[Federal Register: June 5, 1997 (Volume 62,
Number 108)]
[Rules and Regulations]
[Page 30935-30978]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr05jn97-17]
[[Page 30935]]
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Part II
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; Final Rule
[[Page 30936]]
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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: Final rule.
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SUMMARY: The Food and Drug Administration (FDA) is amending its
regulations to provide that animal protein derived from mammalian
tissues for use in ruminant feed is a food additive subject to certain
provisions in the Federal Food, Drug, and Cosmetic Act (the act). The
final rule establishes a flexible system of controls designed to ensure
that ruminant feed does not contain animal protein derived from
mammalian tissues and to encourage innovation in such controls. FDA is
taking this action because ruminants have been fed protein derived from
animals in which transmissible spongiform encephalopathies (TSE's) have
been found. Such proteins may cause TSE's in ruminants. TSE's are
progressively degenerative central nervous system diseases of man and
other animals that are fatal. Epidemiologic evidence gathered in the
United Kingdom 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, there may be an epidemiologic association
between BSE and a form of human TSE known as new variant Creutzfeldt-
Jakob disease (nv-CJD) reported in England. BSE has not been diagnosed
in the United States, and the final rule is intended to prevent the
establishment and amplification of BSE in the United States through
feed and thereby minimize any risk to animals and humans.
DATES: This final rule becomes effective on August 4, 1997, except
Sec. 589.2000(e)(1)(iv), which contains collection of information
provisions subject to review and clearance by the Office of Management
and Budget (OMB). FDA is announcing that the proposed collection of
information has been submitted to OMB for review and clearance under
the Paperwork Reduction Act of 1995. The provision of this section will
be effective upon approval. FDA will announce the effective date of
Sec. 589.2000(e)(1)(iv) in the Federal Register. Submit written
comments on the collection of information provisions by July 7, 1997.
FOR FURTHER INFORMATION CONTACT: George A. (Bert) Mitchell, Center for
Veterinary Medicine (HFV-6), Food and Drug Administration, 7500
Standish Pl., Rockville, MD 20855, 301-827-5587.
SUPPLEMENTARY INFORMATION:
I. Introduction
In the Federal Register of January 3, 1997 (62 FR 552), FDA
published a proposed rule that would regulate persons that manufacture,
blend, process, and distribute certain animal protein products and
ruminant feeds containing such products. The proposed rule would create
a new Sec. 589.2000 entitled, ``Animal proteins prohibited in ruminant
feed.'' In general, the proposed rule would state that protein derived
from ruminant and mink tissues is not generally recognized as safe
(GRAS) for use in ruminant feed, but rather a food additive subject to
certain requirements under the act. The proposed rule also would
require certain cautionary statements on products that contain or may
contain such proteins, and establish recordkeeping requirements. These
proposed recordkeeping requirements were intended to facilitate
compliance with the rule. For example, an invoice obtained from a feed
manufacturer for a protein product not labeled with the cautionary
statement could be used to trace the product back to the supplier to
ensure that the supplier manufactures and distributes animal protein
products from nonruminant sources. The proposed rule also would reduce
or eliminate certain regulatory requirements upon the development of
methods for detecting or deactivating TSE agents, or for verifying
product identity.
The preamble to the proposed rule contained information regarding
available scientific information about TSE's, industry practices, and
regulatory efforts concerning TSE's. The agency refers interested
persons to that document for such information. A list of recently
published, relevant scientific information also appears later in this
document.
The preamble to the proposed rule also contained five alternatives
to the proposed restriction on the use of ruminant protein in ruminant
feed. These alternatives, which are discussed in greater detail later
in this document, included a restriction on the use of all ruminant and
mink materials (except those that have not been found to present a risk
of transmitting TSE's) in ruminant feed, a restriction on the use of
all mammalian protein in ruminant feed, a restriction on the use of
materials from domestic species (such as sheep, goats, mink, deer, and
elk) diagnosed as having a TSE, a restriction on the use of specified
sheep and goat offal in ruminant feed, and a ``no action'' alternative.
The final rule restricts the use of protein derived from mammalian
tissues, with certain exceptions, in ruminant feed. Thus, the final
rule represents a regulatory approach that covers more material and is
easier to implement than the proposed restriction on the use of
ruminant protein in ruminant feed, but is more flexible and better
suited to current industry practices than the alternative restriction
on the use of all mammalian protein in ruminant feed.
FDA continues to believe, as it stated in the preamble to the
proposed rule, that it is prudent to take action prohibiting the use of
certain animal protein products in ruminant feed even though BSE has
not been diagnosed in the United States and there is scientific
uncertainty as to its origin, transmissibility, etc. This final rule
will prevent the establishment and amplification of BSE in the United
States through feed, an action the agency believes is necessary to
protect animal and public health.
FDA received numerous comments, as discussed below, on its proposed
rule. Based on those comments, the agency, in the Federal Register of
April 17, 1997 (62 FR 18728), published the codified provisions of the
draft final rule and provided an opportunity for comment. The codified
provisions of the draft final rule were similar to those in the
proposed rule, but the draft final rule would prohibit the use of
protein derived from mammalian tissue with certain specific exceptions
(such as blood, gelatin, inspected and processed meat products that
have been cooked and offered for human consumption, and products whose
mammalian protein consists entirely of porcine protein). Additionally,
the codified provisions of the draft final rule would eliminate the
cautionary statements on pet food sold at retail, define the term
``ruminant,'' eliminate certain regulatory requirements if a renderer
used exclusively a validated, publicly-available method for controlling
the manufacturing process that minimizes the risk of the TSE agent
entering the product, and simplify the recordkeeping requirements.
[[Page 30937]]
The agency received over 60 comments on the codified provisions of
the draft final rule. Most comments supported the draft final rule,
although several comments suggested technical changes, additional
exemptions, or clarifications. Other comments reiterated their
objections to any rulemaking that would declare tissues to be nonGRAS
for use in ruminant feed or advocated other alternatives (particularly
the use of hazard analysis critical control point programs).
Based on those comments, the agency has made some changes in this
final rule. The final rule provides that protein derived from mammalian
tissues (with certain exclusions) is a food additive under the act. The
act defines a ``food additive'' as ``any substance the intended use of
which results or may reasonably be expected to result, directly or
indirectly, in its becoming a component or otherwise affecting the
characteristics of any food * * * if such substance is not generally
recognized, among experts qualified by scientific training and
experience to evaluate its safety, as having been adequately shown
through scientific procedures (or, in the case of a substance used in
food prior to January 1, 1958, through either scientific procedures or
experience based on common use in food) to be safe under the conditions
of its intended use * * *'' (see section 201(s) of the act (21 U.S.C.
321(s))). 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 a substance is GRAS is on the proponent of
the substance (see U.S. v. An Article of Food * * * Coco Rico, 752 F.2d
11 (1st Cir. 1985).
The preamble to the proposed rule included an extensive discussion
of the basis of FDA's preliminary conclusion that protein derived from
ruminant and mink tissue for use in ruminant feed is not GRAS, but
rather is a food additive under the act. As discussed in detail in the
agency's responses to the comments received on the proposed rule, FDA
did not receive any information that would refute its conclusion that
protein derived from ruminant and mink tissue for use in animal feed is
not GRAS.
With regard to the scope of the final rule, protein derived from
mammalian tissues includes both ruminant and nonruminant tissues. FDA's
basis for its nonGRAS determination for ruminant and mink tissue is
discussed extensively in the preamble to the proposed rule and no
information was submitted to refute that determination. With regard to
nonruminant tissue besides mink, such tissues may include animals such
as cats, dogs, horses, swine, etc. As the preamble to the proposed rule
discussed concerning a mammalian-to-ruminant prohibition (62 FR 552 at
568), industry comments indicated that the usual practice at feed mills
and rendering facilities is to commingle ruminant and nonruminant
protein products. FDA indicated that regular commingling could provide
a basis to determine that protein from mammalian tissues is not GRAS
for use in ruminant feed. The description of industry practice received
in comments on the proposed rule again indicated that the practice is
to commingle ruminant and nonruminant protein. Because of the potential
TSE infectivity caused by mixing tissues from ruminant and mink and
other mammalian tissues, FDA has determined that protein derived from
mammalian tissues (with certain exclusions discussed later in this
preamble) is not GRAS for use in ruminant feed. FDA notes that the
ruminant-to-ruminant prohibition in the proposed rule also would have
prohibited the use in ruminant feed of this commingled tissue because
the definition of protein derived from ruminant and mink tissue would
apply to pure ruminant or mink tissue as well as other mammalian tissue
that could contain ruminant or mink protein due to commingling. This
final rule also reduces the risk of cattle and other ruminants being
exposed to an agent that causes feline spongiform encephalopathy and
acknowledges that feline protein could be a commingled component of
mammalian protein products.
The definition of food additive in section 201(s) of the act does
not apply to substances 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.). The
Commissioner of Food and Drugs (the Commissioner) is unaware of any
prior sanction applicable to the use of protein derived from mammalian
tissue in ruminant feed. No one asserted a prior sanction for the use
of protein derived from ruminant and mink tissues in ruminant feed
based on the agency's discussion of a possible mammalian-to-ruminant
ban in the preamble to the proposed rule (62 FR 552 at 566). In
addition, no one asserted a prior sanction for use of protein derived
from mammalian tissues in ruminant feed in response to the agency's
discussion of a possible mammalian-to-ruminant prohibition in the
preamble to the proposed rule. The failure of any person to come
forward with proof of an applicable prior sanction is a waiver of the
right to assert or rely on a prior sanction at any later time.
The agency notes, that for substances not included in the scope of
the definition of protein derived from mammalian tissues, persons may
continue to self determine whether such substances are GRAS for use in
ruminant feed. FDA's authority to determine substances to be food
additives under the act is discussed in further detail below in
responses to the comments on the proposed rule.
The final rule also simplifies the cautionary statement for animal
feeds containing mammalian-derived proteins, eliminates the labeling
requirements for pet food products sold at the retail level and feeds
for nonruminant laboratory animals, and elaborates on the information
that must be kept and made available for inspection. These changes are
further discussed below in the responses to comments received on the
proposed rule.
II. Comments on the Proposed Rule and Draft Codified Text
FDA received more than 700 comments on the proposed rule. The
comments came from a wide variety of organizations, such as cattlemen,
renderers, feed manufacturers, and pharmaceutical firms, Federal
agencies, foreign governments, State agriculture departments, trade
associations, professional organizations, universities and research
institutions, consumer organizations, and individual consumers.
Additionally, FDA held two public meetings on the proposed rule. The
first meeting was held in St. Louis, MO, on February 4, 1997, and
focused on the rule's economic impact and issues of interest to the
affected industries. The second meeting was
[[Page 30938]]
held in Washington, DC, on February 13, 1997, and focused on the rule's
environmental analysis and issues of interest to consumer groups and
organizations.
Additionally, in the Federal Register of April 17, 1997 (62 FR
18728), FDA published the codified provisions of the draft final rule
and provided an opportunity for public comment. FDA received over 60
comments on the draft codified text.
Most comments (including remarks made at the public meetings)
agreed that the Federal Government should take action to prevent the
establishment and amplification of BSE in the United States through
feed. However, many comments disagreed as to whether more or less
stringent regulatory efforts were needed. FDA also received comments
supporting and opposing each alternative that was described in the
preamble to the proposed rule, as well as numerous comments that
recommended new alternatives. To simplify the nature of the ideas
expressed in the comments, the comments can be divided into two groups.
One group would maximize the scope of the regulations, and the other
would minimize the scope of regulations.
A large number of comments encouraged FDA to increase the scope of
the regulations to include a partial or complete mammalian-to-ruminant
prohibition or a mammalian-to-farm animal prohibition, or to apply a
feed prohibition on all food-producing animals, either to achieve a
greater reduction in the potential risk of human exposure or easier
compliance with less need for enforcement actions. For example, a few
comments asked that the proposed regulations be expanded to prohibit
the feeding of ruminant proteins to felines and zoo animals, and the
feeding of proteins from these animals to ruminants. Some comments
noted the presence of scrapie and other TSE diseases in the United
States and the epidemiological association between scrapie or a
modified scrapie agent and BSE in the United Kingdom in support of
enlarging the scope of the rule. One comment requested a ban on the
feeding of all animal remains to other animals, regardless of species
or processing method. Another comment noted that the specifications for
tallow allowed for the presence of a small amount of protein and the
possibility of a protein-associated infectivity.
Other comments supported a ``minimalist'' approach. For example, a
significant number of comments pointed out that BSE has not been
diagnosed in the United States despite a most exhaustive surveillance
effort by Federal and State veterinary laboratory diagnosticians,
veterinarians accredited by the U.S. Department of Agriculture (USDA),
and veterinary practitioners who have been specifically trained to
diagnose the early clinical signs of BSE in cattle. The USDA through
statutes administered by the Animal and Plant Health Inspection Service
(APHIS) and the Food Safety and Inspection Service (FSIS) has taken
actions to ensure that the border defenses against importing the BSE
agent are as secure as possible. FDA has advised manufacturers of human
and animal drugs and devices, human biologics, dietary supplements, and
cosmetics to obtain bovine derived ingredients from countries which are
free of BSE. Some comments stated that the adoption by industry of
voluntary measures to avoid the rendering of fallen sheep or sale of
sheep proteins for use in ruminant rations, or to stop the feeding of
ruminant proteins to ruminants are sufficient, and no regulation is
warranted. Other comments reminded the agency of its public statements
that the risk of BSE occurring in the United States is low and getting
lower. A comment from a foreign regulatory official observed that zero
risk cannot be achieved and that the calculation of risk through a
mathematical model is essential; this comment also expressed the view
that the agency's proposed regulatory approach exceeded the risk of BSE
in the United States.
A description of the comments and FDA's responses follows.
A. General Comments
1. Exclusions for Certain Products
(Comment 1). Several comments, in addressing either the proposed
rule or the agency's alternatives to a ruminant-to-ruminant
prohibition, suggested exclusions for specific products. The suggested
exclusions included proteinaceous tissues (such as meat),
nonproteinaceous materials (such as grease, fat, tallow, amino acids,
and dicalcium phosphate as a byproduct of the gelatin manufacturing
process), and materials that are not considered to be tissues (such as
paunch meal, feces, and urine). A few sought exclusions for specific
organs, such as hearts and kidneys, or even exclusions for tissues
(such as distal ileum) that have been shown to be infective for TSE's
in experimental studies.
The agency has carefully considered the various exclusions
suggested by the comments and has revised Sec. 589.2000(a)(1) to define
``protein derived from mammalian tissue'' as any protein-containing
portion of mammalian animals, excluding blood and blood products,
gelatin, inspected and processed meat products which have been cooked
and offered for human consumption and further heat processed for feed
(such as plate waste and used cellulosic food casings), milk products,
and products whose only mammalian protein consists entirely of porcine
or equine protein.
FDA excluded these items from the definition because the agency
believes that they represent a minimal risk of transmitting TSE's to
ruminants through feed. The excluded proteins and other items are
materials that the available data suggests do not transmit the TSE
agent, or have been inspected by the FSIS or an equivalent State agency
at one time and cooked and offered for human food and further heat
processed for feed and thus are of lower risk than those products that
the agency has determined to be nonGRAS, or current industry practices
can provide assurances that certain mammalian products can be produced
without becoming commingled with potentially infective materials.
Additional information on specific exemptions appears later in this
document.
The agency did not revise the definition to exclude nonproteins or
items that are not considered tissues. Such products, for example,
tallow, fats, oils, grease, amino acids, and dicalcium phosphate as a
byproduct of the gelatin manufacturing process, are not covered under
this rule and thus do not require a specific exclusion. Moreover,
infectivity studies conducted on some of these products (e.g., tallow)
have demonstrated that they are at low risk of transmitting the TSE
agent. As for those comments suggesting exclusions for specific organs
or tissues, FDA declines to exempt such organs or tissues either
because of their demonstrated infectivity or because they have not been
sufficiently studied to confirm that they cannot transmit TSE disease
to ruminants or may present a higher risk of transmitting a TSE to
ruminants or because current industry practice does not support
separation of these organs or tissues from other higher-risk organs or
tissues. For example, under current industry practices, separation of
muscle meat from potentially infective nervous tissue from spinal cords
or nerve tissue connected to spinal cords cannot be assured. In
addition, FDA notes that the origin of these materials is not easily
determined when they arrive at a rendering facility.
The agency may revise the rule further to add or delete items from
the
[[Page 30939]]
list of exclusions and make necessary corresponding changes to the rule
when sufficient scientific information becomes available about the
ability of those items to transmit TSE disease.
2. Scientific Issues
Numerous comments raised scientific issues regarding BSE, nv-CJD,
and the need for additional scientific research.
a. Causes of BSE.
(Comment 2). Several comments stated that BSE is unlikely to occur
spontaneously in an individual animal.
Although the theory that TSE's occur spontaneously as well as the
other theories as to BSE's origins (see 62 FR 552 at 558 and 559) are
not proven, FDA has not discounted any theory. The final rule would
prevent the establishment and amplification of BSE in ruminants through
feed by prohibiting the use of proteins derived from mammalian tissue
in ruminant feed regardless of whether BSE may occur spontaneously or
enter the United States through imported animals or animal products or
may result from a cross-species or intra-species transmission of a TSE
agent.
(Comment 3). Many comments claimed that scrapie in sheep was the
cause of BSE in the United Kingdom.
FDA agrees that the use of sheep with scrapie which were rendered
and fed to cattle as meat and bone meal is a possible cause of BSE in
the United Kingdom. This final rule prevents sheep materials from being
processed and fed back to cattle and other ruminants. Additionally,
some comments stated that the adoption by industry of voluntary
measures to avoid rendering of fallen sheep and the sale of sheep
proteins to ruminants should provide sufficient safeguards to allow
sheep to be excluded from the final rule. FDA disagrees with this
statement because sheep are known to have a TSE (scrapie) that has a
long incubation period and because of information from an FDA survey
conducted in 1992 that clearly showed that a voluntary ban was not
fully implemented and that sheep that had died of causes other than
slaughter were being rendered and that rendered sheep protein was being
sold for use in the manufacture of cattle feed. This survey is
discussed in the preamble to the proposed rule (62 FR 552 to 582).
(Comment 4). Several comments argued that, in the United Kingdom,
BSE was spread by ruminant-to-ruminant recycling.
FDA agrees that, in the United Kingdom, BSE was spread by the
practice of feeding ingredients from processed BSE-infected cattle to
other cattle, including young calves. The processes that were used did
not completely inactivate the BSE agent. This final rule prevents
ruminant-to-ruminant recycling.
(Comment 5). Several comments pointed out that the cause of BSE is
unknown.
Even though the exact nature of the cause of BSE and many aspects
of its etiology and pathogenesis are unknown, studies indicate that the
feeding of BSE-infected material to cattle spread the disease to
uninfected animals. The final rule is intended to prevent the
establishment and amplification of BSE in the United States through
feed even though many details regarding the BSE agent are unknown.
b. Epidemiology of BSE.
(Comment 6). Numerous comments expressed concern that transmissible
mink encephalopathy (TME) resulted from mink being fed materials
derived primarily from downer cattle. These comments suggested that
this possible link between cattle and TME may indirectly indicate that
BSE is already present in the United States cattle population.
The exact cause of these TME outbreaks, the most recent occurring
in 1985, has not been proven, but FDA agrees that there is a
possibility that the theory is correct. The final rule, however, would
prevent cattle-to-cattle transmission of any undetected BSE in the
United States as well as the transmission of TSE's from mink to cattle.
(Comment 7). Several comments claimed that BSE is present in pigs
in the United States.
Based on the available evidence, FDA does not believe that BSE is
present in pigs in the United States. A naturally-occurring TSE has not
been identified in pigs in the United States or elsewhere in the world.
FDA is aware that, in a study conducted in the United Kingdom, 1 out of
10 pigs appeared to develop TSE lesions after exposure to BSE (Ref. 1),
but this infection occurred through intracerebral, intraperitoneal, and
intravenous inoculation rather than under natural conditions (such as
feeding). Despite these new inoculations, the other nine pigs did not
develop a TSE. In another experiment, newborn pigs fed the BSE agent
have remained healthy at 72 months of age (Ref. 2).
(Comment 7a). One comment claimed that a TSE was observed in U.S.
pigs in 1979.
The cause of the clinical signs and lesions cannot be affirmed or
completely refuted. FDA notes that it has been over 17 years since the
incident was reported and that there have been no reports of a
recurrence. From FDA's evaluation of this comment, the agency notes
that the condition caused by salt toxicity/water deprivation, produces
similar clinical signs and lesions as those reported in the 1979
incident.
(Comment 8). Many comments pointed out that TSE's already exist in
animals in the United States. These comments usually referred to TSE's
in sheep, goats, elk, mink, and deer.
FDA agrees that TSE's already exist in some animals in the United
States and identified several such TSE's in the preamble to the
proposed rule (see 62 FR 552 at 556 and 557 (describing scrapie, TME,
and chronic wasting disease (CWD))). By prohibiting the use of proteins
derived from mammalian tissues in ruminant feed, the final rule should
prevent the transmission of these diseases to ruminants through feed.
(Comment 9). Several comments cited feline spongiform
encephalopathy (FSE) as an example of the BSE agent's ability to cross
species barriers.
The epidemiology of FSE supports this theory, but the risk of BSE
crossing species barriers is present only in a country where BSE
exists. The United States has no BSE, and the final rule provides the
necessary feed controls to limit the risk of BSE crossing species
barriers and infecting U.S. cattle and other ruminants through feed
uses of protein products from infected animals should BSE occur here
(i.e., a preventive barrier to the establishment and amplification of
BSE through feed).
(Comment 10). Some comments argued that TSE diseases may occur in
all animals, and prions have been identified in species as diverse as
salmon and fruit flies.
Prions are proteins and are normal constituents of many living
organisms ranging from yeast to mammals. The function of prions are
unknown. Under one theory, the TSE or BSE agent is an abnormal,
infectious protein that changes a normal ``host'' protein or prion in
an animal or organism into the causative agent (see 62 FR 552 at 558).
At this time, a naturally occurring TSE has not been identified in all
animals. For example, although horses, pigs, poultry, salmon, and fruit
flies have prions, they are not known to have naturally-occurring
TSE's.
(Comment 11). Several comments discussed the possibility of BSE
being present in the feces of poultry that consumed cattle meat and
bone meal in their diets. These comments expressed concern that the BSE
agent would spread to cattle which might consume poultry litter in
their feed or to plants to which poultry litter was applied as a
fertilizer.
[[Page 30940]]
FDA is unaware of any research on this issue that would indicate
that the agency should take regulatory action on poultry litter at this
time.
c. Transmission of BSE.
(Comment 12). Many comments addressed the safety of various tissues
(such as blood, bone, and muscle) relative to TSE diseases. For
example, some comments asserted that ruminant blood will not transmit
TSE whereas others claimed that blood presents some risk of
infectivity. Other comments asserted that bone and muscle are safe, but
that brain, spinal cord, and eyes are high-risk tissues for TSE. Some
comments claimed that oral transmission of TSE is very inefficient.
The research to date on TSE diseases and the infectivity of various
tissues from infected animals consists of 2 types. The first consists
of extensive research carried out over a long period of time in sheep,
using sheep as the model for evaluating scrapie and other TSE diseases.
This research has provided valuable information about the nature of the
diseases in animals and comparatively little on the infectivity of
tissues. The second consists of recent studies that have been carried
out in other animals using agents such as BSE in cattle and TSE's in
mice. Many of the tissue infectivity studies for scrapie and BSE have
been carried out using several different strains of laboratory mice
which have various degrees of natural susceptibility to TSE's. Samples
of tissues taken from TSE infected animals are inoculated into the
brain of these laboratory animals. The assessment of the infectivity of
tissues has been based on the outcome of these studies. The results of
this research indicate that blood, bone, certain other tissues, and
tallow do not transmit TSE to the experimentally exposed mice whereas
samples of brain, spinal cord, eyes, and some areas of the intestinal
tract from cattle that died of BSE transmit a TSE to the mice.
FDA agrees with the comments regarding the comparative infectivity
of oral versus intracerebral routes of exposure and the estimate that
the oral route might be as much as 100,000 times less infective than by
injection (Ref. 3). However, at this time, research has not provided
adequate data on the level of infectivity from oral transmission.
(Comment 13). Other comments pointed to the unproven nature of the
rodent bioassay for safety evaluation of various animal tissues. The
comments stated that the TSE agent may be in other tissues at amounts
below the detection limit of the rodent bioassay. The comments asserted
that, if the lowest infectious dose of BSE is very small, undetected
small amounts of agent in tissues could theoretically transmit TSE to a
new host.
FDA agrees that the infective dose of TSE agents is small and that
bioassays have limitations. The results of these assays cannot
presently be confirmed by more traditional chemical or microbiological
methods. Therefore, while small undetected amounts of the TSE agent
could be present in the tissue, at this time, the agency believes these
amounts present a minimal risk.
(Comment 14). Several comments discussed recent information
describing maternal transmission of BSE. These comments stated that
maternal transmission is at a very low rate and would not maintain the
epidemic in the United Kingdom. Other comments claimed that lateral
transmission (from one animal to another in the same herd) is not
detected in BSE, whereas some comments stated that BSE crosses species
barriers.
FDA acknowledges these characteristics of BSE, and the preamble to
the proposed rule identified possible maternal transmission and BSE's
ability to cross species barriers as being among the various factors
justifying FDA's regulation of proteins intended for use in ruminant
feed in order to prevent the establishment and amplification of BSE in
the United States through feed (see 62 FR 552 at 559 and 560). While it
may be true that the risk of maternal transmission is very low and will
not sustain a significant epidemic as discussed in the preamble to the
proposed rule, the possible use of infected protein from mammalian
tissues in cattle feed may lead to establishment and amplification of
BSE in the United States through feed. Thus, the final rule ensures
that, whatever the mode of transmission, the TSE agent will stop with
the infected animal.
(Comment 15). One comment suggested that FSE-infected cats
transported to the United States from the United Kingdom could
introduce BSE into the United States if the carcasses of those cats
were permitted to be rendered into meat and bone meal.
The probability that such a scenario would occur appears to be
remote since fewer than 100 cats in the United Kingdom have been
diagnosed with FSE, and, therefore, the probability that an infected
cat would be transported to the United States is small. Furthermore,
relatively few domestic cats (those that are considered family pets)
are rendered upon their deaths. Rendering of cat carcasses is much more
common for feral or stray animals, but in the event that FSE-infected
tissues were rendered into meat and bone meal, the final rule prohibits
the use of proteins derived from mammalian tissues, including feline
tissues, in ruminant feed. Therefore, FSE-infected cats will not cause
BSE in the United States through feed.
(Comment 16). Two comments expressed the view that protein derived
from cats and zoo animals should be prohibited from use in feeds
intended for ruminants, cats, and zoo animals. This recommendation was
based on the fact that domestic cats and other members of the family,
Felidae, including zoologic specimens are susceptible to TSE.
The agency agrees that the concerns raised in the comments are
valid, and the final rule prohibits the use of feline and ruminant
protein in ruminant rations including the rations of ruminants
maintained in zoological exhibits. The final rule does not prohibit the
use of mammalian-derived protein in feeds intended for felids or
nonruminant zoo animals because the intent of the rule is to prevent
the establishment and amplification of BSE in the United States through
feed and thereby minimize risk to animals and humans. The feed use of
protein from felids and zoo animals in feed for cats and nonruminant
zoo animals should not present a risk of establishing and amplifying
BSE in the United States through feeds for ruminants.
d. New Variant Creutzfeldt-Jakob Disease (nv-CJD).
(Comment 17). Many comments expressed concern about the emergence
of nv-CJD in the United Kingdom and France and that it may have been
transmitted to humans through meat consumption. Some comments raised
concerns that nv-CJD might occur in the United States.
FDA shares this concern about nv-CJD and, in conjunction with the
Centers for Disease Control and Prevention, is monitoring it closely.
As stated in the preamble to the proposed rule, the epidemiological
studies conducted in the United Kingdom do not directly link nv-CJD to
meat consumption, but suggest that the nv-CJD cases are linked to
exposure to BSE before the introduction of specified tissue bans in the
United Kingdom in 1989 (62 FR 552 at 561). In October 1996, a study
using strain typing techniques for TSE's compared nv-CJD's strain
characteristics against BSE transmitted to mice and macaques. The
results showed nv-CJD's strain characteristics to be consistent with
BSE as the source of nv-CJD. This study, which appeared in the October
24, 1996, issue of Nature (Ref. 4), provided a suggested link between
BSE
[[Page 30941]]
and nv-CJD, but was not direct proof of such a link.
The Centers for Disease Control and Prevention completed a survey
in 1996 of cases of CJD in the United States and found no cases that
fit the characteristics of nv-CJD. Additionally, most meat products
consumed by humans are subject to USDA's jurisdiction, and USDA is
examining this issue to identify any risk and ways to minimize the
risks, if any, to consumers.
e. Research needs for BSE.
(Comment 18). Numerous comments expressed concern about the lack of
adequate published research on TSE diseases, inactivation of the
agents, and public health implications. For example, some comments
noted the lack of information about the minimum infective dose for BSE
while others expressed a need to develop a process to inactivate or
eliminate the BSE agent during rendering or to develop specific and
sensitive analytical methods for animal feeds that would detect
rendered proteins from various species.
FDA agrees, as discussed in the preamble to the proposed rule, that
many scientific issues related to TSE's remain unresolved. The agency
encourages research that addresses these needs, specifically (but not
limited to): Determination of minimum infective oral dose for
establishment of BSE in cattle; development and validation of a process
to inactivate or eliminate the BSE agent during rendering; development
of specific and sensitive analytical methods for the detection of
rendered proteins from various species in animal feeds; development of
a highly sensitive bioassay for determination of the TSE agent presence
in animal tissues; and development of specific antemortem tests to
detect the presence of TSE agents and diseases in animals.
f. New scientific information.
Several recently published articles on TSE's, BSE, and nv-CJD are
not referenced in the proposed rule. In brief, the most relevant of
these scientific publications are listed in the references in section
IX of this document.
In one article, the physicochemical properties of the BSE and nv-
CJD molecules were characterized to identify strain variations with nv-
CJD (Ref. 4). It was found that nv-CJD is distinct from other types of
CJD and resembles BSE transmitted to mice, cats, and macaque, which is
consistent with BSE being the source of nv-CJD.
In another article, the authors used mathematical models to make
assumptions about the incubation period for nv-CJD and the number of
exposed people (Ref. 5). Based on these assumptions, they outlined a
range of scenarios to estimate the future incidence of nv-CJD in the
United Kingdom. A large measure of uncertainty surrounds any modeling
that is based on 14 cases of nv-CJD and a lack of reliable information
about the incubation period for nv-CJD.
The results of USDA's examination of 5,427 cattle brains were
discussed in a recent article (Ref. 6).
Another article discussed the detection of scrapie in peripheral
nerves of scrapie-diseased sheep and concluded that mutton of scrapie-
diseased animals should not be regarded as being free of the scrapie
agent (Ref. 7).
Prion protein was not detected by Western blot analysis in 55
percent of mice inoculated intra-cerebrally with BSE, although it was
detected in 100 percent in subsequent passages (Ref. 8).
The hypothesis that BSE is a zoonosis was described and the risk
characterized as low (Ref. 9).
TSE's, including clinical signs, gross and microscopic lesions, and
ancillary test findings, in wild deer and elk in north-central Colorado
from 1981 to 1995 were described (Ref. 10). The disease in wild cervids
is indistinguishable from that reported in captive deer and elk.
The articles do not provide entirely new information, but rather
add to the basic knowledge about TSE's and the need for this final
rule. FDA has placed these articles in the administrative record for
the final rule.
3. Enforcement-Related Issues
A number of comments addressed issues related to enforcement of the
rule.
(Comment 19). Several comments stated that the proposed rule would
be enforceable. However, several others argued that the rule would not
be enforceable. The latter comments gave several reasons for their
position, including the following: (1) There is no practical analytical
test to distinguish ruminant protein from nonruminant protein.
Enforcement, therefore, would depend on compliance with the rule's
labeling and recordkeeping requirements which could be vulnerable to
falsification or other abuse; (2) the rule's reliance on invoices may
be inadequate because invoices may not contain sufficient information
and may not be kept routinely; and (3) the clean-out procedures for
firms that intend to separate ruminant from nonruminant protein (as
provided by the proposed rule) would not be readily enforceable.
Several comments recommended that the agency adopt a mammalian-to-
ruminant prohibition because a practical analytical test (feed
microscopy) for distinguishing mammalian from nonmammalian proteins is
available.
When the agency issued the proposed rule, it acknowledged that the
mammalian-to-ruminant alternative might be more easily enforced than
the ruminant-to-ruminant prohibition in the proposed rule. However, the
agency intended to commit the resources necessary to enforce the
ruminant-to-ruminant option if adopted. The agency believed that the
rule which it proposed could be enforced. For example, the
establishments that would not separate ruminant from nonruminant
protein would be subject to the simple, enforceable requirement that
labeling for all outgoing products bear the statement cautioning
against use of the product in ruminant feed. The agency estimated that
the great majority of affected establishments--independent renderers,
blenders, and feedmills--would elect not to separate products. Those
that did separate products would be subject to additional scrutiny,
such as on-site inspection that would include inspection of incoming
product as well as observation of facilities and processes for
separation. In addition, the agency has had experience in enforcing the
act in other settings in which it was unable to test for violative
products.
Limiting the mammalian species exclusion to pure porcine or equine
products narrows the number of acceptable mammalian protein sources for
ruminant feeds, thus simplifying the agency's records review and trace
back efforts. The fact that some comments from regulated industries
suggested support for a mammalian-to-ruminant prohibition should foster
voluntary compliance.
(Comment 20). Several comments stated that the role of the States
in enforcing the rule is unclear, but that State agencies lack the
authority to enforce some aspects of the rule. Some comments also asked
whether the rule imposed an unfunded mandate upon States.
Because this regulation is a Federal rule, only those State
employees that are commissioned by FDA under section 702(a) of the act
(21 U.S.C. 372(a)) would have a role in enforcing this rule. For
commissioned State employees that have the same enforcement authority
as FDA employees, such employees would be able to fully enforce the
rule. State employees who are not commissioned do not have authority to
enforce this rule. Comments about unfunded mandates imposed on States
are discussed elsewhere in this document.
[[Page 30942]]
(Comment 21). Several comments suggested additional approaches to
enhance the rule's enforceability. One comment suggested that the
agency allow firms to substitute commercial contract guarantees (that
the product does not contain ruminant material) instead of maintaining
and providing sales invoices. The guarantees would be available for FDA
inspection and copying. The comment asserted that use of such a
guarantee would provide assurance that meat and bone meal containing
ruminant or mink protein would not be inadvertently accepted for
delivery at commercial feedmills.
FDA agrees that such a provision could enhance enforcement, through
both self-regulation within the industry and enforcement of the act
which makes the giving of a false guarantee a violation of section
301(h) of the act (21 U.S.C. 331(h)). However, it is unclear from the
comments whether the commercial contract guarantees would provide
adequate information for FDA to trace back purchases of protein
products and feeds. Therefore, it is unclear whether the guarantees
would enhance enforcement. In any event, the final rule, as written,
provides the necessary tools for enforcement. Therefore, the agency
declines to accept the comment's suggestion.
(Comment 22). One comment suggested that the agency revise the rule
to require renderers to register with FDA.
Through the use of publicly available sources (such as trade
publications), the agency has access to a comprehensive list of
renderers, so a registration requirement is, at this time, unnecessary.
(Comment 23). One comment asked FDA to clarify the penalties that
would be associated with a violation of the rule. Other comments asked
the agency to discuss the consequences of a violation of the regulation
and whether a person must knowingly have committed a violation.
The agency notes that it intends to implement a vigorous
enforcement program. Although FDA cannot specify the penalty that would
be imposed in any given scenario or case, the agency does note that the
act provides several possible sanctions, including, but not limited to,
injunctions (see section 302 of the act (21 U.S.C. 332)), criminal
penalties (see section 303 of the act (21 U.S.C. 333)) and seizure of
the adulterated or misbranded product (see section 304 of the act (21
U.S.C. 334)). Seizure and injunction actions generally do not require
knowledge on the part of responsible persons, and criminal violations
may or may not require such knowledge.
(Comment 24). Some comments asked about the disposition of
adulterated feed, animals that have been fed adulterated feed, and
products, such as milk, from animals that were fed adulterated feed.
The agency has guidance documents for the disposition of products
found to be violative under the act (see for example CPG 675.200). This
guidance can be used to facilitate the disposition of products
determined to be violative as a result of this final rule.
Alternatively, the agency can consider the disposition based upon the
unique factors of the situation.
(Comment 25). One comment expressed concern about the adequacy of
FDA's enforcement resources, stating a need for more frequent
inspections of regulated firms such as feedmills. Another comment
stated that an ``unlevel playing field'' would exist in the animal feed
industry such that FDA would devote more regulatory attention to a
relatively small number of registered (as opposed to unregistered)
feedmills.
FDA reiterates its intention to commit adequate resources to
enforcing this rule and to implement a vigorous enforcement program.
FDA will allocate those resources in such a way that all segments of
the industry receive attention commensurate with the risk presented by
a violation in each segment.
(Comment 26). Several comments expressed the expectation that a
mammalian-to-ruminant prohibition, if adopted by the agency, would also
simplify the requirements placed on the affected industries. For
example, the comments stated that, under a mammalian-to-ruminant
prohibition, no special labeling would be required and that
recordkeeping could be simplified.
Because the mammalian-to-ruminant prohibition in this final rule
includes certain exceptions, the labeling and recordkeeping
requirements are necessary, and the agency has retained them (with some
revisions) in the final rule.
(Comment 27). Several comments implied that certain options, other
than a ruminant-to-ruminant or mammalian-to-ruminant prohibition, would
be enforceable. These options included a partial ruminant-to-ruminant
prohibition, a prohibition only of proteins from TSE species, and a
plan for ``certified ruminant derived protein'' based on a hazard
analysis critical control point (HACCP) program approach. Some comments
also stated that the ruminant-to-ruminant prohibition would be
unenforceable.
As stated earlier, the final rule adopts a mammalian-to-ruminant
prohibition with certain exceptions. The agency agrees that there are
alternatives to a ruminant-to-ruminant or a mammalian-to-ruminant
prohibition. Each alternative, including a ruminant-to-ruminant or a
mammalian-to-ruminant prohibition, presents various enforcement
challenges. FDA believes, however, that the final rule is a reasonable
approach in terms of enforcement.
(Comment 28). One comment, from a cattle producers' organization,
referred to that organization's commitment (along with many others) to
ensure enforcement of the final rule. The organization pledged that it
would work diligently to inform producers of their role in enforcement.
Several other comments advocated use of educational programs, including
education to consumers, and guidelines.
The agency appreciates the comment's commitment and intends to work
closely with industry associations in educational efforts. The agency
also expects to implement an educational program for consumers and the
affected industries and will provide guidance documents to the affected
industries.
4. Comments on the Alternatives
a. Background.
The preamble to the proposed rule listed 6 regulatory alternatives
to prevent the establishment and amplification of BSE in the United
States through feed (62 FR 552 at 567). The alternatives ranged from a
prohibition on the use of mammalian tissue in ruminant feed to a ``no
action'' alternative. FDA received comments supporting and opposing
each alternative, as well as numerous comments that suggested new
alternatives.
The principal alternative was a prohibition on the use of ruminant
proteins in ruminant feed; this was the alternative initially selected
by the agency and used in the proposed rule. Comments on the
``ruminant-to-ruminant'' prohibition are addressed later in this
document. The other alternatives and the comments submitted on those
alternatives are described below.
b. The partial ruminant-to-ruminant prohibition.
The second alternative was to exclude all ruminant and mink
materials, except those that have not been found to present a risk of
transmitting TSE's, from ruminant feed. This was commonly known as the
``partial
[[Page 30943]]
ruminant-to-ruminant'' ban. The exclusions, in addition to milk
products, gelatin, and bovine blood, might have covered products such
as bovine byproducts that have been inspected and passed in inspected
slaughter facilities (except for the brain, eyes, spinal cord, and
distal ileum because these tissues have been shown to transmit TSE's).
This alternative had the advantage of having its prohibitions based
primarily on scientific information related to the infectivity of
specific tissues, yet it also had several important disadvantages. For
example it may be impractical in the slaughter and rendering processes
to segregate and to exclude the protein tissues that have not been
found to present a risk of transmitting TSE disease. USDA expressed
reservations that separating the distal ileum from other intestinal
offal could jeopardize a slaughter plant's ability to meet pathogen
reduction goals required by USDA's HACCP regulations. (The ``ileum'' is
the terminal part of the small intestine, from the free edge of the
ileocecal fold to the ileocecal orifice, and enters the junction of the
cecum and colon obliquely on the medial surface. ``Offal'' refers
generally to material left as a byproduct from the preparation of some
specific product, less valuable portions and the byproducts of
milling.) Enforcement would also be impractical because there is no
specific diagnostic method for identifying protein derived from such
tissues. Additionally, the alternative would not address the risk that
other tissues may present a risk of infectivity (62 FR 552 at 567 and
568).
(Comment 29). Several comments supported this alternative, although
most would modify it to cover only some tissues (such as tissues that
are known to be infective in sheep, cattle, or other species),
conditioned their support on the addition of other requirements (such
as a HACCP program and good manufacturing practices (GMP's)), or
conditioned their support on the feasibility of enforcing this
alternative. A smaller number of comments opposed this alternative;
most reiterated the arguments set forth in the preamble to the proposed
rule by stating that there is inadequate scientific information to
determine whether a particular tissue is or is not safe for use in
ruminant feed, that separating certain tissues may be unsafe or
impractical, and that the absence of a test to detect the TSE agent
warrants rejection of this alternative.
The agency agrees with those comments that oppose a partial
ruminant-to-ruminant prohibition. The agency is persuaded that under
current industry practice, separating acceptable ruminant tissues from
unacceptable ruminant tissue may be impractical, and the current lack
of scientific knowledge about the TSE agent and BSE, coupled with the
lack of a detection method, makes this alternative less acceptable
compared to a mammalian-to-ruminant prohibition which is more
enforceable and also endorsed by the most affected industries.
(Comment 30). Two comments raised the concern that the stunning of
cattle at slaughter by captive bolt results in the formation of brain
emboli which lodge in tissues that are normally considered to be
incapable of transmitting TSE diseases. If protein derived from those
tissues was permitted for use in ruminant rations, it potentially could
transmit TSE diseases to ruminant animals. For this reason, it was
argued that a partial ruminant-to-ruminant prohibition may fail to
prevent the introduction and amplification of BSE in the United States.
The probability of introducing BSE into the United States from the
small amount of nervous tissue that would be expected to result from
brain emboli is minimal under a partial ruminant-to-ruminant
prohibition; however, the final rule eliminates even this minimal
probability because it provides that all mammalian tissues (with
certain exceptions) are prohibited from use in ruminant rations.
c. The mammalian-to-ruminant prohibition.
The third alternative was to prohibit the use of all mammalian
protein in ruminant feed (``mammalian-to-ruminant'' prohibition). The
preamble to the proposed rule noted that some rendering and feed
associations supported this alternative because separating ruminant
from nonruminant materials or proteins might not be feasible due to the
routine industry practice of commingling protein products (62 FR 552 at
568). The preamble to the proposed rule also noted that this
alternative would provide greater assurance of industry compliance than
a partial or total ruminant-to-ruminant prohibition because practical
analytical methods exist for distinguishing mammalian from nonmammalian
proteins and that this alternative would not require additional or new
labeling. Furthermore, the preamble to the proposed rule stated that
this alternative would avoid concerns about permitting some products
containing meat and bone meal to be used in ruminant feeds while
prohibiting others and the effect on financially sensitive commodities
markets for animal protein.
The disadvantages to a mammalian-to-ruminant prohibition included
the absence of scientific data establishing or suggesting TSE
infectivity in nonruminant animals (other than in cats or mink) and
claims from some industries that they would prefer or had the ability
to separate ruminant from nonruminant tissues.
(Comment 31). The mammalian-to-ruminant alternative received the
most support among the alternatives to a ruminant-to-ruminant
prohibition discussed in the preamble to the proposed rule. These
comments came from the affected industries (although most would prefer
alternatives to this rulemaking), consumer groups, other government
agencies (including a foreign government), and academia. Most comments
supporting this alternative explained that it would provide the same or
more protection than the proposed rule, would be both practical and
enforceable, would give greater assurance of industry compliance, and
would be consistent with international initiatives. However, some
comments acknowledged that the current scientific evidence provides
more support for a specified tissue prohibition or ruminant-to-ruminant
prohibition rather than a mammalian-to-ruminant prohibition.
FDA has revised the rule to prohibit the use of protein derived
from mammalian (rather than ruminant) tissues, with certain exclusions.
Numerous comments from the rendering and feed industries advocated a
mammalian-to-ruminant prohibition. These industries indicated that a
mammalian-to-ruminant prohibition would result in easier and greater
compliance (because the usual industry practice is to commingle
ruminant and nonruminant material rather than separate ruminant from
nonruminant material) and provide a higher degree of confidence in the
feed or feed ingredients produced and sold. Given this practice of
commingling tissues, the possibility of cross-contamination of
nonruminant mammalian tissues through contact with ruminant tissues,
and reasons explained elsewhere in this document, FDA has determined
that protein derived from mammalian tissues (as defined in the rule) is
not GRAS for use in ruminant feed and has revised the final rule
accordingly. The agency recognizes that, under current industry
practices, pigs and horses may be slaughtered at dedicated slaughtering
facilities which produce either pure porcine or pure equine material.
The exclusion of equine material in addition to porcine material in the
final rule is a change from the proposed codified
[[Page 30944]]
material. This change was made in response to comments (see comment 44
response) that for mammals which are considered to be major food
animals, neither porcine nor equine species have ever been diagnosed
with a naturally occurring TSE. For porcine and equine materials,
persons may continue to self determine whether their use in ruminant
feed is GRAS.
FDA also considered various exclusions to the rule. These
exclusions are discussed elsewhere in this document.
(Comment 32). Several comments offered alternatives to a mammalian-
to-ruminant prohibition, such as the exclusion of sheep under 12 months
of age and cattle under 30 months of age. The comments claimed that
animals in these age groups seldom exhibit clinical signs of TSE.
FDA declines to revise the rule as suggested by the comments.
Because of the long incubation period for TSE's, an infected animal may
not exhibit any clinical signs. Scrapie has been detected in 7-month-
old sheep (discussed fully in the preamble to the proposed rule) and
results of a BSE maternal transmission study conducted in the United
Kingdom suggest that the risk of maternal transmission is approximately
10 percent for BSE infected cows. Additionally, there is little
specific knowledge about the infectivity of tissues and organs during
this period.
d. The prohibition of materials from U.S. species diagnosed with
TSE's.
The fourth alternative was to prohibit the use of materials from
species in which TSE's have been diagnosed in the United States (sheep,
goats, mink, deer, and elk) in ruminant feed. The preamble to the
proposed rule noted that this alternative would eliminate the scrapie
agent, TME, and CWD from ruminant feed, and thereby reduce the risk of
BSE in cattle by TSE transmission from other animal species (62 FR 552
at 568). However, it also noted that this alternative would not prevent
the spread of BSE in the United States if BSE occurred for another
reason, such as spontaneous mutation in cattle or the importation of
animals infected with BSE (when such imported animals are subsequently
processed and used in ruminant feed).
(Comment 33). FDA received several comments supporting this
alternative and a smaller number opposing it. The comments supporting
this alternative stated that it was the most prudent and pragmatic
alternative and is supported by current scientific evidence. Comments
opposed to this alternative stated that it would not prevent
amplification of BSE, would not exclude cattle (because no U.S. cattle
have been diagnosed as having BSE or a TSE), and would make it more
difficult to exclude potentially infective tissues from ruminant feed.
One comment questioned whether this alternative would extend to
prohibiting any feed materials to any animal, including nonruminants.
After considering the comments, FDA declines to adopt this
alternative. As stated in the preamble to the proposed rule and
elsewhere throughout this document, the rule is intended to prevent the
establishment and amplification of BSE in the United States through
feed. This alternative would restrict some, but not all, routes for the
BSE agent to enter ruminant feed. Consequently, FDA is not adopting
this alternative.
e. The sheep-specified offal prohibition.
The fifth alternative was to prohibit the feeding of specified
sheep and goat offal to ruminants. This alternative would eliminate
scrapie from ruminant feed, but would not prevent the spread of BSE
among cattle if BSE occurred spontaneously or entered the United States
(62 FR 552 at 568 and 569).
(Comment 34). Very few comments addressed this alternative. Two
comments supported this alternative, stating that no TSE's have been
found in the United States or that this alternative would remove much
unsafe protein from ruminant feed.
Three comments opposed this alternative. One comment stated that,
if BSE is already present in the United States, this alternative would
not prevent it from spreading to other cattle. Another comment
expressed similar views, but added that the long incubation period for
TSE's and the infectivity of tissues from preclinical or asymptomatic
animals increased the risk of BSE amplification. Another comment stated
that this alternative had limited effectiveness because it did not
protect against other known TSE's in other species.
The agency agrees with those comments opposing this alternative.
Although it would remove scrapie from ruminant feed, this alternative
would be ineffective against BSE and other TSE's. As a result, FDA is
not adopting this alternative.
f. The ``no action'' alternative.
The sixth alternative was to take no action. The preamble to the
proposed rule explained that this alternative is arguably supported by
the fact that data and information do not document a recognized
immediate threat to the public health in the United States and that any
threat may be minimal. Other arguments supporting this alternative
included: (1) BSE has not been detected in the United States; (2)
surveillance efforts are in place and have not detected BSE; and (3)
there is no empirical evidence available to establish that BSE will be
transmitted to cattle from another species, will occur spontaneously in
cattle, or will be transmitted from imported animals or animal feed (62
FR 552 at 553). The preamble to the proposed rule further noted that:
There is no conclusive scientific evidence that BSE would be spread
through animal feed (although there is strong epidemiological evidence
suggesting that widespread BSE infections in the United Kingdom
occurred through contaminated animal feed and that enforced feed
control regulations appear to be the reason for BSE's decline in the
United Kingdom); the industrial practices in the United Kingdom
believed to be associated with the BSE epidemic in the United Kingdom
differ from those in the United States; transfer of TSE's from sheep to
cattle is suggested by epidemiological evidence, but has not been
confirmed by direct scientific data; and while there is an
epidemiological association between BSE and the nv-CJD cases in the
United Kingdom, the available evidence has not established that BSE
causes nv-CJD.
Arguments against a ``no action'' alternative focused on the
potentially high cost, in animal and human lives and economics, if BSE
appeared in the United States and was transmitted and amplified through
the feeding of ruminant protein to cattle. The preamble to the proposed
rule noted that TSE transmission from other species, spontaneous
occurrence, and transmission from imported animals or animal products
was possible. Experimental evidence also indicated that the BSE agent
may be more susceptible to oral transmission (such as through animal
feed) than other TSE's, thereby increasing the chances that BSE could
spread through the United States whether or not the BSE agent developed
spontaneously, was transmitted by another species, or was introduced by
some other means. Yet the greatest risk factor identified in the
preamble to the proposed rule was the potential for unrecognized
amplification of the BSE agent given the long incubation period for BSE
and the absence of methods for detecting the agent (62 FR 552 at 555).
(Comment 35). Very few comments expressly addressed the ``no
action'' alternative. One comment, without any explanation, supported
the no action alternative, while another comment claimed that the
proposed rule was essentially a ``no action'' alternative
[[Page 30945]]
because it would permit the use of tallow and fat in ruminant feed, and
the comment opposed the use of tallow. Six comments opposed this
alternative, declaring that the Federal Government must act to protect
animal and human health and food safety now, that TSE's are known to
exist in the United States, and that if TSE's exist in cattle, steps
need to be taken to prevent amplification. Other comments opposing a
``no action'' alternative claimed that an undiagnosed TSE may already
exist in the United States cattle population (arguing that TME may have
originated as an undiagnosed TSE in cattle that was transferred to mink
through contaminated feed), that this alternative would not protect
against asymptomatic animals infected with a TSE, and that this
alternative is not acceptable for purposes of international trade
(because other countries will reject U.S. products if they cannot be
assured that the products are not infected with BSE or a TSE).
FDA agrees with the comments that oppose a ``no action''
alternative. The most appropriate course of action is to take steps to
prevent the establishment and amplification of BSE in the United States
through feed before BSE is manifested in the United States. FDA will,
as it does for all regulations, amend or modify its regulations to
reflect any advances in scientific or industry technology, but the
potential consequences to human and animal health are simply too great
to justify a ``no action'' alternative at this time.
5. Miscellaneous Alternatives Suggested by the Comments
Many comments suggested other regulatory approaches, ranging from
more comprehensive prohibitions on the use of animal proteins in feed
to less restrictive alternatives that would focus solely on sheep or
cattle or certain types of cattle. Other comments suggested
alternatives to the nonGRAS status (e.g., issuing a compliance policy
guide (CPG), an interim food additive regulation, a GRAS listing with
restrictions, temporary ban to suspend the use of ruminant protein in
ruminant feed, and HACCP programs). The discussion of these
alternatives and the agency's response appears in section I.B.1.b of
this document, comments 56 through 60. Few comments offered any
detailed rationale or explanation supporting their alternatives.
a. Alternatives involving ``downer'' animals.
(Comment 36). FDA received hundreds of comments (in response to
write-in campaigns) requesting that ``downer'' (nonambulatory) animals
not be used for human food and not processed as ingredients in animal
feed. Few comments offered any detailed rationale (scientific or
otherwise) for their request, although some comments suggested that
downed animals may be unable to walk because they have a TSE agent or
suffer from some central nervous system (CNS) disease.
FDA declines to revise the rule as suggested by the comments. The
final rule is limited to the use of proteins derived from mammalian
tissues in ruminant feed. The rule is intended to prevent the
establishment and amplification of BSE in the United States through
feed. Because BSE has never been detected in the United States, the
agency believes that the actions it has taken in this final rule will
accomplish this regulatory objective.
FDA notes that issues involving downer animals actually have two
components: (1) Animals that are ``down'' and are condemned on
antemortem examination, such as those with clinical signs of CNS
disorders; and (2) animals that are ``down'' but which are passed as
``suspects'' pending post-mortem examination, such as those with broken
legs, mastitis, paralysis, etc. This final rule will prevent any downed
(including CNS-condemned) ruminants from being used in ruminant feed.
This final rule does not address issues related to nonruminant feed
uses. The agency does not have any information that such uses for
nonruminants at this time, present a risk of TSE infection to
ruminants. The use of carcasses of downer animals and the offal of
animals that are slaughtered as suspect for a CNS disorder in the
manufacture of meat and bone meal for use in swine, poultry, and pet
rations presents no known risk to humans. The risk to nonruminants
other than ruminants appears to be limited to felids and mink and is
considered to be extremely small.
Additionally, revising the rule to prohibit the use of all downers
in nonruminant feeds would create significant environmental and
economic problems. Issues further related to use of meat and poultry
for human consumption are outside the scope of this rulemaking since
they are regulated by USDA.
b. Alternatives covering other animals.
(Comment 37). Several comments advocated more inclusive
alternatives, such as prohibiting the use of animals or mammals in
mammalian feed, prohibiting the use of animal byproducts in feed for
all animals or all farm animals, or prohibiting the use, in any
livestock feed, of any potentially infectious tissue from any species
known to have a TSE. Few explained their reasons for such alternatives
other than to declare that a broader alternative would be more
protective, to argue that noncarnivorous animals should eat only
plants, or to argue that the practice of feeding animal protein to
animals was ``cannibalism'' or ``unnatural.''
In developing this rule, the agency sought to create regulatory
requirements that would prevent the establishment and amplification of
BSE in the United States through feed while simultaneously considering
the impact on the affected industries. The comments did not provide
sufficient information to determine that the alternatives suggested by
the comments would be equally or more effective in preventing the
establishment and amplification of BSE in the United States through
feed, and so FDA declines to revise the rule as suggested by the
comments.
(Comment 38). Several comments advocated less restrictive
alternatives to the rule, such as prohibiting cattle-derived protein
from being fed to other cattle, or to sheep and cattle, or to other
animals, prohibiting the use of sick and dying animals in human and
animal food, or prohibiting the use of spinal cords and heads in animal
feed.
FDA declines to revise the rule as suggested by the comments. These
less restrictive alternatives would not meet the agency's goals. The
comments did not offer any explanation as to how these alternatives
would prevent the establishment and amplification of BSE in the United
States through feed.
c. Alternatives covering other subjects.
(Comment 39). One comment requested that FDA revise the rule to
address all food hazards (rather than focus on BSE in ruminants),
prohibit the use of all meat protein supplements in all animal feed,
prohibit the use of antibiotics in food-producing animals, and
concentrate on possible causes of disease.
The agency declines to revise the rule as requested by the comment.
The comment does not explain how the suggested change would prevent BSE
from being established and amplified in the United States through feed.
The comment's requests appear to address issues which are outside the
scope of this rulemaking.
B. Comments on Specific Sections in the Proposed Rule
1. Section 589.2000(a)--Definitions
Proposed Sec. 589.2000(a) would define various terms, such as
``protein derived from ruminant and mink tissues,'' ``renderer,''
``blender,'' ``feed
[[Page 30946]]
manufacturer and distributor,'' and ``nonruminant protein.''
All comments addressing proposed Sec. 589.2000(a) focused on the
terms ``protein derived from ruminant and mink tissues.'' Proposed
Sec. 589.2000(a)(1) would define such proteins as ``any protein-
containing portion of ruminant animals or mink, excluding blood from
bovines, milk proteins and gelatin.''
As noted earlier in this document, the agency has revised
Sec. 589.2000(a)(1) to refer to protein derived from mammalian tissues
and has excluded specific items from that definition. In general, the
exclusions represent tissues that the available data suggests do not
transmit the TSE agent or were, at one time, inspected by FSIS and
found fit for human consumption and further heat processed for feed use
or tissues from species without TSE's that, under current industry
practice, are slaughtered in single species slaughter facilities.
Comments on specific tissues are as follows:
(Comment 40). Several comments would exclude plate waste (food that
has been inspected, prepared, and/or served to humans) from the rule.
Some comments explained that all food products which compose plate
waste have already been cooked and inspected several times before being
offered for human consumption and later thrown away and that commercial
processors of plate waste dehydrate the product at temperatures
reaching 290 to 400 deg.F when converting it to an animal feed
ingredient. The comments also asserted that the plate waste comes from
institutions (universities, retirement homes, hospitals, prisons,
etc.), fast-food establishments, and large restaurants/cafeterias, and
does not consist of tissues that have demonstrated infectivity in
cattle, e.g., brain, spinal column, eye and distal ileum of cattle.
Furthermore, some comments stated that plate waste consists mostly
(approximately 98 percent) of nonmeat products and is high in moisture.
The high moisture content requires the addition of 50 to 60 percent
corn, soybeans, or similar products to aid in the dehydration and the
extrusion process. The comments also noted that the feeding of plate
waste remains a common practice in many parts of the United States and
around the world and that plate waste comprises approximately 8.9
percent of the Municipal Solid Waste stream in the United States.
The draft codified provisions that appeared in the Federal Register
of April 17, 1997, included as an exclusion from the definition protein
derived from mammalian tissue, ``inspected and processed meat products
which have been cooked and offered for human consumption (plate waste
and used cellulosic food casings).'' The initial decision to exclude
plate waste was based on the fact that a small proportion of meat is
included in plate waste and that plate waste represents a small
proportion of ruminant feed. Additionally, the heat and pressure used
to process plate waste should further reduce the risk of transmitting
the TSE agent through feed in a product that is of minimal risk prior
to the processing as plate waste.
Several comments addressed the reference to ``plate waste,'' and
the majority of the comments supported the exclusion of plate waste
from the definition of ``protein derived from mammalian tissues.''
However, many of these comments also sought a broader exemption by
expanding the rule to include ruminant meat which had passed Federal or
state inspection for human consumption. In contrast, one comment, from
the USDA/APHIS, opposed an exclusion for plate waste, stating that the
exclusion was too broad and could be interpreted to be similar to the
USDA definition for garbage at 9 CFR 166.9 and that trimmings (bone and
nervous tissue) from TSE-susceptible species might be included under
the exclusion.
FDA agrees with the USDA/APHIS that the inclusion of trimmings or
high-risk tissue, such as brain and eyes, is inappropriate for use in
ruminant feed. FDA declines to expand the exclusion to include all
ruminant meat that has passed Federal or state inspection for human
consumption. FDA's approach to eliminating trimmings was to describe an
acceptable product as one which was ``cooked and offered for human
consumption.'' After further consideration FDA has revised the
definition of protein derived from mammalian tissues to exclude
``inspected meat products which have been cooked and offered for human
food and further heat processed for feed (plate waste and used
cellulosic food casings).'' This is to clarify that the high risk
tissues USDA/APHIS described in their comment are not covered by this
exclusion.
FDA declines to expand the exclusion to include all ruminant meat
that has passed Federal or state inspection for human consumption
because this would require FDA to remove the safeguard against
trimmings and also would allow brains and eyes which have passed
inspection to be fed to ruminants.
The agency acknowledges that accurately describing products which
are acceptable under this exclusion is difficult. In general, FDA
interprets this exclusion as being restricted to food prepared in
restaurants or restaurant-like establishments, offered to consumers for
consumption on the premises, and then discarded by the consumer.
Precooked food items, such as hot dogs, casings from cooked hot dogs,
and cooked deli items, would be excluded from regulation under this
rule by this exclusion. FDA has revised the definition to better
reflect its position that the product must be cooked, offered to the
consumer for human food, and then further heat processed before it can
be fed to animals.
The Association of American Feed Control Officials, Inc. (AAFCO) is
in the process of developing definitions for products described in this
section. In general, the ``plate waste'' exclusion is similar to the
AAFCO definition of ``restaurant waste.''
(Comment 41). A few comments questioned why meat and meat products
inspected by the USDA and found acceptable for human consumption are
not acceptable for ruminant consumption.
The risks posed to humans and those posed to animals are different.
The significant steps advanced by this rule are supported by public
health experts as an effective means to decrease the risk of TSE's in
ruminants through feed and the potential risk to humans. To date, the
occurrence of nv-CJD in Europe has not been definitively linked to
human consumption of meat, and no cases of nv-CJD have been detected in
the United States.
(Comment 42). One comment objected to the exclusion of gelatin and
blood from the definition of ``protein derived from ruminant and mink
tissues.'' The comment argued that gelatin and blood meal may be
infectious and that blood meal may not be used as a feed ingredient or
a fertilizer in the United Kingdom. The comment further noted that the
USDA prohibits the importation of ruminant protein and blood meal from
countries with documented BSE cases; the comment stated that if the
USDA prohibits such imports because they may be infective, then FDA
should not permit the use of domestic gelatin and blood meal.
The agency disagrees with the comment. As the agency discussed in
the preamble to the proposed rule (62 FR 552 at 572) available data
suggests that gelatin and blood do not transmit the TSE agent and USDA
surveillance has not detected BSE in the United States. However, to
minimize the risk of infected material being imported into
[[Page 30947]]
the United States, USDA has prohibited the importation of such
products.
(Comment 43). Several comments addressed the reduction in TSE titer
that results from the process that is used to make gelatin. Two
comments added that dicalcium phosphate, which is derived from the
gelatin manufacturing process, should be excluded from the rule; one
described the processes for obtaining dicalcium phosphate. Another
comment sought clarification whether amino acids derived from gelatin
would be exempt from the rule.
Amino acids and dicalcium phosphate are excluded from the final
rule because both products are by-products or the result of further
processing of gelatin and do not contain proteins. Dicalcium phosphate
is an inorganic mineral source that does not contain protein, and
individual amino acids are not proteins. (Instead, proteins consist of
amino acids.) Although the codified provision to the draft rule that
was published in the Federal Register of April 17, 1997, expressly
exempted amino acids and dicalcium phosphate derived from gelatin, and
one comment sought to revise that language regarding dicalcium
phosphate, the agency has reconsidered the need for this express
language and decided that, because amino acids and dicalcium phosphate
are not proteins, the express language is unnecessary.
(Comment 44). Several comments requested that FDA revise the rule
to exclude pure porcine (swine) products. These comments argued that
swine are not known to have TSE's and are often slaughtered in
dedicated swine slaughter facilities so that pure porcine products can
be easily separated from other mammalian products.
Other comments, submitted after the publication of the draft
codified provisions in the Federal Register of April 17, 1997,
suggested that FDA revise the rule to exclude pure equine products.
FSIS commented that the rationale for the change from a ruminant-to-
mink prohibition in the proposed rule to a mammalian prohibition, with
porcine exclusion, is insufficiently supported by scientific fact and
suggested that FDA consider an alternative to the draft final.
The agency agrees with the comments and has excluded products whose
only mammalian protein consists entirely of porcine or equine protein
from the definition of ``protein derived from mammalian tissues.'' This
exclusion is scientifically defensible because swine and horses have
not been shown or reported to have a condition that can be linked to a
TSE and can be accomplished within the current industry structure and
practice. Because most swine and horses are slaughtered in dedicated
facilities, and the ease of verifying compliance at the source, FDA has
excluded products containing pure porcine or pure equine protein from
the rule and, where appropriate, revised other provisions in the final
rule to reflect an exclusion for pure porcine or equine protein. FSIS
is in agreement with these changes.
(Comment 45). A few comments asked the agency to provide a
mechanism for exempting animals from flocks or herds that are
designated by a Federal agency to be absent from TSE's, such as the
USDA's Voluntary Scrapie Flock Certification Program.
The agency supports any initiative such as this which is designed
to reduce or eliminate a naturally occurring TSE. However, there
appears to be little assurance that the proteins derived from these
flocks or herds could be kept separate as pure single-species proteins,
and therefore, FDA declines to revise the rule as suggested by the
comments.
(Comment 46). Proposed Sec. 589.2000(a)(2) would define
``renderer,'' in part, as ``any firm or individual that processes
slaughter byproducts, animals unfit for human consumption, meat scraps
or food waste.''
The agency has removed ``food waste'' from the definition. This
change is necessary because, as explained above, the agency has
excluded plate waste from the definition of ``protein derived from
mammalian tissues.'' The agency does note, however, that it interprets
the term ``animals unfit for human consumption'' as including parts of
animals that are unfit for human consumption.
(Comment 47). Proposed Sec. 589.2000(a)(3) would define the term
``blender.''
The agency received no comments on this definition and has
finalized it without change.
(Comment 48). Proposed Sec. 589.2000(a)(4) would define ``feed
manufacturer and distributor'' as including manufacturers and
distributors of complete and intermediate feeds intended for animals,
including on-farm and off-farm feed manufacturing and mixing
operations.
FDA has revised the definition to separate ``feed manufacturer''
from ``distributor.'' The agency made this change to clarify that both
feed manufacturers and distributors are subject to the rule rather than
persons who perform both functions (manufacturing and distributing).
Thus, Sec. 589.2000(a)(4) defines ``feed manufacturer'' as including
manufacturers of complete and intermediate feeds intended for animals
and including on-farm in addition to off-farm feed manufacturing and
mixing operations. Section 589.2000(a)(6) defines ``distributor'' as
including persons who distribute or transport feeds or feed ingredients
intended for animals. The substance of these definitions are similar to
the definition in the draft codified provisions that appeared in the
Federal Register of April 17, 1997. The agency has also made
corresponding changes throughout the rule to clarify that feed
manufacturers are distinct from distributors and deleted the reference
to ``haulers'' from proposed Sec. 589.2000(e) because the definition of
``distributor'' includes persons who transport feed and feed
ingredients.
(Comment 49). Proposed Sec. 589.2000(a)(5) would define
``nonruminant protein'' as including protein from nonruminant animals
and vegetable sources.
The agency has revised Sec. 589.2000(a)(5) to define ``nonmammalian
protein'' as including protein from nonmammalian animals and vegetable
sources. This corresponds to the final rule's change to a mammalian-to-
ruminant prohibition.
(Comment 50). As stated earlier, FDA has revised the rule to create
a new Sec. 589.2000(a)(6) to define ``distributor.'' While the codified
provisions of the draft rule that appeared in the Federal Register of
April 17, 1997, initially defined ``distributor'' as including
distributors of complete and intermediate feeds intended for animals,
FDA, on its own initiative, has revised the definition further to
clarify that persons who transport feed or feed ingredients intended
for animals are distributors.
(Comment 51). The agency has also revised the rule to create a new
Sec. 589.2000(a)(7) to define ``ruminant'' as including ``any member of
the order of animals which has a stomach with four chambers (rumen,
reticulum, omasum, and abomasum) through which feed passes in
digestion. The order includes, but is not limited to, cattle, buffalo,
sheep, goats, deer, elk, and antelopes.'' FDA elected to define the
word ``ruminant'' because several comments noted that some people might
not know what animals are ``ruminants.''
2. Section 589.2000(b)--Food Additive Status
Proposed Sec. 589.2000(b) would state that protein derived from
ruminant and mink tissues is not generally recognized as safe for use
in ruminant feed because it may contain TSE's and is a food
[[Page 30948]]
additive subject to section 409 of the act (21 U.S.C. 348). Thus, under
the proposed rule, the use or intended use of any ruminant or mink-
derived protein in ruminant feed would cause the feed to be adulterated
and in violation of the act (unless it was the subject of an effective
notice of claimed investigational exemption for a food additive or was
the subject of a food additive regulation). Proposed Sec. 589.2000(b)
would also state that FDA has determined that ruminant and mink-derived
protein is not prior sanctioned for use in ruminant feeds.
a. NonGRAS status.
At the outset, FDA notes that no comments provided FDA with any
published studies, data, or other information or expert opinions upon
which FDA could conclude that the material is safe or that there is a
reasonable certainty that the material is not harmful under the
intended conditions of use. FDA received no scientifically valid
information, or expert opinion based on that information, that
addressed: (1) Whether it is reasonably certain that BSE does not, or
will not, occur in the United States; (2) whether the BSE agent can be
detected; (3) whether it is reasonably certain that the BSE agent will
not be transmitted to ruminants 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; or (4) whether it is
reasonably certain that the agent will not be transmitted to humans
through consumption of ruminant products. As discussed extensively in
the preamble to the proposed rule (see 62 FR 552 at 553 and 564) and
herein, these significant safety questions have been raised by credible
currently available information about the transmission of BSE and TSE's
to ruminants through feed. As a result of these questions, as provided
in this final rule, FDA has determined that protein derived from
mammalian tissues in ruminant feed is not GRAS.
(Comment 52). Many comments stated that ruminant protein had been
safely used as components of animal feed for 100 years as well as
before the enactment of the Food Additive Amendments of 1958. These
comments seemed to assert that ruminant protein for use in ruminant
feed is GRAS based on common use in food prior to 1958, and based on
this history of safe use, FDA cannot now declare it to be a food
additive.
FDA disagrees. As noted in the preamble to the proposed rule, if a
substance was used in food before 1958, general recognition that the
use of a feed ingredient is safe can be based on scientific procedures
or experience based on common use in food (see 62 FR 552 at 566;
section 201(s) of the act (21 U.S.C. 321(s)); and 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 procedures required for approval of a food
additive regulation, but it nonetheless requires a demonstration of:
(1) Safe use based on common use, and (2) an expert consensus of
safety, based on that common use (see 21 CFR 570.30). The simple
assertion of this safe use thus does not satisfy the burden the
proponents of the use bear to establish general recognition. Although
FDA agrees that, until recently, this material appears to have had a
long history of use without known adverse effects (see 62 FR 552 at
566), FDA has never affirmatively declared the material to be GRAS
based on common use in food.
Moreover, even if a substance is GRAS based on common use in food
or GRAS based on scientific procedures, FDA may reassess the GRAS
status of a food ingredient based on new information (see 21 CFR
530.30(g); see also, e.g., 51 FR 25021, July 9, 1986 (Sulfiting Agents;
Revocation of GRAS Status for Use on Fruits and Vegetables to be Served
or Sold Raw to Consumers)). Thus, even if ruminant protein for use in
ruminant feed were GRAS based on common use in feed prior to 1958, that
does not preclude FDA from reassessing it now that there exist new
studies, data, or other information that show that the substance is, or
may be, no longer safe (this is true whether the studies or data are
published or unpublished (see 50 FR 27294 at 27296 (July 2, 1985))) or
that there is no longer the basis for an expert consensus that it is
safe.
Expert opinion that the substance for use in ruminant feed is GRAS
would need to be supported by scientific literature, and other sources
of data and information. ``General recognition'' cannot be based on an
absence of studies that demonstrate that a substance is unsafe; there
must be studies or other information to establish that the substance is
safe (see U.S. v. An Article of Food * * * Coco Rico, 752 F.2d 11 (1st
Cir. 1985)). Furthermore, if there are studies and other data or
information that raise questions about the safety of the use of the
material, this conflict--just like a conflict in expert opinion--may
prevent general recognition of the substance.
As the agency explained in the preamble to the proposed rule,
research and other information have raised questions regarding the safe
use of protein derived from certain animal tissue in ruminant feeds.
The agency stated that ``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'' (see 62 FR 552 at
566).
Because the expert opinion must be ``general,'' a substance is not
GRAS if there is no recognition among experts, or there is a genuine
dispute among the experts, as to whether it is safe. Although there
need not be unanimity among qualified experts that a substance is safe
for ``general recognition'' of its safety to exist, an ``expert
consensus'' is required (see Weinberger v. Hynson, Wescott & Dunning,
Inc., 412 U.S. 606, 632 (1073)).
Accordingly, there must be no genuine difference of opinion among
qualified experts as to the substance's safety (see Coco Rico, 752 F.2d
at 15 n.6; United States v. Articles of Drug * * * 5,906 Boxes, 745
F.2d 105, 119 n.22 (1st Cir. 1984)). As the Court of Appeals for the
Second Circuit explained in Premo Pharmaceutical Laboratories, Inc. v.
United States, 629 F.2d 795, 803 (2d Cir. 1980), when there is a
dispute among experts as to ``general recognition,''
The * * * issue (of actual safety) is to be determined by the
FDA which, as distinguished from a court, possesses superior
expertise, usually of a complex scientific nature, for resolving
that issue.
See also 5,906 Boxes, 745 F.2d at 119 n.22; United States v. 50 Boxes *
* * Cafergot P-B Suppositories, 721 F.Supp. 1462, 1465 (D. Mass. 1989),
aff'd, 909 F.2d 24 (1st Cir. 1990); An Article of Drug * * * Furestrol
Vaginal Suppositories, 251 F.Supp. 1307 (N.D. Ga. 1968), aff'd, 415
F.2d 390 (5th Cir. 1969).
The World Health Organization (WHO), in an April 1996 consultation
on public health issues related to TSE, recommended that all countries
ban the use of ruminant tissues in ruminant feed. This recommendation
was intended to minimize the risk associated with exposure to BSE from
beef and beef products. The background for WHO recommendation pointed
out that the BSE epidemic in the United Kingdom appeared to have been
due mainly to the recycling of infected bovine material back to cattle.
In response to the agency's request in the preamble to the proposed
rule for comments on a ruminant-to-ruminant prohibition as well as
other alternatives including a full mammalian to ruminant
[[Page 30949]]
ban, no one submitted or cited published studies to support the
contention that the use of protein derived from ruminant tissue or from
mammalian tissue in ruminant feed is GRAS. Furthermore, no comments
refuted the agency's basis for determining protein derived from
ruminant tissue for use in ruminant feed to be nonGRAS as set out in
the preamble to the proposed rule. In addition, no one submitted or
cited published studies to support a finding that the use of mammalian
tissue in ruminant feed is GRAS either in response to the request for
comments on the alternative set out in the preamble to the proposed
rule or the request for comments on the draft rule, which included the
mammalian (with certain exclusions) to ruminant ban. FDA believes that
the same research and information set out in the proposed rule and the
industry practice of commingling mammalian, including ruminant and
mink, tissues, demonstrate that the use of protein derived from
mammalian tissues can no longer be categorically regarded as safe.
Therefore, this final rule provides that such protein for use in
ruminant feed is a food additive subject to section 409 of the act.
(Comment 53). Numerous comments appeared to argue that the agency
could not promulgate a rule declaring ruminant protein to be a food
additive when intended for ruminant feed because there is no BSE in the
United States.
Because these comments did not provide any legal or scientific
explanation to support this argument, it is unclear to FDA whether they
are arguing: (1) That FDA cannot rely on new information from foreign
sources to reassess the GRAS status of a food ingredient, or (2) that
FDA cannot take action until BSE actually occurs on United States soil.
Whichever argument is meant, FDA disagrees. First, the act does not
require evidence of actual harm to exist before a substance can be
declared to be not GRAS by FDA; all that is required is information--
which exists here--that the use of certain protein in ruminant feed may
not be safe or that there is no expert consensus that the use of the
substance is safe.
In addition, in response to comments that point out that there is
no evidence of BSE in the United States, FDA notes that nothing in the
act would support a blanket conclusion that FDA should only rely on
data generated or conditions present in the United States when making
this reassessment. Indeed, since, under the act, FDA must take into
account relevant evidence of foreign use when assessing a claim that a
food ingredient is GRAS based on common use in food prior to 1958 (see
Fmali Herb, Inc. v. Heckler, 715 F.2d 1385 (9th Cir. 1985)), FDA
believes it should likewise take relevant foreign data and expertise
into account when reassessing safety and general recognition. Here,
while there have been no reported cases of BSE in the United States,
other conditions exist that make the foreign experience relevant, such
as the fact that, in the United Kingdom, BSE was spread by the practice
of feeding ingredients from processed BSE-infected cattle to other
cattle, and the processes that were used failed to inactivate the BSE
agent.
Moreover, the act as a whole and the 1958 Food Additives Amendment
in particular were intended to give FDA the tools to prevent harm to
the public health before it occurs (see, e.g., United States v. Ewig
Bros Co., 502 F.2d 715, 721 & n.24 (7th Cir. 1974), cert. denied, 420
U.S. 945 (1975); see also S. Rep. No. 2422, 85th Cong., 2d Sess. 1-3
(1958); H.R. Rep. No. 2284, 85th Cong., 2d Sess. 1 (1958)). As a result
of the 1958 amendment, the burden of proof shifted to manufacturers,
and the 1958 amendment ``permit(s) FDA to regulate the use of
substances affecting foods without first determining that they are in
fact dangerous; the method is to require that such substances be
established as safe before being used'' (see Natick Paperboard Corp. v.
Weinberger, 525 F.2d 1103, 1106 (1st Cir. 1975), cert. denied, 429 U.S.
819 (1976); see also Ewig Bros., 502 F.2d at 721).
Thus, to claim that FDA cannot declare a substance to be a food
additive until it has actually done damage in the United States and FDA
can prove that actual harm has occurred would eviscerate the act. It
would be contrary to the public health if FDA could not use this
authority--based data and other relevant information from other
countries--to prevent harm from occurring through the use of certain
ingredients in feed.
FDA notes that section 801 of the act (21 U.S.C. 381), which gives
the agency the authority to prevent the import into the United States
of food that violate the act unless such items are intended for export
rather than domestic distribution, underscores the weakness of the
comments' arguments. If the act did not allow FDA to consider
conditions that exist in, or evidence from, other countries when
determining whether an article violates the provisions of the act, FDA
would not be able to implement section 801 of the act and keep
violative food from entering the country. Furthermore, if the comments'
interpretation of the act is correct--that FDA can only look at
conditions in this country--then FDA would not be able to declare
animal protein from other countries to be an unsafe food additive, even
if there had been cases of BSE reported in the country in which the
animal protein originated.
(Comment 54). Several comments argued that more research is needed
before FDA can take action and that the agency must establish that all
feed components affected by this rulemaking may transmit TSE's.
These comments misunderstand the structure of the food safety
provisions of the act. As noted above and in the preamble to the
proposed rule (62 FR 552 at 566), the act places the burden to
establish safety of a feed component on the proponent of the substance,
not on the government to prove actual harm. Research of the type
suggested by the comments could take years to complete. The agency
believes that it is neither required nor appropriate to delay
regulatory action to prevent transmission of BSE pending the completion
of research.
The information presented in the preamble to the proposed rule set
out the basis for the agency's nonGRAS determination for the use of
protein derived from ruminant and mink tissue in ruminant feed. As
discussed earlier in this preamble to the final rule, after evaluating
the issues and information presented in the comments on the proposal
and all other evidence, the agency has determined that a consensus does
not exist that the use of protein derived from mammalian tissues is
safe for use in ruminant feed. The agency finds that the potential
remains for ruminants to be exposed to TSE agents in ruminant feed.
When a ruminant is fed protein derived from mammalian tissues, TSE's
may be transmitted. Therefore, FDA concludes that the use of protein
derived from mammalian tissues in ruminant feed can no longer be
considered GRAS.
(Comment 55). The draft rule that appeared in the Federal Register
of April 17, 1997, revised Sec. 589.2000(b) to eliminate unnecessary
phrases that were included in proposed Sec. 589.2000(b). These phrases
were statements referring to FDA's determination that these proteins
are nonGRAS, the absence of a regulation providing for safe use, and
FDA's determination that these proteins are not prior sanctioned for
use in ruminant feeds. A small number of comments questioned why the
language was removed (because it did not alter the fact that proteins
derived from
[[Page 30950]]
mammalian tissues for use in ruminant feed are food additives subject
to section 409 of the act), and one comment asked FDA to restore the
nonGRAS language.
FDA eliminated the text described above from Sec. 589.2000(b)
because the language was unnecessary. These revisions are solely
editorial in nature and do not affect the substance of the agency's
rulemaking or its determination that protein derived from mammalian
tissues is not GRAS for use in ruminant feed and is not prior
sanctioned for use in ruminant feeds.
b. Alternatives to nonGRAS status and other legal comments.
Several comments advocated alternatives to declaring proteins
derived from ruminant tissues to be nonGRAS.
(Comment 56). Several comments suggested that FDA refrain from
issuing the rule and instead issue a CPG. Some comments stated that a
CPG could be used to determine that certain proteins are adulterants
when added to ruminant feed and that use of a CPG would meet FDA's goal
of increasing prevention of BSE. Some comments stated that a CPG would
prevent the loss of GRAS status for the protein products and claimed
that this loss will have serious ramifications, such as stigmatizing
the protein products, as well as affecting the companies' ability to
compete in the global market. One comment advocated the use of a CPG
because it would allow the agency additional time to do a reasoned
analysis of the scientific information before taking a final action.
Some comments stated that use of a CPG would allow the agency to
respond more quickly to scientific and technical changes than the use
of notice and comment rulemaking.
FDA disagrees with these comments. Contrary to the arguments
presented in the comments, FDA cannot use CPG's to impose any
requirement. CPG's are guidance documents issued by the agency. These
documents are not binding on the agency or any person. As the agency
explained in its ``Good Guidance Practice'' document published in the
Federal Register of February 27, 1997 (62 FR 8961), guidance documents
``represent the agency's current thinking on (a) subject'' and ``do not
themselves establish legally enforceable rights or responsibilities and
are not legally binding on the public or the agency.'' To issue a
binding prohibition, the agency must follow an appropriate rulemaking
procedure (see Community Nutrition Institute v. Young, 818 F.2d 943
(D.C. Cir. 1987)). Therefore, if the agency issues a CPG, it would not
be binding and, as such, would be an ineffective means of banning the
use of protein derived from certain tissues in ruminant feed.
Furthermore, a CPG that states that certain proteins used in ruminant
feed are adulterants under the act would require the agency, on a case-
by-case basis, to bring enforcement actions for violations of section
402(a)(1) or section 402(a)(2)(C) of the act. Again, the agency does
not believe this is an effective approach to preventing the
establishment and amplification of BSE through feed. The agency
believes it has made a reasoned analysis of the scientific information
available and based on this analysis, the agency is taking the approach
set out in this final rule.
(Comment 57). Several comments urged FDA to use an interim food
additive regulation rather than declare certain proteins for use in
ruminant feed are not GRAS. These comments explained that an interim
food additive regulation would prevent their products from being
stigmatized by a not GRAS determination. These comments also explained
that the interim food additive regulation would keep the administrative
record open to new evidence, permit FDA and the industry to react to
new research findings, and permit FDA to require the industry to
conduct planned research. Some comments cited the regulations in part
180 (21 CFR part 180) and the interim selenium rule as precedent for
FDA issuing an interim food additive regulation.
FDA disagrees with these comments. The regulations in part 180,
issued under section 409 of the act, apply to ``substances having a
history of use in food for human consumption or in food contact
surfaces'' (see Sec. 180.1(a)). The definition of ``food'' for the
subchapter (which includes part 180) includes ``human food, substances
migrating to food from food-contact articles, pet food, and animal
feed'' (see 21 CFR 170.3(m)). The language of Sec. 180.1, however, only
refers to human food and substances migrating to food from food contact
surfaces. The limiting language in Sec. 180.1 makes it clear that it
does not apply to pet food or animal feed. The agency recognizes that
Sec. 570.38(c)(2) (21 CFR 570.38(e)(2)), applicable to animal feeds,
provides that an interim food additive regulation may be issued. This
provision was carried over when the rules at part 121 (21 CFR part 121
(1976)), which addressed both human food and animal feed additives,
were reorganized to separate the human food and animal feed provisions.
Section 121.41 of FDA's regulations, which included the reference to
interim food additive regulations, was republished as Sec. 570.38. The
provisions governing promulgation of interim food additive regulations
at Sec. 121.4000 (now Sec. 180.1) were not republished in part 570 (21
CFR part 570) governing animal feed (41 FR 38618, September 10, 1976).
A decision to extend the use of interim food additive regulations to
animal feeds and the creation of a procedure for doing so would likely
require rulemaking under the Administrative Procedure Act (5 U.S.C. 501
et seq.)
Furthermore, even if this procedure were available to the agency
here, it would not prevent the stigma that the comments state is
created by the agency's determination that protein derived from certain
tissues for use in ruminant feed is not GRAS since the same
determination must be made to issue an interim food additive regulation
(see, e.g., 61 FR 7990 March 1, 1996) (interim food additive for
mannitol). Any determination by the agency that a substance is a food
additive is also a determination that the substance is not GRAS. This
is true regardless of whether the agency takes an action as in this
final rule or the agency issues an interim food additive regulation.
With regard to the interim rule on selenium cited by some comments
as an interim food additive regulation, the agency disagrees that the
interim rule on selenium is an interim food additive regulation like
those for human food issued under part 180. The selenium regulation at
21 CFR 573.920 was initially based on an approved food additive
petition submitted under section 409 of the act. The interim final rule
on selenium that appeared in the Federal Register of October 17, 1995
(60 FR 53702) was issued as an interim rule under the Administrative
Procedure Act (5 U.S.C. 501 et seq.), not as an interim food additive
regulation under section 409 of the act. The interim selenium rule
implements Pub. L. 103-354 regarding the allowable levels of selenium
in certain animal feeds. The rule is designated as an interim rule
because it was issued under an exception in the Administrative
Procedure Act (5 U.S.C. 553(b)(B)). This exception allows a final rule
to be issued without prior notice and public comment if use of the
procedures is impracticable, unnecessary, or contrary to the public
interest. As stated in the preamble to the selenium rule, the agency
determined that prior notice and public comment was unnecessary because
the rule merely repeated the terms of Pub. L. 103-354 (see 60 FR 53702
and 53703). As stated above, an interim food additive regulation would
be issued under section 409 of the act. Therefore, the interim selenium
rule is
[[Page 30951]]
not precedent for the agency to issue an interim food additive
regulation in this case.
(Comment 58). One comment stated that, instead of publishing a
regulation under part 589 (21 CFR part 589) which lists substances
prohibited in animal feed, the agency should do a GRAS listing with
restrictions similar to the action taken in the propylene glycol rule
that was published in the Federal Register of May 10, 1995 (60 FR
24808). The comment asserted that the GRAS listing (which is referred
to as a ``GRAS affirmation'') would reduce the possible taint from
listing the protein in part 589 as a prohibited substance. The comment
explained that the GRAS listing could limit the animal feed that could
contain the protein as it is listed in the proposed rule and include an
exemption for use of approved deactivation and detection methods. The
comment stated that the preamble to the rule should state the agency's
view that all uses excepted from GRAS status must be subject to a food
additive provision.
FDA does not agree with this comment. The action on propylene
glycol that the comment cites was a proposed rule that would exclude
from GRAS status propylene glycol used in or on cat food. The final
rule was published in the Federal Register of May 2, 1996 (61 FR
19542). The proposed rule cited by the comment, as well as the final
rule, included two provisions. One provision amended Sec. 582.1666 (21
CFR 582.1666), which sets out the GRAS status of propylene glycol, to
except its use in cat food. The second provision was a new
Sec. 589.1001 which lists propylene glycol in or on cat food as a
substance prohibited from use in animal food or feed. In this case, no
regulation exists that sets out a FDA determination of GRAS for protein
derived from certain tissues for use in animal feed. Therefore, there
is no GRAS regulation to amend as in the case with propylene glycol.
Furthermore, this final rule, like the propylene glycol regulation,
will list the substances as prohibited from use in animal feed in part
589.
The current regulations at Secs. 570.30 and 570.35 (21 CFR 570.30
and 570.35) describe the information necessary to determine a substance
as GRAS or to affirm GRAS status. The comment did not include or cite
any information that would provide a basis for the agency to determine
that the other feed uses of protein derived from certain tissues is
GRAS or to affirm it as GRAS. FDA notes, however, that the act does not
preclude manufacturers from making their own decisions on the GRAS
status of uses not covered by this final rule. If FDA disagrees with
this self-determination, FDA may take action, as it has done in this
final rule or by enforcement action, to end that self-determined GRAS
status (see FDA's proposed rule, Substances Generally Recognized as
Safe, published on April 17, 1997 (62 FR 18938), for proposed revisions
to the GRAS affirmation process.
(Comment 59). Several comments suggested that FDA adopt a
``temporary ban'' or a ``temporary moratorium'' to suspend the use of
the ruminant protein in ruminant feed. The comments claimed that such
temporary measures, unlike a formal rule, would be quickly modified or
rescinded based on new information. The comments also stated that FDA
should consider other alternative, yet ef | 
