Association of Medical Diagnostics Manufacturers

The final rule was published in the Federal Register June 5, 1997. This rule amends 21 CFR 589 to prohibit the use of protein derived from mammalian tissues in ruminant feed with specified exclusions ( "blood and blood products; gelatin; inspected meat products which have been cooked and offered for human food and further heat processed for feed; milk products; and any product whose only mammalian protein consists entirely of porcine or equine protein."). The final rule is addressed to renderers, protein blenders, feed manufacturers, distributors, and persons responsible for feeding ruminant animals. These groups are required to certify their compliance and are subject to FDA inspection. Further exemptions from the ban may be permitted in the future if manufacturers use a method "that has been validated by the Food and Drug Administration to deactivate the agent that causes transmissible spongiform encephalopathy (TSE)" and routinely test for that agent using "a test method that has been validated by the Food and Drug Administration to detect the presence of the agent". The final rule became effective August 4, 1997. Concern has been expressed about the United Staes ban because of the exceptions it contains. The AMDM was pushing for a stronger ban.

The Food and Drug Administration (FDA) published recommendations for the use of bovine-derived materials in the manufacture of products intended for human use in December of 1993 and again in May 1996. These letters require manufacturers to maintain records of the origin of the materials used. The most recent letter states, "We strongly recommend you take whatever steps are necessary to assure...you are not using materials that have come from cattle born, raised, or slaughtered in countries where BSE is known to exist."

The United States Department of Agriculture (USDA) continues to maintain that BSE is not known to exist in the United States or Canada.

The list of countries where BSE is known to exist includes France, Great Britain (includes the Falkland Islands), Northern Ireland, the Republic of Ireland, Oman, Switzerland, Portugal, and the Netherlands. Canada had a single case of BSE that was highly publicized and well managed. It resulted from an British import prior to the ban on imports from Great Britain. Canada was not added to the list of "BSE-countries" Other countries with some BSE traceable to British imports but not on the BSE list include Germany, Denmark, and Italy.

The USDA has taken aggressive measures to prevent BSE in the United States. These measures include prevention, education, surveillance, and response. Since 1989 the Animal and Plant Health Inspection Service (APHIS) has prohibited the importation of ruminants and ruminant products from countries where BSE has been diagnosed in native cattle. APHIS has an extensive education program for veterinary practitioners, lab personnel, industry personnel, and producers. APHIS has implemented the most comprehensive BSE surveillance program in the world. As of September 30, 1997 6459 brains of suspect cattle have been examined for evidence of BSE. No evidence of BSE or other TSE has been detected. AHIS has drafted an emergency response plan for use in the unlikely event that BSE should be detected in North America. For more information on USDA=s actions check under BSE at http://www.ahpis.usda.gov on the internet.

European Actions

Since the outbreak of BSE, Europe has been very active in regulatory actions to prevent its spread. For a great review of BSE issues in the United Kingdom and in Europe check http://www.maff.gov.uk. Many of these actions taken by the European Union have affected import/export regulations. For example:

The Committee for Proprietary Medicinal Products (CPMP) in the Europeans Agency for the Evaluation of Medicinal Products is currently revising its Note For Guidance on Minimizing The Risk Of Transmitting Animal Spongiform Encephalopathy Agents Via Medicinal Products. Where bovine materials are used in manufacturing processes the source of animals, the nature of the animal tissue used in manufacture, and the production process must be considered. In February 1994 the German Federal Health Office published safety requirements for pharmaceuticals made from body components of the cow, sheep, or goat to avoid the risk of transmission of Bovine Spongiform Encephalopathy (BSE) or scrapie. This risk assessment considers country of origin and animal environment, type of material used, methods used to inactivate or remove TSE pathogens, quantities of raw material required to produce one daily dose of the product, number of daily doses, and route of administration. More recently (July 30, 1997) the European Union placed a ban on the use of "specified risk materials in the manufacture of pharmaceuticals and cosmetics (Commission Decision 97/534/EC). Specified risk materials are defined as:

a) the skull, including the brain and eyes, tonsils and spinal cord of:

-bovine animals aged over 12 months,

-ovine and caprine animals which are aged over 12 months or have permanent incisor tooth erupted through the gum;

b)the spleens of ovine or caprine animals.

The European Union is drafting a similar assessment of animal tissues and their derivatives utilized in the manufacture of medical devices (Draft prEN 12442).

Updates on medicinal product European Notes for Guidance can be found on the internet at http://www.edura.org/emea.html.

Actions to control the spread of traditional adventitious viral contaminants have also been taken.

The following documents published by the European Uniton illustrate the efforts governments are taking to minimize the risk of spreading viral disease through the use of animal derived materials:

EEC regulatory document, note for guidance, validation of virus removal and inactivation procedures (Biologicals 1991 19,247-251) reviews the sources of viral contamination, the choice of viruses for validation, the design and implications of validation studies, and the limitations of validation studies. The CPMP Biotechnology Working Party is currently revising the validation document as Note For Guidance On Virus Validation Studies: The Design, Contribution And Interpretation Of Studies Validating The Inactivation And Removal of Viruses. Council Directive 92/118/EEC of 17 December 1992 or "Balai Directive" covers the animal health and public health requirements governing trade in certain products not covered by other directives. Draft commission decision of 1993, laying down the animal health requirements and veterinary certification for the import from third countries of blood products of animals not intended for human or animal consumption and amending Commission Decision 94/278/EC is the further definition of the specific annex chapter dealing with blood and blood products of animal origin from the "Balai" Directive. It is currently in draft revision 10. It requires that blood product for pharmaceutical or technical use imported from third countries where Foot-and-Mouth Disease and/or Blue Tongue are known to exist be treated in one of three ways:

Heat to 65^o for at least 3 hours; or,

Change in pH to 5 for 3 hours; or,

Gamma radiation at 2.5 mega rads

As action on this directive has stalled due to focus on BSE issues, individual countries have enacted legislation to prevent the spread of traditional viral agents. These countries include the United Kingdom, France, Germany, Belgium, the Netherlands.

These are just some of the current animal derived materials issues. If you have more information about issues to share please contact Greg Hanson at HyClone Laboratories, Inc. 1725 South HyClone Road, Logan, Utah 84321 or by E-Mail at greg.hanson@perstorp.com.