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Part IV
Department of Health and Human Services
_______________________________________________________________________
Food and Drug Administration
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21 CFR Part 589
Substances Prohibited From Use in Animal Food or Feed; Animal Proteins
Prohibited in Ruminant Feed; Proposed Rule
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 589
[Docket No. 96N-0135]
RIN 0910-AA91
Substances Prohibited From Use in Animal Food or Feed; Animal
Proteins Prohibited in Ruminant Feed
AGENCY: Food and Drug Administration, HHS.
ACTION: Proposed rule.
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SUMMARY: The Food and Drug Administration (FDA) is proposing to amend
the regulations to provide that animal protein derived from ruminant
and mink tissues is not generally recognized as safe (GRAS) for use in
ruminant feed, and is a food additive subject to certain provisions of
the Federal Food, Drug, and Cosmetic Act (the act). The proposed
regulations would establish a flexible system of controls, designed to
ensure that ruminant feed does not contain animal protein derived from
ruminant and mink tissues in a manner that encourages innovation. FDA
is also considering alternatives to this proposed ruminant-to-ruminant
prohibition, and is requesting comment on the relative merits and
disadvantages of the alternatives. FDA is proposing this action because
the feeding to ruminants of protein derived from potentially
transmissible spongiform encephalopathy (TSE)-infective tissues may
cause TSE in animals. TSE's are progressively degenerative central
nervous system (CNS) diseases of man and animal that are fatal.
Epidemiologic evidence gathered in the United Kingdom (U.K.) suggests
an association between an outbreak of a ruminant TSE, specifically
bovine spongiform encephalopathy (BSE) and the feeding to cattle of
protein derived from sheep infected with scrapie, another TSE. Also,
scientists have postulated that there is an epidemiologic association
between BSE and a form of human TSE, new variant Creutzfeldt-Jakob
disease (nv-CJD) reported recently in England. BSE has not been
diagnosed in the United States. However, this proposed rule is intended
to prevent the establishment and amplification of BSE in cattle in the
United States, and thereby minimize any risk which might be faced by
animals and humans.
DATES: Written comments by February 18, 1997. FDA proposes that any
final rule that may issue based on this proposal become effective 60
days after the date of its publication in the Federal Register. Submit
written comments on the collection of information requirements by February 18, 1997.
ADDRESSES: Submit written comments to the Dockets Management Branch
(HFA-305), Food and Drug Administration, 12420 Parklawn Dr., rm. 1-23,
Rockville, MD 20857. Submit written comments on the information
collection requirements to the Office of Information and Regulatory
Affairs, Office of Management and Budget (OMB), New Executive Office
Bldg., 725 17th St. NW., rm. 10235, Washington, DC 20503, ATTN: Desk
Officer for FDA.
FOR FURTHER INFORMATION CONTACT:
Regarding Scientific and Industry Issues:
George A. (Bert) Mitchell, Center for Veterinary Medicine (HFV-1),
Food and Drug Administration, 7500 Standish Pl., Rockville, MD 20855,
301-594-1761.
Regarding Procedural and Regulatory Issues:
Richard E. Geyer, Center for Veterinary Medicine (HFV-201), Food
and Drug Administration, 7500 Standish Pl., Rockville, MD 20855, 301-
594-1761.
SUPPLEMENTARY INFORMATION
Table of Contents
I. Summary
A. Introduction
B. GRAS Status of Ruminant and Mink Tissues
C. The ``No Action'' Alternative
D. The Basis for the Agency's Proposed Action
1. General Discussion
2. Analysis of Risk Factors
a. The risk of BSE occurring in the United States
b. The risk of amplification in the cattle population
c. The risk of transmission to humans
E. Enforcement Provisions
F. Alternatives
II. Background
A. TSE's
1. Scrapie
2. BSE
3. Other Animal TSE's
4. TSE's of Humans
a. CJD
b. nv-CJD
c. Gertsmann-Strausller-Scheinker (GSS) syndrome
d. Kuru
e. Fatal familial insomnia (FFI)
5. Etiology
6. Pathogenesis
7. Transmission
8. Genetics
9. Diagnostics
10. Inactivation
B. The Association Between Scrapie and BSE
C. The Association Between Animal TSE's and Human TSE's
D. Infectivity of Specific Tissues
E. Potential Risk of TSE's to the United States
1. Overview
2. Comparison with the U.K. Conditions
F. Historical Efforts to Control TSE's
1. U.S. Actions
a. FDA
b. USDA
c. Public Health Service
i. CDC
ii. National Institutes of Health (NIH)
iii. Other actions
2. International Actions
a. United Kingdom
b. WHO
c. OIE
d. European Community (EC)
3. Voluntary Measures by the U.S. Animal Industries
a. Voluntary ban on rendering adult sheep
b. Voluntary ban on feeding ruminant proteins to ruminants
G. Processing Animal Tissues for Feed Ingredients
1. Current Rendering Practices
2. Assay Methodologies for Proteins
III. Statutory Provisions Regarding Food Additives
A. GRAS Determination
B. Prior Sanction
C. Food Additive Status of Ruminant Tissues
IV. Comments
V. Analysis of Alternatives
A. Overview
B. Ruminant-to-Ruminant Prohibition
C. Partial Ruminant-to-Ruminant Prohibition
D. Mammal-to-Ruminant Prohibition
E. Prohibition of Materials from U.S. Species diagnosed with TSE's (sheep, goats, mink, deer, and elk)
F. Sheep-Specified Offal Prohibition
G. No Action
VI. Description of the Proposed Rule
A. Introduction
1. Regulatory Alternatives
2. The Regulated Industry
3. Enforcement Consideration
B. Outline of the Proposed Regulation
VII. Specific Protein Sources
A. Milk Proteins
B. Gelatin Proteins
C. Blood Meal Proteins
D. Canine and Feline Derived Proteins
VIII. Environmental Impact
IX. Analysis of Impacts
A. The Need for Regulation
B. Benefits
1. Methodology
2. Reduced Risk to Public Health
3. Reduced Risk of Direct Livestock Losses
4. Costs of Future Regulation
5. Reduced Risk of Losses in Domestic Sales and Exports
6. Total Losses Averted
7. Comparison of Alternatives
C. Industry Impacts
1. The Proposed Rule
2. Partial Ruminant-to-Ruminant Prohibition
3. Mammalian-to-Ruminant Prohibition
4. Other Regulatory Alternatives
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D. Small Business Impacts
E. Unfunded Mandates Analysis
X. The Paperwork Reduction Act of 1995
XI. Federalism
XII. References
XIII. Request for Comments
I. Summary
A. Introduction
In the Federal Register of May 14, 1996 (61 FR 24253), FDA
published an advance notice of proposed rulemaking (ANPRM) that
solicited information and public comment on the issue of using protein
derived from ruminants (cattle, sheep, goats, deer, and elk) in
ruminant feed. The agency requested information and comment on a number
of issues because it was assessing whether to prohibit the use of
ruminant protein in ruminant feed. BSE has not been identified in the
United States. The agency issued an ANPRM because of its concern about
the possible adverse effect on animal and human health if TSE's were to
be spread through animal feed. After reviewing the ANPRM comments and
other sources of information, the agency is proposing to prohibit the
use of ruminant and mink animal tissue in the feed of ruminants.
Because TSE has been found in U.S. mink, the agency is also including
mink tissue in the proposed prohibition. The agency is also considering
alternatives to the proposed ruminant-to-ruminant prohibition,
including the alternative of taking no action.
B. GRAS Status of Ruminant and Mink Tissues
The agency is proposing to declare that protein derived from tissue
from ruminant animals and mink is not GRAS, by qualified experts, for
use in ruminant feed and is therefore a ``food additive'' under the
law. As a result, because neither a food additive regulation nor an
exemption is in effect for ruminant and mink tissues intended for
feeding to ruminants, such tissues would be deemed adulterated. Milk
and gelatin proteins derived from ruminants, and blood from cattle are
exempt from the proposed prohibition. The proposed rule does not apply
to any nonprotein animal tissues such as tallow or other fats.
Expert opinion that the tissues are GRAS would need to be supported
by scientific literature, and other sources of data and information,
establishing that there is a reasonable certainty that the material is
not harmful under the intended conditions of use. Expert opinion would
need to address topics such as whether it is reasonably certain that
BSE does not, or will not, occur in the United States; whether it is
reasonably certain that the BSE agent will not be transmitted through
animal feed, i.e., that the processed tissues are not infected by the
agent, are deactivated by the rendering process or are not transmitted
orally; and whether it is reasonably certain that the agent will not be
transmitted to humans through consumption of ruminant products.
``General recognition'' cannot be based on an absence of studies that
demonstrate that a substance is unsafe; there must be studies to
establish that the substance is safe. Also, the burden of establishing
that substance is GRAS is on the proponent of the substance. See U.S.
v. An Article of Food * * * Co Co Rico, 752 F.2d 11 (1st Cir. 1985).
Although the ANPRM did not specifically ask for opinion on the GRAS
issue, a number of comments from scientific organizations and
individual scientists strongly suggest that the comments would support
the view that ruminant and mink tissue is not GRAS when fed to
ruminants. Some of these comments submitted data and information that
would support such opinions. Only a few comments included statements by
scientists, or scientific organizations, to the contrary. Similarly,
the opinions stated by scientists who spoke during a 1996 symposium on
TSE's would, in general, support the ``nonGRAS'' position. The
symposium, ``Tissue Distribution, Inactivation and Transmission of
Transmissible Spongiform Encephalopathies,'' was cosponsored by FDA and
USDA, and was held in Riverdale, MD, on May 13 and 14, 1996.
FDA has searched for but has not found sufficient literature or
other sources of data and information that would, on balance, support
expert opinion that ruminant and mink protein is GRAS as a ruminant
feed additive. Previous comments on the agency's proposal to prohibit
the feeding of specified sheep and goat offal (59 FR 44584, August 29,
1994) did not include either written GRAS opinions from qualified
experts, or data and information that would support such opinions. The
relevant data and information, and lack thereof, are discussed more
fully in this section, and in section II. of this document. See Section
III.A., of this document, for a further explanation of ``GRAS'' and
``food additive.''
C. The ``No Action'' Alternative
Even when, as in this case, FDA has taken steps leading to a
tentative determination that a substance added to food is not GRAS, the
agency is not required to issue a proposal declaring that the substance
is not GRAS and is a food additive subject to section 409 of the act.
Section 570.38 provides that the agency may take such an action. The
agency considered the possibility of not issuing a proposal with regard
to the feeding of ruminant and mink tissues to ruminants.
The fact that the data and information do not document an immediate
threat to the U.S. public health supports this ``no action''
alternative. Moreover, certain of the available data and information
can be used to support the view that the threat, if any, is minimal.
The evidence suggesting that there is no immediate threat is
summarized as follows. First, BSE has not been detected in cattle in
the United States despite an extensive surveillance effort that has
been in place for several years. Restrictions on the importation of
cattle, cattle products and feed ingredients from BSE-affected
countries are in place to minimize the possibility of BSE entering into
the United States. Surveillance, training of veterinary practitioners
and diagnosticians, and other efforts are in place to detect any
occurrence of BSE quickly, and to minimize its spread among the cattle
population. No empirical scientific evidence is available to establish
that BSE will occur from any of the possible sources, such as
transmission from another U.S. species in which TSE's have been
diagnosed; spontaneous occurrence in cattle; or importation of live
animals or animal feed products carrying the BSE agent. For example,
transmission between any two species is difficult to predict, based on
available data, because of variability in species barriers (Ref. 1).
Second, even if BSE did develop in the United States there is no
conclusive scientific evidence that the disease would be spread through
animal feed, the product that provides FDA's jurisdictional nexis.
Although there is strong epidemiological evidence that the feeding of
processed tissue from sheep containing scrapie to cattle caused the
widespread BSE infections in the United Kingdom, many experts believe
that the chances that the United States will have a BSE outbreak,
similar to the epidemic that took place in the United Kingdom, are low.
For example, most of the industry practices and other conditions
believed to have been associated with the BSE epidemic in the United
Kingdom do not exist in the United States. Further, the U.K.
epidemiological evidence of transfer from sheep to cattle has not been
confirmed by direct scientific data. This has caused some to question
the assumption that the BSE originated from scrapie (Ref. 1). Further,
some
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experimental information suggests that the TSE's in general are not
readily transferred by the oral route. Experimentally, the oral route
has been suggested to be the least efficient means of transmission for
TSE's (Ref. 1).
Third, the postulated connection between BSE and CJD has not been
definitively established. Scientists have theorized an association
between BSE and the recent appearance of nv-CJD in the United Kingdom.
While the epidemiological association, both in time and geography, of
these two diseases in the United Kingdom provides suggestive evidence
of an association between the two, the available evidence does not
establish causation. Although the BSE agent has been transmitted to
laboratory animals, the species barrier between cattle and humans may
be higher than between cattle and mice (Ref. 1). Epidemiological
evidence linking BSE with classical CJD is even less supportive.
Although CJD occurs in the United States, nv-CJD has not been reported
in this country.
The FDA's conclusion that there is no immediate threat to the
public health in the United States is supported by a statement from the
World Health Organization (WHO) that the ``risk, if any, of exposure to
the BSE agent in countries other than the U.K. is considered lower than
in the U.K.'' (Ref. 2). A number of comments to the ANPRM made a
similar assertion, urging that FDA's regulatory decision be made on the
basis of scientific information and contending that the available
information did not support the contemplated action.
D. The Basis for the Agency's Proposed Action
1. General Discussion
Even though there is no immediate threat to the U.S. public health
and some information that indicates that a threat, if any, is minimal,
after careful consideration the agency has tentatively concluded that
regulatory action is necessary to protect animal and human health. The
agency has reached that tentative conclusion because there is a growing
body of data and information that affirmatively raises public health
concerns.
The data and information raise concern that BSE could occur in
cattle in the United States; and that if BSE does appear in this
country, the causative agent could be transmitted and amplified through
the feeding of processed ruminant protein to cattle, and could result
in an epidemic. The agency believes that the high cost, in animal and
human lives and economics, that could result if this scenario should
occur, justifies the preventive measure reflected by the proposed
regulation. Although the agency expects some continued voluntary
reduction in the feeding of ruminant and mink tissues to ruminants, the
reduction is not expected to be extensive enough to obviate the need
for mandatory preventive measures.
Statements from several prominent public and animal health
organizations support this proposal to regulate the feeding of ruminant
tissues to ruminant animals. For example, the Centers for Disease
Control and Prevention (CDC) has urged the agency to adopt a ruminant-
to-ruminant feed prohibition (Ref. 3), and USDA has recommended the
same action. Although WHO considers the risk in countries such as the
United States to be minimal, that organization has nevertheless called
on all countries to prohibit the use of ruminant tissues in ruminant
feed (Ref. 2).
A number of comments to the ANPRM, including comments by several
consumer groups, supported regulatory action by FDA. The Pharmaceutical
Research and Manufacturers of America urged FDA to take all necessary
steps to prevent an outbreak of BSE, and to prevent the potential
spread of BSE should a case occur in the United States. One
pharmaceutical firm emphasized the importance of acknowledging public
perception, stating that a ruminant-to-ruminant prohibition would
``significantly decrease the concern regarding this perceived risk.''
Another pharmaceutical firm characterized the risk as ``small but
real.'' A group of livestock producers, veterinary associations and
scientific organizations cited the WHO recommendations to support their
call for a voluntary ruminant-to-ruminant prohibition. The group stated
that such a prohibition would ``eliminate any risk, no matter how
remote [and would] totally prevent BSE from ever occurring in the
United States.''
The agency is concerned about the public health issues raised but
not resolved by the available scientific information. The fact that the
causative agent or agents for TSE's have not been clearly identified,
and their transmissibility has not been fully characterized, adds to
the concern. However, certain information that is well documented
supports the agency's decision as well. TSE's are 100-percent fatal
diseases that have been diagnosed in humans and a number of animal
species. The diseases are progressively degenerative CNS diseases that
are characterized by a relatively short clinical course of neurological
signs. TSE's have a prolonged incubation period, i.e., 2 to 8 years in
animals, and scientific evidence supports the view that TSE's can be
transmitted in the preclinical stage. There is no practical method to
detect the presence of TSE's during the preclinical stage.
2. Analysis of Risk Factors
This section describes the evidence that supports the agency's
tentative conclusion. The evidence relates to the risks that BSE could
occur in cattle in the United States; that the BSE agent or other TSE
agents could be amplified in the cattle population by the feeding of
ruminant and mink tissues to cattle; and that the agent could
potentially be transmitted to humans.
a. The risk of BSE occurring in the United States. BSE has not been
diagnosed in the United States. FDA does not have evidence to support
the theory that BSE already exists, undiagnosed, in this country.
However, the agency does find plausible the arguments of the theory
that BSE could develop in the United States from three possible
sources: Transmission of TSE's from other susceptible species,
spontaneous occurrence, and importation in live animals or animal
products.
The evidence concerning transmission from other species is
summarized as follows. TSE's other than BSE have been diagnosed in
animals in the United States. These include scrapie in sheep and goats,
transmissible mink encephalopathy (TME), and chronic wasting disease
(CWD) in deer and elk. Feline spongiform encephalopathy (FSE) has been
diagnosed in cats in other countries. In general, the TSE's have been
shown to be naturally transmissible within species and are believed by
some scientists to be naturally transmissible (as distinguished from
experimentally transmissible), at least to a limited extent, between
species. Consumption of meat and bone meal (the predominant animal
tissue-containing product fed to animals) which was produced under
conditions similar to the meat and bone meal which was implicated in
the U.K. BSE epidemic, as well as the feeding of raw bovine tissue,
also appeared to cause TSE in exotic cats and various zoo animals. This
implies that the species barrier for BSE may be uncharacteristically
low. (See e.g., Refs. 3 and 4). In addition to the epidemiological
evidence relating to TSE transmission from sheep to cattle in the
United Kingdom, there is limited experimental evidence of transmission
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of the BSE agent from cattle to sheep. Many laboratory animal species
have also been experimentally infected following the administration of
tissues from animals with TSE disease.
There is some evidence to support the theory that BSE can occur
spontaneously in cattle. The leading theory as to the causative agent,
e.g., infectious protein or prion, inherently suggests that the BSE
could occur spontaneously. Additional support arises from the fact that
85 percent of CJD cases are sporadic, and have no familial or
identifiable link as to their cause. Recent surveillance information
from Northern Ireland and Switzerland also supports the spontaneous
theory. In these countries, BSE has occurred in cases in which no
exposure to rendered protein can be found, and there is no evidence of
BSE in the parental stock or herd mates of affected animals (Ref. 5).
As described more fully in section II.F.1.b. of this document,
USDA-APHIS has implemented import restrictions on live animals and
animal products from BSE-affected countries. As a result of the
restrictions, the potential risk of BSE occurring in this country as a
result of exposure from imported cattle and imported animal protein
products appears to be small (Ref. 6). However, the risk from foreign
sources of BSE introduction into the United States cannot be dismissed
entirely because the USDA import restrictions are unlikely to be 100
percent effective even though no cases of BSE have been diagnosed to
date in the United States. The USDA regulations are intended to reduce
or control risk, not completely eliminate it. See e.g., 56 FR 63866,
December 6, 1991.
b. The risk of amplification in the cattle population. Research has
shown that various animal tissues can transmit BSE infectivity. There
is also evidence supporting the view that the agent could be
transmitted orally (e.g., through animal feed). Although some
experimental evidence suggests that the TSE's in general are more
readily transmitted by means other that the oral route, research also
suggests that the BSE agent is more susceptible to oral transmission.
In most cases (e.g., the U.K. epidemic) the natural route of exposure
to TSE's including BSE is suspected to be oral. This belief is
supported by the dramatic decline in BSE cases in the United Kingdom
following implementation of the ruminant-to-ruminant feeding
prohibition. In the United Kingdom, where more than 160,000 cases of
BSE have been diagnosed, a 1988 ban on the feeding of ruminant-derived
protein supplements to other ruminants was associated with a steady
decrease in the disease incidence starting in 1993. The 5-year period
between the initiation of the ruminant-to-ruminant ban and the decline
in the incidence of BSE is consistent with the known incubation period
in cattle of 2 to 8 years. Further, preliminary experimental data show
that the BSE agent can be transmitted orally to cattle through feeding
of material from an infected cow (Ref. 3). Thus, there is a chance that
BSE could be spread in animal feed if it developed in the U.S. cattle
population, whether spontaneously, from another species or by some
other means.
The greatest risk factor for cattle may not be the single
occurrence of a BSE case. Instead, the greatest risk may arise from the
potential, given the prolonged incubation period, for unrecognized
amplification of BSE in the cattle population, resulting in a potential
for greater animal exposure. The possibility of risk from recycling
ruminant tissues is enhanced by the fact that current rendering methods
have not been shown, and are not expected, to completely deactivate the
BSE agent, and that practical tests are not available for detecting
either the BSE agent in rendered material or the presence of ruminant
material in feed.
The preliminary experimental cow-to-cow TSE transmission data
previously described occurred with as little as a single dose (one-time
exposure) of 1 gram of brain material from the infected cow, indicating
a low transmitting dose. This means, among other things, that FDA
cannot determine the level of feed ingredients from animals tissues, if
any, that is considered safe in ruminants.
c. The risk of transmission of humans. Finally, there exists the
theoretical possibility of the transmission of a TSE in animals, such
as BSE, to humans. CDC agrees that the link between BSE, and TSE's in
humans, has not been fully demonstrated. Some of the ANPRM comments
agreed. For example, one pharmaceutical firm stated that the evidence
is not entirely conclusive. Nevertheless, a body of epidemiological and
experimental evidence is developing to support the postulated
association between BSE and nv-CJD. This and other scientific evidence
developed more fully in section II leads the agency to propose for
comment the prudent risk reduction regulatory action that is
incorporated in the proposed rule.
E. Enforcement Provisions
The agency is issuing this proposed rule within the context of
comprehensive government-wide efforts to minimize the risks previously
described, and within the statutory authority provided to the agency.
The proposed rule has two major components. First, the agency proposes
to prohibit feeding animal materials derived from ruminant and mink
tissues to ruminants, in the absence of a food additive regulation or
investigational exemption. Thus, the prohibition would ensure that
tissues which could contribute to a TSE epidemic by spreading the
causative agent rapidly would not be allowed in ruminant feed.
The second component of the rule provides for a system of controls
to ensure that the proposed rule would achieve its intended purpose.
These provisions are necessary because limited controls are in place,
or available, to prevent the spread of BSE through animal feed in the
United States, should BSE occur. The proposed regulation places two
general requirements on persons that manufacture, blend, process and
distribute animal protein products, and feeds made from such products.
The first requirement is to place cautionary labeling on the protein
and feed products. The second is to provide FDA with access to sales
and purchase invoices, for compliance purposes.
Firms that handle animal protein products from both ruminant and
nonruminant sources, and that intend to keep the two kinds of products
separate, would have certain additional requirements. These
requirements would relate to the need for separate facilities or
cleanout procedures; the need for standard operating procedures
(SOP's); and in the case of renderers, their source of nonruminant
material. Similar requirements would be placed on firms that handle
animal feed containing animal protein products from both ruminant and
nonruminant sources, and intend to keep the two kinds of feed separate.
Requirements would be greater for the firms that intend to separate the
animal protein products and feeds, because of the greater risk these
operations would present for the possibility that ruminant protein
might be fed, inadvertently, to ruminants.
However, the regulatory system would be flexible, allowing the
regulated firms to innovate and choose the most cost-effective means of
compliance. For example, some or all of the regulatory requirements
previously described would not apply if any of the following
innovations were developed and validated by FDA: Processing methods
that deactivate the agent that causes BSE; test methods to detect the
presence of the agent; or methods of marking or otherwise identifying
the
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material that contains ruminant protein. Further, the agency will
consider modifying or revoking any final rule that is published
prohibiting the use of ruminant and mink tissues in ruminant feed, if
scientific and technical advances permit even greater flexibility than
that offered in the proposed regulation. Conversely, the diagnosis of
one or more cases of BSE in the United States, or new scientific
findings, could lead to stricter regulatory requirements.
F. Alternatives
The agency is soliciting comments on several alternative means of
minimizing the risk of transmitting TSE's in ruminant feed, in addition
to the proposed ruminant-to-ruminant prohibition. These alternatives
include:
(1) A partial ruminant-to-ruminant prohibition which would exclude
all ruminant and mink tissues from ruminant feed except those bovine
tissues that have not been found to present a risk of transmitting
spongiform encephalopathy. Possible exclusions include slaughter
byproducts from cattle that have been inspected and passed in inspected
slaughter facilities, except tissues that have been shown through
experimental trials and bioassays to transmit spongiform
encephalopathy. Examples of the latter might include the brain, eyes,
spinal cord and distal ileum. The agency solicits comments on the scope
of this alternative;
(2) A prohibition on the feeding of all mammalian tissues to
ruminants;
(3) A prohibition on the feeding of rendered material from those
animal species in which TSE's have been diagnosed in the United States
(sheep, goats, mink, elk, and deer);
(4) A prohibition on the feeding of specified offal from adult
sheep and goats as proposed in 1994;
(5) Other alternative approaches that meet the agency's regulatory
objectives and that might be suggested in comments to the proposed
rule. The agency may in any final rule issued adopt such alternative
approaches. Such alternatives may be more or less stringent than this
proposal or may be a combination of provisions from this proposal and
other alternatives. For example, one such option might be a proposal to
exclude from the scope of any regulation certain facilities that apply
specified risk-reduction measures in addition to, or in place of, those
included in the regulation FDA is proposing in this publication.
Therefore, the agency specifically requests comments on other
approaches that would achieve the agency's regulatory objectives. Any
proposed alternative approaches should be explained in detail, and
their justification should be well documented. To the extent possible,
please include information on costs and benefits of the proposals; and
(6) The ``no action'' alternative as it relates to this proposed
rule. Again, detailed explanation and well-documented justification
should be presented.
The agency's views on the advantages and disadvantages of these
options appears in section V of this document. The agency invites
comments on the relative merits and disadvantages of all these
alternative concepts.
FDA has estimated that the annualized costs of the proposal,
comprised of both the direct compliance costs and various indirect
gains and losses, would range from $21.4 to $48.2 million. The agency
also estimated that the annualized costs could range from $45.0 to
$56.5 million for the mammalian-to-ruminant option; from $28.5 to $37.3
million for the partial ruminant-to-ruminant option; and would total
less than $10 million for each of the remaining options. On the other
hand, if the agency chooses the ``no action'' option and a BSE epidemic
occurs, the above costs could be expanded by a great magnitude.
Because the body of scientific research related to TSE's is growing
rapidly, the agency will place in the Docket copies of relevant
scientific literature published after the agency completes work on this
proposal, and before the agency completes work on any final regulation.
The agency will add to the Docket, as appropriate, a brief statement of
its assessment of the significance of the literature, and will invite
comments. However, substantive changes from the proposed rule would be
made in accordance with the discussions in the preceding paragraphs and
the Administrative Procedure Act.
II. Background
A. TSE's
1. Scrapie
Scrapie is a slowly progressive, transmissible disease of the CNS
in sheep and goats. Scrapie is characterized by a prolonged incubation
period averaging 2 years, followed by a clinical course of 2 to 6
months when the animal exhibits sensory and motor malfunction,
hyperexcitability, and death. The agent presumably moves from infected
to susceptible animals by direct or indirect contact and enters through
the gastrointestinal tract. Consequently, its spread appears to be both
vertical (mother to offspring in utero) (Ref. 7) and horizontal (direct
contact) between sheep (Ref. 8). Early signs of scrapie include subtle
changes in behavior or temperament which may be followed by scratching
and rubbing against fixed objects. Other signs include loss of
coordination, weight loss despite a good appetite, biting of feet and
limbs, tremor around head and neck, and unusual walking habits (Ref.
9).
The scrapie agent is found in lymphatic tissue (spleen, thymus,
tonsil, and lymph nodes) in sheep with preclinical infections; however,
in clinically affected sheep, the agent is identified in the
intestines, nervous tissues (brain and spinal cord), and lymphatic
tissues as determined by experimental infectivity studies in a
susceptible animal model (Ref. 8). The brain has been demonstrated to
have the highest level of infectivity of all tissues (Ref. 10).
Scrapie is known to have existed in Britain, Ireland, France, and
Germany for over 200 years. It has been observed in the United States
and Canada for about 50 years. The first case of scrapie in the United
States was diagnosed in Michigan in 1947. From 1947 through January
1993, approximately 653 flocks have been diagnosed with scrapie (Ref.
11). At the present time, there are 67 known scrapie-infected flocks
(flocks with sheep diagnosed with scrapie), and there are 8 known
scrapie-source flocks (flocks to which scrapie-infected sheep were
traced) (Ref. 12). In the absence of an antemortem diagnostic test, it
is not possible to establish with absolute certainty that a flock is
free of scrapie. Moreover, lack of reporting, the long incubation
period, and open range husbandry practices in the western United States
make it difficult to detect classical clinical signs and completely
monitor scrapie in the United States.
2. BSE
BSE is a transmissible, slowly progressive, degenerative disease of
the CNS of adult cattle. This disease has a prolonged incubation period
in cattle following oral exposure (2 to 8 years) and is always fatal.
BSE is characterized by abnormalities of behavior, sensation, posture,
and gait. These signs are similar to those seen in sheep that are
infected with scrapie. BSE is associated with spongiform lesions in the
gray matter neuropil of the brainstem and neuronal vacuolization (Ref.
13). The clinical signs usually begin with changes in animal behavior,
and may include separation from the rest of the herd while at pasture,
disorientation, or excessive licking of the nose or flanks (Ref. 14).
The most common history given by the herdsman was nervousness
[[Page 557]]
or altered behavior or temperament, weakness associated with pelvic
limb ataxia, paresis, and loss of body weight (Ref. 15). In some
animals there are few gross pathological changes at necropsy associated
with BSE other than the loss of body weight. However, postmortem
histopathology of BSE distinguish it from other neurological disorders
(Refs. 16 and 17). Neither vertical nor horizontal transmission has
been documented for BSE.
BSE was first recognized as a new cattle disease by researchers at
the Central Veterinary Laboratory of the British Ministry of
Agriculture, Fisheries, and Foods at Weybridge, England in November
1986. As of November 15, 1996, BSE had been diagnosed in Great Britain
in more than 165,000 head of cattle from more than 31,000 herds. Cases
have been confirmed in 59.2 percent of the dairy herds and 15.3 percent
of the beef herds (Ref. 18). The BSE epidemic curve for Great Britain
peaked in January 1993 and is decreasing steadily, concomitantly with
changes in rendering and feeding practices. BSE has also been reported
in native cattle of Northern Ireland, Guernsey, Jersey, Isle of Man,
the Republic of Ireland, Switzerland, France, and Portugal. BSE has
been confirmed in cattle exported from Great Britain to Oman, the
Falkland Islands, Germany, Denmark, Canada, and Italy.
There have been no cases of BSE in cattle in the United States.
There has been one case of BSE in a cow imported into Canada from Great
Britain. That cow was destroyed, along with its herdmates and other
nearby cattle considered by animal health authorities in Canada to have
possibly been exposed to the cow with BSE (Ref. 19).
3. Other Animal TSE's
Other animals have TSE's with typical characteristics of long
incubation, neurological degeneration, and a 100-percent death rate.
These animals include: Mink, elk and deer, zoo ruminants, and exotic
and domestic cats.
TME is a mink disease with clinical signs and brain lesions similar
to those of sheep infected with scrapie. TME is a rare disease in the
United States. Since the disease was first recognized in 1947, in
Wisconsin, four additional outbreaks have occurred in the United
States. The last outbreak occurred in 1985 and was limited to a single
mink ranch in Wisconsin (Ref. 20).
CWD of deer and elk is characterized by emaciation, changes in
behavior and excessive salivation, polydipsia, and polyuria. The
clinical course is from several weeks to 8 months, and the disease is
invariably fatal (Ref. 20). From 1967 to 1979, CWD was observed in 53
captive mule deer in Colorado and Wyoming. Clinical signs were seen in
adult deer and included behavioral alterations, progressive weight loss
and death in 2 weeks to 8 months. Consistent histopathologic change was
limited to the CNS and characterized by widespread spongiform
transformation of the neuropil. The disease is a specific,
spontaneously occurring form of spongiform encephalopathy (Ref. 21).
Topographic distribution and lesion severity were most similar to those
of scrapie and BSE. The duration of the clinical disease did not
significantly influence lesion distribution or severity in either
species (Ref. 22).
Scrapie-like encephalopathies have been described in certain zoo
ruminants, i.e., a nyala, an Arabian oryx, and a greater kudu. Clinical
signs included ataxia and loss of coordination with a short,
progressive clinical course. Histopathological examination of the
brains revealed spongiform encephalopathy characteristic of that
observed in scrapie and BSE (Refs. 23, 24, and 25). Strain typing of
the agent suggests that all of the cases are directly related to BSE.
Seventy domestic cats in the United Kingdom have developed FSE, a
spongiform encephalopathy that was never previously reported. The cats
all had progressive, neurological disease involving locomotor
disturbances, abnormal behavior and, in most cases, altered sensory
responses. Histopathological examination of the central nervous system
revealed changes pathognomonic of spongiform encephalopathy; this
included widespread vacuolization of the gray matter neuropil and
neuronal perikarya (Refs. 26 and 27). Infective tissue from several of
these cases, when injected into mice, resulted in brain lesions with a
distribution and morphology that is undistinguishable from the lesions
produced by BSE infective tissue injected into mice.
4. TSE's of Humans
The TSE's of humans are divided into specific clinical types, which
may appear similar histopathologically but are either transmitted
differently or demonstrate different patterns of distribution and
prevalence.
a. CJD. CJD was first described in 1920 and 1921 when it was known
as ``spastic pseudosclerosis'' or ``subacute spongiform
encephalopathy'' (Ref. 28). The illness exists throughout the world and
is claimed to have a similar prevalence in each of the countries tested
with an annual incidence of approximately one case per million of the
population. Autopsies are sometimes not performed on persons who may
have died of CJD and many older people dying of a dementing illness do
not have autopsies performed. There is an increased incidence among
Libyan Jews (26 cases per million) and spatial or temporal clusters in
areas of Slovakia, Hungary, England, the United States, and Chile. The
average age of a typical CJD victim is 56 years of age, and only a few
cases involving persons between 4 and 29 years have been reported prior
to 1993. Between 4 and 15 percent of cases have a familial connection
with other cases. There is a slightly higher incidence of CJD in women
compared to men. Clinical prodromal symptoms start with changes in
sleeping and eating patterns, and often include confusion,
inappropriate behavior, vague visual complaints and/or ataxia. Those
symptoms progress over a few weeks to a clearly neurological syndrome.
A rapid onset of neurological symptoms appears in 20 percent of cases,
most commonly myoclonic jerks and dementia with loss of higher brain
function and behavioral abnormalities. The disease progresses with
continued deterioration in cerebral and cerebellar function, and the
onset of seizures. Ninety percent of the cases end in death within 1
year of onset. Diagnosis is by clinical assessment of patients and by
examination of electroencephalogram patterns. Post mortem diagnosis is
currently carried out by histological examination of cerebral tissue
under the light microscope, although this is not always reliable.
Research techniques that have been used to demonstrate CJD (and other
TSE's) include electron microscopic examination of brain tissue
extracts for scrapie-associated fibrils (SAF), immuno-staining of the
tissue for prion-protein (PrP) antigens, western blotting of extracted
PrP antigens and the intracerebral injection of tissue suspensions into
test animals.
In some patients, the source of CJD has been claimed to be an
infection transferred from other patients with the condition. For
example, in one case, cerebral electrodes that had been sterilized with
alcohol and formalin vapor after use in a patient with CJD, were used
in the brains of two young epileptic patients, both of whom contracted
CJD after a short incubation. The transfer of CJD by corneal transplant
in 1 patient, by cadaveric dura mater grafts in several patients and by
pituitary-derived human growth hormone injections in over 80 patients
has also been reported.
[[Page 558]]
Only the medical procedures described previously have been
conclusively linked to transmission. The transmission of the disease
from animal sources has been suggested; see further discussion in
section II.C. of this document.
b. nv-CJD. A previously undetected new variant of CJD (nv-CJD) was
reported by British scientists at a meeting of international experts
convened by WHO on April 2 and 3, 1996 (Ref. 29), and published 3 days
later (Ref. 30).
The major evidence for the existence of nv-CJD is the recognition
of a new neuropathologic profile and the unusually young ages of 10
U.K. patients. Although all the cases had evidence of the pathognomonic
spongiform changes characteristic of classic CJD, and therefore were
appropriately classified as a form of CJD, the clinical course of the
disease was atypical of classic CJD. The most striking and consistent
neuropathologic feature of nv-CJD was the formation of amyloid plaques
surrounded by halos of spongiform change. Plaques were extensively
distributed throughout the cerebrum and cerebellum. Many of these
plaques resembled those in kuru and were visible when examined by
routine staining methods.
The temporal cluster of cases of nv-CJD in young patients (three
were teenagers, five were in their twenties, and two were in their
thirties at onset of disease) is highly unusual. Five of the eight
deceased patients died before 30 years of age. (The expected annual
mortality rate for CJD in persons under 30 years of age is less than
five per billion.) The characteristic clinical features of the nv-CJD
cases were: (1) A psychiatric presentation, (2) onset of a progressive
cerebellum syndrome with ataxia within weeks or months of the initial
presentation, (3) memory impairment with dementia in the late stages,
(4) myoclonus, and (5) the absence of electroencephalographic changes
typical of classic CJD.
Review of the patients' medical histories and consideration of
various risk factors for CJD yielded no adequate clues as to the cause
of this disease. The PrP genotype was determined for eight cases. The
researchers noted that all genotypes were methionine homozygotes at
codon 129 of the PrP gene. The research did not identify any of the
known mutations associated with the inherited forms of CJD (Ref. 30).
Although scientists have stated that exposure to the BSE agent
prior to the U.K. bans described in section II.F. of this document is
the most plausible explanation for these findings, no clear
epidemiologic link to BSE was identified. (See further discussion in
section II.C. of this document.) Another potential explanation is
exposure to TSE agents from animals other than cattle. Because the
United Kingdom reinstituted epidemiological surveillance for CJD in
1990, increased surveillance is still another potential reason for the
identification of this cluster of 10 cases of nv-CJD.
c. Gertsmann-Strausller-Scheinker (GSS) syndrome. GSS syndrome is
an autosomal dominant condition in about 50 percent of siblings of
reference cases (Ref. 28). The disease is similar to CJD except that it
has a more extended onset and duration, a tendency towards cerebellar
ataxia as the initial predominant neurological sign, and a large number
of amyloid plaques present among the spongiform encephalopathic changes
of the brain. The extensive distribution of amyloid plaques in the
patient's brain is an observation shared by GSS syndrome and v-CJD. It
has been transmitted to monkeys and rodents by intracerebral
inoculation.
d. Kuru. Kuru is a condition of the Fore people of the Okapa
district of the Eastern Highland in Papua New Guinea, in which a
practice of ritual cannibalism of fellow tribesmen took place until
approximately 1956 (Ref. 28). This TSE disease, which affected mainly
adult women and children of both sexes, caused an annual disease
specific mortality of approximately 3 percent. Most deaths of women in
the tribe occurred through this disease. Some men who died from this
disease were thought to have contracted it when they were young. Kuru
may be transmitted by eating infected tissue or through open wounds.
The brains of dead tribal members were eaten by women and children and
the muscle tissue by men. The cohort of children born since 1957 have
not suffered from kuru at all.
Clinically the disease causes a progressive cerebellar ataxia,
uncoordinated movements, neurological weakness, palsies, and decay in
brain stem function. Most patients dying of kuru are not demented, a
major clinical difference between kuru and CJD.
e. Fatal familial insomnia (FFI). FFI is another inherited TSE-
linked disease (Ref. 31). FFI is characterized clinically by
untreatable progressive insomnia, dysautonomia, and motor dysfunctions.
The disease often starts between 35 and 60 years of age and leads to
death within 7 to 32 months. FFI is characterized pathologically by
atrophy, neuronal loss, and gliosis in the anterior and dorsomedial
nuclei of the thalamus (Ref. 32). FFI has been successfully transmitted
to mice (Ref. 33), but not to primates.
5. Etiology
The cause of TSE's is controversial. The TSE agent: (1) Is
presumably smaller than most viral particles and is highly resistant to
heat, ultraviolet light, ionizing radiation, and common disinfectants
that normally inactivate viruses or bacteria; (2) causes little
detectable immune or inflammatory response in the host; and (3) has not
been observed microscopically.
Resistance of the TSE agent to physical and chemical methods that
destroy nucleic acid have essentially ruled out conventional
microbiological agents as the cause. Currently, the infectious protein
or prion theory is favored. Other proposed causes are an unconventional
virus, consisting of virus-coded protein and virus-specific nucleic
acid with unconventional properties, and a ``virino'' consisting of a
core of nontranslated nucleic acid associated with host cell proteins
(Ref. 34). Proposed causes of TSE's with less supporting evidence are:
(1) Retroviruses (Ref. 35), (2) a spiroplasma (Refs. 36 and 37), (3)
organophosphates (Ref. 38), and (4) peptide hormones (Ref. 39).
The prion theory suggests that the causative agent is a normal host
protein (PrP or PrP-C) that is posttranslationally transformed into the
causative agent or PrP-Sc. Transformation of the PrP can occur from
rare somatic mutation of the prion gene, spontaneously or from contact
with extraneous PrP-Sc. The spread of BSE in the United Kingdom is
postulated to have occurred through the feeding of ruminant protein
that contained the PrP-Sc protein and thus follows the portion of the
theory that involves contact with extraneous PrP-Sc. This explanation
requires that one accept that abnormal prion protein from sheep crossed
the species barrier and resulted in BSE in cattle. An alternate
explanation is that a spontaneous mutation or transformation or other
nonorally induced event, occurred and resulted in undetected disease in
a bovine. These explanations are not mutually exclusive and it is
possible that both occurred.
Recent surveillance information from Northern Ireland and
Switzerland tend to support the spontaneous mutation as a method by
which BSE can occur. Northern Ireland has had more than 10 cows produce
offspring, after the feeding ban, that developed BSE. Thus, 10+ cases
are theorized to be spontaneous because there is no evidence of feeding
meat and bone meal to the offspring and the dams are alive
[[Page 559]]
and show no signs of BSE (Ref. 5). Switzerland, which has one of the
most aggressive BSE investigational surveillance of any European Union
(EU) country, has reported 205 cases of BSE. Some of these cases are in
animals that were fed only grass and hay (Ref. 5). Regardless of how
the initial cases occurred, however, the resulting unrecognized disease
was amplified by the feeding of ruminant protein to ruminants.
Additional support for the feasibility of the TSE spontaneous
mutation explanation is the fact that 85 percent of all CJD cases are
sporadic and have no familial or identifiable link as to their cause.
It is these cases that give rise to the very stable, 1 in a million per
year, world wide incidence of the disease. DeArmond and Prusiner (Ref.
40), and Lansbury and Caughey (Ref. 41) have postulated that a
noninduced somatic cell mutation or the spontaneous conversion of PrP-C
into PrP-Sc are plausible explanations for the sporadic cases of CJD.
DeArmond and Prusiner theorized that the 1 in a million
* * * may represent the combined probabilities that a mutation
occurs in the PRNP gene, the probability that the mutation leads to
the synthesis of the PrP-cjd (the abnormal protein), and the
probability that the resultant PrP-cjd targets other neurons for the
synthesis of more PrP-cjd at a rate fast enough to cause clinical
disease in the patient's lifetime.
The etiology of human and animal TSE's are similar. Therefore the
spontaneous mutation explanation cannot be dismissed with regard to
BSE.
6. Pathogenesis
Following oral exposure of goats or sheep to the scrapie agent, the
agent first accumulates in gut-associated lymphoid organs (tonsils and
Peyers patches of terminal ileum) and later in other lymphoid organs,
such as spleen and thymus, and finally in the spinal cord and brain
(Ref. 8).
Likewise, in mice inoculated intra-peritoneally with the CJD agent,
the agent localizes first in Peyer's patches and spleen, followed by
the central nervous system (Ref. 42). The agent may enter the body
through macrophages in the tonsils and domes over Peyer's patches in
the intestine (distal ileum). The proposed routes of spread from the
point of entry to other tissues and central nervous system are blood
stream or nerve trunks. In experimentally inoculated animals, spread
from the inoculation site in the eye of monkeys and peritoneum of mice
has been shown to be by optic and splanchnic nerves respectively (Ref.
43).
Other investigators have demonstrated transient infectivity in the
blood of experimentally infected laboratory animals, and naturally
occurring infections of humans and mink, causing speculation that the
agent is carried in the blood (Refs. 45 to 49). With one exception in
serum (Ref. 50), all attempts to isolate TSE agents from the blood or
milk of sheep or cattle have failed (Refs. 51 to 54). When TSE agents
are injected intravenously into mice, the rate of clearance from the
blood is extremely rapid (Ref. 55). In natural cases of BSE,
infectivity has been found only in the brain, spinal cord, and eye; in
experimental cases the agent has also been identified in the ileum
(Ref. 56).
The question of disease mechanism remains open. Candidate
mechanisms are the storage or accumulation of a large amount of
abnormal PrP in the brain (Refs. 57 to 60), or insufficient amounts of
normal PrP.
7. Transmission
There is little information about the natural transmission of TSE's
of animals. In most cases the natural route of exposure to the TSE
agent is suspected to be oral, although genetic disposition is known to
play a role in sheep scrapie (Ref. 61). Investigators have suspected
transmission of scrapie in sheep and goats by ingestion of placenta and
have been successful in experimentally transmitting scrapie by feeding
placenta to sheep (Ref. 62); however, genotyping of the PrP gene was
not conducted.
In 1993, a study by Foster, et al., (Ref. 63) using a line of sheep
in which natural scrapie does not occur demonstrated that sheep can be
experimentally infected with BSE by intracerebral or oral
administration. The intracerebral challenge resulted in five of six
sheep developing the disease. The oral challenge resulted in one of six
sheep developing the disease. Brain and spleen were recovered from the
orally infected sheep and from one of the intracerebrally injected
sheep. Goldmann, et al. (Ref. 64), confirmed that both sheep had the
same PrP genotype. In 1996, Foster, et al. (Ref. 65) reported the
results of injecting homogenized tissue harvested from these infected
animals into a panel of mice. Transmission from the brains and spleen
of both sheep gave incubation periods and pathology in mice similar to
those seen in direct BSE transmissions from cattle to mice. Foster's
work supports the position that BSE can cross species barriers by the
oral route and that, when judged by the mouse bioassay, the disease
manifested in sheep retains the incubation time and pathology
characteristic of BSE rather than scrapie. However, the manifestation
of BSE in the sheep is histopathologically and clinically
indistinguishable from natural scrapie.
Information regarding the interaction of the TSE agents and the
environment is limited. In 1964, Gordon reported the transmission of
scrapie among bands of unrelated sheep on pasture. The mode of
transmission was unknown (Ref. 66). In an effort to eradicate scrapie
from Iceland a large area was depopulated of sheep and restocked with
new sheep following a period of 3 years. Despite this effort, a few
flocks of the new sheep developed scrapie; the origin was believed to
be from scrapie that survived in the environment and not from
reintroduction of the agent with the new sheep or through contaminated
hay remaining on farms. However, a 1996 report suggests that six
species of hay mites may be potential vectors associated with
transmission of TSE's in Iceland (Ref. 67).
8. Genetics
There is a genetic component associated with several of the human
TSE diseases. A specific point mutation at codon 178 is associated with
fatal familial insomnia (Ref. 68). Point mutations at codons 102, 105,
117, 145, 198, and 217 are associated with GSS syndrome (Ref. 69).
Point mutations at codons 178, 180, 200, 210, and 232 are associated
with CJD (Refs. 68 and 70). Various insertions into the octapeptide
repeat region of the PrP gene have also been associated with human
TSE's (Ref. 71). It appears that the methionine/valine polymorphism at
codon 129 may modify the phenotype and the transmission rate from GSS
syndrome patients to mice (Ref. 72). No abnormalities in the sequence
of the PrP gene in kuru patients were found.
There is also a genetic component associated with sheep scrapie.
Point mutations at codon 171 of the sheep PrP gene are linked to the
disease in the Corriedale, Lacaune, Romanov, Suffolk, and Texel breeds
(Refs. 73 to 76).
An analysis of 370 cattle from Scotland revealed no difference
between healthy cattle and cattle with BSE in the number of octapeptide
repeat sequences (either five or six) and in a silent HindII
restriction site polymorphism on the PrP gene (Ref. 77). No data were
found that compared the sequence of the PrP gene of healthy deer, elk,
mink, and goats with those afflicted by TSE's.
9. Diagnostics
Because of the long incubation period, the ability to diagnose the
presence of a BSE infection prior to the onset of the
[[Page 560]]
clinical disease would enhance the efficacy of surveillance and
prevention programs. Because there is no fully characterized immune
response to BSE or scrapie, diagnosis in live animals has been thought
to be possible only when clinical signs are evident and must be
confirmed by histopathology at post mortem (Ref. 10), or brain biopsy
of moribund patients. Recently published research suggests antemortem
tests for the TSE agent may be possible.
The observation of histopathological changes in the brain, such as
vacuolization of the brainstem in BSE are positive indicators of
disease (Ref. 78). Other available diagnostic tests are
immunohistochemical staining and immunoblotting of the abnormal protein
(Ref. 10). Detection and titration of the TSE agent can also be
accomplished by intracerebral inoculation in mice or hamsters with a
brain homogenate from a suspected animal. After an appropriate
incubation period, the brain of the laboratory animal is examined for
histopathological changes characteristic of TSE (Ref. 8).
The potential antemortem tests that have been published are
described as follows: (1) Tests specific for PrP: (a) A capillary
electrophoresis test (Ref. 79), and (b) a western blot test with
increased sensitivity (Ref. 80); and (2) tests which identify
metabolites of infected animals or humans: (a) A cyclic voltametric
method which describes metabolites in urine (Ref. 81), and (b) an
immunoblot test describing metabolites in cerebral spinal fluid (Ref.
82). Antemortem tests have not yet been validated for practical use.
Recent research has shown some promise for antemortem testing.
Research by Shreuder et al. (Ref. 83), detected scrapie-associated
PrPsc protein in tonsils from scrapie susceptible sheep about a year
before the expected onset of the clinical disease. The research holds
promise for preclinical detection in sheep, but needs further
development. With regard to cattle, the researchers concluded that the
technique may not work but is worth investigating. Research by Hsich et
al. (Ref. 84), describes an experimental assay in humans and animals.
The research found that a positive immunoassay in human dementia
patients supports a diagnosis of CJD. The authors concluded that the
assay may be helpful in premortem diagnosis of TSE in humans and
animals showing clinical signs associated with TSE's. The validity of
the test as a preclinical screen has not been established.
10. Inactivation
The agency considered requiring procedures for the manufacture of
animal-derived proteins that would inactivate TSE infectivity. There
have been several studies on the inactivation of TSE agents. The only
broad generalization that can be drawn is that agents that denature
protein can diminish the infectivity of the TSE agents. TSE infectivity
does not appear to be markedly diminished by radiation or UV-light.
Recent research (Ref. 85) showed that 11 of the 15 rendering
procedures tested produced meat and bone meal with no detectable BSE
infectivity in a mouse bioassay. Only limited conclusions can be drawn
about safety from these 11 procedures because the infectivity titer of
the spiked starting material (which consisted of 10 percent brain) was
several logs lower than that typically found in brain that is not
minced and not stored at -20 deg.C. Also, the question of the adequacy
of the mouse bioassay as the regulatory test which acceptably assures
the absence of TSE infectivity to animals or man remains to be answered
through future research investigations.
The four procedures that failed included two protocols using
continuous vacuum rendering of high fat material and two protocols
using continuous atmospheric rendering of natural fat material. The
continuous vacuum rendering processes that failed were 120 deg.C for
20 minutes at a vacuum of 0.38 bar and 121 deg.C for 57 minutes at a
vacuum of 0.4 bar. The continuous atmospheric rendering processes of
natural fat material that failed were end temperatures of 112 and 122
deg.C after 50 minutes; however, end temperatures of 123 and 139 deg.C
after 125 minutes both inactivated the BSE agent. Unexpectedly, the BSE
agent was inactivated by three wet rendering processes that only
reached a maximum temperature of 119 deg.C with a cooking time of 240
minutes, a maximum temperature of 101 deg.C with a cooking time of 120
minutes, and a maximum temperature of 72 deg.C with a cooking time of
240 minutes under a vacuum of 0.85 bar.
Preliminary, unpublished results indicate that the only rendering
process which completely inactivates the scrapie agent (which was
spiked with higher infectivity than that in the BSE experiments
described in this section) is batch rendering under pressure (Ref. 86).
The agency encourages more research in this area.
B. The Association Between Scrapie and BSE
Epidemiological studies of the outbreak of BSE in the United
Kingdom, including a computer simulation of the BSE epidemic, have
characterized it as an extended common-source epidemic. Each case has
been considered a primary case resulting from exposure to a single
common source of infection. It is believed in the United Kingdom that
rendered feed ingredients contaminated with scrapie infected sheep, or
cattle with a previously unidentified TSE, served as the common source
of infection. One study demonstrated that meat and bone meal could be
incorporated into cattle feed in sufficient quantity to transmit BSE to
some of the animals that consumed the feed (Ref. 87). Thus far, other
research including research by USDA has not confirmed that the feeding
of U.S.-origin scrapie-infected feed ingredients to cattle produces
BSE. Therefore, the theory that BSE evolved naturally in cattle has not
been ruled out (Ref. 88). See also the discussion in II.A.5. of this
document.
Furthermore, the U.K. studies suggest that the spread of BSE
appeared to have been exacerbated by the practice of feeding
ingredients from rendered BSE-infected cattle to cattle, including
young calves, a practice that was subsequently banned. Incomplete
immediate compliance with the feeding ban may account for the fact that
some cattle born after the ban continue to be infected with BSE and has
complicated any theory of vertical transmission of the disease. The
research findings of maternal transmission of BSE are inconclusive, but
if it occurs, it does so at a rate insufficient to maintain the
epidemic (Ref. 89).
C. The Association Between Animal TSE's and Human TSE's
All the animal and human TSE's have been shown to be transmissible
experimentally to laboratory animals. The human and animal diseases are
pathologically similar and share some etiological similarities. TSE's
are not officially considered zoonotic diseases, i.e., known to be
naturally transmissible from animals to humans. The distribution of CJD
in the world does not coincide with that of scrapie in sheep or of BSE
in cattle. Human exposure to sheep or cattle has a low correlation with
CJD. However, the recent report from the United Kingdom of nv-CJD, and
its possible relationship to BSE, is causing scientists around the
world including those at CDC to
[[Page 561]]
reevaluate whether BSE may be a zoonotic disease.
This concern is further supported by the recent report of
experimental BSE transmission to macaques, with the development of nv-
CJD-like plaques in these monkeys (see the following discussion in this
section).
The possibility of transmission of TSE's from animals to humans has
been suggested, most recently in connection with the identification of
nv-CJD in the United Kingdom. Scientists in the United Kingdom
concluded that the nv-CJD cases may be unique to the United Kingdom,
raising the possibility that they are causally linked to BSE. The
scientists stated that ``the common neuropathological picture may
indicate infection by a common strain of the causative agent, as in
sheep scrapie in which strains of the disease have been identified * *
* '' (Ref. 30). The United Kingdom Spongiform Encephalopathy Advisory
Committee (SEAC) stated that ``although there is no direct evidence of
a link, on current data and in absence of any credible alternative the
most likely explanation at present is that these cases are linked to
exposure to BSE before introduction of the SBO [specified bovine offal]
ban in 1989'' (Ref. 90). A WHO consultation in April 1996 concluded
that ``a link has not yet been proven between v-CJD in the U.K. and the
effect of exposure to the BSE agent. The most likely hypothesis for v-
CJD is the exposure of the United Kingdom population to BSE'' (Ref. 2).
However, a second WHO consultation, in May 1996 concluded that ``the
clinical and neuropathological features of the newly recognized CJD
variant do not provide information which could be used to prove the
possible link between this disease and BSE in cattle'' (Ref. 91).
The recent finding of florid amyloid plaques in the brains of
macaques inoculated with suspensions of BSE-infected cow brains
increases suspicion that exposure to the BSE agent may be the source of
nv-CJD. Amyloid plaques have never before been seen in monkeys with
TSE's, and the florid plaques resembled those in nv-CJD patients (Ref.
92). In a recent paper by Collinge, et al. (Ref. 93), it is stated that
``strains of transmissible encephalopathies are distinguished by
differing physicochemical properties of PrPsc, the disease-related
isoform of prion protein, which can be maintained on transmission to
transgenic mice. 'New variant' CJD has a strain characteristic distinct
from other types of CJD and which resembles those of BSE transmitted to
mice, domestic cat and macaque, and is consistent with BSE being the
source of this new disease. Strain characteristics revealed here
suggest that the prion protein may itself encode disease phenotypes.''
The possible association between BSE and nv-CJD may be further
clarified by results from studies that are under way (e.g.,
experimental inoculation of brain tissue from the nv-CJD patients into
mice).
D. Infectivity of Specific Tissues
The WHO in a recent publication has summarized the infectivity of
various tissues from sheep, goat, and cattle (Ref. 94). Scientific
studies are currently being conducted in which calves are fed
homogenized brain tissue from United Kingdom cattle confirmed to have
BSE, and then various tissues are collected from the calves at 4-month
intervals (Refs. 56 and 95). The tissues from these calves are being
analyzed for the presence of the BSE agent. The study has been in
progress for 18 months and only brain, spinal cord, and retina have
been shown to be highly infectious. Distal ileum has been shown to be
infectious, but much less than the previously mentioned tissues. No
other tissues, most notably, muscle meat, milk, or blood have been
shown to be infectious. The results of these current experiments
parallel the previous research as summarized by WHO. However, the
agency notes that infectivity of other tissues that might be fed to
ruminants has not been definitively determined. This is, in part,
because of the lack of desired sensitivity in the available assay
methods.
In summary, meat, milk, milk products, and blood have not been
shown to transmit BSE infectivity. These products are considered safe
for human consumption by health authorities including the WHO.
E. Potential Risk of TSE's to the United States
1. Overview
This proposed FDA action is designed to reduce the risk of a BSE
epidemic in the United States and thereby protect the health of animals
and possibly of people if there is, in fact, a zoonotic relationship
between BSE and CJD. Risk is defined as the probability of an adverse
effect to an individual or a population. The four steps that are
typically involved in risk analysis are hazard identification, hazard
exposure, dose response, and risk characterization.
While BSE has not been found in the United States, the agency
believes it presents a potential risk to the health of animals and
people. There are incubational and symptomatic similarities (as well as
several differences) among the TSE's. The scientific characterization
of these diseases is incomplete. However, interspecies cross-infections
have been scientifically demonstrated by parenteral injection and oral
routes of exposure.
The typically long incubation period and the potentially
devastating effect that a BSE outbreak would have on animal health and
U.S. agribusiness also supports a conservative regulatory approach
aimed at prevention. While the current level of exposure to products
derived from animals with a TSE is extremely low or absent, the
potential consequences of such exposure and the apparent small intake
of the agent needed to achieve infection in some animals further
encourage a conservative regulatory policy.
Dose response assessments will be difficult because of the lack of
good exposure data and the possibility of different susceptibilities,
e.g., age or genetic factors, in different subpopulations. Although the
TSE's are generally transmissible to laboratory animals following
intraperitoneal (ip) or intracerebral (ic) routes of administration,
the limited data that are available following the oral route of
administration suggests that this route is much less efficient than ip
or ic. Currently, it is quite difficult to make an accurate dose
response assessment for a TSE agent following oral administration.
A number of actions, in addition to this proposed rule, have been
taken to manage a reduction in risk that BSE will enter the United
States cattle population. Restrictions have been placed on the
importation of live cattle (July 1989) and ruminant products (e.g.,
meat and bone meal, bone meal, blood meal, offal, fat, and glands) from
countries which have BSE. Live animals imported prior to the
restrictions on imports have been regularly monitored by Animal and
Plant Health Inspection Service (APHIS) veterinarians, and APHIS is
currently in the process of purchasing the remaining live cattle for
diagnostic research purposes. Histopathological examination of brain
tissues has been carried out on more than 5,000 specimens from cattle
that were disabled or that demonstrated neurological signs prior to
slaughter or on the farm, e.g., nonambulatory or rabies-negative
cattle. Histopathological and immunohistochemical examination of the
nonambulatory or ``downer'' cows has been carried out since 1993. There
has been no finding of BSE in tissues from these animals. These animals
represent the highest BSE risk in the country, however, they also
represent an extremely small percentage of the cattle
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slaughtered in the United States. This active surveillance program is
continuing and may be expanded. The expansion of this program was
indirectly supported by a comment to the ANPRM that all ``downer'' cows
should be examined for BSE.
Voluntary actions by industry have reduced the feeding of rendered
sheep proteins to ruminants and the rendering of adult sheep. A
voluntary Scrapie Flock Certification Program was implemented in 1992.
The program, a cooperative effort among industry, State animal health
officials and APHIS, seeks to reduce the prevalence of scrapie in U.S.
sheep. A considerable educational effort continues to increase the
awareness of veterinarians, veterinary laboratory diagnosticians,
livestock and related industry businesses, and producers to the early
clinical signs of BSE. Videos of United Kingdom BSE affected animals
have been distributed to USDA veterinarians to enhance their ability to
clinically diagnose BSE in suspect live animals. CDC has recently
published an update (Ref. 96) of its previous review of national CJD
mortality and the results of active CJD surveillance in five sites in
the United States. These reviews did not detect evidence of the
occurrence of the newly described variant form of CJD in the United
States. As an important complement to these other public health
efforts, this proposed rule would declare that animal protein derived
from ruminant and mink tissues is an unapproved food additive for use
in ruminant feeds, and would establish enforcement procedures. These
actions, individually and collectively, contribute to a greatly reduced
risk of a BSE epidemic ever occurring in the United States.
2. Comparison With the U.K. Conditions
Investigators have identified several major risk factors that
apparently contributed to the emergence of the disease and the
resultant epidemic in the United Kingdom. These are: (1) A large sheep
population relative to the cattle population, (2) a large,
uncontrolled, scrapie incidence rate, (3) the production of
``greaves,'' an incompletely processed intermediate product in the
rendering process, (4) changes in rendering processes, such as the
reduced use of solvent extraction, and (5) the feeding of significant
amounts, up to 4 percent of the diet, of meat and bone meal to young
dairy calves.
In addition to the risk factors described in section II.E.2. of
this document, the practice of processing dead sheep and cattle in the
United Kingdom likely contributed to the amplification of the TSE
agent. In the United Kingdom, sheep which may have died of scrapie and
cattle with BSE, were picked up by ``knackers'' for rendering into
animal feed. This material was partially rendered into ``greaves,''
which might have contained large amounts of the scrapie/BSE agent, and
was fed to dairy calves in large amounts. The spread of BSE appeared to
be facilitated by the feeding of rendered BSE-infected cattle back to
calves. The BSE agent is postulated to have recycled from cows to
calves through ruminant-to-ruminant feeding until the practice ceased
following the 1989 ban on the practice.
In the United States, the cattle population is much larger than the
sheep population, the incidence of scrapie is much lower and a scrapie
control program is in place; renderers in the United States do not
manufacture greaves; and the rendering processes used in the United
States are thought to reduce the titre (level) of TSE agents if any.
The lack of a practice of feeding large amounts of meat and bone meal
to calves in the United States, and the comparatively younger average
age of U.S. dairy cattle are also differences that are believed to be
important in protecting the United States against a U.K.-type BSE
epidemic. Nevertheless, scrapie does exist in the United States, sheep
are rendered and included in ruminant feed, the rendering process does
not totally inactivate TSE agents, and calves are fed meat and bone
meal. Therefore the risk of a BSE epidemic in the United States, while
much less, cannot be completely discounted.
F. Historical Efforts to Control TSE's
1. U.S. Actions
a. FDA. FDA is the Federal agency responsible for the safety and
effectiveness of a large number of products and commodities. Briefly,
these include, drugs for use in people and animals, human biological
products, medical devices, food, dietary supplements, cosmetics, and
animal feeds. Each of these product groups provides the potential for
the transmission of spongiform encephalopathies in man or animals. FDA
formed a Working Group composed of the Deputy Commissioner for
Operations and representatives from the Centers to consider TSE's in
relation to FDA regulated products. As a result of the Working Group's
deliberations, FDA has taken the following actions:
--- In 1992, letters were sent to manufacturers of dietary
supplements asking those manufacturers to reformulate their products to
be certain they do not contain materials from BSE or scrapie infected
animals;
--- In 1993, letters were sent to manufacturers of drugs,
biologics, and devices asking them not to use bovine-derived materials
from countries with BSE; and
--- In 1996, letters were sent to manufacturers of drugs,
biologics, devices, and animal feeds noting a possible relationship
between BSE and nv-CJD and asking that they not use materials from BSE
countries.
In 1992, FDA conducted a survey of major sheep rendering plants to
determine compliance with a 1989 voluntary industry ban on the use of
adult sheep offal in ruminant feeds. The voluntary ban and results of
the survey are described in section I.F.3. of this document. In the
Federal Register of August 29, 1994 (59 FR 44584), FDA published a
proposed rule proposing to declare that specified offal from adult
sheep and goats is an unapproved feed additive in ruminant feed
(hereinafter referred to as the August 1994 proposed rule). In the
Federal Register of May 14, 1996, FDA published an ANPRM stating that
FDA was considering whether to provide that the use of protein derived
from ruminants in ruminant feed be prohibited.
An international symposium entitled ``Tissue Distribution,
Inactivation, and Transmission of Transmissible Spongiform
Encephalopathies'' and cohosted by APHIS and FDA's Center for
Veterinary Medicine (CVM) was held on May 13 and 14, 1996, in
Riverdale, MD. The symposium participants engaged in discussion of
findings from unpublished, recently completed, and in-progress
scientific investigations on TSE's, and optimal approaches to managing
any risk of TSE's to animal health.
b. USDA. USDA policy has been both proactive and preventive. The
Food Safety and Inspection Service (FSIS) and APHIS have been active in
taking measures in surveillance, prevention, and education about TSE's.
In 1990, APHIS created a BSE Issues Management Team to analyze risks of
BSE to the United States, disseminate accurate information about the
disease, and act as a reference source for responding to questions
about BSE. APHIS has also collaborated in the education of veterinary
practitioners, veterinary laboratory diagnosticians, industry and
producers on the clinical signs and pathology of BSE.
APHIS has increased its surveillance efforts to verify that the
United States is free of BSE and to detect the disease should it be
introduced into the United
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States. As part of an ongoing active surveillance program, more than 60
veterinary diagnostic laboratories across the United States, and the
National Veterinary Service Laboratories (NVSL) of APHIS, continue to
examine bovine brains from the following sources: (1) APHIS
investigations in the United States where suspected encephalitic
conditions in cattle are reported under the foreign animal disease
investigation program; (2) CDC and State public health laboratories
(specimens from bovine that were found negative for rabies); and (3)
FSIS (specimens from ``downer'' cows or those exhibiting CNS
abnormalities). More than 5,000 bovine brains have been examined, and
none of these specimens contained lesions with the characteristics and
distribution typical for BSE (Refs. 12 and 97). APHIS is currently in
the process of purchasing the 69 living cattle (from a total of 496
cattle) imported from the United Kingdom between 1981 and 1989. In July
1989, the importation of live ruminants and ruminant products from all
countries known to have BSE in native animals was banned.
USDA continues to analyze and report epidemiologic findings and
potential risks to the United States. In 1991, USDA issued two reports
analyzing risk factors associated with BSE in the United Kingdom based
on the British hypothesis of the disease occurring as a result of
feeding scrapie-contaminated meat and bone meal (Refs. 98 and 84).
Because of some similarities in the animal industries between the two
countries, the possibility of BSE occurring in the United States could
not be eliminated. However, the probability of occurrence was
determined to be very low as the amount of sheep offal was found to be
0.6 percent of all U.S. rendered product compared to the estimate of 14
percent of all U.K. rendered product. Furthermore, the incidence of
scrapie in the United States is much lower than in Great Britain; a
scrapie eradication or control program has been in effect in the United
States and rendered products are not routinely incorporated into calf
diets as was the practice in the United Kingdom.
Since 1991, USDA has closely followed scientific findings and has
updated the BSE risk factor analysis, first in 1993 (Ref. 99) and as
recently as February 1996 (Ref. 4). Changes within each of the risk
factors have been evaluated, and because there has either been no
change or a decrease in the magnitude of risk factors, the overall risk
of BSE in the United States is believed to have decreased. The
February, 1996 report estimated the maximum potential 1-year period
prevalence of BSE to range from 2.3 to 12 cases per 1 million adult
cattle. In other words, under the worst case scenario between
approximately 115 and 600 adult cattle would become infected with BSE
each year, in a U.S. population of nearly 50 million adult cattle.
APHIS has had a scrapie control program in effect since 1952.
Flocks that have been enrolled in the voluntary certification program
for sheep for 5 years, and have not had a diagnosed case of scrapie
within 5 years or a case traced back to the flock during that period,
may apply for APHIS certification and be officially identified as such.
This new control effort provides a mechanism to recognize flocks as
scrapie-free in the absence of a live animal diagnostic test.
There is no official USDA program on TME or CWD. Although the last
TME case detected in the United States was in 1985, monitoring for this
disease continues. APHIS cooperates with State wildlife and diagnostic
officials in Colorado and Wyoming in the limited areas where CWD has
been reported.
In December 1991, APHIS placed a ban on importation of certain
products of ruminant origin from countries known to have BSE (56 FR
63865, December 6, 1991). These products include: Meat and bone meal,
bone meal, blood meal, offal, fat, and glands. In addition to
prohibiting the materials listed previously, the regulation requires
that imported meat for human or animal consumption from bovines be
deboned, with visible lymphatic and nervous tissue removed; that it be
obtained from animals which have undergone a veterinary examination
prior to slaughter; and that it be obtained from ruminants which have
not been in any country in which BSE has been reported during a period
of time when that country permitted the use of ruminant protein in
ruminant feed. APHIS may allow the importation of the banned products
under a special permit for scientific or research purposes, or under
special conditions to be used in cosmetics. No bovine meat from the
United Kingdom has been allowed to be imported into the United States
by FSIS for human consumption since before the BSE epidemic occurred in
the United Kingdom. The network of private veterinary practitioners
that refers unusual cases to veterinary schools or State diagnostic
laboratories around the United States provides an extensive
surveillance system. FSIS performs both antemortem and post mortem
inspections at all federally-inspected slaughter establishments, and
inspectors condemn all animals with central nervous system disorders.
State-inspected slaughter operations follow the same procedures.
USDA also maintains a database on these and other conditions. The
Veterinary Diagnostic Laboratory Reporting System (VDLRS) is a database
of selected disease conditions submitted by 29 State and university
veterinary diagnostic laboratories throughout the United States, and
includes the results of histologic examinations for BSE. The VDLRS is a
cooperative effort of the American Association of Veterinary Laboratory
Diagnosticians (AAVLD), the U.S. Animal Health Association (USAHA),
APHIS' Veterinary Service Centers for Epidemiology and Animal Health,
and the 29 laboratories mentioned previously.
c. Public Health Service (PHS). i. CDC. CDC conducts surveillance
for CJD through examination of death certificate data compiled by the
National Center for Health Statistics, CDC, for U.S. residents for whom
CJD was listed as one of the multiple causes of death (Ref. 100). These
data indicate that the annual CJD mortality rates in the United States
between 1979 and 1993 have been relatively stable, ranging between only
0.8 case per million in both 1979 and 1990 and 1.1 cases per million in
1987. In addition, CJD deaths in persons younger than 30 years of age
in the United States remain extremely rare (<5 cases per billion per
year) (Ref. 101).
CDC is working with the Council of State and Territorial
Epidemiologists to consider expansion of current CJD surveillance. CDC
is also working with its four established Emerging Infections Programs
(Minnesota, Oregon, Connecticut, and the San Francisco Bay area,
California), the Georgia Department of Human Resources, and the Atlanta
Metropolitan Active Surveillance Program to pilot enhanced surveillance
efforts for CJD (Ref. 101). This effort includes an active search for
v-CJD as described in the United Kingdom (Ref. 30). On August 9, 1996,
the results of this enhanced CJD surveillance effort was published; no
evidence of the occurrence of the newly described variant form of CJD
was found in the United States. No evidence of v-CJD has been found in
the United States.
ii. National Institutes of Health (NIH). A project of the
Laboratory of Central Nervous System Studies of the National Institute
of Neurological Diseases and Stroke is conducting investigations on
slow, latent, and temperate viral infections associated with chronic
degenerative neurological diseases. Important areas of study are the
pathogenesis of slow infections and mechanisms of persistence in kuru
and
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CJD. Also intensive molecular, biological, genetic, and immunological
studies are being conducted on amyloid formation in the brain in
Alzheimer's disease, normal aging, Down's syndrome, and slow viral
infections, and the elucidation of the de novo generation of infectious
amyloid proteins from normal host precursor proteins in kuru, CJD, GSS
syndrome, scrapie and BSE. Research on TSE's has also been conducted by
the NIH Laboratory of Persistent Viral Disease. FDA maintains close
contact with scientists in the laboratories and expects to use their
expertise in the evaluation of inactivation methods and transmission
studies.
iii. Other actions. On April 8, 1996, an interagency meeting at CDC
including representatives from CDC, NIH, FDA, USDA, and the U.S.
Department of Defense was held to disseminate conclusions from the WHO
consultation regarding v-CJD and to coordinate preventive activities
among these agencies to address the BSE and CJD issues.
2. International Actions
a. United Kingdom. Regulatory controls taken to manage the BSE
epidemic in the United Kingdom and to address public health concerns
include: (1) An action in June 1988 to make the disease reportable; (2)
a ban in July 1988 on the feeding of ruminant-derived protein
supplements to other ruminants; (3) an order in August 1988 for the
compulsory slaughter and incineration of BSE suspect cattle; (4) a ban
in November 1989 on the inclusion of specified bovine offal (brain,
spinal cord, thymus, spleen, tonsils, and intestines) for human
consumption; and (5) a ban in September 1990 on use of specified bovine
offal in any animal feed.
A CJD Surveillance Unit was established to monitor CJD numbers in
the United Kingdom. SEAC, consisting of experts in neurology,
epidemiology, and microbiology from outside the British government, was
established in 1990 to oversee all aspects of TSE's and human and
animal health. USDA has a representative on this committee.
Major regulatory actions occurring after the SEAC report on nv-CJD
(Ref. 90) include legislation to ban the feeding of mammalian meat and
bone meal to any farmed animal, and legislation to ban the use of
cattle head meat for human consumption.
b. WHO. WHO has held meetings on the spongiform encephalopathies in
1991, 1993, 1995, and 1996, and a meeting in collaboration with the
Office International des Epizooties (OIE) in 1994. The general purposes
of these meetings were to review the existing state of knowledge on
spongiform encephalopathies including BSE, to evaluate possible means
of transmission, and to identify risk factors for infection. A specific
purpose was to review the possible human public health implications of
animal spongiform encephalopathies, with special emphasis on BSE. The
group of international experts convened in April 1996 by WHO
recommended that all countries should ban the use of ruminant tissues
in ruminant feed. The WHO group also declared that milk and milk
products, including such products from the United Kingdom, are safe for
human consumption and that gelatin in the food chain is considered safe
because its preparation effectively destroys BSE. Finally, the group
concluded that tallow could be safe if effective rendering procedures
are in place (i.e., rendered as protein-free) (Ref. 2).
c. OIE. OIE has supported the U.K. ban on the use of specified
offals and has recommended that the same action be taken in other
countries with a high incidence of the disease (Ref. 102). OIE has held
meetings in 1990, 1991, 1992, 1995, and 1996, and has developed
guidelines concerning animals and animal products to prevent movement
to unaffected countries.
d. European Community (EC). The EC has held a series of meetings
related to BSE. Following issuance of the U.K. SEAC statement
suggesting a possible link between nv-CJD and BSE, the EC imposed a ban
on British cattle, beef and bovine derivatives (Ref. 103).
3. Voluntary Measures by the U.S. Animal Industries
a. Voluntary ban on rendering adult sheep. In 1989, the National
Renderers Association (NRA) and the Animal Protein Producers Industry
(APPI) recommended to their members that they stop rendering adult
sheep or providing sheep offal for sale as meat and bone meal for
inclusion in cattle feed (Ref. 104). Following the recommendation of
the voluntary ban, FDA carried out a survey of current practices in the
United States for rendering or otherwise disposing of adult sheep
carcasses and parts, specifically head, brain, and spinal cord. Limited
inspections of rendering plants were conducted in 1992 to: (1) Assess
compliance by U.S. renderers with the voluntary ban; (2) identify
rendering plant practices concerning adult sheep; and (3) determine if
rendered adult sheep protein byproducts were being sold or labeled for
use as feed or feed components for cattle. Of the 19 plants surveyed,
15 rendered carcasses or offal of adult sheep. These 15 plants
processed more than 85 percent of the adult sheep rendered in the
United States. Eleven of the 15 plants rendered carcasses of adult
sheep with heads, 7 of the 15 rendered sheep carcasses separately from
other species, 6 of the 15 maintained meat and bone meal from adult
sheep separate from meat and bone meal from other species, and 4 of the
15 rendered sheep that had died of causes other than slaughter. Six of
the 11 renderers processing adult sheep with heads had sold meat and
bone meal to manufacturers of cattle feed. Thus, the rendering
industry's voluntary ban on the rendering of adult sheep or providing
sheep offal for use in cattle feed was not fully implemented at the
time of the survey (Ref. 105).
b. Voluntary ban on feeding ruminant proteins to ruminants. On
March 29, 1996, the National Cattlemen's Beef Association (NCBA), the
National Milk Producers Federation, the American Sheep Association, the
American Veterinary Medical Association, the American Association of
Veterinary Medical Colleges, and the American Association of Bovine
Practitioners announced the recommendation of a voluntary ban on the
feeding of ruminant-derived proteins to ruminant animals (Ref. 106).
USDA, PHS, the American Society of Animal Science, and other
organizations announced support for the voluntary ban (Refs. 107 and
108). According to the NCBA (Ref. 109), a comprehensive communication
strategy, seeking removal of ruminant-derived proteins from the rations
of ruminants, was implemented in May 1996 by the feed industry,
nutritionists, veterinarians, extension specialists, and dairy and beef
producers. NCBA has not conducted a survey to assess the impact of its
communication strategy; however, NCBA did point out that past requests
for voluntary action by the cattle industry have been quite successful,
approaching 90 percent compliance. In contrast, an anonymous comment to
the ANPRM suggested a compliance level of less than 5 percent (Ref.
110). FDA has not conducted a survey to ascertain the level of
compliance with the voluntary ban.
G. Processing Animal Tissues for Feed Ingredients
1. Current Rendering Practices
The following discussion on current rendering practices comes
directly from comments supplied to FDA in response to the ANPRM from
representatives of
[[Page 565]]
APPI and NRA. Knowledge about the four basic types of rendering systems
that are most commonly used in the United States today may be crucial
in dealing with the TSE issue in this country. Data on the inactivation
of the BSE and scrapie agents following simulation of the most commonly
used basic types of rendering systems in the United States could be
quite useful, especially because some of these systems do not appear to
have been used in the only published rendering study on BSE
inactivation (Ref. 85).
Rendering, the process of cooking raw material to remove the
moisture and fat from the solid protein portion of animal tissues, has
been practiced by humans for more than 2,000 years. The United States
rendering industry has developed over the last 160 years. Modern
rendering systems are high-technology recycling processes that
efficiently convert animal byproducts (shop fat and bone, beef and pork
slaughterhouse materials, poultry offal, fish, etc.) to stable protein
and fat supplements for feed.
Current technology consists of four basic types of rendering
systems--batch cooker, continuous cooker, continuous multi-stage
evaporator, and continuous preheat/press/evaporator. All systems
consist of three basic steps: Grinding the raw material, cooking it to
remove moisture, and separating the melted fat from the protein solids.
Batch cookers are multiple units, each consisting of a horizontal,
steam-jacketed cylindrical vessel with an agitator. Batch cookers are
operated at atmospheric pressure. The cooked material is discharged to
the percolator drain pan, which contains a perforated screen that
allows the free-run fat to drain and be separated from the protein
solids known as ``tankage.''
Because ``tankage'' contains considerable fat, it is processed
through a screw press to complete the separation of fat from solids.
The fat discharged from the screw press usually contains fine solid
particles that are removed by either centrifuging or filtration. The
protein solids discharged from the screw press are known as
``cracklings,'' which normally are screened and ground with a hammer
mill to produce protein meal.
The continuous cooker rendering system normally consists of a
single continuous cooker, operating at atmospheric pressure. The
discharge from the continuous cooker usually passes across either a
vibrating screen or stationary perforated screen to allow the free-run
fat to drain. The subsequent steps in the continuous cooker rendering
process are similar to those described before for the batch cooker.
In the continuous multi-stage evaporator rendering system, crushing
is used as the first stage of size reduction of the raw material. A fat
recycle stream is then used to deliver the material as a pumpable
slurry through the secondary grinding step to reduce further the
particle size. Particle size and fat ratios are important components of
this system. The slurry discharge from the final stage of evaporation
is pumped to a centrifuge which removes most of the fat and part of it
is recycled back to the second stage of size reduction. The solids
discharged from the centrifuge are conveyed to screw presses which
complete the separation of fat from the protein solids.
The continuous preheat/press/evaporator rendering system is known
by a variety of names including the Stord dewatering rendering system
and the Atlas low temperature wet rendering system. In either case, raw
material is ground in two stages and passes through the preheater to
raise the temperature to 180 to 190 deg.EF before entry to the twin
screw press. The press separates this material into two phases: A
presscake of solids containing moisture and a low fat concentration,
and a liquid containing mostly water (stickwater) with fine solids,
soluble protein, insoluble protein and melted fat.
The press liquid is processed either by passing through a
multistage evaporator system to remove the water before centrifuging to
remove the fine solids from the fat, or by passing through a centrifuge
to separate the fat before multistage evaporation of the remaining
water/fine solids fraction. The liquid separation system consisting of
two stages of centrifuges completes the separation of the melted fat
from the solids and water. In this system, the screw press normally
used to process the ``tankage'' is no longer needed. Longer drying
times are needed with this system as compared to previous systems
because of the early fat removal (less fat means less effective heat
transfer).
The agency encourages further research into methods of deactivation
of the BSE agent during the rendering process.
2. Assay Methodologies for Proteins
Enforcement of the proposed regulation would be facilitated if a
test to detect and distinguish ruminant from nonruminant materials in
feeds or feed ingredients was available. However, practical assays that
could be used to enforce the proposed regulation are not available at
this time. The test procedure would need to exhibit a high degree of
sensitivity and selectivity; that is, the test must be able to detect
the analyte of interest to the exclusion of other components. A test
for acceptable rendered products in animal feed must therefore be able
to discriminate and differentiate between permitted and prohibited
animal derived proteins. Other factors of importance are the ruggedness
of the test method, speed, and simplicity of design.
An enzyme-linked immunosorbant assay (ELISA) based analytic method
that is both sensitive (detects low levels of analyte) and specific
(detects primarily the analyte of interest) is one possibility. ELISA
is a relatively straightforward methodology. There are numerous
commercial sources for antisera capable of binding to bovine, ovine,
porcine, and caprine proteins. Antisera have also been generated from
muscle extracts and validated for use in USDA-approved ELISA methods to
determine the identity of raw and cooked meats (Refs. 111 and 112).
However, rendered products present a unique problem because rendering
causes the destruction of most of the antibody binding epitopes needed
for an ELISA test. Therefore, detection of rendered proteins by a given
antibody cannot be automatically assumed.
Other potential methodologies include western blot analysis,
capillary electrophoresis, and high pressure liquid chromatography. The
applicability of these three methods to this issue has not been
addressed. Furthermore, they require expensive, specialized equipment
and a high degree of technical competence.
The agency encourages research to detect and distinguish ruminant
from nonruminant materials in rendered products and animal feeds.
III. Statutory Provisions Regarding Food Additives
The term ``food'' as defined in the act includes animal feed.
Section 201(f) of the act (21 U.S.C. 321(f)) defines food as ``articles
used for food or drink for man or other animals'' and ``articles used
for components of any such article.'' Furthermore, any substance whose
intended use results or may reasonably be expected to result in its
becoming a component of food is a food additive unless, among other
things, it is GRAS or is the subject of a prior sanction. Section
402(a)(2)(C) of the act (21 U.S.C. 342(a)(2)(C)) deems food adulterated
``if it is, or it bears or contains, any food additive which is unsafe
within the meaning of section 409 * * *.'' Under section 409(a) of the
act (21 U.S.C 348(a)), a food additive is unsafe unless
[[Page 566]]
a food additive regulation or an exemption is in effect with respect to
its use or its intended use.
A food additive regulation is established by the submission and
approval of a food additive petition, as provided in 21 CFR 571.1, or
on FDA's initiative as provided in 21 CFR 570.15. FDA on its own
initiative or at the request of an interested party, also may propose
to determine that a substance intended for use in animal feed is not
GRAS and is a food additive subject to section 409 of the act as
provided in Sec. 570.38 (21 CFR 570.38). Subsequent to the publication
of such a proposal and after consideration of public comments, FDA may
issue a final rule declaring the substance to be a food additive and
require discontinuation of its use except when used in compliance with
a food additive regulation.
A. GRAS Determination
A determination that a substance added directly or indirectly to a
food is GRAS, is generally based on specific information regarding the
composition of the substance, its use, method of preparation, methods
for detecting its presence in food, and information about its
functionality in food (21 CFR 570.35) as determined by experts
qualified by scientific training and experience to evaluate the safety
of such a substance. A substance added to food becomes GRAS as the
result of a common understanding about the substance throughout the
scientific community familiar with safety of such substances. The basis
of expert views may be either scientific procedures, or, in the case of
a substance used in food prior to January 1, 1958, experience based on
common use in food (Sec. 570.30(a)) (21 CFR 570.30(a)). General
recognition of safety through experience based on common use in food
prior to January 1, 1958, may be determined without the quantity or
quality of scientific studies required for the approval of a food
additive regulation. However, substances that are GRAS based on such
use must be currently recognized as safe based on their pre-1958 use.
(See United States v. Naremco, 553 F.2d 1138 (8th Cir. 1977); compare
United States v. Western Serum, 666 F.2d 335 (9th Cir. 1982).) A
recognition of safety through common use is ordinarily to be based on
generally available data and information (Sec. 570.30(c)). An
ingredient that was not in common use in food prior to January 1, 1958,
may achieve general recognition of safety only through scientific
procedures.
General recognition of safety based upon scientific procedures
requires the same quantity and quality of scientific evidence as is
required to obtain approval of a food additive regulation for the
ingredient (Sec. 570.30(b)). (See United States v. Naremco, 553 F.2d at
1143.) A substance is not GRAS if there is a genuine dispute among
experts as to its recognition (An Article of Drug * * * Furestrol
Vaginal Suppositories, 251 F. Supp. 1307 (N.D. Ga. 1968), aff'd 415
F.2d 390 (5th Cir. 1969).) Further, general recognition of safety
through scientific procedures must be based upon published studies
(United States v. Articles of Food and Drug Colitrol 80 Medicated, 372
F. Supp. 915 (N.D. Ga. 1974), aff'd, 518 F.2d 743, 747 (5th Cir.
1975)), so that the results are generally available to experts. It is
not enough, in attempting to establish that a substance is GRAS, to
establish that there is an absence of scientific studies that
demonstrate the substance to be unsafe; there must be studies that show
the substance to be safe (United States v. An Article of Food * * * Co
Co Rico, supra.)
Conversely, a substance may be ineligible for GRAS status if
studies show that the substance is, or may be, unsafe. This is true
whether the studies are published or unpublished (50 FR 27294 at 27296,
July 2, 1985). If there are studies that tend to support a finding that
a particular substance is GRAS, but also studies that tend to support a
contrary position, the conflict in the studies, just as a conflict in
expert opinion, may prevent the general recognition of the safe use of
the substance.
B. Prior Sanction
Under section 201(s) of the act, the term ``food additive'' does
not apply to any substance used in accordance with a sanction or
approval granted prior to enactment of section 201(s) of the act and
granted under the act, the Poultry Products Inspection Act (21 U.S.C.
451 et seq.), or the Federal Meat Inspection Act (21 U.S.C. 601 et
seq.). Section 570.38(d) provides that if the Commissioner of Food and
Drugs is aware of any prior sanction for use of a substance, he will,
concurrently with a notice determining that a substance is not GRAS and
is a food additive subject to section 409 of the act, propose a
separate regulation covering such use of the substance.
In the case of the materials subject to this proposed rule, FDA has
determined that it is unaware of any applicable prior sanction. Any
person who intends to assert or rely on such sanction is required to
submit proof of the existence of the applicable prior sanction. The
failure of any person to come forward with proof of such an applicable
prior sanction in response to this notice will constitute a waiver of
the right to assert or rely on such sanction at any later time.
C. Food Additive Status of Ruminant Tissues
The agency recognizes that processed ruminant byproducts have a
long history of use in animal feeds without known adverse effects.
However, the evidence as discussed in sections I and II.A. through
II.D. of this document, for the development of a new pattern of disease
transmission, now indicates that these ingredients can no longer be
categorically regarded as safe. The agency tentatively concludes that,
based on this evidence, use of such products in ruminant feed is not
GRAS. The agency is proposing this regulation in light of the findings
and conclusions described in sections I and II in this notice. Nor is
the agency aware of a prior sanction for any feed products that contain
these tissues. Therefore, FDA is proposing that the addition of protein
derived from ruminant tissues to ruminant feed would constitute the use
of an unapproved food additive because no regulation is in effect
providing for such use. Any ruminant feed that contains protein derived
from ruminant and mink tissues would be adulterated. Accordingly, FDA
is proposing to list protein derived from ruminant tissues in part 589.
IV. Comments
FDA's May 1996 ANPRM requested public comment and information on
all aspects of TSE's, including BSE, and the potential consequences of
a prohibition on the feeding of ruminant protein to ruminants. The
agency received nearly 600 comments, including many that were submitted
long after the comment period ended. The agency has attempted to
address the comments in this proposal. If there are any significant
concerns that the agency has not addressed, these concerns should be
brought to the agency's attention in timely comments on this proposal.
Comments that were specific to the topics covered by the other sections
of this preamble were considered in the preamble as written. Comments
are discussed in the text of some of these sections. The following is a
general discussion of the comments received.
Many comments, especially from renderers, meat packers, feed
companies and farmers, opposed the prohibition of ruminant protein
being fed to ruminants. The main reasons offered were the lack of
evidence of BSE in the United States, lack of scientific data to
support the proposal in the absence of
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BSE, environmental concerns, lack of an assay or other practical means
to support enforcement, and the economic hardship that would fall upon
the animal producers, slaughter facilities, renderers, feed
manufacturers, and packers. Support for such a prohibition from
consumer groups, pharmaceutical firms, scientists and veterinarians,
and some livestock organizations, emphasized a potential effect on
human health, the experience and data from the United Kingdom, and
significant economic detriment if a BSE epidemic were to occur in this
country. Other comments described a need to ensure that exported U.S.
bovine-derived products met international standards and guidelines, and
to maintain consumer confidence in the beef and dairy industries even
though those comments acknowledged that there is a minimal potential
risk of infectivity to animals and humans.
The agency requested scientific information regarding the
occurrence, transmission, etiology, pathogenesis, epidemiology, and
inactivation of TSE agents. Many comments were received that contained
useful scientific information that was considered in the preparation of
this proposed rule, as described in this preamble and supporting
documents.
Three comments suggested that the documented existence of nonBSE
TSE's, and the presence of ``downer'' cows (cows unable to walk) in the
United States is evidence that BSE is present in this country. Three
comments stated that the BSE surveillance in the United States provides
sufficient assurance that BSE does not exist in this country. A number
of persons commented on whether specific tissues, such as milk, blood,
and gelatin, should be excluded from any prohibition, with nearly all
supporting such exclusion.
The agency requested information on the economic impact of the
described action. Numerous comments provided data on volume of product
impacted, potential economic benefits, and cost of compliance to
affected persons. The data were used to develop the preliminary
economic assessment supporting this proposed rule.
The agency requested information on the environmental impact and
potential mitigating factors of the described action. Many comments
stated that alternative disposal of the prohibited carcasses would be
less environmentally safe than rendering. These and other comments were
considered in the development of the environmental assessment.
Numerous comments were received regarding the need to prohibit only
tissues that have been demonstrated to be infective. Generally, the
comments stated that tissues that have been proven to be noninfective
should be exempted. Although the agency is proposing a rule that would
prohibit the use of all ruminant-derived protein in ruminant feeds, the
agency will, as explained elsewhere in this document, consider a
partial ruminant-to-ruminant prohibition as well as a mammalian-to-
ruminant prohibition.
Many comments supported establishment of Hazard Analysis Critical
Control Points (HACCP) for the rendering industry, often with
concurrent support for current good manufacturing practices (CGMP's)
for animal-derived proteins. For example, the American Feed Industry
Association proposed a specific set of Good Manufacturing Practices for
the producers of animal protein products, and the National Renderers
Association proposed a specific HACCP regulation for rendering
operations. The agency agrees that the need for HACCP, perhaps
supported by CGMP's, for animal-derived proteins could be considered in
future rulemaking. Several comments were received regarding labeling
requirements for animal-derived proteins. The majority of the comments
supported a statement of the origin of animal-derived protein. The
agency has included a labeling requirement in the proposed rule.
V. Analysis of Alternatives
A. Overview
In addition to the proposed ruminant-to-ruminant rule, the agency
is considering alternative approaches. The alternatives include: (1)
excluding from ruminant feed all ruminant and mink materials except
those that have not been found to present a risk of transmitting
spongiform encephalopathy (partial ruminant-to-ruminant prohibition);
(2) prohibiting the use in ruminant feed of all mammalian protein
(mammalian-to-ruminant prohibition); (3) prohibiting the feeding of
materials from species in which TSE's have been diagnosed in the United
States (sheep, goats, mink, deer, and elk); (4) prohibiting the feeding
of specified sheep and goat offal, as proposed by the agency in 1994;
(5) other alternatives that might be proposed by the comments; and (6)
no action.
Analysis of the advantages and disadvantages of the options
follows. Analysis of costs and benefits, including detailed economic
analysis, also appears in section IX. of this document. Environmental
consequences are discussed in section VIII. of this document.
In determining the scope of the final rule, the agency will weigh
carefully the comments received, along with material contained in the
administrative record for this proposal and the comments submitted in
response to the ANPRM. Comments regarding the scope of the rule,
including those comments supporting other options other than the
proposed option, should be addressed accordingly.
B. Ruminant-to-Ruminant Prohibition
Advantages of this option, compared with the ``no action'' option,
are discussed in detail in section I. of this document. The advantages
of this option that are discussed in that section would apply if BSE
were to occur in this country. As discussed in separate sections that
follow, there would also be environmental and economic advantages to
the ruminant-to-ruminant option, if BSE were to occur in this country.
Disadvantages of the ruminant-to-ruminant option, compared to the ``no
action'' option, would be relevant primarily if BSE did not occur in
the United States. These disadvantages would include the time and
expense required to comply with the provisions of the regulation, and
the limited, short term environmental effects described in section
VIII. of this document.
Compared with the mammalian-to-ruminant option, the ruminant-to-
ruminant option has the advantages of being tailored more precisely to
the identified scientific concerns, and less burdensome on the affected
industries. Economic and environmental costs would be less. The major
disadvantage is that the ruminant-to-ruminant option results in more
complexity for the regulated industries, and thereby provides less
assurance of compliance. This is explained further in the discussion of
the mammalian-to-ruminant option, in section V.D. of this document.
Compared to the other remaining options, which are less
restrictive, the ruminant-to-ruminant option provides greater assurance
of protection of the public health and, if BSE were to occur in the
United States, lower economic and environmental costs. The
disadvantages relate generally to the greater economic and
environmental costs that would be incurred if BSE did not occur in the
United States.
C. Partial Ruminant-to-Ruminant Prohibition
As an alternative to the proposed ruminant-to-ruminant prohibition,
the agency is considering a partial
[[Page 568]]
ruminant-to-ruminant prohibition which would exclude from ruminant feed
all ruminant and mink materials except those that have not been found
to present a risk of transmitting spongiform encephalopathy. The
exclusions would be in addition to milk products, gelatin and bovine
blood, which are excluded in the proposed rule. Possible exclusions
include slaughter byproducts from bovine that have been inspected and
passed in inspected slaughter facilities, except the brain, eyes,
spinal cord, and distal ileum. The four named tissues would be
prohibited because they have been shown through experimental trials and
bioassays to transmit spongiform encephalopathy. The remaining tissues
have not been demonstrated to transmit spongiform encephalopathy.
This option has the advantage of having its prohibitions based
primarily on scientific information related to infectivity of specific
tissues. A number of persons who commented on the ANPRM urged the
agency to base its regulation entirely on such scientific information.
In addition, this option would likely involve lower lost sales revenues
to the affected industries, and could have fewer adverse economic
effects, than would the other options.
However, the agency has three concerns with regard to the adequacy
of this option in providing sufficient protection for the public
health. First, FDA recognizes that it may be impractical in the
slaughter and rendering processes to segregate and exclude the bovine
tissues that have not been found to present a risk. For example, USDA
has expressed reservations that separating the distal ileum from the
other intestinal offal could jeopardize a slaughter plant's ability to
meet pathogen reduction goals required under USDA's HACCP regulations.
Furthermore, regulatory enforcement of a prohibition affecting only
specified bovine tissues may be impractical in the absence of specific
diagnostic methods for identifying protein derived from such tissues.
If a partial prohibition were adopted, it would be based on a finding
that practical methods can be implemented for segregating, processing,
storing, and identifying feed materials derived from tissues that have
not been found to present a risk.
Second, this option would be inconsistent with actions taken in a
number of other nations. For example, CDC has commented that any
prohibition of lesser scope than a ruminant-to-ruminant prohibition
would place the United States out of step with the international public
health community.
Third, limiting the prohibition of tissues to those that have been
shown to be infective would not address the risk that may be presented
by other tissues. Definitive assays using methods more sensitive than
currently available methods might identify such additional tissues as
infective. The possibility of undetected low dose exposure cannot be
eliminated, particularly for tissues such as lymph nodes and spleens
which would be expected to be infective (Ref. 1).
These issues raise a substantial question as to whether the tissues
could be GRAS. To achieve the highest level of public health
protection, the agency believes that it may be reasonable to assume
that, in the absence of scientific data definitively establishing that
each tissue does not transmit spongiform encephalopathy, all ruminant
tissues present a risk of infectivity.
The agency nevertheless welcomes comments on this alternative to
the proposed ruminant-to-ruminant prohibition and especially invites
comments on possible practical means of separating the distal ileum in
compliance with USDA and industry standards, as well as the
practicality of the removal of brain, spinal cord, and eye and the
segregation of these tissues from others in the slaughter plant.
D. Mammal-to-Ruminant Prohibition
The agency received comments in support of a rule that would
prohibit the use in ruminant feed of all mammalian-derived protein. For
instance, the American Feed Industry Association, NRA, and APPI
expressed concerns that segregating certain mammalian derived proteins
from others would not be feasible because of regular commingling of
protein products at feed mills and rendering facilities. A mammalian-
to-ruminant prohibition would provide greater assurance of industry
compliance than either a partial or total ruminant-to-ruminant
prohibition because practical analytical methods exist for
distinguishing mammalian from nonmammalian proteins. Implementation of
a mammal-to-ruminant prohibition by the regulated industries would be
less complex, and would reduce the potential for contamination of
cattle feeds with material intended for feeding monogastric animals.
Contamination of cattle feeds with material intended for feeding
nonruminants was the primary reason that the United Kingdom has
prohibited mammalian proteins in the rations of cattle. A mammal-to-
ruminant prohibition would enable the continued use of Association of
American Feed Control Officials definitions for the purpose of
identifying and labeling products covered by the prohibition, and would
not require additional or new labeling. Finally, concerns were
expressed that allowing certain products containing meat and bone meal
to be used in ruminant feeds while prohibiting others would lead to
instability in financially sensitive commodity markets for animal
protein.
On the other hand, the agency is not aware of any scientific data
that establish or suggest TSE infectivity in nonruminant mammals except
in mink. Thus, excluding nonruminant tissues from ruminant feed would
be based primarily on the view that the possibility of infection of
nonruminant tissue through cross-contamination or commingling with
ruminant tissue is sufficient to preclude GRAS status for the
nonruminant tissue. However, FDA is aware that some portions of the
affected industries would prefer to segregate ruminant from nonruminant
tissues, and believe that such separation is practical. Accordingly,
the agency invites comments on the relative merits and disadvantages of
a mammal-to-ruminant prohibition compared with a total or partial
ruminant-to-ruminant prohibition.
E. Prohibition of Materials From U.S. Species Diagnosed With TSE's
(Sheep, Goats, Mink, Deer, and Elk)
This option would involve requiring that ruminants not be fed any
proteins derived from any U.S. animal species in which a TSE has been
diagnosed. This includes sheep, goats, mink, deer, and elk. This
approach would eliminate the scrapie agent, along with TME and CWD,
from ruminant feed, and thereby reduce the risk of BSE in cattle caused
by TSE transmission from other species. However, it would not prevent
the spread of BSE among cattle if BSE occurred for some other reasons,
e.g., by a spontaneous mutation in cattle or importation of animals
with BSE, and the animals were processed and subsequently included in
ruminant feed. As explained in section IX. of this document, this
option involves lower economic costs than the three options previously
described, in the absence of a BSE outbreak.
F. Sheep-Specified Offal Prohibition
The option of prohibiting only protein from specified offal from
sheep and goats for use in ruminant feed would eliminate the scrapie
agent from bovine feed. However, it would not prevent the spread of BSE
among cattle if BSE occurred for some other reason, e.g., by
[[Page 569]]
a spontaneous mutation in cattle or importation of animals with BSE,
and the animals were processed and subsequently included in ruminant
feed. The agency notes that if it were to select this option, it would
reconsider its statement in the 1994 proposed rule that sheep less than
12 months of age presented a minimal risk. Cases of scrapie in sheep as
young as 7 months have been reported (Ref. 113). Although the risk
presented by young animals may be minimal, excluding them may provide
inadequate protection to the public health. As explained in section IX.
of this document, this option involves lower economic costs than the
options described previously, in the absence of a BSE outbreak.
G. No Action
The advantages and disadvantages of this option, in relation to the
other options, are discussed in detail in section I. of this document
and in the preceding subsections of this section, as well as the
environmental and economic sections. In general, this option offers
lower economic and environmental costs if BSE does not occur in the
United States, and higher such costs (in addition to public health
implications) if BSE does occur.
VI. Description of the Proposed Rule
A. Introduction
1. Regulatory Alternatives
Typically, FDA regulates products that are of public health concern
through a combination of regulatory tools including: labeling for
appropriate use; CGMP regulations and, recently, HACCP regulations;
specifications for the product or its manufacture; and testing to
determine the presence or level of the agent of concern. Use of two or
more of these means provides for appropriate reinforcement to ensure
that the public is protected.
The agency's choice of readily available approaches for regulating
animal protein products derived from ruminant and mink tissues is
limited. For example, there are no practical tests for the presence of
the TSE agent or of ruminant protein in animal feed. No commercial
method of deactivating the TSE agent in animal protein products has
been scientifically validated as effective. None of the agency's CGMP
or HACCP regulations apply to this situation. Labeling requirements can
be used but, by themselves, do not meet the agency's regulatory
objectives.
2. The Regulated Industry
Often, the industry that manufactures and distributes an FDA-
regulated product is fairly easily characterized. This facilitates
regulation. That is not the case for animal protein products, as the
following brief overview makes clear.
Renderers collect animal tissues from a variety of sources, and
process these tissues into both protein and nonprotein products. The
renderers may be specialized (packer/renderer) or independent. The
packer/renderer, which involves a renderer associated with a large
slaughter operation, specializes in one species--primarily cattle,
swine, or poultry. Thus, whether the packer/renderer handles ruminant
materials is fairly easily determined. The independent renderer, on the
other hand, obtains a variety of raw materials ranging from restaurant
scraps to byproducts from multi-species slaughtering operations to dead
animals obtained from farmers. Typically, the independent renderer does
not have a practical method to separate incoming ruminant from
nonruminant materials, and thus commingles both ruminant and
nonruminant materials in the rendering process. The rendered product is
typically designated ``meat and bone meal,'' but rendering operations
produce a variety of other products. Renderers sell their products to
animal protein blenders, animal feed manufacturers or pet food
manufacturers. Virtually all rendered material at present is used
ultimately for pet food or the feed of livestock or poultry.
Animal protein blenders mix animal and plant protein materials to
meet a protein guarantee stated on the label, and to make a balanced
nutritional product. Typically, the blender does not separate ruminant
from nonruminant animal protein in its blending operation, although it
may keep mammalian, poultry, fish and soybean meal protein separate at
least in the initial stages. The blender sells its products to feed or
pet food manufacturers. Some renderers also blend animal protein
products.
Feed manufacturers use the protein material to make a complete feed
(ready to be feed to animals), or a concentrated feed that needs to be
further diluted (blended) before it can be fed to animals. The feed may
be manufactured by an off-farm miller, or on the farm. Feed that is
manufactured off-farm may be sold to one or more persons (for blending
and/or further distribution) before reaching the farm.
Farmers that feed animals typically raise one species, but may have
more than one (including both ruminants and nonruminants). Only about
10 percent of all animal protein products are fed to ruminants (mainly
cattle) but approximately half of all animal protein products comes
from ruminants.
3. Enforcement Considerations
The industry scenario described in the preceding section presents
unique enforcement challenges. The agency is aware, from the comments
to the ANPRM and other sources, of concerns that the regulatory impact
be minimized. The agency is also aware of the need to provide incentive
for innovation, e.g., in testing methodology and manufacturing
technology, that would reduce the need for regulation. Finally, the
agency is aware of the need, in designing a regulatory program, to
acknowledge the different circumstances that exist in the industries
previously described.
Therefore, the agency has designed a proposed regulatory scheme
using the following principles. First, the agency has identified
minimally necessary requirements to meet its regulatory objectives. The
agency's goal is to apply risk management principles that minimize
risk. Second, the proposed regulation applies greater restriction where
the risk is greater--for example, where a firm handles both ruminant
and nonruminant materials and intends to keep them separated. Third,
the agency intends to rely on normal business records for much of the
documentation it needs.
A fourth and most important principle concerns the related
objectives of flexibility and providing incentives to reduce
recordkeeping and labeling requirements. The proposed regulation
provides for the reduction or elimination of recordkeeping and labeling
requirements, upon the development of methods for detection,
deactivation, or verification of product identity. These provisions are
described further in the discussion that follows.
Industry-wide adoption of scientific advances including, or in
addition to, those specified in the regulation, could ultimately lead
to amendment or revocation of any final regulation. An example of an
additional method would be the development of a practical method to
detect the presence of ruminant protein in animal protein products or
feed, which could be used for quality control by firms that separate
ruminant from nonruminant protein, and by firms downstream from
renderers.
Similarly, research leading to identification of the TSE causative
agent and the etiology of BSE, and the characterization of the zoonotic
nature of animal TSE's, could also lead to amendment or revocation of
any final regulation.
[[Page 570]]
The agency has tentatively decided not to place any record keeping,
labeling or other specific requirement on firms that handle only
protein materials from nonruminant sources. An example would be a
rendering operation that is part of a swine slaughter operation.
However, if these firms would use or intend to use animal protein
products containing ruminant tissues in ruminant feed, or caused such
use or intended use, the feed would be adulterated under the act.
The agency has also tentatively decided to require farmers (those
responsible for feeding ruminant animals) only to make available copies
of invoices and labeling for feed purchases. Farmers would not be
required to maintain written procedures for handling animal protein
products. These minimal requirements would apply even if the farmers
were feeding both ruminant and nonruminant animals. Purchase records
would be used primarily for traceback purposes. Because only minimal
requirements would be placed on farmers, the proposed rules require
that labeling for the animal protein and feed products caution against
feeding the products to ruminants. Comments on these two tentative
decisions are encouraged.
B. Outline of the Proposed Regulation
The proposed regulation places two general requirements on persons
that manufacture, blend, process, and distribute animal protein
products and feeds made from such products. The first requirement is to
place cautionary labeling on the protein and feed products. The second
is a requirement to provide FDA with access to sales and purchase
invoices, for compliance purposes. For example, an invoice obtained
from a feed manufacturer for a protein product not labeled with the
cautionary statement could be used to trace back to the supplying
renderer to ensure that it manufactures and distributes animal protein
product from nonruminant sources.
Firms (renderers, blenders, and feed manufacturers and
distributors) that handle animal protein products from both ruminant
and nonruminant sources, and that intend to keep the products separate,
would have certain additional requirements related to their source of
nonruminant material; the need for separate facilities or cleanout
procedures; and the need for SOP's. The same requirements would apply
to firms that handle feeds containing animal protein products from both
ruminant and nonruminant sources, and that intend to keep the feeds
separate. Requirements would be greater for these operations because of
the greater risk they would present for the possibility of ruminant
protein being fed to ruminants.
The proposed rule provides that some or all of the regulatory
requirements would not apply if innovations such as development of test
methods and deactivation processes for TSE agents were scientifically
validated and put into commercial use. Provisions for use of such
methods do not imply that the agency believes that such agents are or
will be in the animal protein products. The objective is to minimize
the risk that the agent would occur in the products, regardless of the
level of risk. Certain minimal but additional requirements would be
imposed in such circumstances. For example, because the innovations
likely would be applied by renderers, the renderers would need to
certify to downstream customers that the methods were being utilized.
Section 589.2000(a) presents definitions of certain words used in
the regulation. The definition of ``protein derived from ruminant and
mink tissues'' excludes blood from bovines, milk proteins, and
gelatins. Thus, those products are not subject to the regulatory
provisions of the regulation. The proposed rule does not apply to any
nonprotein animal tissues such as tallow or other fats. ``Renderer''
includes firms, not traditionally considered to be included within the
definition of that term, but that collect animal tissues from various
sources and subject them to minimal processing before offering the
materials for use in animal feed. Also, ``feed manufacturers'' is
defined to include both off-farm and on-farm feed manufacturing
operations.
Section 589.2000(b) declares that protein derived from ruminant and
mink tissues is not GRAS when intended for use in the feed of ruminant
animals. The use or intended use of such material in ruminant animal
feed causes the feed to be adulterated.
Section 589.2000(c) establishes regulatory requirements for
renderers that manufacture products that contain or may contain protein
derived from ruminant and mink tissues. (``May contain'' allows for the
fact that the renderer may not be able to determine the species of some
incoming material). These renderers typically process both ruminant and
nonruminant materials, but do not attempt to separate ruminant from
nonruminant materials. Section 589.2000(e) covers renderers that intend
to separate such materials. As mentioned, renderers that process
exclusively nonruminant materials are not covered by the specific
requirements of the regulation. Section 589.2000(c) applies to animal
protein products intended for use in animal feeds, as well as animal
feeds containing such products.
Two requirements would be placed on renderers covered by
Sec. 589.2000(c). First, they would be required to label their products
to indicate that they contain (or may contain) protein derived from
ruminant and mink tissues, and that the materials should not be fed to
ruminant animals or used to manufacture feed for ruminants. Second, the
renderers would be required to maintain copies of sales invoices for
all their animal protein products, and to make those copies readily
available for inspection. As an example, FDA would use the invoices to
follow up with customers to verify that the customers are not using the
products to manufacture ruminant feed. Because sales invoices are
normal business records, the agency believes that the additional burden
imposed by this requirement would be minimal.
Section 589.2000(c) renderers would be exempted from the labeling
and record requirements if they used a manufacturing method that
deactivates the agent that causes TSE's, or a test method that detects
the presence of the agent that causes TSE's. Both methods would have to
be validated by FDA, and made available to the public. The regulation
would require ``routine'' use. That is, renderers would be required to
use the test method on all incoming material or in each batch it
manufactures.
Section 589.2000(c) renderers would be exempted from the record
requirements (but not the labeling requirement) if they used a safe
method to mark the presence of the materials. The marking could be
visible to the naked eye, e.g., through use of a dye, or by a nonvisual
means. One ANPRM comment recommended use of a colored uniform fine iron
product to identify specific feed ingredients. If the marking is not
visible, the marking agent must be detectable by a method that has been
validated by FDA, and made available to the public. The mark must be
permanent, i.e., it must be visible in mixed feed as used on the farm.
Section 589.2000(d) establishes regulatory requirements for persons
other than renderers and persons responsible for feeding ruminants that
handle animal protein products or feeds containing such products. This
includes protein blenders, and feed manufacturers and distributors.
However, as in the case of renderers, those firms that would otherwise
be included in Sec. 589.2000(d) but that handle both ruminant and
nonruminant
[[Page 571]]
materials and intend to separate the materials would be covered by
Sec. 589.2000(e) instead. Protein blenders, and feed manufacturers and
distributors, that handle only nonruminant materials are excluded from
the regulatory requirements of the proposed rule.
Persons covered by Sec. 589.2000(d) would be subject to the same
requirements as renderers, i.e., labeling and records. The records
would include invoices both to cover purchases and sales of animal
protein products and feeds containing those products. For on-farm
mixers, production records could be substituted for sales invoices.
Section 589.2000(d) firms would be exempt from the labeling and
record requirements if they purchased materials from renderers that
certified the use of deactivation or detection methods as described in
Sec. 589.2000(c). They would also be exempt from the labeling and
record requirements if they purchased materials from persons other than
renderers who certified that they purchased materials from renderers
who certified the use of deactivation and detection methods as
described in Sec. 589.2000(c). Paragraph (d) firms would also be exempt
if they used the deactivation or detection methods described in
Sec. 589.2000(c), where use of such method is appropriate for the
particular firm.
Paragraph (d) firms would be exempt from the record requirements if
they purchased visibly-marked materials, or purchased from renderers
that certified the use of marking methods as described in
Sec. 589.2000(c). They would also be exempt from the record
requirements if they used the marking methods as described in
Sec. 589.2000(c).
Section 589.2000(e) establishes regulatory requirements for
renderers, protein blenders, feed manufacturers and distributors, and
independent haulers that handle both ruminant and nonruminant
materials, and intend to keep the products separate. Section
589.2000(e) establishes four kinds of requirements. First, the firms
would have the same labeling and recordkeeping requirements as
specified in paragraphs (c) and (d) of Sec. 589.2000, except that the
labeling requirement would apply only to the ruminant and mink
materials. Second, a renderer's source of nonruminant protein materials
would be limited to single-species facilities, i.e., facilities
slaughtering only swine. A renderer could purchase nonruminant protein
from more than one single-species facility. The agency believes that
this restriction is necessary because of its understanding that it is
not likely to be feasible for mixed species slaughterhouses to
undertake the additional compliance costs, and possibly additional
facility costs, that would be required to assure separation of ruminant
and nonruminant materials. The restriction would therefore help assure
that enforcement of Sec. 589.2000(e) would be practicable. However, the
agency specifically requests comments on this provision.
Third, the firms would be required to establish separate equipment
and facilities for the two kinds of materials, or cleanout procedures
to prevent cross contamination. Fourth, the firms would need to
establish written SOP's specifying the cleanout procedures, if used,
and specifying procedures for separating the materials from the time of
receipt until the time of shipment. Although Sec. 589.2000(e) applies
to several different kinds of firms, the agency's preliminary
expectation is that only feed manufacturers and distributors will find
it feasible to separate ruminant and nonruminant materials. As an
example, a feed manufacturer might obtain ruminant materials from an
independent renderer and swine materials from a packer/renderer, and
use these materials to manufacture feed both for ruminants and
nonruminants. The feed manufacturer would be required to meet the
criteria listed previously, including the use of separate equipment and
facilities or cleanout procedures, and the establishment of SOP's. The
requirements of Sec. 589.2000(e) would be applicable in the
transportation process, whether the material is hauled by the feed
manufacturer or another party such as an independent hauler. The
requirement for separate facilities, procedures or SOP's would not
apply to a firm, e.g., a feed mill or hauler, that handles only
nonruminant materials, or only ruminant materials. Nor would it apply
to a firm that handles both ruminant and nonruminant materials but does
not attempt to separate the two kinds of materials.
The paragraph (e) firms would be exempted from the labeling and/or
record keeping requirements, and the requirements related to sourcing,
facilities and SOP's, if they meet the appropriate criteria for
exemption. That is, renderers covered by Sec. 589.2000(e) would be
exempt from the labeling and recordkeeping requirements if they used
deactivation or detection methods, and from the recordkeeping
requirements if they used marking methods. Blenders and feed
manufacturers and distributors would be exempt in a similar manner.
Section 589.2000(f) establishes requirements for those who are
responsible for feeding ruminant animals. The only requirement
contained in this paragraph is that those persons make available to FDA
copies of purchase invoices and labeling for all incoming feeds.
However, Sec. 589.2000(f) does not apply to the feed manufacturing
portion of farms and feedlots that have on-farm feed manufacturing
operations. Section 589.2000 (d) and (e) would apply in those
instances. Furthermore, persons who feed or intend to feed ruminant
protein to ruminant animals would be subject to regulatory action for
using or intending to use an unapproved feed additive as established in
Sec. 589.2000 (b).
Section 589.2000(g) establishes that violations of Sec. 589.2000
(c) through (f) would cause animal protein products or feed containing
animal protein products to be adulterated under sections 402(a)(4) or
402(a)(2)(d) of the act, or misbranded under section 403(a)(1).
Section 589.2000(h) establishes inspection and records retention
requirements for persons covered by section 589.2000 (c) through (f).
Records that are required under those paragraphs would need to be kept
for a minimum of 2 years. The agency believes that this time period is
adequate for purposes of verifying compliance with the regulation's
procedural requirements. The agency invites comments on the need for a
longer retention period related to the BSE incubation period,
especially the practicality of using such records for epidemiologic
investigation.
Section 589.2000(h) also requires that written procedures required
by the regulation be made available for inspection and copying by FDA.
The written procedures referred to are those specified in
Sec. 589.2000(e)(3). Affected firms would be required to have a copy of
the current procedures available at all times.
VII. Specific Protein Sources
A number of comments discussed the exemption of certain tissues,
including fluids, from any prohibitory rule. Most commentors favored
the exemption of one or more tissues, including milk products; blood
products; skeletal muscle and gelatin; and a variety of other tissues
including both protein and nonprotein materials. Most of the comments
cited published studies as well as positions taken by the European
Union, European Commission, WHO and the government of France. The
agency's comments on the status of milk, gelatin and blood follow. In
addition, we discuss a comment on the use of canine and feline derived
protein.
[[Page 572]]
A. Milk Proteins
Data available to the agency suggests that milk proteins do not
transmit the TSE agent. Research with oral exposure, intracerebral, and
intraperitoneal administration of milk or mammary glands from BSE-
infected bovine to normal and BSE-sensitive mice has not demonstrated
the development of TSE's (Refs. 42 and 52). An expert group under the
auspices of WHO recommended that all countries prohibit the use of
ruminant tissues in ruminant feed. The WHO expert group also declared
that milk and milk products, including such products from the United
Kingdom, are safe for human consumption. In addition, OIE has
recommended, because of lack of infectivity, that restriction of import
or transit of milk products from healthy animals from BSE countries
need not be instituted. Therefore, the proposed rules provide that
protein derived from ruminant tissues does not include milk proteins
derived from bovine, ovine, caprine, and cervine.
B. Gelatin Proteins
Data available to the agency suggest that gelatin does not transmit
the TSE agent. The WHO has concluded that gelatin in the food chain is
considered to be safe, as the conventional manufacturing process for
gelatin has been demonstrated to significantly inactivate any residual
infective activity that may have been present in source tissues (Ref.
2). FDA concurs with this statement and the scientific information on
which it is based. Thus, the proposed rule excludes gelatin from
protein derived from ruminant tissues.
C. Blood Meal Proteins
Data available to the agency suggests that bovine blood components
do not transmit the TSE agent (Refs. 56, 78, and 94). Therefore, the
proposed rule does not include blood meal from bovine as a protein
derived from ruminant tissues.
D. Canine and Feline Derived Proteins
One comment suggesting that canine- and feline-derived proteins
should not be fed to ruminants because of the finding of FSE in
domestic cats in the United Kingdom. The agency is also aware of an
ethically-based objection by some to the rendering of the carcasses of
pet animals. TSE has not been diagnosed in dogs or other canines. FSE
has not been diagnosed in the United States. The agency has considered
the information provided by the comments and the published scientific
literature (Refs. 26 and 27), and has preliminarily determined that
there is no measurable risk of the spread of TSE's from canine- or
feline-derived proteins to ruminants in the United States. However, the
agency is inviting further comment on this issue.
VIII. Environmental Impact
FDA has carefully considered the potential environmental effects of
this proposed rule and of five possible alternative actions. In doing
so, the agency reviewed ANPRM comments submitted by a number of
organizations and individuals. The comments were mostly concerned with
the volume of material (e.g., dead animals and slaughter byproducts)
that would be affected, and the nonrendering or rendering alternative
means by which these materials could be disposed of, or utilized,
safely. Comments suggested a number of uses for the processed
materials, other than ruminant feed, including use in nonruminant
animal feed and fertilizers, and disposal methods such as on-farm
burial, landfilling, and incineration.
In the environmental assessment that accompanies this proposed
rule, FDA evaluated the environmental consequences of six different
options. These included: No action; ruminant and mink-to-ruminant
prohibition (the proposed action); partial ruminant and mink-to-
ruminant prohibition; mammalian-to-ruminant prohibition; prohibition of
feeding tissues from any animal species in which TSE has been detected
in the United States; and sheep and goat specified offal prohibition.
The environmental assessment considered each of the alternatives in
the context of two scenarios. The first assumes that BSE does not occur
in the United States, regardless of the alternative selected. The
second scenario assumes that BSE does occur in the United States, again
regardless of the alternative selected. In the first scenario, the
assessment considered environmental impacts related to on-farm
disposal, landfill, incineration, and industry wastes produced. The
second scenario considered environmental impacts related to production
losses and impacts, wildlife exposure, on-farm disposal, landfill, and
incineration.
In the first scenario (no BSE), the ``no action'' alternative does
not have environmental consequences because it is the ``status quo'' or
baseline alternative. Environmental impacts for the other alternatives
ranged from slight to moderate increases in environmental effects. For
the proposed option (ruminant-to-ruminant) there would be moderate
increases in environmental effects from on-farm disposal and landfill
use, and slight increases in the other effects. Increases in waste
disposal (on-farm, landfill, etc.) are anticipated to be temporary,
however, as the markets are expected to adjust quickly to the more
restricted uses of the ruminant materials.
In the second scenario (occurrence of BSE), the greatest negative
environmental effect would occur in the case of the ``no action''
alternative. This is because the likely spread of the BSE agent through
animal feed before the first BSE case is diagnosed would result in
disposal of large numbers of animals by means other than rendering.
Similar large impacts would occur with the sheep and goat, and TSE
animal, options. Minimum environmental consequences would occur with
the proposed option (ruminant-to-ruminant), because the spread of the
BSE agent would have been controlled. Minimum to small effects would
result from the remaining two options, partial ruminant prohibition and
mammalian-to-ruminant prohibition.
The agency has concluded that the proposed rule will not have a
significant impact on the human environment, and that an environmental
impact statement is not required. FDA's finding of no significant
impact (FONSI) and the evidence supporting that finding, contained in
an environmental assessment (EA) prepared under 21 CFR 25.31, may be
seen in the Dockets Management Branch (address above) between 9 a.m.
and 4 p.m., Monday through Friday. FDA invites comments and submission
of data concerning the EA and FONSI.
IX. Analysis of Impacts
FDA has examined the impacts of the proposed rule under Executive
Order 12866, under the Regulatory Flexibility Act (5 U.S.C. 601-612),
and under the Unfunded Mandates Reform Act (Pub. L. 104-4). Executive
Order 12866 directs agencies to assess all costs and benefits of
available regulatory alternatives and, when regulation is necessary, to
select regulatory approaches that maximize net benefits (including
potential economic, environmental, public health and safety, and other
advantages; and distributive impacts and equity). The Regulatory
Flexibility Act requires agencies to analyze regulatory options that
would minimize any significant impact of a rule on small entities. The
Unfunded Mandates Reform Act requires that agencies prepare an
assessment of anticipated costs and benefits before proposing any rule
that may result in an annual expenditure by State, local, and tribal
governments, in the aggregate, or by the private sector, of
$100,000,000 (adjusted annually for inflation). FDA
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concludes that this proposed rule is consistent with the principles set
forth in the Executive Order and in these two statutes.
A study of the impacts on industry of the proposed rule (on file
with the Docket Management Branch (Ref. 114)) conducted for FDA by the
Eastern Research Group (ERG), a private consulting firm, and the
discussion in the remainder of this section, demonstrate that the
proposed rule constitutes an economically significant rule as described
in the Executive Order. The agency has further determined that the
proposed rule will have a significant impact on a substantial number of
small entities. The proposal makes no mandates on government entities
and is estimated to result in aggregate net annual costs ranging from
$21.4 to $48.2 million to the private sector.
A. The Need for Regulation
Although BSE has not been diagnosed in the United States, the need
for regulatory action is based on a need to protect U.S. livestock from
the risk of contracting BSE. In its guidelines for the preparation of
Economic Impact Analyses, the Office of Management and Budget (OMB)
directs Federal regulatory agencies to determine whether a market
failure exists, and if so, whether that market failure could be
resolved by measures other than new Federal regulation. In this
instance, private incentive systems for both suppliers and purchasers
may fail in markets for cattle, rendering, and ruminant feed. The
potential for market failure among the suppliers in these sectors
results from the externality that could be created by individual
suppliers imposing economic hardships on other suppliers within the
industry. The potential for market failure among the purchasers results
from the inadequate information that would be available to purchasers
of potentially infective products.
Any renderer, feed manufacturer, or cattle producer that permits
animal protein derived from ruminants and mink to be placed in ruminant
feed increases the risk that other renderers, feed manufacturers, or
cattle producers will suffer the severe economic consequences that
would follow an outbreak of BSE in the United States. The industry is
aware of this risk, as evidenced by the existence of voluntary programs
aimed at reducing the transmission of the infectious agent. These
include an adult sheep rendering ban recommended by the NRA, a
recommended ban on the feeding of rendered ruminant protein to
ruminants by the NCBA and others, and scrapie-free certification
programs by individual sheep producers. Although the benefits of such
programs--the reduction or elimination of the risk of an outbreak of
BSE and the increased consumer confidence in the safety of the
industries' products--accrue to all members of these industries,
compliance with these measures is incomplete, because individual
noncomplying members can avoid the costs of risk reduction measures
while still enjoying the benefits of compliance by others in the
industry.
If purchasers could easily identify the risks of infective agent
contamination associated with products from specific suppliers, they
could more easily take defensive actions to reduce these risks (e.g.,
refusing products from cattle known to have consumed specified ruminant
proteins). Purchasers are unlikely to obtain the information they need,
however, for several reasons. First, the long incubation period for BSE
creates a lag between the actual onset and the recognition of the
disease and could lead to a suboptimal level of risk prevention by the
concerned parties during the incubation period. By the time the first
signs of disease are observed, many animals may have been already
exposed. Moreover, renderers sell their product to feed manufacturers
who frequently combine proteins from many different plant sources and
animal species to produce cattle feed. Ruminant producers, therefore,
have no sure way of knowing whether a particular batch of feed is free
from potentially infective proteins and cannot easily avoid purchasing
risky feed. Finally, if renderers or feed manufacturers do not believe
that BSE is an important threat they may choose not to take preventive
action, regardless of the risk levels perceived by epidemiological
experts or consumers.
B. Benefits
The proposed rule would reduce the risk of an outbreak and
subsequent proliferation of BSE disease in the United States. It may
also forestall the loss of consumer confidence in the U.S. beef market
due to concerns about BSE and its implications. Thus, the benefits of
this proposal would include the value of reduced risks to human and
animal health and to the economic stability of the U.S. livestock and
livestock dependent industries compared to the ``no action'' option. In
technical terms, these benefits measure the expected value of the
future disease-related costs that might be averted by the proposed
rule. Specifically, they are calculated as a product of three factors:
(1) The probability that, in the absence of this rule, BSE would be
introduced and proliferate in the United States, (2) the costs, both
direct and indirect, that would be associated with the spread of BSE in
the United States, and (3) the extent to which the proposed rule would
reduce the likelihood of BSE proliferation.
BSE has not been detected in the United States and the probability
that it currently exists is remote. Nevertheless, it is possible that
BSE could develop in the future. Once developed, BSE could remain
undetected for several years because of its long incubation period and
because, at present, it can be diagnosed reliably only by microscopic
brain examination after death. During the period between introduction
and diagnosis, the disease could spread as it apparently did in the
U.K. via intake of infective feed. If regulation was delayed until
after discovery, the costs would be substantial. By addressing the
central risk factors associated with BSE, FDA believes that the
proposed rule would eliminate the vast majority of the BSE-related
risks and costs.
BSE was first detected in the U.K. in November 1986, and a ban on
ruminant offal in ruminant feed was imposed in the U.K. in July 1988
(Ref. 115). An analysis of cattle born before and after the feed ban
went into effect suggests that the feed ban significantly decreased
disease transmission (Ref. 116). This analysis found that the incidence
of confirmed BSE roughly doubled each year for animals born between
July 1985 and July 1988, but declined precipitously in animals born in
August 1988 compared to the previous year and continued to fall
thereafter. Because BSE has a long incubation period, however, a
decrease in the incidence was not evident until several years after the
initial feed ban was implemented. The incidence of BSE peaked in 1992
at 36,681 detected cases, or approximately 0.3 percent of the UK's 11.5
million cattle. Despite a sharp decrease in the incidence rate since
then, by the end of 1996, more than 165,000 cases of BSE will have been
detected, with one-third of all U.K. cattle herds infected (Refs. 115
and 117).
The likelihood that BSE will someday be developed in the United
States cannot be estimated with any confidence, although U.S. risk
factors are believed to be significantly smaller than existed in the
United Kingdom of the early 1980's. As described previously, the
various remaining modes include transmission from scrapie-infected
sheep or other animals with TSE, e.g., through meat and bone meal;
introduction via imported
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animals; and spontaneous introduction (which in some TSE's has been
hypothesized to occur at a rate of about 1 case per million per year).
USDA import controls and the voluntary bans on sheep offal and ruminant
tissues in ruminant foods reduce the risk of disease introduction but
cannot completely eliminate it.
Although FDA cannot quantitatively estimate the risk of a
significant BSE outbreak in the United States, the agency has used the
U.K. experience, modified to account for major differences in
circumstances, to assess the consequences of the potential spread of
the disease within the United States. If BSE were introduced in this
country, the pattern of disease spread would presumably be similar to
that in the United Kingdom, with most symptomatic disease appearing in
older cattle (the average time for BSE symptoms is approximately 5
years after infection (Ref. 115)). The rate of spread of symptomatic
disease would probably differ, however, because compared with the pre-
BSE U.K. dairy industry, U.S. dairy cows are younger and are exposed to
meat and bone meal in feed later in life than was true in the United
Kingdom (Ref. 118). United Kingdom dairy animals were historically fed
meat and bone meal as calves, whereas U.S. dairy cows ingest meat and
bone meal primarily as adults.
1. Methodology
To develop an illustrative estimate of the number of cattle that
might be lost to BSE infection if the disease were to occur in the
United States in the absence of regulation, FDA extrapolated from the
experience in the United Kingdom, but adjusted for the differences in
cattle age and potential age of exposure to meat and bone meal. This
extrapolation assumes that the detection of BSE in this country would
quickly lead to a ruminant-to-ruminant feed prohibition but that, as in
the United Kingdom, BSE incidence would nonetheless continue to
increase for 6 years due to the disease's long incubation time (hence
several years of disease spread before the diagnosis of the first
case). To account for the difference in cattle age-related risk
factors, FDA assumed that, if BSE occurred in the United States, the
affected animals would be predominately dairy cows of age 4 or more,
rather than age 3 and up as in the U.K. (due to the differences in age
of exposure.) The difference of 1 year is based on the agency's
estimate that U.S. cattle are first exposed to meat and bone meal 1
year later than U.K. cattle. Therefore, the onset of the clinical
disease is estimated to start 1 year later. Accordingly, only 47
percent of U.S. dairy cows are age 4 and up (about 4.8 million cows),
while 90 percent of United Kingdom cows are age 3 and up (about 2.6
million cows). Thus, a lower percentage of U.S. cattle were assumed to
be at risk of symptomatic BSE, and the projected rate of death was
proportionately lower. Based on the relative size of the U.S. and U.K.
dairy cattle populations, these projections suggest that if BSE were
introduced in the United States and spread in a similar manner, the
disease would destroy 299,000 U.S. cattle over 11 years (4.8 x 2.6 x
162,000 U.K. BSE deaths). (These calculations assume that a feed
prohibition would be implemented very soon after the first case is
diagnosed, and that the prohibition would immediately begin to affect
the underlying rate of new infection. If a feed prohibition were not
implemented at that time, the number of cattle deaths would be much
higher.)
Other adjustments could be made to this estimate, but their effect
on the direction of the results would be uncertain. For example,
compared with U.K. practices before 1988, U.S. dairy cattle consume a
higher proportion of concentrated feed that contains meat and bone
meal. On the other hand, most U.S. concentrate contains a lower
percentage of meat and bone meal (and a higher percentage of vegetable-
based proteins). If BSE infectivity in feed is highly dose-dependent,
these factors could cause FDA's cost estimate to be either too high or
too low, if one of the factors is dominant over the other.
The risks and costs associated with BSE when it occurs are
primarily of three types. First, there is the possible risk and
associated cost of ruminant-to-human transmission of TSE disease. The
proposed rule would reduce this risk by eliminating the main routes by
which ruminants might acquire transmissible TSE, greatly reducing any
risk incurred by the human consumption of ruminant-derived products.
Thus, the proposed rule would reduce the risk of future mortality,
morbidity, and health care costs due to human TSE. Second, there is the
risk of livestock losses. These losses include not only the deaths of
BSE-infected animals, but also the loss and disposal costs of other
animals that would be destroyed, either to contain the immediate spread
of disease or to restore consumer confidence in the safety of beef and
dairy products. Third, there are the costs associated with decreased
domestic sales and exports of beef and other bovine-derived products
until consumer and international confidence could be restored.
2. Reduced Risk to Public Health
As discussed earlier, scientists believe that the nv-CJD cases
identified in the U.K. may have been associated with the BSE epidemic.
If indeed there were such an association, and if BSE were to occur in
this country, there would be a risk of spreading BSE-related human TSE
in the United States The proposed rule therefore might avert human
deaths in the United States, although the number of deaths cannot be
estimated. The proposed rule would also save the health care and other
costs associated with treating individuals with the disease.
3. Reduced Risk of Direct Livestock Losses
For estimating the present value of livestock losses if BSE
occurred in the United States, FDA assumed that the first case of BSE
would not be detected--even in the absence of the proposed rule--for 4
years. Based on an estimated value of $502 per animal (Ref. 119) and
disposal costs of $4 per animal, direct losses from the death of
299,000 BSE-infected cattle would reach $151 million over 11 years
(starting 4 years from now). At a discount rate of 7 percent, the total
present value of these losses is $75 million.
In addition to the animal losses from direct infection, a
significant outbreak would probably lead to the eradication of high-
risk animals to restore consumer confidence. Switzerland, for example,
has proposed slaughtering all cattle born before that country
implemented a feed ban, or approximately one-eighth of its national
herd (Ref. 120). The United Kingdom has begun a program to destroy and
incinerate all animals over age 30 months as they reach the end of
their useful life, or about 1 million animals in 1996 and a total of
4.7 million over 6 years. In addition, the United Kingdom has a program
to slaughter some unmarketable male dairy calves (126,000 had been
slaughtered as of August 1996) and up to 147,000 additional ``high-
risk'' animals (Refs. 115 and 121). Even if the U.K. eradication of
animals were limited to a one-time total of 1 million cattle (about 8.7
percent of their cattle stock), similar measures in the United States,
if they occurred immediately upon detection of the disease, would
result in the one-time destruction of $4.58 billion worth of cattle,
with a present value of $3.49 billion.
4. Costs of Future Regulation
Moreover, the ability to control a BSE outbreak once it occurred
would require putting in place restrictions on the use
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of ruminant proteins in ruminant feeds that would be at least as
restrictive as the measure under this proposed rule. Presumably, the
total costs of implementing a ruminant-to-ruminant feed prohibition at
that point would be at least as great as the low estimates for this
proposed rule, or $21.4 million per year. The present value of these
future regulatory costs would total approximately $240 million.
Moreover, this estimate may vastly understate the economic impact
because the market value of ruminant-derived proteins could disappear
if there were an actual outbreak.
5. Reduced Risk of Losses in Domestic Sales and Exports
If BSE were to emerge in the United States, the news could greatly
reduce both domestic sales and exports of bovine products. In the
United Kingdom, domestic consumption fell by more than 20 percent
between 1988 and 1990 and has not yet fully recovered (Ref. 122),
presumably due to continuing concerns about possible links between BSE
and CJD. If U.S. consumers acted similarly, U.S. producers of beef
products could lose over $9 billion in annual sales (Ref. 123).
Alternatively, U.S. consumers might demonstrate considerably less
concern, as the U.K. experience may have improved the ability of U.S.
risk managers to communicate both the extent of the risk of contracting
CJD from the consumption of beef and the responsiveness of the
government's safety policies. Nonetheless, it remains probable that the
uncertainty surrounding a serious BSE outbreak would lead U.S.
consumers to reduce their consumption and spending on beef by a
significant amount. Also, at the same time that U.K. domestic sales of
beef were declining due to the fear of BSE, the volume of U.K. exported
beef fell by nearly 16 percent (Ref. 122). Based on U.S. beef exports
in 1994 of approximately $2.2 billion (Ref. 109), a proportional
decline of this magnitude would reduce U.S. exports by up to $0.3
billion per year.
While the values of such lost domestic and international sales
would reduce the profits of the U.S. beef industry and the enjoyment of
some U.S. consumers of beef, they do not provide an accurate measure of
societal costs, because competitor industries, such as poultry, pork,
and seafood, would gain new profits. Thus, the net costs that would
result from such potential shifts in consumer spending cannot be
precisely discerned without extensive economic modeling. While FDA
examined a partial equilibrium model for projecting the approximate
losses of consumer and producer surplus within the market for beef
products, the agency could not adequately quantify the likely effects
on the markets for substitutes of beef. Consequently, FDA could not
estimate the net economic cost of these lost sales. Nevertheless, the
magnitude of these potential costs could be substantial and the agency
requests public comment on how the appropriate measurement
methodologies could be developed and applied.
Finally, even in the absence of evidence of BSE in the United
States, consumer concern about BSE could affect beef consumption and
expenditures. Thus, one benefit of implementing the proposed rule now
is that it might prevent a loss of consumer confidence in the beef
market, irrespective of the actual risk of BSE. FDA did not attempt to
quantify this potential loss, but believes that it also may be
substantial, particularly in light of the recent increased U.S.
publicity of BSE and its hypothesized links to CJD.
6. Total Losses Averted
In summary, the losses averted by the proposed rule include the
expected value of the costs associated with BSE itself, and the
potential value of forestalling a drop in domestic and international
demand for U.S. beef due to BSE-related causes. The first component
largely reflects the statistical probability that BSE could occur and
spread within the United States and the potential $3.7 billion cost of
destroying BSE-exposed livestock. The second primarily measures the
expected loss to U.S. consumers and producers that would result from
reduced sales. While FDA has not quantified these latter costs,
plausible scenarios indicate that they could reach billions of dollars.
Moreover, these figures have not included the possibility of lost lives
and treatment costs associated with treating human TSE.
Finally, the expected benefits of the proposed rule are slightly
lower than the sum of the expected value of all the costs associated
with BSE, because the rule would not totally eliminate all of the
related risk (e.g., due to the possibility of spontaneous introduction
of disease and the possible incomplete compliance with the rule). FDA
believes, however, that any remaining risk would be extremely small. In
addition, because the rate of BSE infection and the associated costs
would probably vary geographically (as scrapie does now) (Ref. 98) ,
the benefits would vary across regions of the country.
7. Comparison of Alternatives
As described elsewhere in this document, FDA is considering five
alternatives to the proposed rule, in addition to other options that
might be offered in the comments. The first three of these alternatives
are: (1) No action (relying on voluntary industry activities), (2)
prohibit only materials from U.S. species in which TSE has been
diagnosed, and (3) a prohibition on proteins from specified sheep and
goat offal in ruminant feed. Compared with the proposed action,
prohibiting proteins from all U.S. TSE species provides similar
reductions in the risk that BSE might be introduced, with a sheep/goat
specified offal protein ban and no action providing progressively less
risk reduction. The TSE species alternative, however, would be
significantly less effective in limiting the spread of BSE (e.g., after
spontaneous introduction) until BSE was diagnosed and cattle were added
to the list of TSE species. Likewise, the two other alternatives would
be significantly less effective in inhibiting the spread of ruminant-
to-ruminant transmission of disease once BSE is introduced. Thus, the
expected value of the benefits of each of the three rejected options is
substantially lower than the proposed rule, although the amount of
difference cannot be estimated precisely.
The agency is also considering two other alternatives: (1) A
mammalian-protein-to-ruminant prohibition, and (2) a partial ruminant-
to-ruminant prohibition which would exclude all ruminant and mink
tissues except certain bovine tissues. Compared with the proposed rule,
both alternatives offer similar benefits in substantially inhibiting
the initial introduction of BSE. The extent of inhibition of the spread
of disease (and associated costs), however, would be different.
The mammalian protein alternative would further reduce the spread
of disease compared with the proposed rule, by reducing the risk of
cross-contamination within rendering and processing plants. Thus, this
alternative would bring the expected value of the BSE-related costs
even closer to zero than would the proposed measure. However, the
incremental benefit is small if cross- contamination under the proposed
measure does not pose a substantial risk.
The partial ruminant-to-ruminant prohibition would be less
effective than the proposed measure, because it would be more
administratively difficult to enforce. Thus, this alternative would not
reduce the expected value of the
[[Page 576]]
BSE-related costs as much as the proposal. Again, however, the exact
difference cannot be estimated, but would vary depending on the likely
level of compliance under the alternative.
C. Industry Impacts
The ERG study examines the composition, size, and scale of economic
activity for the various affected industry sectors and provides
estimates of the cost and high and low market impacts (depending on the
size of the price change for restricted meat and bone meal of five
regulatory options (see Table 1).
Table 1.--Estimated Costs of Alternative Regulatory Prohibitions \1\
Ruminant-to- Partial
Mammalian- ruminant ruminant-to- Sheep/Mink- Sheep/Goat-
to-ruminant (proposal) ruminant to-ruminant to-ruminant
Annualized Impacts----------------------------------------------------------------------------------------------
(4) ($ million)
----------------------------------------------------------------------------------------------------------------
Low Market Impact Scenario ($25/ton)
----------------------------------------------------------------------------------------------------------------
Capital Costs.................................. 8.8 1.0 3.2 0.0 0.0
Operating/Disposal Costs....................... 10.1 0.1 14.4 5.1 0.2
Transportation................................. 10.7 7.6 5.3 0.0 0.0
Documentation.................................. 1.9 1.5 0.5 0.0 0.0
Substitution Costs............................. 9.7 8.0 3.7 0.0 0.0
Renderer Revenue Losses........................ 76.4 63.2 28.8 4.2 0.1
Nonruminant Gains.............................. (72.6) (60.0) (27.4) 0.0 0.0
----------------------------------------------------------------
Totals................................... 45.0 21.4 28.5 9.3 0.3
----------------------------------------------------------------------------------------------------------------
High Market Impact Scenario ($100/ton)
----------------------------------------------------------------------------------------------------------------
Capital Costs.................................. 8.8 8.2 4.9 0.0 0.0
Operating/Disposal Costs....................... 10.1 10.1 16.9 5.1 0.2
Transportation................................. 10.7 7.6 5.3 0.0 0.0
Documentation.................................. 1.9 1.8 0.7 0.0 0.0
Substitution Costs............................. 9.7 8.0 3.7 0.0 0.0
Renderer Revenue Losses........................ 305.6 252.8 115.4 4.2 0.1
Nonruminant Gains.............................. (290.3) (240.2) (109.6) 0.0 0.0
Totals................................... 56.5 48.3 37.3 9.3 0.3
----------------------------------------------------------------------------------------------------------------
\1\ Totals may not match text due to rounding error.
1. The Proposed Rule
The proposed alternative would prohibit the use of ruminant and
mink protein in ruminant feeds. Currently, only about 10 percent of the
meat and bone meal supply is used in ruminant feed, but over 80 percent
of the meat and bone meal contains some ruminant material. ERG forecast
that because no mixed-species slaughtering or rendering establishments
would find it profitable to separate ruminant from nonruminant offal,
most would continue to contain ruminant material. ERG estimated that
affected renderers and feedmills would incur total direct compliance
costs ranging from $10.2 to $27.6 million per year. Renderers would
bear annual costs of about $6.3 million and feed mills would bear
annual costs of from $3.8 to $21.3 million. Arrayed by compliance
category, transportation costs were estimated at $7.6 million;
documentation costs for activities to ensure control of ruminant feed
constituents ranged from $1.5 to $1.8 million; and capital costs and
operating costs ranged from $1.0 to $8.2 million and $0.1 to $10.1
million, respectively, due primarily to the need for some feedmills to
expand their capacity to offer both ruminant and nonruminant feed
products under a high market impact scenario.
Because consumer response to the rule is uncertain, ERG could not
develop a precise projection of future meat and bone meal prices. ERG
estimated, however, that the regulatory prohibition of marketing
ruminant meat and bone meal to ruminants would lower the price of this
product by from $25 to $100 per ton, decreasing rendering industry
revenues by from $63.2 to $252.8 million per year. In contrast, a lower
MBM price would increase sales of meat and bone meal to the nonruminant
sector and the resulting increased profits for that sector would
offset, at an aggregate level, most revenue losses. Although ERG did
not quantify this effect, FDA determined that the assumption of a fixed
supply of meat and bone meal and a linear demand for nonruminant feed
implies that purchasers of mixed-species meat and bone meal for
nonruminant uses would save from $60.0 to $240.2 million annually,
because of the lower meat and bone meal costs. This estimate assumes a
total meat and bone meal supply of 2.5 million tons, changes in price
ranging from $25 to $100 per ton, and an increase in nonruminant
consumption of meat and bone meal of about 250,000 tons. In addition,
manufacturers of ruminant feed would incur higher costs if they could
not use ruminant proteins. In an analysis prepared for the feed
industry, protein substitutes, such as soybean meal and other minerals
necessary to provide the same nutritional level as that provided by the
meat and bone meal, were estimated to cost approximately $31.75 per ton
more than meat and bone meal (Ref. 125). FDA believes that this
estimate is overstated, because it assumes that soybean meal alone
sells for $20 per ton more than meat and bone meal. In fact, their
respective market prices are currently similar. Nevertheless, FDA used
the reported $31.75 per ton differential to estimate that the higher
price of alternative proteins would increase ruminant feed costs by
about $8.0 million per year.
As a result, FDA estimates that the aggregated annualized costs of
this proposal, comprised of both the direct compliance costs and the
various indirect gains and losses, would total
[[Page 577]]
from $21.4 to $48.2 million. Although the greatest initial burden would
fall on the rendering and feed manufacturing sectors, ERG noted that
the final distribution of these impacts would shift; renderers would
pass back the economic impacts to slaughterers, who, in turn, would
pass them back to cattle producers. FDA judged, however, that of the
small renderers dependent upon farmers' and ranchers' dead stock for
their raw materials, 20 to 25 would be likely to close. ERG also
forecast that these impacts would cause a decline in prices for
slaughter-weight cattle of $1 to $5 per head. In the long run, ERG
foresaw a modest reduction in the size of the U.S. cattle herd.
In response to its ANPRM, FDA received comments on the possible
impacts of the proposal from both individuals and industry. The
submission from the American Feed Industry Association (AFIA) contained
an analysis of the animal feed market that was based on the assumption
that the proposal would taint the safety of all meat and bone meal
(both ruminant and nonruminant), to the extent that even nonruminant
animal producers would refuse to purchase the product. This loss of
wholesale value was estimated at $523 million. Further, the AFIA
comment estimated the cost for disposing of this meat and bone meal at
$349 million and for substituting to higher priced feeds at $74 million
annually.
FDA questions the conclusions of the AFIA report, largely because
the proposed rule does not prohibit the use of ruminant proteins in
nonruminant feeds and there is no evidence that this market would
disappear. As noted earlier, nonruminant feed use currently constitutes
about 90 percent of the meat and bone meal market. While some
nonruminant producers may be wary of ruminant MBM after the proposal
becomes final, the broad media coverage of BSE in the United Kingdom
and the voluntary prohibition of ruminant MBM in ruminant feeds have
already provided nonruminant producers with substantial information on
the relevant risks. The implications of the ERG study are that most of
the major nonruminant sectors that use ruminant meat and bone meal in
their feeds would continue this practice, particularly at sharply lower
MBM prices. Because ERG believed that all stocks of meat and bone meal
would find a commercial outlet within the nonruminant feed sector, they
projected no additional disposal costs and far smaller revenue losses
than AFIA.
2. Partial Ruminant-to-Ruminant Prohibition
ERG also estimated the economic impact of a partial ruminant-to-
ruminant prohibition, which would prohibit only the use of proteins
from designated ruminant tissues in ruminant feeds. ERG projected that
cattle packer/renderers and approximately one-half of the large cattle
packers would choose to separate the designated and nondesignated
tissues. As shown in Table 1, this change in processing would lead to
increased costs from capital investments, increases in operating and
transportation expenses, training, and documentation activities.
Further, ERG projected, under the high market impact scenario, that
some feedmills would expand their facilities to offer both restricted
and nonrestricted meat and bone meal. They estimated the annualized
direct compliance costs for this option at from $23.5 to $27.9 million.
In addition, ERG projected that this option would cause price declines
of from $25 to $100 per ton for the meat and bone meal derived from
designated tissues, leading to decreases in renderer revenues of from
$28.8 to $115.4 million per year. As discussed previously, FDA again
assumed a fixed supply of meat and bone meal and a linear demand for
nonruminant feed to calculate that purchasers of mixed-species meat and
bone meal for nonruminant uses would save from $27.4 million to $109.6
million annually because of the lower meat and bone meal costs. Adding
additional protein substitution costs of $3.7 million and other
indirect costs raises the estimated net aggregate costs for this
alternative to $28.6 to $37.4 million.
3. Mammalian-to-Ruminant Prohibition
The third option assessed was the prohibition of mammalian protein
in ruminant feeds. ERG projected that slaughtering and rendering
establishments would have no reason to separate offal because very few
of these establishments process both mammals and nonmammals. They
estimated annualized direct compliance costs for this option at $31.6
million. ERG forecast that, regardless of the size of the price decline
for restricted meat and bone meal, some feedmills would expand their
capacity to offer both restricted and nonrestricted meat and bone meal,
resulting in increased capital and plant operating costs. The majority
of the remaining regulatory costs are composed of documentation costs.
Assuming that a regulatory prohibition on marketing restricted meat and
bone meal to ruminants would cause the price of the restricted meat and
bone meal to fall by from $25 to $100 per ton, ERG projected that this
option would reduce renderer revenues by from $76.4 to $305.6 million
per year. Alternatively, under the same assumptions as applied above,
FDA found that purchasers of mixed-species meat and bone meal for
nonruminant uses would save from $72.6 million to $290.3 million
annually, because of the lower meat and bone meal costs. Adding
additional protein substitution costs of $9.7 million and other
indirect costs raises the estimated net aggregate costs for this third
option to from $45.1 to $56.6 million.
4. Other Regulatory Alternatives
FDA also considered two less restrictive options for controlling
the spread of an outbreak of BSE in the United States: A prohibition of
all sheep, goat, mink, deer, and elk proteins in ruminant feed; and a
prohibition of sheep and goat proteins in ruminant feed. The first of
these alternatives would require that ruminants not be fed proteins
from any species in which a TSE was diagnosed in the United States,
which includes sheep, goats, mink, deer, and elk. ERG anticipated
minimal regulatory impacts for sheep, lamb, and goat producers because
most renderers already require that sheep, lamb, and goat offal be
excluded from mixed species meat and bone meal. ERG estimated that this
alternative could restrict the use of up to 34,150 tons of offal
annually from the various species, or about 0.3 percent of all
mammalian offal rendered. Using an estimated cost of $150/ton for
landfill disposal, ERG calculated that the disposal costs for this
alternative could equal $5.1 million. Furthermore, ERG estimated that
the meat and bone meal and tallow manufactured from offal generates
revenues of about $500/ton of processed material. Under this option,
meat and bone meal production would fall by 8,450 tons per year,
reducing industry revenues by an estimated $4.2 million annually.
The final alternative would restrict only sheep and goat protein
from use in ruminant feed. This alternative is similar to the agency's
1994 proposal, which pertained only to adult sheep and goats. Most
sheep and goats are currently excluded by renderers from being rendered
into mixed species meat and bone meal. ERG estimated that this
alternative would restrict the use of up to 1,200 tons of offal, or
about 0.01 percent of all mammalian offal rendered. At $150/ton for
landfill disposal, the disposal costs would equal $0.2 million. ERG
calculated that
[[Page 578]]
production of meat and bone meal under this option would be restricted
by only 300 tons per year, leading to revenue losses of about $0.1
million.
ERG noted that the disposal costs presented for the latter two
alternatives are high-end estimates because of the likelihood of onsite
disposal for deer and elk taken by hunters. Further, these alternatives
were not expected to have a measurable effect on the price of meat and
bone meal because they would affect only 0.3 percent and 0.01 percent
of the meat and bone meal markets, respectively. In contrast to the
first three options, these rules would not change the demand for meat
and bone meal, but would restrict the supply of meat and bone meal. Any
postregulation increase in price, therefore, would increase revenues of
renderers and costs of purchasers of meat and bone meal by an almost
equal amount. ERG reported that this decrease in supply would have a
negligible effect on meat and bone meal prices.
D. Small Business Impacts
The Regulatory Flexibility Act requires agencies to prepare a
regulatory flexibility analysis if a rule would have a significant
impact on a substantial number of small entities. The discussion in
this section, as well as in other sections of this document, and the
ERG report, constitute the agency's compliance with this requirement.
The Regulatory Flexibility Act asks for a succinct statement of the
purpose and objectives of the rule. As explained previously in this
document, FDA is proposing this measure to address the risk to U.S.
livestock associated with feeding ruminant proteins to ruminants.
Existing epidemiological evidence suggests a link between an outbreak
of BSE in the United Kingdom and the practice of feeding products to
cattle that included ruminant proteins. This rule would prohibit that
practice. Thus, the need for regulatory action is based on the need to
prevent the spread of BSE and thereby to protect the health of animals
and to minimize any risk that might be posed to humans from BSE.
The Regulatory Flexibility Act also requires a description of the
affected small entities. The ERG study includes counts of entities in
each class of industry that are involved in ruminant production and
meat preparation. The vast majority of all of these firms are
considered small businesses according to size standards set by the
Small Business Administration. There are 282 rendering plants, of which
204 have fewer than 500 employees, including all of the 152 independent
renderers. ERG also estimated that 30,000 feedmills, all with fewer
than 500 employees, could be affected by this rule. An estimated 1.4
million enterprises are engaged in ruminant production. These include
businesses engaged in the production of beef and dairy cattle,
including farmers and ranchers, stocker operators, and cattle feeders,
and other ruminant producers. The slaughtering industry contains more
than 4,000 establishments. Of this total, however, only 130 are packer/
renderers that could have compliance requirements and about 52 of these
establishments have fewer than 500 employees. ERG estimated that almost
300,000 small establishments are engaged in meat processing. These
businesses would have no direct compliance activities, but could be
affected indirectly by altered renderer practices. Also, about 150,000
small producers of nonruminant animals could gain from lower feed
costs.
The RFA also requires a description of the recordkeeping
requirements of the proposed rule. The ERG report presents detailed
estimates of these costs. ERG found that the rule would require certain
feed manufacturers to develop new written operating procedures. In
addition, affected firms would have to retain invoices but FDA believes
this activity is already generally accepted business practice.
Finally, the Regulatory Flexibility Act asks for an evaluation of
any regulatory overlaps and regulatory alternatives that would minimize
costs to small entities. FDA is unaware of any significant regulatory
conflicts with other Federal rules. FDA examined five regulatory
alternatives in addition to no action: (1) The ruminant-to-ruminant
prohibition; (2) the partial ruminant-to-ruminant prohibition; (3) the
mammalian-to- ruminant prohibition; (4) the prohibition of all sheep,
goat, mink, deer, and elk proteins in ruminant feed; and (5) the
prohibition of specified sheep and goat proteins in ruminant feed. The
ERG report provides a detailed comparison of the respective impacts of
these alternatives and found that the estimated direct compliance costs
are lower under the proposed rule ($10.2 to $27.6 million) than under
two of the alternative rules ($23.5 to $27.9 million for the partial
ruminant-to-ruminant option, $31.6 million for the mammalian-to-
ruminant option). The other alternatives would not be nearly as
effective at reducing the risk of an outbreak and spread of BSE, but
are considerably less costly. As many of the above projections are
uncertain, FDA particularly invites additional data or comment on the
effects of the proposed and alternative rules on any group of small
businesses.
E. Unfunded Mandates Analysis
Based on the ERG study, FDA estimated that aggregate expenditures
by the private sector that result from the proposed rule, issued under
21 CFR 589.2000, will range from $10.2 to $27.6 million per year. As
described in section IX.B. of this document, the benefits of this
measure accrue both to the general public (through decreased risks to
health) and to the livestock and associated industries. The costs of
the measure are borne by the private sector, primarily the rendering
and animal feed industries. Because FDA anticipates no significant
additional costs to State, local, or tribal governments, this
regulatory action does not require an assessment under the Unfunded
Mandates Reform Act.
X. The Paperwork Reduction Act of 1995
This proposed rule contains recordkeeping requirements that are
subject to public comment and review by OMB under the Paperwork
Reduction Act of 1995 (Pub. L. 104-13). Therefore, in accordance with 5
CFR part 1320, a description of reporting requirements is given in
Table 2 of this document, with an estimate of the annual collection of
information burden. Included in the estimate is the time for reviewing
instructions, gathering and maintaining the data needed, and completing
and reviewing the collection of information.
With respect to the following collection of information, FDA is
soliciting comments on: (1) Whether the proposed collection of
information is necessary for proper performance of FDA's functions,
including whether the information will have practical utility; (2) the
accuracy of FDA's estimate of the burden of the proposed collection of
information, including the validity of the methodology and assumptions
used; (3) ways to enhance the quality, utility, and clarity of the
information to be collected; and (4) ways to minimize the burden of the
collection of information on those who are to respond, including
through the use of automated collection techniques or other forms of
information technology, when appropriate.
Title: Substances Prohibited from Use in Animal Food or Feed;
Animal Proteins Prohibited in Ruminant Feed.
Description: The proposed rule (Sec. 589.2000) provides that
protein derived from ruminant and mink tissues is not GRAS for use in
ruminant feed and is a food additive subject to section 409 of the act.
Proteins derived from
[[Page 579]]
animal tissues contained in such feed ingredients in distribution
cannot be readily determined by recipients engaged in the manufacture,
processing and distribution, and use of animal feeds and feed
ingredients. To achieve the public and animal health objectives of this
proposed rule, the agency believes that manufacturers, processors,
distributors, and users must be responsible for ensuring and
appropriately maintaining the identity of the specific nature of the
components of animal protein products and animal feeds containing these
products.
Thus, under the agency's authority in section 701(a) (21 U.S.C.
371(a)) of the act to issue regulations for the efficient enforcement
of the act, this proposed rule places three general requirements on
persons that manufacture, blend, process and distribute products that
contain or may contain protein derived from ruminant and mink tissues,
and feeds made from such products. The first requirement is for
cautionary labeling of these products with direct language developed by
FDA. The second requirement is for these establishments to provide FDA
with access to their purchase and sales invoices for compliance
purposes. FDA believes that maintenance of such records is a usual and
customary part of normal business activities for such firms. These two
requirements are not within the scope of the Paperwork Reduction Act.
The third requirement is recordkeeping which requires that the firms
develop standard operating procedures if they intend to keep ruminant
and mink material separate from nonruminant material. The agency is
aware that the certification procedures provided in Sec. 589.2000(d) of
the regulation could be interpreted as imposing a paperwork burden on
certain industry segments. However, the agency notes that the
certification procedures apply only where new technology (e.g., a
deactivation method) is developed. The agency was unable to estimate
when such technology might be developed, what its characteristics and
costs would be, and other essential information needed to make
realistic estimates of any paperwork burden. Therefore, such costs are
not included in this proposed rule. However, the agency specifically
requests comments and information related to the factors that would
determine the extent of any paperwork burden.
The recordkeeping burden in Table 2 has been estimated using the
typical average size establishment that is expected to handle animal
protein from both ruminant and nonruminant sources, or feeds containing
these products, and intend to keep them separate. FDA's preliminary
estimate is that only a fraction of feed manufacturers and distributors
will separate their products. Independent renderers were excluded from
the burden estimates based on information provided for the economic
estimate. Packer/renderers were excluded because they are single
species processors.
Under these recordkeeping requirements, for which records must be
made available for FDA inspection, an estimated 2,000 feed mills would
handle both restricted and nonrestricted products and would develop
standard operating procedures for keeping ruminant and mink material
separate from nonruminant material from the time of receipt to time of
shipment. The estimate in the burden chart is based on the time
required to develop and establish the written procedures and is a one
time requirement. The 2,000 firms will also incur annual operating cost
estimated at $10 million, because of the flushing, sequencing and other
procedures that will be required. It is estimated that 1,000 of the
firms may incur capital cost for the construction of separate
facilities. These costs have been annualized for 10 years, at $7.119
million per year. The remaining firms are expected to be able to meet
the regulation's requirements without incurring capital cost.
The agency has submitted copies of the proposed rule to OMB for its
review of these requirements. Interested persons are requested to send
comments regarding this collection of information by February 18, 1997,
but not later than March 4, 1997 to the Office of Information and
Regulatory Affairs, OMB (address above), Attn: Desk Officer for FDA.
Description of Respondents: Distributors, feed manufacturers,
blenders and renderers.
Table 2.--Estimated Annual Recordkeeping Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
No. of
record Total Hours per Capital cost Operating cost
21 CFR section keepers/ Frequency annual record Total hours (annualized) (yearly)
firms records
--------------------------------------------------------------------------------------------------------------------------------------------------------
589.2000 (e)(1)(iv).................................... 2,000 1 2,000 14 28,000 $7,119,000 $10,000,000
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ Costs are only incurred under the high-impact scenario.
XI. Federalism
FDA has analyzed this proposal in accordance with the principles
and criteria set forth in Executive Order 12612 and has determined that
this proposal does not warrant the preparation of a Federalism
Assessment.
XII. References
The following references have been placed on display in the Dockets
Management Branch (address above) and may be seen by interested persons
between 9 a.m. and 4 p.m., Monday through Friday.
1. Transcript, FDA and USDA Symposium, ``Tissue Distribution,
Inactivation and Transmission of Transmissible Spongiform
Encephalopathies,'' Riverdale, MD, 1996.
2. WHO, ``Report of a WHO Consultation on Public Issues Related
to Human and Animal Transmissible Spongiform Encephalopathies,''
With the participation of FAO and OIE, Geneva, Switzerland, WHO/EMC/
DIS/96.147, 2-3 April 1996.
3. Centers for Disease Control and Prevention, Memorandum, July
25, 1996.
4. USDA, APHIS, ``Bovine Spongiform Encephalopathy: Implications
for the United States, a Follow-up,'' 1996.
5. Personal Communications, Will Hueston, 1996.
6. Walker, K. D., et al., ``Comparison of bovine spongiform
encephalopathy risk factors in the United States and Great
Britain,'' Journal of the American Veterinary Medicine,
199(11):1554, 1991.
7. Foster, J. D., et al., ``Studies on Maternal Transmission of
Scrapie in Sheep,'' Veterinary Record, 130:341-343, 1992.
8. Hadlow, W. J., R. C. Kennedy, and R. E. Race, ``Natural
Infection of Suffolk Sheep With Scrapie Virus,'' Journal of
Infectious Diseases, 146:657, 1982.
9. Kimberling, C. V., ``Jensen and Swift's Diseases of Sheep,''
Lea and Febiger, pp. 336-340, 1988.
10. Detweiler, L. A., ``Scrapie, Revue Scientifique et
Technique,'' Office Internationale Epizootics, 11(2):491-537, 1992.
11. USDA, APHIS, Veterinary Services, ``Fact Sheet: Scrapie,''
June 1993.
[[Page 580]]
12. Davis, A., USDA-APHIS-U.S., personal communication, April
1996.
13. Bradley, R., ``Editorial: Bovine Spongiform Encephalopathy:
The Need for Knowledge, Balance, Patience, and Action,'' Journal of
Pathology, 160:283-285, 1990.
14. Hueston, W., ``Clinical Signs of BSE, Animal Health
Insight,'' Summer:4, 1991.
15. Wilesmith, J. W., G. A. H. Wells, M. P. Cranwell, and J. B.
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XIII. Request for Comments
Interested persons may, on or before February 18, 1997, submit to
the Dockets Management Branch (address above) written comments
regarding this proposal. Two copies of any comments are to be
submitted, except that individuals may submit one copy. Comments are to
be identified with the docket number found in brackets in the heading
of this document. Received comments may be seen in the office above
between 9 a.m. and 4 p.m., Monday through Friday.
List of Subjects in 21 CFR Part 589
Animal feeds, Animal foods, Food additives.
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, it is
proposed that 21 CFR part 589 be amended as follows:
PART 589--SUBSTANCES PROHIBITED FROM USE IN ANIMAL FOOD OR FEED
1. The authority citation for 21 CFR part 589 continues to read as
follows:
Authority: Secs. 201, 402, 409, 701 of the Federal Food, Drug,
and Cosmetic Act (21 U.S.C. 321, 342, 348, 371).
2. New Sec. 589.2000 is added to subpart B to read as follows:
Sec. 589.2000 Animal proteins prohibited in ruminant feed.
(a) Definitions. (1) Protein derived from ruminant and mink tissues
means any protein-containing portion of ruminant animals or mink,
excluding blood from bovines, milk proteins and gelatin.
(2) Renderer means any firm or individual that processes slaughter
byproducts, animals unfit for human consumption, meat scraps or food
waste. The term includes persons who collect such materials and subject
them to minimal processing, or distribute them to firms other than
renderers whose intended use for the products may include animal feed.
The term includes renderers that also blend animal protein products.
(3) Blender means any firm or individual which obtains processed
animal protein from more than one source or from more than one species,
and subsequently mixes (blends) or redistributes an animal protein
product.
(4) Feed manufacturer and distributor includes manufacturers and
distributors of complete and intermediate feeds intended for animals,
and includes on-farm in addition to off-farm feed manufacturing and
mixing operations.
(5) Nonruminant protein includes protein from nonruminant animals
and from vegetable sources.
(b) Food additive status. The Food and Drug Administration has
determined that protein derived from ruminant and mink tissues is not
generally recognized as safe for use in ruminant feed because it may
contain transmissible spongiform encephalopathy (TSE)-infective
material, and is a food additive subject to section 409 of the Federal
Food, Drug, and Cosmetic Act (the act). In the absence of a regulation
providing for its safe use as a food additive under section 409 of the
act, the use or intended use in ruminant feed of any material that
contains protein derived from ruminant and mink tissues causes the feed
to be adulterated and in violation of the act, unless it is the subject
of an effective notice of claimed investigational exemption for a food
additive under Sec. 570.17 of this chapter. The Food and Drug
Administration has determined that ruminant and mink derived protein is
not prior sanctioned for use in ruminant feeds.
(c) Requirements for renderers that are not included in paragraph
(e) of this section. (1) Renderers that manufacture products that
contain or may contain protein derived from ruminant and mink tissues
and that are intended for use in animal feed shall take the following
measures to ensure that materials identified in paragraph (b) of this
section are not used in the feed of ruminants:
(i) Label the materials as follows: ``Contains (or may contain)
protein derived from ruminant and mink tissues. Do not feed to ruminant
animals, and do not use to manufacture feed intended for ruminant
animals''; and
(ii) Maintain copies of sales invoices for the materials, and make
the copies available for inspection and copying by the Food and Drug
Administration.
(2) Renderers described in paragraph (c)(1) of this section will be
exempted from the requirements of paragraphs (c)(1)(i) and (c)(1)(ii)
of this section if they:
(i) Use exclusively a manufacturing method that has been validated
by the Food and Drug Administration to deactivate the agent that causes
TSE's and whose design has been made available to the public; or
(ii) Use routinely a test method that has been validated by the
Food and Drug Administration to detect the presence of the agent that
causes TSE's and whose design has been made available to the public.
Products found to contain the agent that causes TSE's shall be labeled
``Not for Use in Animal Feed.'' Records of the test results shall be
made available for inspection by the Food and Drug Administration.
(3) Renderers described in paragraph (c)(1) of this section who are
not exempted under paragraph (c)(2)(i) or paragraph (c)(2)(ii) of this
section will be exempted from the requirements of paragraph (c)(1)(ii)
of this section if they use a permanent method, approved by FDA, to
mark the presence of the materials. If the marking is by the use of an
agent that cannot be detected on visual inspection, the renderer must
use an agent whose presence can be detected by a method that has been
validated by the Food and Drug Administration and whose design has been
made available to the public.
(d) Requirements for protein blenders, and feed manufacturers and
distributors, that are not included in paragraph (e) of this section.
(1) Protein blenders, and feed manufacturers and distributors, that
manufacture, blend, process and distribute products that contain or may
contain protein derived from ruminant and mink tissues shall:
(i) Comply with paragraph (c)(1) of this section, and
(ii) Maintain copies of invoices for purchase of animal protein
products or feeds containing such products, and make copies available
for inspection and copying by the Food and Drug Administration.
(2) Protein blenders, and feed manufacturers and distributors,
shall be exempt from paragraphs (d)(1)(i) and (d)(1)(ii) of this
section if they:
(i) Purchase animal protein products from renderers that certified
compliance with paragraph (c)(2) of this section or purchase such
materials from parties
[[Page 583]]
that certify that the materials were purchased from renderers that
certified compliance with paragraph (c)(2); or
(ii) Comply with the requirements of paragraph (c)(2) of this
section where appropriate.
(3) Protein blenders, and feed manufacturers and distributors,
shall be exempt from paragraph (c)(1)(ii) of this section if they:
(i) Purchase animal protein products that are marked or purchase
such materials from renderers that certified compliance with paragraph
(c)(3) of this section, or purchase such materials from parties that
certify that the materials were purchased from renderers that certified
compliance with paragraph (c)(3) of this section; or
(ii) Comply with the requirements of paragraph (c)(3) of this
section where appropriate.
(4) Copies of certifications as described in paragraphs (d)(2) and
(d)(3) of this section, shall be made available for inspection and
copying by the Food and Drug Administration.
(e) Requirements for persons that intend to separate ruminant/mink
and nonruminant/mink materials. (1) Renderers, protein blenders, feed
manufacturers and distributors, haulers and others that manufacture,
process, blend and distribute both protein products derived from
ruminant and mink tissues or feeds containing such products, and
protein products from other animal tissues or feeds containing such
products, and that intend to keep those products separate shall:
(i) Comply with paragraphs (c)(1) or (d)(1) of this section as
appropriate except that the labeling requirement shall apply only to
products derived from ruminant and mink tissues or feeds containing
such products;
(ii) In the case of a renderer, obtain nonruminant (excluding mink)
materials only from single-species facilities;
(iii) Provide for measures to avoid commingling or cross-
contamination:
(A) Maintain separate equipment or facilities for the manufacture,
processing, or blending of such materials; or
(B) Use clean-out procedures or other means adequate to prevent
carry-over of ruminant and mink derived protein into animal protein
products or feeds that may be used for ruminants; and
(iv) Maintain written procedures specifying the clean-out
procedures or other means, and specifying the procedures for separating
ruminant and mink materials from nonruminant materials (excluding mink)
from the time of receipt until the time of shipment.
(2) Renderers, blenders, and feed manufacturers and distributors
will be exempted from appropriate requirements of paragraph (e)(1) of
this section, if they meet the appropriate criteria for exemption under
paragraphs (c)(2) or (c)(3), and (d)(2) or (d)(3) of this section.
(f) Requirements for establishments and individuals that are
responsible for feeding ruminant animals. Establishments and
individuals that are responsible for feeding ruminant animals shall
maintain copies of purchase invoices and labeling for all feeds
received, and make the copies available for inspection and copying by
the Food and Drug Administration.
(g) Adulteration and misbranding. (1) Animal protein products, and
feeds containing such products, that are not in compliance with
paragraphs (c) through (f) of this section, excluding labeling
requirements, will be deemed adulterated under section 402(a)(2)(C) or
402(a)(4) of the act.
(2) Animal protein products, and feeds containing such products,
that are not in compliance with the labeling requirements of paragraphs
(c) through (f) of this section will be deemed misbranded under section
403(a)(1) of the act.
(h) Inspection; records retention. (1) Records that are to be made
available for inspection and copying, as required by this section,
shall be kept for a minimum of 2 years.
(2) Written procedures required by this section shall be made
available for inspection and copying by the Food and Drug
Administration.
Dated: December 27, 1996.
David A. Kessler,
Commissioner of Food and Drugs.
Donna E. Shalala,
Secretary of Health and Human Services.
[FR Doc. 97-37 Filed 1-2-97; 8:45 am]
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