set appropriate limits for impurities. These limits should be based upon appropriate toxicological data, or the limits described in national compendial requirements. Manufacturing processes should be adequately controlled so that the impurities do not exceed such established specifications. Solvents or catalysts used in the excipient production process should be removed to appropriate levels. If naturally derived, excipients should meet endotoxin levels and may require further testing for bovine spongiform encephalopathy (BSE) /... 

Excipients of human or animal origin should be identified. The genus, species, country of origin, source (e.g., pancreas), and manufacturer or supplier should be clearly indicated. Furthermore, for excipients derived from ruminant materials, the application should state whether the materials are from bovine spongiform encephalopathy countries as defined by the U.S. Department of Agriculture (9 CFR 94.11). 

BSE CBER CDER cGMP CHO CNS CPMP CTNBio bovine spongiform encephalopathy Center for Biologies Evaluation and Research Center for Drug Evaluation and Research current good manufacturing practices Chinese hamster ovary cell line Conselho Nacional de Saude (Brazilian National Health Council) Committee for Proprietary Medicinal Products Comissao Tecnica Nacional de Biosseguranca (Brazilian National Biosafety Technical Commission)... 

A few cases of Creutzfeldt-Jakob disease have been transmitted by corneal transplantation, dural transplantation, surgical equipment, and human growth hormone extracted from human pituitary glands (195). This has of course raised concern that Creutzfeldt-Jakob disease might prove to be transmissible by blood and blood products (196). The concern has been further accentuated by recent fears of transmission bovine spongiform encephalopathy through food consumption by humans. Some manufacturers of plasma products have reacted by recalling products from the market (197). 

However, the emergence of variant Creutzfeldt-Jakob disease (vCJD) in the UK and France has raised concern about a new theoretical risk of infection in patients treated with blood and blood products (198). Animal experiments in which blood from sheep infected with bovine spongiform encephalopathy and natural scrapie-infected sheep into scrapie-free recipient animals have suggested disease transmission by the blood transfusion route in 2 of 24 sheep with bovine spongiform encephalopathy and in 4 of 21 sheep with scrapie (199). Many European countries have incorporated leukodepletion of all blood products, as leukocytes are believed to play a key role in the pathogenesis of variant Creutzfeldt-Jakob disease (198). In some countries, people who have lived in the UK for a period longer than 6 months between 1980 and 1996 are excluded from blood donation (13). Furthermore, it has been shown that various steps used in the manufacture of plasma-derived products also contribute to reduced infectivity by bovine spongiform encephalopathy (198). 

Cholesterol is generally regarded as an essentially nontoxic and nonirritant material at the levels employed as an excipient. It has, however, exhibited experimental teratogenic and reproductive effects, and mutation data have been reported. Cholesterol is often derived from animal sources and this must be done in accordance with the regulations for human consumption. The risk of bovine spongiform encephalopathy (BSE) contamination has caused some concern over the use of animal-derived cholesterol in pharmaceutical products. However, synthetic methods of cholesterol manufacture have been developed. ... 

A fresh boost was given to plant-based molecular farming in recent years, as the biopharmaceutical industry is trying to eliminate manufacturing processes that rely on production in animal cells due to the possible contamination of these products by human pathogens such as bovine spongiform encephalopathy (BSE) or Creutzfeld-Jakob disease (CJD, vCJD) (see-Part IV, Chapters 1, 2, 3, and 4). 

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