The FDA has recently changed its position with regard to the use of gelatin. A guidance document has been issued regarding the use of gelatin in FDA-regulated products for human use (Attachment 4). The guidance pertinent to medical devices reads:
"Gelatin produced from bones and hides obtained from cattle residing in, or originating from, countries reporting BSE or from countries that do not meet the latest BSE-related standards of the Office International des Epizooties (OIE) should not be used either in injectable, ophthalmic, or implanted FDA regulated products, or in their manufacture."
The guidance also states:
"At this time there does not appear to be a basis for objection to the use of gelatin produced from bovine hides and bones in FDA products for human use if the gelatin is produced in the United States from US-derived raw materials or from cattle born, raised and slaughtered in other countries that have no reported BSE cases and that meet OIE BSE standards."
Bovine Spongiform Encephalopathy (BSE) is a degenerative disease which affects the central nervous system of cattle. It is similar to other transmissible spongiform encephalopathies (TSEs) such as scrapie in sheep and Creutzfeldt-Jakob Disease (CJD) in humans. At this point in time the incubation period of BSE appears to be from 2 to 8 years. There is currently no treatment, nor is there a validated test to detect the disease in a live animal. Diagnosis is determined by microscopic examination of brain tissue. The nature of the BSE agent is widely theorized to be a prion, an abnormally folded version of a normal cellular protein. The abnormal protein then recruits additional molecules of normal protein and facilitates their conversion to the abnormal form. The agent is extremely resistant to traditional forms of disinfection and sterilization. As new information on the diagnosis, treatment and nature of the agent becomes available, this guidance will be modified as appropriate.
Epidemiologic data suggest that the BSE epidemic in Great Britain which began in 1986 occurred through feeding cattle contaminated meat and bone meal as a protein source. The BSE agent may have been present for a long time, but changes in rendering procedures in the late 70's and early 80's may have enabled the active agent to survive in the animal feeds. The agent is thought to be from scrapie-infected sheep, but cattle with a previously unidentified TSE have not been ruled out. An association between cases of variant CJD in Great Britain and BSE seems likely, although causality has not been proved. To date, there have been no cases of BSE in the United States.
The possibility of introducing the BSE agent through a medical device requires special attention on the part of manufacturers with regard to the sourcing and processing of bovine-derived material. At present this can most easily be accomplished by assuring that the source cattle are free of BSE. In 1993 and more recently, on May 9, 1996, the Food and Drug Administration (FDA) issued letters to manufacturers to request that bovine-derived materials from cattle which have resided in or originated from countries where BSE has been diagnosed not be used in the manufacture of FDA-regulated products. (Attachments 1, 2 and 3)
Since 1989, the USDA has restricted the importation of live ruminants from Great Britain. Currently the USDA restricts the importation of live ruminants from countries where BSE is known to exist, and from those countries that present a significant risk of introducing BSE into the United States. Also restricted (by USDA) from import from these countries are other ruminant-derived products such as bone meal, meat and bone meal, blood meal, offal, glands, and gelatin for animal consumption. FDA recently prohibited protein derived from mammalian tissues to be used in ruminant feed for animals in the US (Federal Register June 5, 1997; 21 CFR Part 589 "Substances Prohibited From Use in Animal Food or Feed; Animal Proteins Prohibited in Ruminant Feed").
To track medical devices which either contain or are exposed to animal-derived materials during manufacturing (e.g., human cells grown in media containing fetal calf serum), CDRH has developed the CDRH Biomaterials Database which contains an inventory of these devices, including type of material, animal species and country of origin, and target organ or tisssue for each device. Originally proposed in response to the BSE issue, the Database was expanded to include all animal-derived products (including human) in order to respond to other animal material-based sourcing concerns that may arise in the future.
