[Federal Register Volume 59, Number 166 (Monday, August 29, 1994)]
[Unknown Section]
[Page 0]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 94-21279]


[[Page Unknown]]

[Federal Register: August 29, 1994]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

 

Bovine-Derived Materials; Agency Letters to Manufacturers of FDA-
Regulated Products

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is publishing the texts 
of four letters it recently issued to manufacturers of FDA-regulated 
products requesting that bovine-derived materials from certain cattle 
not be used in the manufacture of FDA-regulated products intended for 
humans or animals. FDA believes that bovine spongiform encephalopathy 
(BSE), a neurological disease of bovine animals, is a concern in the 
manufacture of FDA-regulated products. FDA believes that precautionary 
measures will reduce potential risk of exposure to, or transmission of, 
the agents that cause BSE in cattle. FDA is publishing the texts of the 
four letters at the end of this document in addition to mailing them 
directly to manufacturers.

FOR FURTHER INFORMATION CONTACT:
    For dietary supplements and cosmetics: Elisa L. Elliot, Center for 
Food Safety and Applied Nutrition (HFS-22), Food and Drug 
Administration, 200 C St. SW., Washington, DC 20204, 202-205-5140.
    For medical devices: Kiki B. Hellman, Center for Devices and 
Radiological Health (HFZ-113), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-443-7158.
    For human drugs: Gayle R. Dolechek, Center for Drug Evaluation and 
Research (HFD-335), Food and Drug Administration, 7520 Standish Pl., 
Rockville, MD 20855, 301-594-0104.
    For biological products: Timothy W. Beth, Center for Biologics 
Evaluation and Research (HFM-635), Food and Drug Administration, 1401 
Rockville Pike, Rockville, MD 20852-1448, 301-594-3074.
    For veterinary drugs: William C. Keller, Center for Veterinary 
Medicine (HFV-210), Food and Drug Administration, 7500 Standish Pl., 
Rockville, MD 20855, 301-594-1722.
    For animal feeds: John P. Honstead, Center for Veterinary Medicine 
(HFV-222), Food and Drug Administration, 7500 Standish Pl., Rockville, 
MD 20855, 301-594-1728.
    For information on countries with BSE: Harvey Kryder, U.S. 
Department of Agriculture, Animal and Plant Health Inspection Service, 
Federal Bldg., rm. 757, 6506 Belcrest Rd., Hyattsville, MD 20782, 301-
436-7885.

SUPPLEMENTARY INFORMATION: FDA has recently issued four letters 
requesting that bovine-derived materials from cattle that have resided 
in, or originated from, countries designated by the U.S. Department of 
Agriculture (USDA), Animal and Plant Health Inspection Service (APHIS), 
as countries where BSE exists, not be used in the manufacture of FDA-
regulated products intended for humans or animals. A letter dated 
November 9, 1992, was issued to manufacturers of dietary supplements. A 
letter dated December 17, 1993, was issued to manufacturers of human 
drugs, biologics, and medical devices. (With respect to the December 17 
letter, the agency has subsequently clarified that FDA does not object 
to the use of bovine-derived materials from BSE-countries in the 
manufacture of pharmaceutical grade gelatin at this time.) A letter 
dated August 17, 1994, was issued to manufacturers of FDA-regulated 
products for animals. A letter dated August 17, 1994, was issued to 
manufacturers and importers of dietary supplements and cosmetics.
    BSE is a neurological disease of bovine animals. USDA has 
regulations that prohibit and restrict the importation of certain 
animal products and animal byproducts from ruminants that have been in 
countries where BSE exists. These countries are designated by USDA and 
listed in 9 CFR 94.18.
    The BSE agent is extremely resistant to traditional forms of 
processing and sterilization. The disease was first identified in 1986. 
Since that time, over 100,000 cattle in Great Britain have either died 
or been destroyed as a result of BSE infection. At the present time, 
BSE is not known to exist in the United States. The disease is not 
known to be contagious by direct transmission.
    BSE is a neurological disease classified as a transmissible 
spongiform encephalopathy (TSE), and is similar to other TSE's such as 
scrapie in sheep and Creutzfeldt-Jakob disease (CJD) in humans. Its 
continued spread within countries where BSE exists appears to be 
through the use of feed containing protein and other products from 
ruminants infected with BSE. In the United Kingdom, scrapie in sheep 
has been epidemiologically associated with the occurrence of BSE in 
cattle. Scrapie in sheep is known to have existed in Britain, Ireland, 
France, and Germany for over 200 years and has been observed in the 
United States and Canada for about 50 years. Because FDA cannot 
positively rule out a direct association between scrapie and BSE, FDA 
is proposing elsewhere in this issue of the Federal Register to 
prohibit the use in ruminant feed of specified offal from adult sheep 
and goats.
    CJD is a rare neurological disease of humans that has similarities 
to BSE in cattle. The cause of CJD is unknown except in a few cases of 
specific genetic mutations and iatrogenic CJD in the case of CJD-
contaminated growth hormone injections, dura mater grafts, and corneal 
transplants. Even though there is no direct evidence supporting an 
association between BSE and human disease, FDA believes that it is 
prudent to reduce any potential risk of human exposure to the BSE 
agent.
    The purpose in issuing these four letters is to request that 
bovine-derived materials from cattle that have resided in or originated 
from USDA-designated BSE countries not be used in the manufacture of 
FDA-regulated products intended for humans or animals. Meat (i.e., 
skeletal muscle) is not covered by these letters. For guidance on 
importation of meat and other USDA-regulated products, refer to Title 9 
of the Code of Federal Regulations.
    The text of the November 9, 1992, letter to manufacturers of 
dietary supplements follows:
November 9, 1992
Dear Manufacturer of Dietary Supplements:
    In a series of recent meetings, representatives of the dietary 
supplement industry have suggested that if FDA has concerns 
involving dietary supplement products, it should communicate its 
concerns directly to the industry. We agree that this is a 
reasonable and appropriate suggestion. Therefore, I wish to bring a 
matter of some importance to FDA to your attention. I would like to 
share with you FDA's concerns regarding the marketing of certain 
nutritional supplements. We have become aware that some supplements 
contain brain, nervous tissue, or glandular materials from a variety 
of animal species, including bovine (oxen, beef) and ovine (sheep) 
species. We are concerned that some amount of these materials may 
have come from countries experiencing Bovine Spongiform 
Encephalopathy (BSE) in the case of bovine tissues, or scrapie in 
the case of ovine tissues.
    As you may know, BSE is an infectious neurologic disorder of 
cattle, and is prevalent in certain parts of the world (``BSE 
countries''). Scrapie is a spongiform encephalopathy of sheep, and 
is a disease that is endemic in many parts of the world, including 
the United States. It is believed that the rapid spread of BSE among 
animals in Great Britain was caused by inadequately rendered, 
scrapie agent-containing material being fed to cattle. Thus, it is 
suggested that BSE is the clinical manifestation of scrapie in 
cattle. It is further suggested that cattle became infected by the 
orogastric route. Both scrapie and BSE are classified as 
transmissible spongiform encephalopathies. The causal agent is 
unknown, but suspected to be an agent known variously as ``prion,'' 
``virino,'' ``unconventional virus,'' or ``slow virus.'' That these 
agents can infect across species, and infect primates, has been 
demonstrated repeatedly in laboratory studies.
    Although cases are rare, spongiform encephalopathies can affect 
humans, most notably, Creutzfeldt-Jakob Disease (CJD). CJD is a rare 
disease, its incidence being about 1 case per million population. It 
is 100% fatal. Human-to-human transmission by iatrogenic means 
(e.g., contaminated neurosurgical instruments, corneal and dura 
mater implants, human growth hormone injections) has been 
documented. The possibility of transmission of animal spongiform 
encephalopathy agents to humans from consumption of animal brains 
from a variety of species, such as squirrel, goat, sheep, and hogs, 
and from consumption of sheep's eyeballs has been examined in the 
past. Although proof of such dietary transmission is lacking, some 
suspicions remain. The rarity of the disease, coupled with what is 
believed to be a long onset time (median - 13 years), make more 
precise epidemiological studies extremely difficult. Additionally, 
there may be a genetic or other susceptibility in some individuals.
    FDA has recently been involved in investigating a consumer 
complaint involving a confirmed case of CJD. It is standard 
procedure for FDA to follow-up on all consumer complaints involving 
death or serious injury. In the course of this investigation, FDA 
learned that the woman had taken a bovine tissue-containing dietary 
supplement. Although, at the present there is no basis to conclude 
that this supplement played any role in causing this disease, FDA 
and NIH have decided that it is prudent to further investigate this 
matter. Therefore, both agencies have begun to conduct cooperative 
studies to determine whether nutritional supplements containing 
brain, nervous tissue or glandular materials from bovine and ovine 
species might be linked to human spongiform encephalopathies.
    In 1991, the United States Department of Agriculture published a 
rule (9 CFR 95.4) which prohibits imports of various tissues and 
organs from ruminants in countries where BSE exists. Similar 
prohibitions have been in place for scrapie for many years. The 
concern addressed by the rules was that BSE - or scrapie-containing 
materials may find their way into cattle or sheep in the U.S. 
Nevertheless, FDA feels that the principle embodied in the USDA rule 
is an appropriate standard for tissues, organs, glands, and 
processed extracts from these articles insofar as they may be used 
for human food, including in supplement form.
    FDA is requesting that you investigate the source of your neural 
and glandular tissue(s) or tissue extracts of bovine or ovine 
species to determine if they are being produced in known BSE 
countries or from flocks in which scrapie may be present. We would 
recommend that you reformulate your products using neural or 
glandular tissues that you are assured are BSE or scrapie free. We 
suggest within the next two months, that you gather information and 
determine the source of bovine or ovine materials used in your 
product(s). If you use bovine-derived materials in your product(s), 
we suggest that you develop a plan to assure, with a high degree of 
certainty, that there is no possibility that materials of bovine 
origin are being supplied by BSE countries, either directly or 
indirectly. If you use ovine materials in your product(s), we 
suggest that you also develop a similar plan for assuring that these 
tissues are from scrapie-free animals. We fully recognize that there 
is no proven link between BSE or scrapie, and human disease, but 
given the devastating consequences of human spongiform 
encephalopathies such as CJD, we believe that our request is a 
prudent step at this time.
    FDA requests that you communicate your plan(s) to us once you 
have developed them. We recognize that the steps you take to secure 
the assurances you need from exporting countries may be difficult, 
but we are certain you will agree with us that they are desirable.
    If you need any additional information or guidance, please 
contact Dr. Douglas L. Archer, Deputy director, Center for Food 
Safety and Applied Nutrition at 202-205-4057. We appreciate you 
cooperation and attention to this matter.
    Sincerely,
    Fred R. Shank, Ph.D.
    Director
    Center for Food Safety and Applied Nutrition
    The text of the December 17, 1993, letter to manufacturers of 
drugs, biological drugs, medical devices, and biological device 
products follows:

    December 17, 1993
    TO: Manufacturers of FDA-regulated Products
    The Food and Drug Administration (FDA, the Agency) is issuing 
this letter to request that bovine-derived materials from cattle 
which have resided in or originated from countries where Bovine 
Spongiform Encephalopathy (BSE) has been diagnosed not be used in 
the manufacture of FDA-regulated products intended for 
administration to humans. We are advising you of our current 
recommendations pertaining to the use of such bovine-derived 
products.
    FDA is providing the following information to explain why the 
Agency thinks that an animal disease (such as BSE) may potentially 
be a concern in the manufacture of FDA-regulated products intended 
for administration to humans. BSE has been reported for more than 
109,000 cattle in the United Kingdom [Fall, 1993 quarterly report of 
the Ministry of Agriculture, Fisheries, and Food (MAFF)], and to a 
much lesser extent in other European countries. This neurological 
disease is a transmissible spongiform encephalopathy (TSE), and is 
similar to other TSEs such as scrapie in sheep and Creutzfeldt-Jakob 
Disease (CJD) in humans. The spongiform encephalopathies are 
uniformly fatal, and no rapid diagnostic test for infection in 
living animals (or humans) is currently available. Iatrogenic 
transmissions of CJD from both pituitary-derived human growth 
hormone (somatotropin) and dura mater\1\ have been reported. 
Research projects into the exact nature of both the BSE agent and 
other spongiform encephalopathy agents, host range, patterns of 
pathogenicity, and development of rapid antemortem diagnostic tests 
are ongoing. Available scientific information indicates that these 
agents are extremely resistant to inactivation by normal 
disinfection or sterilization procedures. The list of countries 
where BSE is known to exist (BSE-countries) is maintained by the 
United States Department of Agriculture (USDA). Countries listed in 
the Federal Register on December 6, 1991 (56 FR 63865 through 63870) 
include France, Great Britain (includes the Falkland Islands), 
Northern Ireland, the Republic of Ireland, Oman, and Switzerland.
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    \1\Brown P, Preece MA, Will RG. ``Friendly fire in medicine: 
hormones, homografts, and Creutzfeldt-Jakob disease''. Lancet 
1992:340:24-27.
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    While transmission of the causative agent of BSE to humans has 
not been reported to date, FDA considers the recommendations below 
to be prudent at this time to further reduce any potential risk of 
exposure or transmission of a BSE-agent to humans by FDA- regulated 
products.
    The Agency notes that regulated products intended for 
administration to humans and manufactured with bovine-derived 
materials derived from cattle that have at any time been in BSE-
countries may be adulterated under Section 501(a)(2)(B) of the 
Federal Food, Drug, and Cosmetic Act (the Act), for drugs and 
biological drug products; or Section 501(h) of the Act, for medical 
devices and biological device products. The Agency is considering 
rulemaking to restrict the use of bovine-derived materials from BSE-
countries. At this time, FDA recommends that bovine-derived 
materials from BSE-countries not be used in the manufacture of FDA-
regulated products.
    The Agency is providing the following suggestions to prevent the 
use of bovine-derived materials from cattle which have resided in or 
originated from BSE-countries. FDA recommends that manufacturers:
    a. identify bovine-derived materials used in the regulated 
product and identify all countries where the animals used for the 
material have lived. This information may be provided to the 
regulated-product manufacturer by the supplier of the bovine 
product. The supplier may also provide the manufacturer with 
appropriate veterinary regulatory inspection certification of 
slaughter, as required by the country of origin of live animals.
    b. maintain traceable records for each lot of bovine material 
and each lot of FDA-regulated product using these materials. These 
records should be part of the batch records, and available for FDA 
inspection.
    c. document the country of origin of the live animal source of 
any bovine-derived materials used in the manufacture of the 
regulated product. Documentation should be maintained for any new or 
in-process lots of licensed, cleared, or approved products; products 
pending clearance or approval; and investigational products intended 
to be administered to humans. Such documentation should be a part of 
the traceable records maintained in conjunction with batch 
production records, and such information should be available for 
review during FDA inspections.
    d. maintain copies of the records identified above for FDA-
regulated products that are manufactured with bovine-derived 
materials at foreign sites, or by the foreign manufacturers. The 
U.S. firms responsible for marketing these products should be 
responsible for these records. Manufacturers of products subject to 
licensure should maintain records at the site of manufacture.
    The Agency recommends that the information identified above be 
obtained for all currently approved, cleared, or licensed products, 
pending or approvable products, and investigational products.
    Some manufacturers of FDA-regulated products may have already 
provided some of this information in applications to the USDA for 
permits to import certain animal products into the United States. In 
some instances, copies of these applications and permits may contain 
some of the information that the FDA is requesting. FDA suggests 
that this information be documented, recorded, and maintained for 
all bovine-derived products currently manufactured or marketed in 
the U.S. This information should be available for FDA inspection.
    If you have any questions regarding the above items please 
contact the appropriate center as follows:
    Center for Devices and Radiological Health: 301-594-4692 ext. 
158
    Center for Drug Evaluation and Research: 301-594-0054
    Center for Biologics Evaluation and Research--contact the 
Application Division in the CBER Office responsible for the 
regulation of your product. These Offices are:
    Office of Vaccines Research and Review 301-594-2090
    Office of Therapeutics Research and Review 301-594-5109
    Office of Blood Research and Review 301-594-2012
    Regulated-product manufacturers are referred to the USDA for 
current information and countries on the ``BSE-list''. Additional 
information and regulations concerning bovine spongiform 
encephalopathy (BSE) and affected animals may be obtained from the 
open veterinary literature and the United States Department of 
Agriculture (see 9 CFR 94.18).
    Sincerely yours,
    Jane E. Henney, M.D.
    Deputy Commissioner for Operations
    The text of the August 17, 1994, letter to manufacturers of FDA-
regulated products for animals follows:
    August 17, 1994
    To: Manufacturers of FDA-regulated products for animals
    The Food and Drug Administration is issuing this letter to 
request that bovine-derived materials from cattle which have resided 
in, or originated from, countries designated as bovine spongiform 
encephalopathy (BSE) countries by United States Department of 
Agriculture (USDA), Animal and Plant Health Inspection Service, not 
be used in the manufacture of FDA-regulated products (drugs and 
feed) intended for animals. FDA believes that this action is 
necessary to prevent the occurrence of BSE in U.S. cattle. Meat 
(i.e., skeletal muscle) is not covered by this letter. For guidance 
on importation of meat and other USDA-regulated products, refer to 
Title 9 of the Code of Federal Regulations.
    FDA is providing the following information to explain why the 
Agency thinks that BSE may potentially be a concern in the 
manufacture of FDA-regulated products intended for administration to 
animals. BSE has been identified in more than 100,000 cattle in the 
United Kingdom and to a much lesser extent in other European 
countries. BSE has not been diagnosed in the U.S. This neurological 
disease is a transmissible spongiform encephalopathy (TSE), and is 
similar to other TSE's such as scrapie in sheep and Creutzfeldt-
Jakob Disease (CJD) in humans. The spongiform encephalopathies are 
uniformly fatal and no rapid diagnostic test for infection in living 
animals is currently available. A range of research projects into 
the exact nature of both the BSE agent and other TSE agents, host 
range, patterns of pathogenicity, and development of rapid ante 
mortem diagnostic tests is ongoing. Available scientific information 
indicates that these agents are extremely resistant to inactivation 
by normal disinfection or sterilization procedures. The list of 
countries where BSE is known to exist is maintained by the USDA and 
codified in Title 9, Code of Federal Regulations, Part 94.18.
    The Agency notes that products intended for animals and 
manufactured with bovine-origin materials derived from cattle that 
have, at any time, been in BSE countries may be adulterated under 
Section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act. 
The Agency is considering rulemaking to restrict the use of bovine-
derived materials from BSE countries in the manufacture of FDA-
regulated products for animals. At this time, we request that 
bovine-derived materials from BSE countries not be used in the 
manufacture of FDA-regulated products intended for animals.
    FDA considers the recommendations below to be prudent at this 
time to further reduce any potential risk of exposure to, or 
transmission of, a BSE agent to animals by FDA-regulated products.
    We recommend that manufacturers:
    a. Identify bovine-origin materials used in regulated products 
for animals and identify all countries where the cattle used for the 
material have lived. This information may be provided to the 
regulated product manufacturer by the supplier of the bovine 
material. The supplier may also provide the manufacturer with 
appropriate veterinary regulatory inspection certification of 
slaughter if already required by USDA for import from BSE countries 
which verify the country of origin.
    b. Maintain traceable records for each lot of bovine-derived 
material and each lot of FDA-regulated products intended for animals 
that are manufactured using these materials. These records should be 
part of the batch records and available for FDA inspection.
    c. Document the country of origin of the live animals for 
bovine-origin materials used in the manufacture of any new or in-
process lots of FDA-regulated products intended for animals. Such 
documentation should be a part of the traceable records maintained 
in conjunction with batch production records and such information 
should be available for FDA inspection.
    d. Maintain copies of the appropriate records identified above 
for FDA-regulated products intended for animals that are 
manufactured with bovine-derived materials at foreign sites, or by 
the foreign manufacturers. The U.S. firms responsible for marketing 
these animal products should be responsible for these records. 
Registered product manufacturers should maintain records at the site 
of manufacture.
    The Agency recommends that the information identified above be 
obtained and maintained for all FDA-regulated products intended for 
animals.
    Some manufacturers of FDA-regulated products intended for 
animals may have already provided some of this information in 
applications to the USDA for permits to import certain bovine 
materials into the U.S. In some instances, copies of these 
applications and permits may contain some of the information 
requested. We request that this information be documented, recorded, 
and maintained for all bovine-origin materials for use in FDA-
regulated products intended for animals currently manufactured or 
marketed in the U.S. This information should be available for FDA 
inspection.
    If you have any questions regarding the above items, please 
contact the Center for Veterinary Medicine:
    For Veterinary Drugs: Dr. William Keller, Director, Division of 
Surveillance, HFV-210, 7500 Standish Place, Rockville, Maryland 
20855, 301-594-1722
    For Animal Feeds: Dr. John Honstead, Division of Animal Feeds, 
HFV-222, 7500 Standish Place, Rockville, Maryland 20855, 301-594-
1728
    Regulated product manufacturers are referred to the USDA for 
current information and countries on its list of countries with BSE 
in native animals. Additional information and regulations concerning 
BSE and affected animals may be obtained from the USDA, Animal and 
Plant Health Inspection Service (301-436-7830).
    Sincerely yours,
    Linda A. Suydam
    Interim Deputy Commissioner for Operations
    The text of the August 17, 1994, letter to manufacturers and 
importers of dietary supplements and cosmetics follows:
    August 17, 1994
    To Manufacturers and Importers of Dietary Supplements:
    To Manufacturers and Importers of Cosmetics:
    The Food and Drug Administration (FDA) is recommending that 
firms that manufacture or import dietary supplements and cosmetics 
containing specific bovine tissues (see Appendix A) ensure that such 
tissues do not come from cattle born, raised, or slaughtered in 
countries where bovine spongiform encephalopathy (BSE) exists (BSE-
countries). Extracts of these tissues and ingredients derived from 
these tissues are also of concern. The recommended actions are 
precautionary measures to reduce potential risk of human exposure 
to, or transmission of, the agent which causes BSE in cattle.
    At this time, FDA is not extending the recommendation in this 
letter to dairy products or gelatin, because available evidence does 
not suggest transmission via these foods. Furthermore, meat (i.e., 
skeletal muscle) is not covered by this letter. For guidance on 
importation of meat and other products regulated by the United 
States Department of Agriculture (USDA), refer to Title 9 of the 
Code of Federal Regulations.
    The Agency is providing the following information to explain why 
it believes that BSE may potentially be a concern with certain 
dietary supplements and cosmetic products. BSE has been identified 
in more than 100,000 cattle in the United Kingdom and, to a much 
lesser extent, in several other countries. BSE has not been 
diagnosed in the United States. This neurological disease is a 
transmissible spongiform encephalopathy (TSE) and is similar to 
other TSEs such as scrapie in sheep and Creutzfeldt-Jakob Disease 
(CJD) in humans. The spongiform encephalopathies are uniformly fatal 
and no rapid diagnostic test for infection in living animals or 
humans is presently available. Current scientific information 
indicates that the causative agent is extremely resistant to 
inactivation by normal disinfection or sterilization procedures. A 
range of research projects into the exact nature of both the BSE 
agent and other TSE agents, host range, patterns of pathogenicity, 
and development of rapid ante mortem diagnostic tests is ongoing.
    Since 1991, USDA has prohibited the importation into the U.S. of 
certain tissues and organs from ruminants from countries where BSE 
exists (BSE-countries; see 9 CFR 94.18). USDA's regulations are 
intended to protect livestock in the United States from contracting 
TSEs and address known or strongly suspected modes of transmission. 
For the up-to-date listing of BSE-countries please contact USDA, 
Animal and Plant Health Inspection Service (APHIS) at (301) 436-
7830.
    The USDA regulations permit, under certain conditions, the 
importation of some cosmetic ingredients (i.e., collagen, collagen 
products, amniotic liquids or extracts, placental liquids or 
extracts, serum albumin, and serocolostrum) derived from ruminants 
from BSE-countries; see 9 CFR 95.4.
    The USDA regulations do not apply to imports of:
    * cosmetic products that are packaged and ready for sale;
    * bovine-derived materials intended for human consumption as 
either finished dietary supplement products or for use as 
ingredients in dietary supplements; or
    * human food (except meat, i.e., skeletal muscle).
    While documented transmission of the causative agents of BSE or 
scrapie to humans has not been reported to date, the FDA wrote to 
manufacturers of dietary supplements in November 1992, alerting them 
to the developing concern about TSEs in animals and CJD in man. That 
letter recommended that manufacturers voluntarily investigate the 
geographic source(s) of any bovine or ovine material used in their 
products (generally neural or glandular tissue or tissue extracts). 
The Agency also suggested that each manufacturer develop a plan ``to 
assure, with a high degree of certainty,'' that such materials are 
not from BSE-countries, as identified by USDA's APHIS, or from 
scrapie-infected sheep flocks, either foreign or domestic.
    FDA now considers further protective steps to be reasonable and 
is restating and expanding its recommendation to manufacturers and 
importers of dietary supplements and their ingredients, to develop 
plans for ensuring, with a high degree of certainty, that specific 
bovine-derived materials (see Appendix A) from BSE-countries are not 
being used. The Agency is also recommending that manufacturers and 
importers of cosmetic products and their ingredients develop the 
same type of plans. FDA is not, at this time, recommending 
restrictions on the use of ovine-derived materials in the 
manufacture of dietary supplement and cosmetic products and 
ingredients, as the epidemiological evidence now appears convincing 
that scrapie is not related to TSEs in humans.
    FDA believes it is prudent to expand its recommendation to 
cosmetics and cosmetic ingredients because extracts of listed 
tissues, e.g. sphingolipids isolated from brain tissue and extracts 
of bovine placenta, are used in cosmetics. Additionally, FDA is 
unaware of data demonstrating that processing techniques used in the 
manufacture of cosmetics will inactivate TSE agents. Further, little 
is known about the potential human risk of transmission from topical 
application of cosmetics containing TSE agents to intact, broken or 
abraded skin.
    To assist manufacturers and importers whose products are within 
the scope of this recommendation in developing their plans, the 
following guidance is provided:
    a. To ensure that bovine-derived materials (listed in Appendix 
A) used in the product(s) are from non BSE-countries, identify all 
countries where the animals used were born, raised or slaughtered. 
The supplier of the bovine-derived materials should provide the 
necessary records.
    b. Maintain traceable records for each lot of bovine-derived 
material and records of products containing the materials.
    c. Maintain records for those products manufactured at foreign 
sites or by foreign manufacturers which contain bovine-derived 
materials.
    The Agency recommends that manufacturers and importers of 
dietarysupplements and cosmetic products and ingredients used in the 
manufacture of these products develop their plans within the next 
two months and notify the Agency, in writing, that their plans have 
been developed. The designated contact is Dr. Elisa Elliot, Science 
Policy Analyst, Executive Operations Staff, HFS-22, Center for Food 
Safety and Applied Nutrition, FDA, 200 C Street, S.W., Washington, 
DC, 20204 or FAX (202) 205-5025. FDA recommends that the plans be 
implemented as soon after development as possible, and be available 
for review by the Agency during inspections.
    The Agency is continuing to examine all available information 
about TSEs and will provide additional guidance as necessary. If you 
need more information please contact Dr. Elliot by telephone at 
(202) 205-5140.
    We appreciate your attention to and cooperation in this matter.
    Sincerely,
    Linda A. Suydam
    Interim Deputy Commissioner for Operations
    Attachment

Appendix A

List of Tissues With Suspected Infectivity

Category I (High infectivity)
     Brain
     Spinal cord
Category II (Medium infectivity)
     Ileum
     Lymph nodes
     Proximal colon
     Spleen
     Tonsil
     Dura mater
     Pineal gland
     Placenta
     Cerebrospinal fluid
     Pituitary gland
     Adrenal gland
Category III (Low infectivity)
     Distal colon
     Nasal mucosa
     Sciatic nerve
     Bone marrow
     Liver
     Lung
     Pancreas
     Thymus gland
    List taken from ``Report of a WHO Consultation on Public Health 
Issues Related to Animal and Human Spongiform Encephalopathies,'' 
World Health Organization, Office of International Epizootics, 
Geneva, Switzerland, November 12-14, 1991.

    Dated: August 19, 1994.
Linda A. Suydam,
Interim Deputy Commissioner for Operations.
[FR Doc. 94-21279 Filed 8-26-94; 8:45 am]
BILLING CODE 4160-01-F