NR AHYJ
AU Marwick,C.
TI BSE sets agenda for imported gelatin
QU JAMA. Journal of the American Medical Association 1997 Jun 4; 277(21): 1659-60
PT news
VT
THE FALLOUT from "mad cow disease" continues, although incidence of the disease itself has been decreasing steadily since January 1993 (JAMA. 1996;276;438-440). The latest worry is a renewal of the uncertainties surrounding the risk of human exposure to the agent or agents of spongiform encephalopathy in gelatin, which is manufactured from the bones and hides of cows and pigs.
The concern has prompted a Food and Drug Administration (FDA) committee to advise the agency to reimpose a restriction on the use of gelatin manufactured from parts of cows imported from countries that have reported cases of bovine spongiform encephalopathy (BSE). Humans are exposed to a wide variety of products that contain or use gelatin, from sausage casings and jellies to medicinal capsules and at least 1 vaccine.
In January, for example, Italian health authorities suspended distribution of a Haemophilus influenzae b conjugate vaccine (named HibTITER, manufactured by Wyeth-Lederle Vaccines and Pediatrics, Radnor, Pa) because the nutrient on which the organisms are cultivated contains bovine brain and heart, hence a possibility of contamination with BSE. The step was purely precautionary. No specific risk is known. At the time, the FDA issued a statement saying the agency was convinced that the vaccine is safe.
The Gelatin Exemption
In 1994, the FDA allowed bovine-derived materials to be imported for the manufacture of pharmaceutical grade gelatin from countries that reported cases of BSE. The decision relaxed a position the agency had taken the previous year, namely, that bovine materials from countries with BSE should not be used in FDA-regulated products - the so-called gelatin exemption.
"The decision reflected a conclusion that the available evidence did not suggest transmission of BSE via gelatin and was based on an assessment that the manufacturing conditions were likely to inactivate the infectious agent," said David Asher, MD, PhD, chief of the FDA's Laboratory of Method Development, Center for Biologics Evaluation and Research, addressing a meeting last month of the agency's Transmissible Spongiform Encephalopathies Advisory Committee.
In light of more recent events, the FDA decided to reconsider the gelatin exemption and other issues relevant to BSE, Asher said. The most dramatic of these events was the report last year of a new variant of Creutzfeldt-Jakob disease (CJD), a human disorder akin to BSE, found in 15 persons in Great Britain and 1 in France. A previous report of feline spongiform encephalopathy in Britain also suggested that the so-called species barrier was not absolute. In addition, Asher said, the FDA has not been provided with scientific evidence that the processing of gelatin removes all infectivity from the original materials; and finally, there was concern that some source material for gelatin - particularly imported gelatin - may contain bovine neural tissue.
Since 1986, when BSE was first reported in Britain, more than 165,000 cattle from about 33,000 herds have been diagnosed with the disease. It has been reported in cattle in France, Switzerland, Portugal, the Republic of Ireland, Northern Ireland, and the Netherlands, said Kiki Hellman, PhD, a senior scientist at the FDA's Center for Devices and Radiological Health. The disease has not been detected in cattle in the United States. The US Department of Agriculture (USDA) has an ongoing program of histopathologic examination of specimens of central nervous system tissue from US cattle that exhibit unusual neurologic symptoms, and no cases of BSE have been found. Since 1989, no cattle have been imported into the United States from the USDA's list of BSE-designated countries.
Evidence and Recommendation
For a day and a half, the committee listened to gelatin manufacturers describe the sources of the raw materials and processes by which gelatin is made. What the committee heard included data from a study that allegedly validated that neural tissues were removed from the source materials during gelatin manufacture; a summary of a March 1997 recommendation by the World Health Organization stating that bovine sources for preparing medicinal products and devices should be avoided; and, finally, a directive from the European Community Commission that banned "all high-risk materials of bovine and ovine origin" in the manufacture of pharmaceuticals regardless of their source, not just animals from countries reporting BSE.
After pondering the possibility that gelatin, manufactured from bones obtained from cows possibly exposed to BSE, could be infected with the disease agent and so trigger a spongiform disease in humans, the majority of the members concluded that the process of making gelatin does not fully inactivate the agent. It was, as one committee member put it, "a decision in the face of uncertainty." At the same time, said William Hueston, DVM, PhD, associate dean of Virginia-Maryland Regional College of Veterinary Medicine, College Park, Md, "there is no evidence to date of transmission of spongiform encephalopathy to animals or humans via gelatin."
The committee agreed to recommend that the agency adopt a risk-based approach based on the source and categories of use. Hueston laid it out for his fellow committee members: There is no concern about gelatin produced in the United States from US sources; there is a concern about gelatin produced from foreign sources. But, he added, "from the presentations we have heard it would appear that there are currently in place regulations that limit the introduction of the raw material into the United States, and this includes no material coming from countries that currently report cases of BSE." Finally, he said, there is concern about gelatin produced in other countries and imported into the United States.
So, he said, what must be considered is the BSE status of the country of origin of the source materials, the effectiveness of surveillance, and what the source materials are and the methods by which they are processed and put to use.
Gradation of Risk
From the reports presented at the meeting, Hueston said, it was evident that bovine source materials carry a higher risk than do porcine source materials; that bones, particularly skulls and backbones, are greater sources of risk than are hides; that alkaline processing procedures are more effective in terms of safety than is the acid-extraction process; and that the risk for users descends in severity from parenteral products to oral products to industrial products.
With nods of approval around the table, committee chair Paul W. Brown, MD, medical director of the National Institute of Neurological Disorders and Stroke, Bethesda, Md, said, "We could recommend that if any restrictions are put in place they be based on this type of risk assessment."
At the end of the meeting, Brown polled committee members for their response to a question put by the FDA: Does current scientific evidence justify continuing to exempt gelatin from the restrictions recommended by the FDA for other bovine-derived materials from BSE countries?
Of the members present and eligible to vote, 11 of 15 replied: "No," many of them enlarging on their response. For example, Lawrence B. Schonberger, MD, MPH, assistant director for public health at the Centers for Disease Control and Prevention, Atlanta, Ga, said that while gelatin was most likely safe, "the data on the risk of exposure were insufficient, particularly in light of the large numbers of people who are being exposed." Sidney M. Wolfe, MD, director of the Public Citizen Health Research Group, Washington, DC, said, "We're more worried now about the crossing of the species barrier; there is evidence of residual neural tissue in the materials used for gelatin, and we have no guarantee that the infectivity has been removed."
IN 1994 hatte die amerikanische Food and Drug Administration (FDA) verantwortungsloserweise den Import von Rinderrohmaterial für die Gelatineproduktion aus Ländern mit BSE-Fällen. 1997 sah sie endlich ihren Fehler ein und verbot den Import dieses Rohmaterials aus BSE-Ländern.
MH Animal; Cattle; *Drug Industry/standards; *Encephalopathy, Bovine Spongiform/prevention & control/transmission; Human; *Meat Products/standards; United States; United States Food and Drug Administration
SP englisch
PO USA