552 Federal Register / Vol. 62, No. 2 / Friday, January 3, 1997 / Proposed Rules

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

21 CFR Part 589

[Docket No. 96N–0135]

RIN 0910–AA91

Substances Prohibited From Use in

Animal Food or Feed; Animal Proteins

Prohibited in Ruminant Feed

AGENCY: Food and Drug Administration,

HHS.

ACTION: Proposed rule.

SUMMARY: The Food and Drug

Administration (FDA) is proposing to

amend the regulations to provide that

animal protein derived from ruminant

and mink tissues is not generally

recognized as safe (GRAS) for use in

ruminant feed, and is a food additive

subject to certain provisions of the

Federal Food, Drug, and Cosmetic Act

(the act). The proposed regulations

would establish a flexible system of

controls, designed to ensure that

ruminant feed does not contain animal

protein derived from ruminant and

mink tissues in a manner that

encourages innovation. FDA is also

considering alternatives to this

proposed ruminant-to-ruminant

prohibition, and is requesting comment

on the relative merits and disadvantages

of the alternatives. FDA is proposing

this action because the feeding to

ruminants of protein derived from

potentially transmissible spongiform

encephalopathy (TSE)-infective tissues

may cause TSE in animals. TSE’s are

progressively degenerative central

nervous system (CNS) diseases of man

and animal that are fatal. Epidemiologic

evidence gathered in the United

Kingdom (U.K.) suggests an association

between an outbreak of a ruminant TSE,

specifically bovine spongiform

encephalopathy (BSE) and the feeding

to cattle of protein derived from sheep

infected with scrapie, another TSE.

Also, scientists have postulated that

there is an epidemiologic association

between BSE and a form of human TSE,

new variant Creutzfeldt-Jakob disease

(nv-CJD) reported recently in England.

BSE has not been diagnosed in the

United States. However, this proposed

rule is intended to prevent the

establishment and amplification of BSE

in cattle in the United States, and

thereby minimize any risk which might

be faced by animals and humans.

DATES: Written comments by February

18, 1997. FDA proposes that any final

rule that may issue based on this

proposal become effective 60 days after

the date of its publication in the Federal

Register.

Submit written comments on the

collection of information requirements

by February 18, 1997.

ADDRESSES: Submit written comments

to the Dockets Management Branch

(HFA–305), Food and Drug

Administration, 12420 Parklawn Dr.,

rm. 1–23, Rockville, MD 20857. Submit

written comments on the information

collection requirements to the Office of

Information and Regulatory Affairs,

Office of Management and Budget

(OMB), New Executive Office Bldg., 725

17th St. NW., rm. 10235, Washington,

DC 20503, ATTN: Desk Officer for FDA.

FOR FURTHER INFORMATION CONTACT:

Regarding Scientific and Industry

Issues:

George A. (Bert) Mitchell, Center for

Veterinary Medicine (HFV–1), Food

and Drug Administration, 7500

Standish Pl., Rockville, MD 20855,

301–594–1761.

Regarding Procedural and Regulatory

Issues:

Richard E. Geyer, Center for

Veterinary Medicine (HFV–201),

Food and Drug Administration,

7500 Standish Pl., Rockville, MD

20855, 301–594–1761.

SUPPLEMENTARY INFORMATION

Table of Contents

I. Summary

A. Introduction

B. GRAS Status of Ruminant and Mink

Tissues

C. The ‘‘No Action’’ Alternative

D. The Basis for the Agency’s Proposed

Action

1. General Discussion

2. Analysis of Risk Factors

a. The risk of BSE occurring in the United

States

b. The risk of amplification in the cattle

population

c. The risk of transmission to humans

E. Enforcement Provisions

F. Alternatives

II. Background

A. TSE’s

1. Scrapie

2. BSE

3. Other Animal TSE’s

4. TSE’s of Humans

a. CJD

b. nv-CJD

c. Gertsmann-Strausller-Scheinker (GSS)

syndrome

d. Kuru

e. Fatal familial insomnia (FFI)

5. Etiology

6. Pathogenesis

7. Transmission

8. Genetics

9. Diagnostics

10. Inactivation

B. The Association Between Scrapie and

BSE

C. The Association Between Animal TSE’s

and Human TSE’s

D. Infectivity of Specific Tissues

E. Potential Risk of TSE’s to the United

States

1. Overview

2. Comparison with the U.K. Conditions

F. Historical Efforts to Control TSE’s

1. U.S. Actions

a. FDA

b. USDA

c. Public Health Service

i. CDC

ii. National Institutes of Health (NIH)

iii. Other actions

2. International Actions

a. United Kingdom

b. WHO

c. OIE

d. European Community (EC)

3. Voluntary Measures by the U.S. Animal

Industries

a. Voluntary ban on rendering adult sheep

b. Voluntary ban on feeding ruminant

proteins to ruminants

G. Processing Animal Tissues for Feed

Ingredients

1. Current Rendering Practices

2. Assay Methodologies for Proteins

III. Statutory Provisions Regarding Food

Additives

A. GRAS Determination

B. Prior Sanction

C. Food Additive Status of Ruminant

Tissues

IV. Comments

V. Analysis of Alternatives

A. Overview

B. Ruminant-to-Ruminant Prohibition

C. Partial Ruminant-to-Ruminant

Prohibition

D. Mammal-to-Ruminant Prohibition

E. Prohibition of Materials from U.S.

Species diagnosed with TSE’s (sheep,

goats, mink, deer, and elk)

F. Sheep-Specified Offal Prohibition

G. No Action

VI. Description of the Proposed Rule

A. Introduction

1. Regulatory Alternatives

2. The Regulated Industry

3. Enforcement Consideration

B. Outline of the Proposed Regulation

VII. Specific Protein Sources

A. Milk Proteins

B. Gelatin Proteins

C. Blood Meal Proteins

D. Canine and Feline Derived Proteins

VIII. Environmental Impact

IX. Analysis of Impacts

A. The Need for Regulation

B. Benefits

1. Methodology

2. Reduced Risk to Public Health

3. Reduced Risk of Direct Livestock Losses

4. Costs of Future Regulation

5. Reduced Risk of Losses in Domestic

Sales and Exports

6. Total Losses Averted

7. Comparison of Alternatives

C. Industry Impacts

1. The Proposed Rule

2. Partial Ruminant-to-Ruminant

Prohibition

3. Mammalian-to-Ruminant Prohibition

4. Other Regulatory Alternatives
Federal Register / Vol. 62, No. 2 / Friday, January 3, 1997 / Proposed Rules 553

D. Small Business Impacts

E. Unfunded Mandates Analysis

X. The Paperwork Reduction Act of 1995

XI. Federalism

XII. References

XIII. Request for Comments

I. Summary

A. Introduction

In the Federal Register of May 14,

1996 (61 FR 24253), FDA published an

advance notice of proposed rulemaking

(ANPRM) that solicited information and

public comment on the issue of using

protein derived from ruminants (cattle,

sheep, goats, deer, and elk) in ruminant

feed. The agency requested information

and comment on a number of issues

because it was assessing whether to

prohibit the use of ruminant protein in

ruminant feed. BSE has not been

identified in the United States. The

agency issued an ANPRM because of its

concern about the possible adverse

effect on animal and human health if

TSE’s were to be spread through animal

feed. After reviewing the ANPRM

comments and other sources of

information, the agency is proposing to

prohibit the use of ruminant and mink

animal tissue in the feed of ruminants.

Because TSE has been found in U.S.

mink, the agency is also including mink

tissue in the proposed prohibition. The

agency is also considering alternatives

to the proposed ruminant-to-ruminant

prohibition, including the alternative of

taking no action.

B. GRAS Status of Ruminant and Mink

Tissues

The agency is proposing to declare

that protein derived from tissue from

ruminant animals and mink is not

GRAS, by qualified experts, for use in

ruminant feed and is therefore a ‘‘food

additive’’ under the law. As a result,

because neither a food additive

regulation nor an exemption is in effect

for ruminant and mink tissues intended

for feeding to ruminants, such tissues

would be deemed adulterated. Milk and

gelatin proteins derived from ruminants,

and blood from cattle are exempt from

the proposed prohibition. The proposed

rule does not apply to any nonprotein

animal tissues such as tallow or other

fats.

Expert opinion that the tissues are

GRAS would need to be supported by

scientific literature, and other sources of

data and information, establishing that

there is a reasonable certainty that the

material is not harmful under the

intended conditions of use. Expert

opinion would need to address topics

such as whether it is reasonably certain

that BSE does not, or will not, occur in

the United States; whether it is

reasonably certain that the BSE agent

will not be transmitted through animal

feed, i.e., that the processed tissues are

not infected by the agent, are

deactivated by the rendering process or

are not transmitted orally; and whether

it is reasonably certain that the agent

will not be transmitted to humans

through consumption of ruminant

products. ‘‘General recognition’’ cannot

be based on an absence of studies that

demonstrate that a substance is unsafe;

there must be studies to establish that

the substance is safe. Also, the burden

of establishing that substance is GRAS

is on the proponent of the substance.

See U.S. v. An Article of Food * * * Co

Co Rico, 752 F.2d 11 (1st Cir. 1985).

Although the ANPRM did not

specifically ask for opinion on the

GRAS issue, a number of comments

from scientific organizations and

individual scientists strongly suggest

that the comments would support the

view that ruminant and mink tissue is

not GRAS when fed to ruminants. Some

of these comments submitted data and

information that would support such

opinions. Only a few comments

included statements by scientists, or

scientific organizations, to the contrary.

Similarly, the opinions stated by

scientists who spoke during a 1996

symposium on TSE’s would, in general,

support the ‘‘nonGRAS’’ position. The

symposium, ‘‘Tissue Distribution,

Inactivation and Transmission of

Transmissible Spongiform

Encephalopathies,’’ was cosponsored by

FDA and USDA, and was held in

Riverdale, MD, on May 13 and 14, 1996.

FDA has searched for but has not

found sufficient literature or other

sources of data and information that

would, on balance, support expert

opinion that ruminant and mink protein

is GRAS as a ruminant feed additive.

Previous comments on the agency’s

proposal to prohibit the feeding of

specified sheep and goat offal (59 FR

44584, August 29, 1994) did not include

either written GRAS opinions from

qualified experts, or data and

information that would support such

opinions. The relevant data and

information, and lack thereof, are

discussed more fully in this section, and

in section II. of this document. See

Section III.A., of this document, for a

further explanation of ‘‘GRAS’’ and

‘‘food additive.’’

C. The ‘‘No Action’’ Alternative

Even when, as in this case, FDA has

taken steps leading to a tentative

determination that a substance added to

food is not GRAS, the agency is not

required to issue a proposal declaring

that the substance is not GRAS and is

a food additive subject to section 409 of

the act. Section 570.38 provides that the

agency may take such an action. The

agency considered the possibility of not

issuing a proposal with regard to the

feeding of ruminant and mink tissues to

ruminants.

The fact that the data and information

do not document an immediate threat to

the U.S. public health supports this ‘‘no

action’’ alternative. Moreover, certain of

the available data and information can

be used to support the view that the

threat, if any, is minimal.

The evidence suggesting that there is

no immediate threat is summarized as

follows. First, BSE has not been

detected in cattle in the United States

despite an extensive surveillance effort

that has been in place for several years.

Restrictions on the importation of cattle,

cattle products and feed ingredients

from BSE-affected countries are in place

to minimize the possibility of BSE

entering into the United States.

Surveillance, training of veterinary

practitioners and diagnosticians, and

other efforts are in place to detect any

occurrence of BSE quickly, and to

minimize its spread among the cattle

population. No empirical scientific

evidence is available to establish that

BSE will occur from any of the possible

sources, such as transmission from

another U.S. species in which TSE’s

have been diagnosed; spontaneous

occurrence in cattle; or importation of

live animals or animal feed products

carrying the BSE agent. For example,

transmission between any two species is

difficult to predict, based on available

data, because of variability in species

barriers (Ref. 1).

Second, even if BSE did develop in

the United States there is no conclusive

scientific evidence that the disease

would be spread through animal feed,

the product that provides FDA’s

jurisdictional nexis. Although there is

strong epidemiological evidence that the

feeding of processed tissue from sheep

containing scrapie to cattle caused the

widespread BSE infections in the

United Kingdom, many experts believe

that the chances that the United States

will have a BSE outbreak, similar to the

epidemic that took place in the United

Kingdom, are low. For example, most of

the industry practices and other

conditions believed to have been

associated with the BSE epidemic in the

United Kingdom do not exist in the

United States. Further, the U.K.

epidemiological evidence of transfer

from sheep to cattle has not been

confirmed by direct scientific data. This

has caused some to question the

assumption that the BSE originated from

scrapie (Ref. 1). Further, some
554 Federal Register / Vol. 62, No. 2 / Friday, January 3, 1997 / Proposed Rules

experimental information suggests that

the TSE’s in general are not readily

transferred by the oral route.

Experimentally, the oral route has been

suggested to be the least efficient means

of transmission for TSE’s (Ref. 1).

Third, the postulated connection

between BSE and CJD has not been

definitively established. Scientists have

theorized an association between BSE

and the recent appearance of nv–CJD in

the United Kingdom. While the

epidemiological association, both in

time and geography, of these two

diseases in the United Kingdom

provides suggestive evidence of an

association between the two, the

available evidence does not establish

causation. Although the BSE agent has

been transmitted to laboratory animals,

the species barrier between cattle and

humans may be higher than between

cattle and mice (Ref. 1). Epidemiological

evidence linking BSE with classical CJD

is even less supportive. Although CJD

occurs in the United States, nv–CJD has

not been reported in this country.

The FDA’s conclusion that there is no

immediate threat to the public health in

the United States is supported by a

statement from the World Health

Organization (WHO) that the ‘‘risk, if

any, of exposure to the BSE agent in

countries other than the U.K. is

considered lower than in the U.K.’’ (Ref.

2). A number of comments to the

ANPRM made a similar assertion,

urging that FDA’s regulatory decision be

made on the basis of scientific

information and contending that the

available information did not support

the contemplated action.

D. The Basis for the Agency’s Proposed

Action

1. General Discussion

Even though there is no immediate

threat to the U.S. public health and

some information that indicates that a

threat, if any, is minimal, after careful

consideration the agency has tentatively

concluded that regulatory action is

necessary to protect animal and human

health. The agency has reached that

tentative conclusion because there is a

growing body of data and information

that affirmatively raises public health

concerns.

The data and information raise

concern that BSE could occur in cattle

in the United States; and that if BSE

does appear in this country, the

causative agent could be transmitted

and amplified through the feeding of

processed ruminant protein to cattle,

and could result in an epidemic. The

agency believes that the high cost, in

animal and human lives and economics,

that could result if this scenario should

occur, justifies the preventive measure

reflected by the proposed regulation.

Although the agency expects some

continued voluntary reduction in the

feeding of ruminant and mink tissues to

ruminants, the reduction is not expected

to be extensive enough to obviate the

need for mandatory preventive

measures.

Statements from several prominent

public and animal health organizations

support this proposal to regulate the

feeding of ruminant tissues to ruminant

animals. For example, the Centers for

Disease Control and Prevention (CDC)

has urged the agency to adopt a

ruminant-to-ruminant feed prohibition

(Ref. 3), and USDA has recommended

the same action. Although WHO

considers the risk in countries such as

the United States to be minimal, that

organization has nevertheless called on

all countries to prohibit the use of

ruminant tissues in ruminant feed (Ref.

2).

A number of comments to the

ANPRM, including comments by several

consumer groups, supported regulatory

action by FDA. The Pharmaceutical

Research and Manufacturers of America

urged FDA to take all necessary steps to

prevent an outbreak of BSE, and to

prevent the potential spread of BSE

should a case occur in the United States.

One pharmaceutical firm emphasized

the importance of acknowledging public

perception, stating that a ruminant-toruminant prohibition would

‘‘significantly decrease the concern

regarding this perceived risk.’’ Another

pharmaceutical firm characterized the

risk as ‘‘small but real.’’ A group of

livestock producers, veterinary

associations and scientific organizations

cited the WHO recommendations to

support their call for a voluntary

ruminant-to-ruminant prohibition. The

group stated that such a prohibition

would ‘‘eliminate any risk, no matter

how remote [and would] totally prevent

BSE from ever occurring in the United

States.’’

The agency is concerned about the

public health issues raised but not

resolved by the available scientific

information. The fact that the causative

agent or agents for TSE’s have not been

clearly identified, and their

transmissibility has not been fully

characterized, adds to the concern.

However, certain information that is

well documented supports the agency’s

decision as well. TSE’s are 100-percent

fatal diseases that have been diagnosed

in humans and a number of animal

species. The diseases are progressively

degenerative CNS diseases that are

characterized by a relatively short

clinical course of neurological signs.

TSE’s have a prolonged incubation

period, i.e., 2 to 8 years in animals, and

scientific evidence supports the view

that TSE’s can be transmitted in the

preclinical stage. There is no practical

method to detect the presence of TSE’s

during the preclinical stage.

2. Analysis of Risk Factors

This section describes the evidence

that supports the agency’s tentative

conclusion. The evidence relates to the

risks that BSE could occur in cattle in

the United States; that the BSE agent or

other TSE agents could be amplified in

the cattle population by the feeding of

ruminant and mink tissues to cattle; and

that the agent could potentially be

transmitted to humans.

a. The risk of BSE occurring in the

United States. BSE has not been

diagnosed in the United States. FDA

does not have evidence to support the

theory that BSE already exists,

undiagnosed, in this country. However,

the agency does find plausible the

arguments of the theory that BSE could

develop in the United States from three

possible sources: Transmission of TSE’s

from other susceptible species,

spontaneous occurrence, and

importation in live animals or animal

products.

The evidence concerning

transmission from other species is

summarized as follows. TSE’s other

than BSE have been diagnosed in

animals in the United States. These

include scrapie in sheep and goats,

transmissible mink encephalopathy

(TME), and chronic wasting disease

(CWD) in deer and elk. Feline

spongiform encephalopathy (FSE) has

been diagnosed in cats in other

countries. In general, the TSE’s have

been shown to be naturally

transmissible within species and are

believed by some scientists to be

naturally transmissible (as distinguished

from experimentally transmissible), at

least to a limited extent, between

species. Consumption of meat and bone

meal (the predominant animal tissuecontaining product fed to animals)

which was produced under conditions

similar to the meat and bone meal

which was implicated in the U.K. BSE

epidemic, as well as the feeding of raw

bovine tissue, also appeared to cause

TSE in exotic cats and various zoo

animals. This implies that the species

barrier for BSE may be

uncharacteristically low. (See e.g., Refs.

3 and 4). In addition to the

epidemiological evidence relating to

TSE transmission from sheep to cattle in

the United Kingdom, there is limited

experimental evidence of transmission
Federal Register / Vol. 62, No. 2 / Friday, January 3, 1997 / Proposed Rules 555

of the BSE agent from cattle to sheep.

Many laboratory animal species have

also been experimentally infected

following the administration of tissues

from animals with TSE disease.

There is some evidence to support the

theory that BSE can occur

spontaneously in cattle. The leading

theory as to the causative agent, e.g.,

infectious protein or prion, inherently

suggests that the BSE could occur

spontaneously. Additional support

arises from the fact that 85 percent of

CJD cases are sporadic, and have no

familial or identifiable link as to their

cause. Recent surveillance information

from Northern Ireland and Switzerland

also supports the spontaneous theory. In

these countries, BSE has occurred in

cases in which no exposure to rendered

protein can be found, and there is no

evidence of BSE in the parental stock or

herd mates of affected animals (Ref. 5).

As described more fully in section

II.F.1.b. of this document, USDA–APHIS

has implemented import restrictions on

live animals and animal products from

BSE-affected countries. As a result of

the restrictions, the potential risk of BSE

occurring in this country as a result of

exposure from imported cattle and

imported animal protein products

appears to be small (Ref. 6). However,

the risk from foreign sources of BSE

introduction into the United States

cannot be dismissed entirely because

the USDA import restrictions are

unlikely to be 100 percent effective even

though no cases of BSE have been

diagnosed to date in the United States.

The USDA regulations are intended to

reduce or control risk, not completely

eliminate it. See e.g., 56 FR 63866,

December 6, 1991.

b. The risk of amplification in the

cattle population. Research has shown

that various animal tissues can transmit

BSE infectivity. There is also evidence

supporting the view that the agent could

be transmitted orally (e.g., through

animal feed). Although some

experimental evidence suggests that the

TSE’s in general are more readily

transmitted by means other that the oral

route, research also suggests that the

BSE agent is more susceptible to oral

transmission. In most cases (e.g., the

U.K. epidemic) the natural route of

exposure to TSE’s including BSE is

suspected to be oral. This belief is

supported by the dramatic decline in

BSE cases in the United Kingdom

following implementation of the

ruminant-to-ruminant feeding

prohibition. In the United Kingdom,

where more than 160,000 cases of BSE

have been diagnosed, a 1988 ban on the

feeding of ruminant-derived protein

supplements to other ruminants was

associated with a steady decrease in the

disease incidence starting in 1993. The

5-year period between the initiation of

the ruminant-to-ruminant ban and the

decline in the incidence of BSE is

consistent with the known incubation

period in cattle of 2 to 8 years. Further,

preliminary experimental data show

that the BSE agent can be transmitted

orally to cattle through feeding of

material from an infected cow (Ref. 3).

Thus, there is a chance that BSE could

be spread in animal feed if it developed

in the U.S. cattle population, whether

spontaneously, from another species or

by some other means.

The greatest risk factor for cattle may

not be the single occurrence of a BSE

case. Instead, the greatest risk may arise

from the potential, given the prolonged

incubation period, for unrecognized

amplification of BSE in the cattle

population, resulting in a potential for

greater animal exposure. The possibility

of risk from recycling ruminant tissues

is enhanced by the fact that current

rendering methods have not been

shown, and are not expected, to

completely deactivate the BSE agent,

and that practical tests are not available

for detecting either the BSE agent in

rendered material or the presence of

ruminant material in feed.

The preliminary experimental cow-tocow TSE transmission data previously

described occurred with as little as a

single dose (one-time exposure) of 1

gram of brain material from the infected

cow, indicating a low transmitting dose.

This means, among other things, that

FDA cannot determine the level of feed

ingredients from animals tissues, if any,

that is considered safe in ruminants.

c. The risk of transmission of humans.

Finally, there exists the theoretical

possibility of the transmission of a TSE

in animals, such as BSE, to humans.

CDC agrees that the link between BSE,

and TSE’s in humans, has not been fully

demonstrated. Some of the ANPRM

comments agreed. For example, one

pharmaceutical firm stated that the

evidence is not entirely conclusive.

Nevertheless, a body of epidemiological

and experimental evidence is

developing to support the postulated

association between BSE and nv–CJD.

This and other scientific evidence

developed more fully in section II leads

the agency to propose for comment the

prudent risk reduction regulatory action

that is incorporated in the proposed

rule.

E. Enforcement Provisions

The agency is issuing this proposed

rule within the context of

comprehensive government-wide efforts

to minimize the risks previously

described, and within the statutory

authority provided to the agency. The

proposed rule has two major

components. First, the agency proposes

to prohibit feeding animal materials

derived from ruminant and mink tissues

to ruminants, in the absence of a food

additive regulation or investigational

exemption. Thus, the prohibition would

ensure that tissues which could

contribute to a TSE epidemic by

spreading the causative agent rapidly

would not be allowed in ruminant feed.

The second component of the rule

provides for a system of controls to

ensure that the proposed rule would

achieve its intended purpose. These

provisions are necessary because

limited controls are in place, or

available, to prevent the spread of BSE

through animal feed in the United

States, should BSE occur. The proposed

regulation places two general

requirements on persons that

manufacture, blend, process and

distribute animal protein products, and

feeds made from such products. The

first requirement is to place cautionary

labeling on the protein and feed

products. The second is to provide FDA

with access to sales and purchase

invoices, for compliance purposes.

Firms that handle animal protein

products from both ruminant and

nonruminant sources, and that intend to

keep the two kinds of products separate,

would have certain additional

requirements. These requirements

would relate to the need for separate

facilities or cleanout procedures; the

need for standard operating procedures

(SOP’s); and in the case of renderers,

their source of nonruminant material.

Similar requirements would be placed

on firms that handle animal feed

containing animal protein products

from both ruminant and nonruminant

sources, and intend to keep the two

kinds of feed separate. Requirements

would be greater for the firms that

intend to separate the animal protein

products and feeds, because of the

greater risk these operations would

present for the possibility that ruminant

protein might be fed, inadvertently, to

ruminants.

However, the regulatory system

would be flexible, allowing the

regulated firms to innovate and choose

the most cost-effective means of

compliance. For example, some or all of

the regulatory requirements previously

described would not apply if any of the

following innovations were developed

and validated by FDA: Processing

methods that deactivate the agent that

causes BSE; test methods to detect the

presence of the agent; or methods of

marking or otherwise identifying the
556 Federal Register / Vol. 62, No. 2 / Friday, January 3, 1997 / Proposed Rules

material that contains ruminant protein.

Further, the agency will consider

modifying or revoking any final rule

that is published prohibiting the use of

ruminant and mink tissues in ruminant

feed, if scientific and technical advances

permit even greater flexibility than that

offered in the proposed regulation.

Conversely, the diagnosis of one or more

cases of BSE in the United States, or

new scientific findings, could lead to

stricter regulatory requirements.

F. Alternatives

The agency is soliciting comments on

several alternative means of minimizing

the risk of transmitting TSE’s in

ruminant feed, in addition to the

proposed ruminant-to-ruminant

prohibition. These alternatives include:

(1) A partial ruminant-to-ruminant

prohibition which would exclude all

ruminant and mink tissues from

ruminant feed except those bovine

tissues that have not been found to

present a risk of transmitting

spongiform encephalopathy. Possible

exclusions include slaughter byproducts

from cattle that have been inspected and

passed in inspected slaughter facilities,

except tissues that have been shown

through experimental trials and

bioassays to transmit spongiform

encephalopathy. Examples of the latter

might include the brain, eyes, spinal

cord and distal ileum. The agency

solicits comments on the scope of this

alternative;

(2) A prohibition on the feeding of all

mammalian tissues to ruminants;

(3) A prohibition on the feeding of

rendered material from those animal

species in which TSE’s have been

diagnosed in the United States (sheep,

goats, mink, elk, and deer);

(4) A prohibition on the feeding of

specified offal from adult sheep and

goats as proposed in 1994;

(5) Other alternative approaches that

meet the agency’s regulatory objectives

and that might be suggested in

comments to the proposed rule. The

agency may in any final rule issued

adopt such alternative approaches. Such

alternatives may be more or less

stringent than this proposal or may be

a combination of provisions from this

proposal and other alternatives. For

example, one such option might be a

proposal to exclude from the scope of

any regulation certain facilities that

apply specified risk-reduction measures

in addition to, or in place of, those

included in the regulation FDA is

proposing in this publication. Therefore,

the agency specifically requests

comments on other approaches that

would achieve the agency’s regulatory

objectives. Any proposed alternative

approaches should be explained in

detail, and their justification should be

well documented. To the extent

possible, please include information on

costs and benefits of the proposals; and

(6) The ‘‘no action’’ alternative as it

relates to this proposed rule. Again,

detailed explanation and welldocumented justification should be

presented.

The agency’s views on the advantages

and disadvantages of these options

appears in section V of this document.

The agency invites comments on the

relative merits and disadvantages of all

these alternative concepts.

FDA has estimated that the

annualized costs of the proposal,

comprised of both the direct compliance

costs and various indirect gains and

losses, would range from $21.4 to $48.2

million. The agency also estimated that

the annualized costs could range from

$45.0 to $56.5 million for the

mammalian-to-ruminant option; from

$28.5 to $37.3 million for the partial

ruminant-to-ruminant option; and

would total less than $10 million for

each of the remaining options. On the

other hand, if the agency chooses the

‘‘no action’’ option and a BSE epidemic

occurs, the above costs could be

expanded by a great magnitude.

Because the body of scientific

research related to TSE’s is growing

rapidly, the agency will place in the

Docket copies of relevant scientific

literature published after the agency

completes work on this proposal, and

before the agency completes work on

any final regulation. The agency will

add to the Docket, as appropriate, a brief

statement of its assessment of the

significance of the literature, and will

invite comments. However, substantive

changes from the proposed rule would

be made in accordance with the

discussions in the preceding paragraphs

and the Administrative Procedure Act.

II. Background

A. TSE’s

1. Scrapie

Scrapie is a slowly progressive,

transmissible disease of the CNS in

sheep and goats. Scrapie is

characterized by a prolonged incubation

period averaging 2 years, followed by a

clinical course of 2 to 6 months when

the animal exhibits sensory and motor

malfunction, hyperexcitability, and

death. The agent presumably moves

from infected to susceptible animals by

direct or indirect contact and enters

through the gastrointestinal tract.

Consequently, its spread appears to be

both vertical (mother to offspring in

utero) (Ref. 7) and horizontal (direct

contact) between sheep (Ref. 8). Early

signs of scrapie include subtle changes

in behavior or temperament which may

be followed by scratching and rubbing

against fixed objects. Other signs

include loss of coordination, weight loss

despite a good appetite, biting of feet

and limbs, tremor around head and

neck, and unusual walking habits (Ref.

9).

The scrapie agent is found in

lymphatic tissue (spleen, thymus, tonsil,

and lymph nodes) in sheep with

preclinical infections; however, in

clinically affected sheep, the agent is

identified in the intestines, nervous

tissues (brain and spinal cord), and

lymphatic tissues as determined by

experimental infectivity studies in a

susceptible animal model (Ref. 8). The

brain has been demonstrated to have the

highest level of infectivity of all tissues

(Ref. 10).

Scrapie is known to have existed in

Britain, Ireland, France, and Germany

for over 200 years. It has been observed

in the United States and Canada for

about 50 years. The first case of scrapie

in the United States was diagnosed in

Michigan in 1947. From 1947 through

January 1993, approximately 653 flocks

have been diagnosed with scrapie (Ref.

11). At the present time, there are 67

known scrapie-infected flocks (flocks

with sheep diagnosed with scrapie), and

there are 8 known scrapie-source flocks

(flocks to which scrapie-infected sheep

were traced) (Ref. 12). In the absence of

an antemortem diagnostic test, it is not

possible to establish with absolute

certainty that a flock is free of scrapie.

Moreover, lack of reporting, the long

incubation period, and open range

husbandry practices in the western

United States make it difficult to detect

classical clinical signs and completely

monitor scrapie in the United States.

2. BSE

BSE is a transmissible, slowly

progressive, degenerative disease of the

CNS of adult cattle. This disease has a

prolonged incubation period in cattle

following oral exposure (2 to 8 years)

and is always fatal. BSE is characterized

by abnormalities of behavior, sensation,

posture, and gait. These signs are

similar to those seen in sheep that are

infected with scrapie. BSE is associated

with spongiform lesions in the gray

matter neuropil of the brainstem and

neuronal vacuolization (Ref. 13). The

clinical signs usually begin with

changes in animal behavior, and may

include separation from the rest of the

herd while at pasture, disorientation, or

excessive licking of the nose or flanks

(Ref. 14). The most common history

given by the herdsman was nervousness
Federal Register / Vol. 62, No. 2 / Friday, January 3, 1997 / Proposed Rules 557

or altered behavior or temperament,

weakness associated with pelvic limb

ataxia, paresis, and loss of body weight

(Ref. 15). In some animals there are few

gross pathological changes at necropsy

associated with BSE other than the loss

of body weight. However, postmortem

histopathology of BSE distinguish it

from other neurological disorders (Refs.

16 and 17). Neither vertical nor

horizontal transmission has been

documented for BSE.

BSE was first recognized as a new

cattle disease by researchers at the

Central Veterinary Laboratory of the

British Ministry of Agriculture,

Fisheries, and Foods at Weybridge,

England in November 1986. As of

November 15, 1996, BSE had been

diagnosed in Great Britain in more than

165,000 head of cattle from more than

31,000 herds. Cases have been

confirmed in 59.2 percent of the dairy

herds and 15.3 percent of the beef herds

(Ref. 18). The BSE epidemic curve for

Great Britain peaked in January 1993

and is decreasing steadily,

concomitantly with changes in

rendering and feeding practices. BSE

has also been reported in native cattle

of Northern Ireland, Guernsey, Jersey,

Isle of Man, the Republic of Ireland,

Switzerland, France, and Portugal. BSE

has been confirmed in cattle exported

from Great Britain to Oman, the

Falkland Islands, Germany, Denmark,

Canada, and Italy.

There have been no cases of BSE in

cattle in the United States. There has

been one case of BSE in a cow imported

into Canada from Great Britain. That

cow was destroyed, along with its

herdmates and other nearby cattle

considered by animal health authorities

in Canada to have possibly been

exposed to the cow with BSE (Ref. 19).

3. Other Animal TSE’s

Other animals have TSE’s with typical

characteristics of long incubation,

neurological degeneration, and a 100-

percent death rate. These animals

include: Mink, elk and deer, zoo

ruminants, and exotic and domestic

cats.

TME is a mink disease with clinical

signs and brain lesions similar to those

of sheep infected with scrapie. TME is

a rare disease in the United States. Since

the disease was first recognized in 1947,

in Wisconsin, four additional outbreaks

have occurred in the United States. The

last outbreak occurred in 1985 and was

limited to a single mink ranch in

Wisconsin (Ref. 20).

CWD of deer and elk is characterized

by emaciation, changes in behavior and

excessive salivation, polydipsia, and

polyuria. The clinical course is from

several weeks to 8 months, and the

disease is invariably fatal (Ref. 20).

From 1967 to 1979, CWD was observed

in 53 captive mule deer in Colorado and

Wyoming. Clinical signs were seen in

adult deer and included behavioral

alterations, progressive weight loss and

death in 2 weeks to 8 months.

Consistent histopathologic change was

limited to the CNS and characterized by

widespread spongiform transformation

of the neuropil. The disease is a

specific, spontaneously occurring form

of spongiform encephalopathy (Ref. 21).

Topographic distribution and lesion

severity were most similar to those of

scrapie and BSE. The duration of the

clinical disease did not significantly

influence lesion distribution or severity

in either species (Ref. 22).

Scrapie-like encephalopathies have

been described in certain zoo

ruminants, i.e., a nyala, an Arabian

oryx, and a greater kudu. Clinical signs

included ataxia and loss of coordination

with a short, progressive clinical course.

Histopathological examination of the

brains revealed spongiform

encephalopathy characteristic of that

observed in scrapie and BSE (Refs. 23,

24, and 25). Strain typing of the agent

suggests that all of the cases are directly

related to BSE.

Seventy domestic cats in the United

Kingdom have developed FSE, a

spongiform encephalopathy that was

never previously reported. The cats all

had progressive, neurological disease

involving locomotor disturbances,

abnormal behavior and, in most cases,

altered sensory responses.

Histopathological examination of the

central nervous system revealed changes

pathognomonic of spongiform

encephalopathy; this included

widespread vacuolization of the gray

matter neuropil and neuronal perikarya

(Refs. 26 and 27). Infective tissue from

several of these cases, when injected

into mice, resulted in brain lesions with

a distribution and morphology that is

undistinguishable from the lesions

produced by BSE infective tissue

injected into mice.

4. TSE’s of Humans

The TSE’s of humans are divided into

specific clinical types, which may

appear similar histopathologically but

are either transmitted differently or

demonstrate different patterns of

distribution and prevalence.

a. CJD. CJD was first described in 1920

and 1921 when it was known as

‘‘spastic pseudosclerosis’’ or ‘‘subacute

spongiform encephalopathy’’ (Ref. 28).

The illness exists throughout the world

and is claimed to have a similar

prevalence in each of the countries

tested with an annual incidence of

approximately one case per million of

the population. Autopsies are

sometimes not performed on persons

who may have died of CJD and many

older people dying of a dementing

illness do not have autopsies performed.

There is an increased incidence among

Libyan Jews (26 cases per million) and

spatial or temporal clusters in areas of

Slovakia, Hungary, England, the United

States, and Chile. The average age of a

typical CJD victim is 56 years of age,

and only a few cases involving persons

between 4 and 29 years have been

reported prior to 1993. Between 4 and

15 percent of cases have a familial

connection with other cases. There is a

slightly higher incidence of CJD in

women compared to men. Clinical

prodromal symptoms start with changes

in sleeping and eating patterns, and

often include confusion, inappropriate

behavior, vague visual complaints and/

or ataxia. Those symptoms progress over

a few weeks to a clearly neurological

syndrome. A rapid onset of neurological

symptoms appears in 20 percent of

cases, most commonly myoclonic jerks

and dementia with loss of higher brain

function and behavioral abnormalities.

The disease progresses with continued

deterioration in cerebral and cerebellar

function, and the onset of seizures.

Ninety percent of the cases end in death

within 1 year of onset. Diagnosis is by

clinical assessment of patients and by

examination of electroencephalogram

patterns. Post mortem diagnosis is

currently carried out by histological

examination of cerebral tissue under the

light microscope, although this is not

always reliable. Research techniques

that have been used to demonstrate CJD

(and other TSE’s) include electron

microscopic examination of brain tissue

extracts for scrapie-associated fibrils

(SAF), immuno-staining of the tissue for

prion-protein (PrP) antigens, western

blotting of extracted PrP antigens and

the intracerebral injection of tissue

suspensions into test animals.

In some patients, the source of CJD

has been claimed to be an infection

transferred from other patients with the

condition. For example, in one case,

cerebral electrodes that had been

sterilized with alcohol and formalin

vapor after use in a patient with CJD,

were used in the brains of two young

epileptic patients, both of whom

contracted CJD after a short incubation.

The transfer of CJD by corneal

transplant in 1 patient, by cadaveric

dura mater grafts in several patients and

by pituitary-derived human growth

hormone injections in over 80 patients

has also been reported.
558 Federal Register / Vol. 62, No. 2 / Friday, January 3, 1997 / Proposed Rules

Only the medical procedures

described previously have been

conclusively linked to transmission.

The transmission of the disease from

animal sources has been suggested; see

further discussion in section II.C. of this

document.

b. nv–CJD. A previously undetected

new variant of CJD (nv–CJD) was

reported by British scientists at a

meeting of international experts

convened by WHO on April 2 and 3,

1996 (Ref. 29), and published 3 days

later (Ref. 30).

The major evidence for the existence

of nv–CJD is the recognition of a new

neuropathologic profile and the

unusually young ages of 10 U.K.

patients. Although all the cases had

evidence of the pathognomonic

spongiform changes characteristic of

classic CJD, and therefore were

appropriately classified as a form of

CJD, the clinical course of the disease

was atypical of classic CJD. The most

striking and consistent neuropathologic

feature of nv–CJD was the formation of

amyloid plaques surrounded by halos of

spongiform change. Plaques were

extensively distributed throughout the

cerebrum and cerebellum. Many of

these plaques resembled those in kuru

and were visible when examined by

routine staining methods.

The temporal cluster of cases of nv–

CJD in young patients (three were

teenagers, five were in their twenties,

and two were in their thirties at onset

of disease) is highly unusual. Five of the

eight deceased patients died before 30

years of age. (The expected annual

mortality rate for CJD in persons under

30 years of age is less than five per

billion.) The characteristic clinical

features of the nv–CJD cases were: (1) A

psychiatric presentation, (2) onset of a

progressive cerebellum syndrome with

ataxia within weeks or months of the

initial presentation, (3) memory

impairment with dementia in the late

stages, (4) myoclonus, and (5) the

absence of electroencephalographic

changes typical of classic CJD.

Review of the patients’ medical

histories and consideration of various

risk factors for CJD yielded no adequate

clues as to the cause of this disease. The

PrP genotype was determined for eight

cases. The researchers noted that all

genotypes were methionine

homozygotes at codon 129 of the PrP

gene. The research did not identify any

of the known mutations associated with

the inherited forms of CJD (Ref. 30).

Although scientists have stated that

exposure to the BSE agent prior to the

U.K. bans described in section II.F. of

this document is the most plausible

explanation for these findings, no clear

epidemiologic link to BSE was

identified. (See further discussion in

section II.C. of this document.) Another

potential explanation is exposure to TSE

agents from animals other than cattle.

Because the United Kingdom

reinstituted epidemiological

surveillance for CJD in 1990, increased

surveillance is still another potential

reason for the identification of this

cluster of 10 cases of nv–CJD.

c. Gertsmann-Strausller-Scheinker

(GSS) syndrome. GSS syndrome is an

autosomal dominant condition in about

50 percent of siblings of reference cases

(Ref. 28). The disease is similar to CJD

except that it has a more extended onset

and duration, a tendency towards

cerebellar ataxia as the initial

predominant neurological sign, and a

large number of amyloid plaques

present among the spongiform

encephalopathic changes of the brain.

The extensive distribution of amyloid

plaques in the patient’s brain is an

observation shared by GSS syndrome

and v–CJD. It has been transmitted to

monkeys and rodents by intracerebral

inoculation.

d. Kuru. Kuru is a condition of the

Fore people of the Okapa district of the

Eastern Highland in Papua New Guinea,

in which a practice of ritual cannibalism

of fellow tribesmen took place until

approximately 1956 (Ref. 28). This TSE

disease, which affected mainly adult

women and children of both sexes,

caused an annual disease specific

mortality of approximately 3 percent.

Most deaths of women in the tribe

occurred through this disease. Some

men who died from this disease were

thought to have contracted it when they

were young. Kuru may be transmitted

by eating infected tissue or through

open wounds. The brains of dead tribal

members were eaten by women and

children and the muscle tissue by men.

The cohort of children born since 1957

have not suffered from kuru at all.

Clinically the disease causes a

progressive cerebellar ataxia,

uncoordinated movements, neurological

weakness, palsies, and decay in brain

stem function. Most patients dying of

kuru are not demented, a major clinical

difference between kuru and CJD.

e. Fatal familial insomnia (FFI). FFI is

another inherited TSE-linked disease

(Ref. 31). FFI is characterized clinically

by untreatable progressive insomnia,

dysautonomia, and motor dysfunctions.

The disease often starts between 35 and

60 years of age and leads to death

within 7 to 32 months. FFI is

characterized pathologically by atrophy,

neuronal loss, and gliosis in the anterior

and dorsomedial nuclei of the thalamus

(Ref. 32). FFI has been successfully

transmitted to mice (Ref. 33), but not to

primates.

5. Etiology

The cause of TSE’s is controversial.

The TSE agent: (1) Is presumably

smaller than most viral particles and is

highly resistant to heat, ultraviolet light,

ionizing radiation, and common

disinfectants that normally inactivate

viruses or bacteria; (2) causes little

detectable immune or inflammatory

response in the host; and (3) has not

been observed microscopically.

Resistance of the TSE agent to

physical and chemical methods that

destroy nucleic acid have essentially

ruled out conventional microbiological

agents as the cause. Currently, the

infectious protein or prion theory is

favored. Other proposed causes are an

unconventional virus, consisting of

virus-coded protein and virus-specific

nucleic acid with unconventional

properties, and a ‘‘virino’’ consisting of

a core of nontranslated nucleic acid

associated with host cell proteins (Ref.

34). Proposed causes of TSE’s with less

supporting evidence are: (1)

Retroviruses (Ref. 35), (2) a spiroplasma

(Refs. 36 and 37), (3) organophosphates

(Ref. 38), and (4) peptide hormones (Ref.

39).

The prion theory suggests that the

causative agent is a normal host protein

(PrP or PrP–C) that is posttranslationally

transformed into the causative agent or

PrP–Sc. Transformation of the PrP can

occur from rare somatic mutation of the

prion gene, spontaneously or from

contact with extraneous PrP–Sc. The

spread of BSE in the United Kingdom is

postulated to have occurred through the

feeding of ruminant protein that

contained the PrP–Sc protein and thus

follows the portion of the theory that

involves contact with extraneous PrP–

Sc. This explanation requires that one

accept that abnormal prion protein from

sheep crossed the species barrier and

resulted in BSE in cattle. An alternate

explanation is that a spontaneous

mutation or transformation or other

nonorally induced event, occurred and

resulted in undetected disease in a

bovine. These explanations are not

mutually exclusive and it is possible

that both occurred.

Recent surveillance information from

Northern Ireland and Switzerland tend

to support the spontaneous mutation as

a method by which BSE can occur.

Northern Ireland has had more than 10

cows produce offspring, after the

feeding ban, that developed BSE. Thus,

10+ cases are theorized to be

spontaneous because there is no

evidence of feeding meat and bone meal

to the offspring and the dams are alive
Federal Register / Vol. 62, No. 2 / Friday, January 3, 1997 / Proposed Rules 559

and show no signs of BSE (Ref. 5).

Switzerland, which has one of the most

aggressive BSE investigational

surveillance of any European Union

(EU) country, has reported 205 cases of

BSE. Some of these cases are in animals

that were fed only grass and hay (Ref.

5). Regardless of how the initial cases

occurred, however, the resulting

unrecognized disease was amplified by

the feeding of ruminant protein to

ruminants.

Additional support for the feasibility

of the TSE spontaneous mutation

explanation is the fact that 85 percent of

all CJD cases are sporadic and have no

familial or identifiable link as to their

cause. It is these cases that give rise to

the very stable, 1 in a million per year,

world wide incidence of the disease.

DeArmond and Prusiner (Ref. 40), and

Lansbury and Caughey (Ref. 41) have

postulated that a noninduced somatic

cell mutation or the spontaneous

conversion of PrP–C into PrP–Sc are

plausible explanations for the sporadic

cases of CJD. DeArmond and Prusiner

theorized that the 1 in a million

* * * may represent the combined

probabilities that a mutation occurs in the

PRNP gene, the probability that the mutation

leads to the synthesis of the PrP–cjd (the

abnormal protein), and the probability that

the resultant PrP–cjd targets other neurons

for the synthesis of more PrP–cjd at a rate fast

enough to cause clinical disease in the

patient’s lifetime.

The etiology of human and animal

TSE’s are similar. Therefore the

spontaneous mutation explanation

cannot be dismissed with regard to BSE.

6. Pathogenesis

Following oral exposure of goats or

sheep to the scrapie agent, the agent first

accumulates in gut-associated lymphoid

organs (tonsils and Peyers patches of

terminal ileum) and later in other

lymphoid organs, such as spleen and

thymus, and finally in the spinal cord

and brain (Ref. 8).

Likewise, in mice inoculated intraperitoneally with the CJD agent, the

agent localizes first in Peyer’s patches

and spleen, followed by the central

nervous system (Ref. 42). The agent may

enter the body through macrophages in

the tonsils and domes over Peyer’s

patches in the intestine (distal ileum).

The proposed routes of spread from the

point of entry to other tissues and

central nervous system are blood stream

or nerve trunks. In experimentally

inoculated animals, spread from the

inoculation site in the eye of monkeys

and peritoneum of mice has been shown

to be by optic and splanchnic nerves

respectively (Ref. 43).

Other investigators have

demonstrated transient infectivity in the

blood of experimentally infected

laboratory animals, and naturally

occurring infections of humans and

mink, causing speculation that the agent

is carried in the blood (Refs. 45 to 49).

With one exception in serum (Ref. 50),

all attempts to isolate TSE agents from

the blood or milk of sheep or cattle have

failed (Refs. 51 to 54). When TSE agents

are injected intravenously into mice, the

rate of clearance from the blood is

extremely rapid (Ref. 55). In natural

cases of BSE, infectivity has been found

only in the brain, spinal cord, and eye;

in experimental cases the agent has also

been identified in the ileum (Ref. 56).

The question of disease mechanism

remains open. Candidate mechanisms

are the storage or accumulation of a

large amount of abnormal PrP in the

brain (Refs. 57 to 60), or insufficient

amounts of normal PrP.

7. Transmission

There is little information about the

natural transmission of TSE’s of

animals. In most cases the natural route

of exposure to the TSE agent is

suspected to be oral, although genetic

disposition is known to play a role in

sheep scrapie (Ref. 61). Investigators

have suspected transmission of scrapie

in sheep and goats by ingestion of

placenta and have been successful in

experimentally transmitting scrapie by

feeding placenta to sheep (Ref. 62);

however, genotyping of the PrP gene

was not conducted.

In 1993, a study by Foster, et al., (Ref.

63) using a line of sheep in which

natural scrapie does not occur

demonstrated that sheep can be

experimentally infected with BSE by

intracerebral or oral administration. The

intracerebral challenge resulted in five

of six sheep developing the disease. The

oral challenge resulted in one of six

sheep developing the disease. Brain and

spleen were recovered from the orally

infected sheep and from one of the

intracerebrally injected sheep.

Goldmann, et al. (Ref. 64), confirmed

that both sheep had the same PrP

genotype. In 1996, Foster, et al. (Ref. 65)

reported the results of injecting

homogenized tissue harvested from

these infected animals into a panel of

mice. Transmission from the brains and

spleen of both sheep gave incubation

periods and pathology in mice similar to

those seen in direct BSE transmissions

from cattle to mice. Foster’s work

supports the position that BSE can cross

species barriers by the oral route and

that, when judged by the mouse

bioassay, the disease manifested in

sheep retains the incubation time and

pathology characteristic of BSE rather

than scrapie. However, the

manifestation of BSE in the sheep is

histopathologically and clinically

indistinguishable from natural scrapie.

Information regarding the interaction

of the TSE agents and the environment

is limited. In 1964, Gordon reported the

transmission of scrapie among bands of

unrelated sheep on pasture. The mode

of transmission was unknown (Ref. 66).

In an effort to eradicate scrapie from

Iceland a large area was depopulated of

sheep and restocked with new sheep

following a period of 3 years. Despite

this effort, a few flocks of the new sheep

developed scrapie; the origin was

believed to be from scrapie that

survived in the environment and not

from reintroduction of the agent with

the new sheep or through contaminated

hay remaining on farms. However, a

1996 report suggests that six species of

hay mites may be potential vectors

associated with transmission of TSE’s in

Iceland (Ref. 67).

8. Genetics

There is a genetic component

associated with several of the human

TSE diseases. A specific point mutation

at codon 178 is associated with fatal

familial insomnia (Ref. 68). Point

mutations at codons 102, 105, 117, 145,

198, and 217 are associated with GSS

syndrome (Ref. 69). Point mutations at

codons 178, 180, 200, 210, and 232 are

associated with CJD (Refs. 68 and 70).

Various insertions into the octapeptide

repeat region of the PrP gene have also

been associated with human TSE’s (Ref.

71). It appears that the methionine/

valine polymorphism at codon 129 may

modify the phenotype and the

transmission rate from GSS syndrome

patients to mice (Ref. 72). No

abnormalities in the sequence of the PrP

gene in kuru patients were found.

There is also a genetic component

associated with sheep scrapie. Point

mutations at codon 171 of the sheep PrP

gene are linked to the disease in the

Corriedale, Lacaune, Romanov, Suffolk,

and Texel breeds (Refs. 73 to 76).

An analysis of 370 cattle from

Scotland revealed no difference between

healthy cattle and cattle with BSE in the

number of octapeptide repeat sequences

(either five or six) and in a silent HindII

restriction site polymorphism on the

PrP gene (Ref. 77). No data were found

that compared the sequence of the PrP

gene of healthy deer, elk, mink, and

goats with those afflicted by TSE’s.

9. Diagnostics

Because of the long incubation period,

the ability to diagnose the presence of

a BSE infection prior to the onset of the
560 Federal Register / Vol. 62, No. 2 / Friday, January 3, 1997 / Proposed Rules

clinical disease would enhance the

efficacy of surveillance and prevention

programs. Because there is no fully

characterized immune response to BSE

or scrapie, diagnosis in live animals has

been thought to be possible only when

clinical signs are evident and must be

confirmed by histopathology at post

mortem (Ref. 10), or brain biopsy of

moribund patients. Recently published

research suggests antemortem tests for

the TSE agent may be possible.

The observation of histopathological

changes in the brain, such as

vacuolization of the brainstem in BSE

are positive indicators of disease (Ref.

78). Other available diagnostic tests are

immunohistochemical staining and

immunoblotting of the abnormal protein

(Ref. 10). Detection and titration of the

TSE agent can also be accomplished by

intracerebral inoculation in mice or

hamsters with a brain homogenate from

a suspected animal. After an appropriate

incubation period, the brain of the

laboratory animal is examined for

histopathological changes characteristic

of TSE (Ref. 8).

The potential antemortem tests that

have been published are described as

follows: (1) Tests specific for PrP: (a) A

capillary electrophoresis test (Ref. 79),

and (b) a western blot test with

increased sensitivity (Ref. 80); and (2)

tests which identify metabolites of

infected animals or humans: (a) A cyclic

voltametric method which describes

metabolites in urine (Ref. 81), and (b) an

immunoblot test describing metabolites

in cerebral spinal fluid (Ref. 82).

Antemortem tests have not yet been

validated for practical use.

Recent research has shown some

promise for antemortem testing.

Research by Shreuder et al. (Ref. 83),

detected scrapie-associated PrPsc

protein in tonsils from scrapie

susceptible sheep about a year before

the expected onset of the clinical

disease. The research holds promise for

preclinical detection in sheep, but needs

further development. With regard to

cattle, the researchers concluded that

the technique may not work but is

worth investigating. Research by Hsich

et al. (Ref. 84), describes an

experimental assay in humans and

animals. The research found that a

positive immunoassay in human

dementia patients supports a diagnosis

of CJD. The authors concluded that the

assay may be helpful in premortem

diagnosis of TSE in humans and

animals showing clinical signs

associated with TSE’s. The validity of

the test as a preclinical screen has not

been established.

10. Inactivation

The agency considered requiring

procedures for the manufacture of

animal-derived proteins that would

inactivate TSE infectivity. There have

been several studies on the inactivation

of TSE agents. The only broad

generalization that can be drawn is that

agents that denature protein can

diminish the infectivity of the TSE

agents. TSE infectivity does not appear

to be markedly diminished by radiation

or UV-light.

Recent research (Ref. 85) showed that

11 of the 15 rendering procedures tested

produced meat and bone meal with no

detectable BSE infectivity in a mouse

bioassay. Only limited conclusions can

be drawn about safety from these 11

procedures because the infectivity titer

of the spiked starting material (which

consisted of 10 percent brain) was

several logs lower than that typically

found in brain that is not minced and

not stored at ¥20 °C. Also, the question

of the adequacy of the mouse bioassay

as the regulatory test which acceptably

assures the absence of TSE infectivity to

animals or man remains to be answered

through future research investigations.

The four procedures that failed

included two protocols using

continuous vacuum rendering of high

fat material and two protocols using

continuous atmospheric rendering of

natural fat material. The continuous

vacuum rendering processes that failed

were 120 °C for 20 minutes at a vacuum

of 0.38 bar and 121 °C for 57 minutes

at a vacuum of 0.4 bar. The continuous

atmospheric rendering processes of

natural fat material that failed were end

temperatures of 112 and 122 °C after 50

minutes; however, end temperatures of

123 and 139 °C after 125 minutes both

inactivated the BSE agent.

Unexpectedly, the BSE agent was

inactivated by three wet rendering

processes that only reached a maximum

temperature of 119 °C with a cooking

time of 240 minutes, a maximum

temperature of 101 °C with a cooking

time of 120 minutes, and a maximum

temperature of 72 °C with a cooking

time of 240 minutes under a vacuum of

0.85 bar.

Preliminary, unpublished results

indicate that the only rendering process

which completely inactivates the

scrapie agent (which was spiked with

higher infectivity than that in the BSE

experiments described in this section) is

batch rendering under pressure (Ref.

86). The agency encourages more

research in this area.

B. The Association Between Scrapie and

BSE

Epidemiological studies of the

outbreak of BSE in the United Kingdom,

including a computer simulation of the

BSE epidemic, have characterized it as

an extended common-source epidemic.

Each case has been considered a

primary case resulting from exposure to

a single common source of infection. It

is believed in the United Kingdom that

rendered feed ingredients contaminated

with scrapie infected sheep, or cattle

with a previously unidentified TSE,

served as the common source of

infection. One study demonstrated that

meat and bone meal could be

incorporated into cattle feed in

sufficient quantity to transmit BSE to

some of the animals that consumed the

feed (Ref. 87). Thus far, other research

including research by USDA has not

confirmed that the feeding of U.S.-origin

scrapie-infected feed ingredients to

cattle produces BSE. Therefore, the

theory that BSE evolved naturally in

cattle has not been ruled out (Ref. 88).

See also the discussion in II.A.5. of this

document.

Furthermore, the U.K. studies suggest

that the spread of BSE appeared to have

been exacerbated by the practice of

feeding ingredients from rendered BSEinfected cattle to cattle, including young

calves, a practice that was subsequently

banned. Incomplete immediate

compliance with the feeding ban may

account for the fact that some cattle

born after the ban continue to be

infected with BSE and has complicated

any theory of vertical transmission of

the disease. The research findings of

maternal transmission of BSE are

inconclusive, but if it occurs, it does so

at a rate insufficient to maintain the

epidemic (Ref. 89).

C. The Association Between Animal

TSE’s and Human TSE’s

All the animal and human TSE’s have

been shown to be transmissible

experimentally to laboratory animals.

The human and animal diseases are

pathologically similar and share some

etiological similarities. TSE’s are not

officially considered zoonotic diseases,

i.e., known to be naturally transmissible

from animals to humans. The

distribution of CJD in the world does

not coincide with that of scrapie in

sheep or of BSE in cattle. Human

exposure to sheep or cattle has a low

correlation with CJD. However, the

recent report from the United Kingdom

of nv-CJD, and its possible relationship

to BSE, is causing scientists around the

world including those at CDC to
Federal Register / Vol. 62, No. 2 / Friday, January 3, 1997 / Proposed Rules 561

reevaluate whether BSE may be a

zoonotic disease.

This concern is further supported by

the recent report of experimental BSE

transmission to macaques, with the

development of nv-CJD-like plaques in

these monkeys (see the following

discussion in this section).

The possibility of transmission of

TSE’s from animals to humans has been

suggested, most recently in connection

with the identification of nv–CJD in the

United Kingdom. Scientists in the

United Kingdom concluded that the nv–

CJD cases may be unique to the United

Kingdom, raising the possibility that

they are causally linked to BSE. The

scientists stated that ‘‘the common

neuropathological picture may indicate

infection by a common strain of the

causative agent, as in sheep scrapie in

which strains of the disease have been

identified * * * ’’ (Ref. 30). The United

Kingdom Spongiform Encephalopathy

Advisory Committee (SEAC) stated that

‘‘although there is no direct evidence of

a link, on current data and in absence

of any credible alternative the most

likely explanation at present is that

these cases are linked to exposure to

BSE before introduction of the SBO

[specified bovine offal] ban in 1989’’

(Ref. 90). A WHO consultation in April

1996 concluded that ‘‘a link has not yet

been proven between v–CJD in the U.K.

and the effect of exposure to the BSE

agent. The most likely hypothesis for v–

CJD is the exposure of the United

Kingdom population to BSE’’ (Ref. 2).

However, a second WHO consultation,

in May 1996 concluded that ‘‘the

clinical and neuropathological features

of the newly recognized CJD variant do

not provide information which could be

used to prove the possible link between

this disease and BSE in cattle’’ (Ref. 91).

The recent finding of florid amyloid

plaques in the brains of macaques

inoculated with suspensions of BSEinfected cow brains increases suspicion

that exposure to the BSE agent may be

the source of nv–CJD. Amyloid plaques

have never before been seen in monkeys

with TSE’s, and the florid plaques

resembled those in nv–CJD patients

(Ref. 92). In a recent paper by Collinge,

et al. (Ref. 93), it is stated that ‘‘strains

of transmissible encephalopathies are

distinguished by differing

physicochemical properties of PrPsc,

the disease-related isoform of prion

protein, which can be maintained on

transmission to transgenic mice. ’New

variant’ CJD has a strain characteristic

distinct from other types of CJD and

which resembles those of BSE

transmitted to mice, domestic cat and

macaque, and is consistent with BSE

being the source of this new disease.

Strain characteristics revealed here

suggest that the prion protein may itself

encode disease phenotypes.’’

The possible association between BSE

and nv–CJD may be further clarified by

results from studies that are under way

(e.g., experimental inoculation of brain

tissue from the nv–CJD patients into

mice).

D. Infectivity of Specific Tissues

The WHO in a recent publication has

summarized the infectivity of various

tissues from sheep, goat, and cattle (Ref.

94). Scientific studies are currently

being conducted in which calves are fed

homogenized brain tissue from United

Kingdom cattle confirmed to have BSE,

and then various tissues are collected

from the calves at 4-month intervals

(Refs. 56 and 95). The tissues from these

calves are being analyzed for the

presence of the BSE agent. The study

has been in progress for 18 months and

only brain, spinal cord, and retina have

been shown to be highly infectious.

Distal ileum has been shown to be

infectious, but much less than the

previously mentioned tissues. No other

tissues, most notably, muscle meat,

milk, or blood have been shown to be

infectious. The results of these current

experiments parallel the previous

research as summarized by WHO.

However, the agency notes that

infectivity of other tissues that might be

fed to ruminants has not been

definitively determined. This is, in part,

because of the lack of desired sensitivity

in the available assay methods.

In summary, meat, milk, milk

products, and blood have not been

shown to transmit BSE infectivity.

These products are considered safe for

human consumption by health

authorities including the WHO.

E. Potential Risk of TSE’s to the United

States

1. Overview

This proposed FDA action is designed

to reduce the risk of a BSE epidemic in

the United States and thereby protect

the health of animals and possibly of

people if there is, in fact, a zoonotic

relationship between BSE and CJD. Risk

is defined as the probability of an

adverse effect to an individual or a

population. The four steps that are

typically involved in risk analysis are

hazard identification, hazard exposure,

dose response, and risk characterization.

While BSE has not been found in the

United States, the agency believes it

presents a potential risk to the health of

animals and people. There are

incubational and symptomatic

similarities (as well as several

differences) among the TSE’s. The

scientific characterization of these

diseases is incomplete. However,

interspecies cross-infections have been

scientifically demonstrated by

parenteral injection and oral routes of

exposure.

The typically long incubation period

and the potentially devastating effect

that a BSE outbreak would have on

animal health and U.S. agribusiness also

supports a conservative regulatory

approach aimed at prevention. While

the current level of exposure to products

derived from animals with a TSE is

extremely low or absent, the potential

consequences of such exposure and the

apparent small intake of the agent

needed to achieve infection in some

animals further encourage a

conservative regulatory policy.

Dose response assessments will be

difficult because of the lack of good

exposure data and the possibility of

different susceptibilities, e.g., age or

genetic factors, in different

subpopulations. Although the TSE’s are

generally transmissible to laboratory

animals following intraperitoneal (ip) or

intracerebral (ic) routes of

administration, the limited data that are

available following the oral route of

administration suggests that this route is

much less efficient than ip or ic.

Currently, it is quite difficult to make an

accurate dose response assessment for a

TSE agent following oral administration.

A number of actions, in addition to

this proposed rule, have been taken to

manage a reduction in risk that BSE will

enter the United States cattle

population. Restrictions have been

placed on the importation of live cattle

(July 1989) and ruminant products (e.g.,

meat and bone meal, bone meal, blood

meal, offal, fat, and glands) from

countries which have BSE. Live animals

imported prior to the restrictions on

imports have been regularly monitored

by Animal and Plant Health Inspection

Service (APHIS) veterinarians, and

APHIS is currently in the process of

purchasing the remaining live cattle for

diagnostic research purposes.

Histopathological examination of brain

tissues has been carried out on more

than 5,000 specimens from cattle that

were disabled or that demonstrated

neurological signs prior to slaughter or

on the farm, e.g., nonambulatory or

rabies-negative cattle. Histopathological

and immunohistochemical examination

of the nonambulatory or ‘‘downer’’ cows

has been carried out since 1993. There

has been no finding of BSE in tissues

from these animals. These animals

represent the highest BSE risk in the

country, however, they also represent an

extremely small percentage of the cattle
562 Federal Register / Vol. 62, No. 2 / Friday, January 3, 1997 / Proposed Rules

slaughtered in the United States. This

active surveillance program is

continuing and may be expanded. The

expansion of this program was

indirectly supported by a comment to

the ANPRM that all ‘‘downer’’ cows

should be examined for BSE.

Voluntary actions by industry have

reduced the feeding of rendered sheep

proteins to ruminants and the rendering

of adult sheep. A voluntary Scrapie

Flock Certification Program was

implemented in 1992. The program, a

cooperative effort among industry, State

animal health officials and APHIS, seeks

to reduce the prevalence of scrapie in

U.S. sheep. A considerable educational

effort continues to increase the

awareness of veterinarians, veterinary

laboratory diagnosticians, livestock and

related industry businesses, and

producers to the early clinical signs of

BSE. Videos of United Kingdom BSE

affected animals have been distributed

to USDA veterinarians to enhance their

ability to clinically diagnose BSE in

suspect live animals. CDC has recently

published an update (Ref. 96) of its

previous review of national CJD

mortality and the results of active CJD

surveillance in five sites in the United

States. These reviews did not detect

evidence of the occurrence of the newly

described variant form of CJD in the

United States. As an important

complement to these other public health

efforts, this proposed rule would declare

that animal protein derived from

ruminant and mink tissues is an

unapproved food additive for use in

ruminant feeds, and would establish

enforcement procedures. These actions,

individually and collectively, contribute

to a greatly reduced risk of a BSE

epidemic ever occurring in the United

States.

2. Comparison With the U.K. Conditions

Investigators have identified several

major risk factors that apparently

contributed to the emergence of the

disease and the resultant epidemic in

the United Kingdom. These are: (1) A

large sheep population relative to the

cattle population, (2) a large,

uncontrolled, scrapie incidence rate, (3)

the production of ‘‘greaves,’’ an

incompletely processed intermediate

product in the rendering process, (4)

changes in rendering processes, such as

the reduced use of solvent extraction,

and (5) the feeding of significant

amounts, up to 4 percent of the diet, of

meat and bone meal to young dairy

calves.

In addition to the risk factors

described in section II.E.2. of this

document, the practice of processing

dead sheep and cattle in the United

Kingdom likely contributed to the

amplification of the TSE agent. In the

United Kingdom, sheep which may

have died of scrapie and cattle with

BSE, were picked up by ‘‘knackers’’ for

rendering into animal feed. This

material was partially rendered into

‘‘greaves,’’ which might have contained

large amounts of the scrapie/BSE agent,

and was fed to dairy calves in large

amounts. The spread of BSE appeared to

be facilitated by the feeding of rendered

BSE-infected cattle back to calves. The

BSE agent is postulated to have recycled

from cows to calves through ruminantto-ruminant feeding until the practice

ceased following the 1989 ban on the

practice.

In the United States, the cattle

population is much larger than the

sheep population, the incidence of

scrapie is much lower and a scrapie

control program is in place; renderers in

the United States do not manufacture

greaves; and the rendering processes

used in the United States are thought to

reduce the titre (level) of TSE agents if

any. The lack of a practice of feeding

large amounts of meat and bone meal to

calves in the United States, and the

comparatively younger average age of

U.S. dairy cattle are also differences that

are believed to be important in

protecting the United States against a

U.K.-type BSE epidemic. Nevertheless,

scrapie does exist in the United States,

sheep are rendered and included in

ruminant feed, the rendering process

does not totally inactivate TSE agents,

and calves are fed meat and bone meal.

Therefore the risk of a BSE epidemic in

the United States, while much less,

cannot be completely discounted.

F. Historical Efforts to Control TSE’s

1. U.S. Actions

a. FDA. FDA is the Federal agency

responsible for the safety and

effectiveness of a large number of

products and commodities. Briefly,

these include, drugs for use in people

and animals, human biological

products, medical devices, food, dietary

supplements, cosmetics, and animal

feeds. Each of these product groups

provides the potential for the

transmission of spongiform

encephalopathies in man or animals.

FDA formed a Working Group

composed of the Deputy Commissioner

for Operations and representatives from

the Centers to consider TSE’s in relation

to FDA regulated products. As a result

of the Working Group’s deliberations,

FDA has taken the following actions:

• In 1992, letters were sent to

manufacturers of dietary supplements

asking those manufacturers to

reformulate their products to be certain

they do not contain materials from BSE

or scrapie infected animals;

• In 1993, letters were sent to

manufacturers of drugs, biologics, and

devices asking them not to use bovinederived materials from countries with

BSE; and

• In 1996, letters were sent to

manufacturers of drugs, biologics,

devices, and animal feeds noting a

possible relationship between BSE and

nv-CJD and asking that they not use

materials from BSE countries.

In 1992, FDA conducted a survey of

major sheep rendering plants to

determine compliance with a 1989

voluntary industry ban on the use of

adult sheep offal in ruminant feeds. The

voluntary ban and results of the survey

are described in section I.F.3. of this

document. In the Federal Register of

August 29, 1994 (59 FR 44584), FDA

published a proposed rule proposing to

declare that specified offal from adult

sheep and goats is an unapproved feed

additive in ruminant feed (hereinafter

referred to as the August 1994 proposed

rule). In the Federal Register of May 14,

1996, FDA published an ANPRM stating

that FDA was considering whether to

provide that the use of protein derived

from ruminants in ruminant feed be

prohibited.

An international symposium entitled

‘‘Tissue Distribution, Inactivation, and

Transmission of Transmissible

Spongiform Encephalopathies’’ and

cohosted by APHIS and FDA’s Center

for Veterinary Medicine (CVM) was held

on May 13 and 14, 1996, in Riverdale,

MD. The symposium participants

engaged in discussion of findings from

unpublished, recently completed, and

in-progress scientific investigations on

TSE’s, and optimal approaches to

managing any risk of TSE’s to animal

health.

b. USDA. USDA policy has been both

proactive and preventive. The Food

Safety and Inspection Service (FSIS)

and APHIS have been active in taking

measures in surveillance, prevention,

and education about TSE’s. In 1990,

APHIS created a BSE Issues

Management Team to analyze risks of

BSE to the United States, disseminate

accurate information about the disease,

and act as a reference source for

responding to questions about BSE.

APHIS has also collaborated in the

education of veterinary practitioners,

veterinary laboratory diagnosticians,

industry and producers on the clinical

signs and pathology of BSE.

APHIS has increased its surveillance

efforts to verify that the United States is

free of BSE and to detect the disease

should it be introduced into the United
Federal Register / Vol. 62, No. 2 / Friday, January 3, 1997 / Proposed Rules 563

States. As part of an ongoing active

surveillance program, more than 60

veterinary diagnostic laboratories across

the United States, and the National

Veterinary Service Laboratories (NVSL)

of APHIS, continue to examine bovine

brains from the following sources: (1)

APHIS investigations in the United

States where suspected encephalitic

conditions in cattle are reported under

the foreign animal disease investigation

program; (2) CDC and State public

health laboratories (specimens from

bovine that were found negative for

rabies); and (3) FSIS (specimens from

‘‘downer’’ cows or those exhibiting CNS

abnormalities). More than 5,000 bovine

brains have been examined, and none of

these specimens contained lesions with

the characteristics and distribution

typical for BSE (Refs. 12 and 97). APHIS

is currently in the process of purchasing

the 69 living cattle (from a total of 496

cattle) imported from the United

Kingdom between 1981 and 1989. In

July 1989, the importation of live

ruminants and ruminant products from

all countries known to have BSE in

native animals was banned.

USDA continues to analyze and report

epidemiologic findings and potential

risks to the United States. In 1991,

USDA issued two reports analyzing risk

factors associated with BSE in the

United Kingdom based on the British

hypothesis of the disease occurring as a

result of feeding scrapie-contaminated

meat and bone meal (Refs. 98 and 84).

Because of some similarities in the

animal industries between the two

countries, the possibility of BSE

occurring in the United States could not

be eliminated. However, the probability

of occurrence was determined to be very

low as the amount of sheep offal was

found to be 0.6 percent of all U.S.

rendered product compared to the

estimate of 14 percent of all U.K.

rendered product. Furthermore, the

incidence of scrapie in the United States

is much lower than in Great Britain; a

scrapie eradication or control program

has been in effect in the United States

and rendered products are not routinely

incorporated into calf diets as was the

practice in the United Kingdom.

Since 1991, USDA has closely

followed scientific findings and has

updated the BSE risk factor analysis,

first in 1993 (Ref. 99) and as recently as

February 1996 (Ref. 4). Changes within

each of the risk factors have been

evaluated, and because there has either

been no change or a decrease in the

magnitude of risk factors, the overall

risk of BSE in the United States is

believed to have decreased. The

February, 1996 report estimated the

maximum potential 1-year period

prevalence of BSE to range from 2.3 to

12 cases per 1 million adult cattle. In

other words, under the worst case

scenario between approximately 115

and 600 adult cattle would become

infected with BSE each year, in a U.S.

population of nearly 50 million adult

cattle.

APHIS has had a scrapie control

program in effect since 1952. Flocks that

have been enrolled in the voluntary

certification program for sheep for 5

years, and have not had a diagnosed

case of scrapie within 5 years or a case

traced back to the flock during that

period, may apply for APHIS

certification and be officially identified

as such. This new control effort

provides a mechanism to recognize

flocks as scrapie-free in the absence of

a live animal diagnostic test.

There is no official USDA program on

TME or CWD. Although the last TME

case detected in the United States was

in 1985, monitoring for this disease

continues. APHIS cooperates with State

wildlife and diagnostic officials in

Colorado and Wyoming in the limited

areas where CWD has been reported.

In December 1991, APHIS placed a

ban on importation of certain products

of ruminant origin from countries

known to have BSE (56 FR 63865,

December 6, 1991). These products

include: Meat and bone meal, bone

meal, blood meal, offal, fat, and glands.

In addition to prohibiting the materials

listed previously, the regulation requires

that imported meat for human or animal

consumption from bovines be deboned,

with visible lymphatic and nervous

tissue removed; that it be obtained from

animals which have undergone a

veterinary examination prior to

slaughter; and that it be obtained from

ruminants which have not been in any

country in which BSE has been reported

during a period of time when that

country permitted the use of ruminant

protein in ruminant feed. APHIS may

allow the importation of the banned

products under a special permit for

scientific or research purposes, or under

special conditions to be used in

cosmetics. No bovine meat from the

United Kingdom has been allowed to be

imported into the United States by FSIS

for human consumption since before the

BSE epidemic occurred in the United

Kingdom. The network of private

veterinary practitioners that refers

unusual cases to veterinary schools or

State diagnostic laboratories around the

United States provides an extensive

surveillance system. FSIS performs both

antemortem and post mortem

inspections at all federally-inspected

slaughter establishments, and inspectors

condemn all animals with central

nervous system disorders. Stateinspected slaughter operations follow

the same procedures.

USDA also maintains a database on

these and other conditions. The

Veterinary Diagnostic Laboratory

Reporting System (VDLRS) is a database

of selected disease conditions submitted

by 29 State and university veterinary

diagnostic laboratories throughout the

United States, and includes the results

of histologic examinations for BSE. The

VDLRS is a cooperative effort of the

American Association of Veterinary

Laboratory Diagnosticians (AAVLD), the

U.S. Animal Health Association

(USAHA), APHIS’ Veterinary Service

Centers for Epidemiology and Animal

Health, and the 29 laboratories

mentioned previously.

c. Public Health Service (PHS). i. CDC.

CDC conducts surveillance for CJD

through examination of death certificate

data compiled by the National Center

for Health Statistics, CDC, for U.S.

residents for whom CJD was listed as

one of the multiple causes of death (Ref.

100). These data indicate that the

annual CJD mortality rates in the United

States between 1979 and 1993 have

been relatively stable, ranging between

only 0.8 case per million in both 1979

and 1990 and 1.1 cases per million in

1987. In addition, CJD deaths in persons

younger than 30 years of age in the

United States remain extremely rare (<5

cases per billion per year) (Ref. 101).

CDC is working with the Council of

State and Territorial Epidemiologists to

consider expansion of current CJD

surveillance. CDC is also working with

its four established Emerging Infections

Programs (Minnesota, Oregon,

Connecticut, and the San Francisco Bay

area, California), the Georgia

Department of Human Resources, and

the Atlanta Metropolitan Active

Surveillance Program to pilot enhanced

surveillance efforts for CJD (Ref. 101).

This effort includes an active search for

v-CJD as described in the United

Kingdom (Ref. 30). On August 9, 1996,

the results of this enhanced CJD

surveillance effort was published; no

evidence of the occurrence of the newly

described variant form of CJD was found

in the United States. No evidence of vCJD has been found in the United States.

ii. National Institutes of Health (NIH).

A project of the Laboratory of Central

Nervous System Studies of the National

Institute of Neurological Diseases and

Stroke is conducting investigations on

slow, latent, and temperate viral

infections associated with chronic

degenerative neurological diseases.

Important areas of study are the

pathogenesis of slow infections and

mechanisms of persistence in kuru and
564 Federal Register / Vol. 62, No. 2 / Friday, January 3, 1997 / Proposed Rules

CJD. Also intensive molecular,

biological, genetic, and immunological

studies are being conducted on amyloid

formation in the brain in Alzheimer’s

disease, normal aging, Down’s

syndrome, and slow viral infections,

and the elucidation of the de novo

generation of infectious amyloid

proteins from normal host precursor

proteins in kuru, CJD, GSS syndrome,

scrapie and BSE. Research on TSE’s has

also been conducted by the NIH

Laboratory of Persistent Viral Disease.

FDA maintains close contact with

scientists in the laboratories and expects

to use their expertise in the evaluation

of inactivation methods and

transmission studies.

iii. Other actions. On April 8, 1996, an

interagency meeting at CDC including

representatives from CDC, NIH, FDA,

USDA, and the U.S. Department of

Defense was held to disseminate

conclusions from the WHO consultation

regarding v-CJD and to coordinate

preventive activities among these

agencies to address the BSE and CJD

issues.

2. International Actions

a. United Kingdom. Regulatory

controls taken to manage the BSE

epidemic in the United Kingdom and to

address public health concerns include:

(1) An action in June 1988 to make the

disease reportable; (2) a ban in July 1988

on the feeding of ruminant-derived

protein supplements to other ruminants;

(3) an order in August 1988 for the

compulsory slaughter and incineration

of BSE suspect cattle; (4) a ban in

November 1989 on the inclusion of

specified bovine offal (brain, spinal

cord, thymus, spleen, tonsils, and

intestines) for human consumption; and

(5) a ban in September 1990 on use of

specified bovine offal in any animal

feed.

A CJD Surveillance Unit was

established to monitor CJD numbers in

the United Kingdom. SEAC, consisting

of experts in neurology, epidemiology,

and microbiology from outside the

British government, was established in

1990 to oversee all aspects of TSE’s and

human and animal health. USDA has a

representative on this committee.

Major regulatory actions occurring

after the SEAC report on nv-CJD (Ref.

90) include legislation to ban the

feeding of mammalian meat and bone

meal to any farmed animal, and

legislation to ban the use of cattle head

meat for human consumption.

b. WHO. WHO has held meetings on

the spongiform encephalopathies in

1991, 1993, 1995, and 1996, and a

meeting in collaboration with the Office

International des Epizooties (OIE) in

1994. The general purposes of these

meetings were to review the existing

state of knowledge on spongiform

encephalopathies including BSE, to

evaluate possible means of

transmission, and to identify risk factors

for infection. A specific purpose was to

review the possible human public

health implications of animal

spongiform encephalopathies, with

special emphasis on BSE. The group of

international experts convened in April

1996 by WHO recommended that all

countries should ban the use of

ruminant tissues in ruminant feed. The

WHO group also declared that milk and

milk products, including such products

from the United Kingdom, are safe for

human consumption and that gelatin in

the food chain is considered safe

because its preparation effectively

destroys BSE. Finally, the group

concluded that tallow could be safe if

effective rendering procedures are in

place (i.e., rendered as protein-free)

(Ref. 2).

c. OIE. OIE has supported the U.K.

ban on the use of specified offals and

has recommended that the same action

be taken in other countries with a high

incidence of the disease (Ref. 102). OIE

has held meetings in 1990, 1991, 1992,

1995, and 1996, and has developed

guidelines concerning animals and

animal products to prevent movement

to unaffected countries.

d. European Community (EC). The EC

has held a series of meetings related to

BSE. Following issuance of the U.K.

SEAC statement suggesting a possible

link between nv-CJD and BSE, the EC

imposed a ban on British cattle, beef

and bovine derivatives (Ref. 103).

3. Voluntary Measures by the U.S.

Animal Industries

a. Voluntary ban on rendering adult

sheep. In 1989, the National Renderers

Association (NRA) and the Animal

Protein Producers Industry (APPI)

recommended to their members that

they stop rendering adult sheep or

providing sheep offal for sale as meat

and bone meal for inclusion in cattle

feed (Ref. 104). Following the

recommendation of the voluntary ban,

FDA carried out a survey of current

practices in the United States for

rendering or otherwise disposing of

adult sheep carcasses and parts,

specifically head, brain, and spinal

cord. Limited inspections of rendering

plants were conducted in 1992 to: (1)

Assess compliance by U.S. renderers

with the voluntary ban; (2) identify

rendering plant practices concerning

adult sheep; and (3) determine if

rendered adult sheep protein

byproducts were being sold or labeled

for use as feed or feed components for

cattle. Of the 19 plants surveyed, 15

rendered carcasses or offal of adult

sheep. These 15 plants processed more

than 85 percent of the adult sheep

rendered in the United States. Eleven of

the 15 plants rendered carcasses of adult

sheep with heads, 7 of the 15 rendered

sheep carcasses separately from other

species, 6 of the 15 maintained meat

and bone meal from adult sheep

separate from meat and bone meal from

other species, and 4 of the 15 rendered

sheep that had died of causes other than

slaughter. Six of the 11 renderers

processing adult sheep with heads had

sold meat and bone meal to

manufacturers of cattle feed. Thus, the

rendering industry’s voluntary ban on

the rendering of adult sheep or

providing sheep offal for use in cattle

feed was not fully implemented at the

time of the survey (Ref. 105).

b. Voluntary ban on feeding ruminant

proteins to ruminants. On March 29,

1996, the National Cattlemen’s Beef

Association (NCBA), the National Milk

Producers Federation, the American

Sheep Association, the American

Veterinary Medical Association, the

American Association of Veterinary

Medical Colleges, and the American

Association of Bovine Practitioners

announced the recommendation of a

voluntary ban on the feeding of

ruminant-derived proteins to ruminant

animals (Ref. 106). USDA, PHS, the

American Society of Animal Science,

and other organizations announced

support for the voluntary ban (Refs. 107

and 108). According to the NCBA (Ref.

109), a comprehensive communication

strategy, seeking removal of ruminantderived proteins from the rations of

ruminants, was implemented in May

1996 by the feed industry, nutritionists,

veterinarians, extension specialists, and

dairy and beef producers. NCBA has not

conducted a survey to assess the impact

of its communication strategy; however,

NCBA did point out that past requests

for voluntary action by the cattle

industry have been quite successful,

approaching 90 percent compliance. In

contrast, an anonymous comment to the

ANPRM suggested a compliance level of

less than 5 percent (Ref. 110). FDA has

not conducted a survey to ascertain the

level of compliance with the voluntary

ban.

G. Processing Animal Tissues for Feed

Ingredients

1. Current Rendering Practices

The following discussion on current

rendering practices comes directly from

comments supplied to FDA in response

to the ANPRM from representatives of
Federal Register / Vol. 62, No. 2 / Friday, January 3, 1997 / Proposed Rules 565

APPI and NRA. Knowledge about the

four basic types of rendering systems

that are most commonly used in the

United States today may be crucial in

dealing with the TSE issue in this

country. Data on the inactivation of the

BSE and scrapie agents following

simulation of the most commonly used

basic types of rendering systems in the

United States could be quite useful,

especially because some of these

systems do not appear to have been

used in the only published rendering

study on BSE inactivation (Ref. 85).

Rendering, the process of cooking raw

material to remove the moisture and fat

from the solid protein portion of animal

tissues, has been practiced by humans

for more than 2,000 years. The United

States rendering industry has developed

over the last 160 years. Modern

rendering systems are high-technology

recycling processes that efficiently

convert animal byproducts (shop fat and

bone, beef and pork slaughterhouse

materials, poultry offal, fish, etc.) to

stable protein and fat supplements for

feed.

Current technology consists of four

basic types of rendering systems—batch

cooker, continuous cooker, continuous

multi-stage evaporator, and continuous

preheat/press/evaporator. All systems

consist of three basic steps: Grinding the

raw material, cooking it to remove

moisture, and separating the melted fat

from the protein solids.

Batch cookers are multiple units, each

consisting of a horizontal, steamjacketed cylindrical vessel with an

agitator. Batch cookers are operated at

atmospheric pressure. The cooked

material is discharged to the percolator

drain pan, which contains a perforated

screen that allows the free-run fat to

drain and be separated from the protein

solids known as ‘‘tankage.’’

Because ‘‘tankage’’ contains

considerable fat, it is processed through

a screw press to complete the separation

of fat from solids. The fat discharged

from the screw press usually contains

fine solid particles that are removed by

either centrifuging or filtration. The

protein solids discharged from the

screw press are known as ‘‘cracklings,’’

which normally are screened and

ground with a hammer mill to produce

protein meal.

The continuous cooker rendering

system normally consists of a single

continuous cooker, operating at

atmospheric pressure. The discharge

from the continuous cooker usually

passes across either a vibrating screen or

stationary perforated screen to allow the

free-run fat to drain. The subsequent

steps in the continuous cooker

rendering process are similar to those

described before for the batch cooker.

In the continuous multi-stage

evaporator rendering system, crushing is

used as the first stage of size reduction

of the raw material. A fat recycle stream

is then used to deliver the material as

a pumpable slurry through the

secondary grinding step to reduce

further the particle size. Particle size

and fat ratios are important components

of this system. The slurry discharge

from the final stage of evaporation is

pumped to a centrifuge which removes

most of the fat and part of it is recycled

back to the second stage of size

reduction. The solids discharged from

the centrifuge are conveyed to screw

presses which complete the separation

of fat from the protein solids.

The continuous preheat/press/

evaporator rendering system is known

by a variety of names including the

Stord dewatering rendering system and

the Atlas low temperature wet rendering

system. In either case, raw material is

ground in two stages and passes through

the preheater to raise the temperature to

180 to 190 °EF before entry to the twin

screw press. The press separates this

material into two phases: A presscake of

solids containing moisture and a low fat

concentration, and a liquid containing

mostly water (stickwater) with fine

solids, soluble protein, insoluble protein

and melted fat.

The press liquid is processed either

by passing through a multistage

evaporator system to remove the water

before centrifuging to remove the fine

solids from the fat, or by passing

through a centrifuge to separate the fat

before multistage evaporation of the

remaining water/fine solids fraction.

The liquid separation system consisting

of two stages of centrifuges completes

the separation of the melted fat from the

solids and water. In this system, the

screw press normally used to process

the ‘‘tankage’’ is no longer needed.

Longer drying times are needed with

this system as compared to previous

systems because of the early fat removal

(less fat means less effective heat

transfer).

The agency encourages further

research into methods of deactivation of

the BSE agent during the rendering

process.

2. Assay Methodologies for Proteins

Enforcement of the proposed

regulation would be facilitated if a test

to detect and distinguish ruminant from

nonruminant materials in feeds or feed

ingredients was available. However,

practical assays that could be used to

enforce the proposed regulation are not

available at this time. The test

procedure would need to exhibit a high

degree of sensitivity and selectivity; that

is, the test must be able to detect the

analyte of interest to the exclusion of

other components. A test for acceptable

rendered products in animal feed must

therefore be able to discriminate and

differentiate between permitted and

prohibited animal derived proteins.

Other factors of importance are the

ruggedness of the test method, speed,

and simplicity of design.

An enzyme-linked immunosorbant

assay (ELISA) based analytic method

that is both sensitive (detects low levels

of analyte) and specific (detects

primarily the analyte of interest) is one

possibility. ELISA is a relatively

straightforward methodology. There are

numerous commercial sources for

antisera capable of binding to bovine,

ovine, porcine, and caprine proteins.

Antisera have also been generated from

muscle extracts and validated for use in

USDA-approved ELISA methods to

determine the identity of raw and

cooked meats (Refs. 111 and 112).

However, rendered products present a

unique problem because rendering

causes the destruction of most of the

antibody binding epitopes needed for an

ELISA test. Therefore, detection of

rendered proteins by a given antibody

cannot be automatically assumed.

Other potential methodologies

include western blot analysis, capillary

electrophoresis, and high pressure

liquid chromatography. The

applicability of these three methods to

this issue has not been addressed.

Furthermore, they require expensive,

specialized equipment and a high

degree of technical competence.

The agency encourages research to

detect and distinguish ruminant from

nonruminant materials in rendered

products and animal feeds.

III. Statutory Provisions Regarding

Food Additives

The term ‘‘food’’ as defined in the act

includes animal feed. Section 201(f) of

the act (21 U.S.C. 321(f)) defines food as

‘‘articles used for food or drink for man

or other animals’’ and ‘‘articles used for

components of any such article.’’

Furthermore, any substance whose

intended use results or may reasonably

be expected to result in its becoming a

component of food is a food additive

unless, among other things, it is GRAS

or is the subject of a prior sanction.

Section 402(a)(2)(C) of the act (21 U.S.C.

342(a)(2)(C)) deems food adulterated ‘‘if

it is, or it bears or contains, any food

additive which is unsafe within the

meaning of section 409 * * *.’’ Under

section 409(a) of the act (21 U.S.C

348(a)), a food additive is unsafe unless
566 Federal Register / Vol. 62, No. 2 / Friday, January 3, 1997 / Proposed Rules

a food additive regulation or an

exemption is in effect with respect to its

use or its intended use.

A food additive regulation is

established by the submission and

approval of a food additive petition, as

provided in 21 CFR 571.1, or on FDA’s

initiative as provided in 21 CFR 570.15.

FDA on its own initiative or at the

request of an interested party, also may

propose to determine that a substance

intended for use in animal feed is not

GRAS and is a food additive subject to

section 409 of the act as provided in

§ 570.38 (21 CFR 570.38). Subsequent to

the publication of such a proposal and

after consideration of public comments,

FDA may issue a final rule declaring the

substance to be a food additive and

require discontinuation of its use except

when used in compliance with a food

additive regulation.

A. GRAS Determination

A determination that a substance

added directly or indirectly to a food is

GRAS, is generally based on specific

information regarding the composition

of the substance, its use, method of

preparation, methods for detecting its

presence in food, and information about

its functionality in food (21 CFR 570.35)

as determined by experts qualified by

scientific training and experience to

evaluate the safety of such a substance.

A substance added to food becomes

GRAS as the result of a common

understanding about the substance

throughout the scientific community

familiar with safety of such substances.

The basis of expert views may be either

scientific procedures, or, in the case of

a substance used in food prior to

January 1, 1958, experience based on

common use in food (§ 570.30(a)) (21

CFR 570.30(a)). General recognition of

safety through experience based on

common use in food prior to January 1,

1958, may be determined without the

quantity or quality of scientific studies

required for the approval of a food

additive regulation. However,

substances that are GRAS based on such

use must be currently recognized as safe

based on their pre-1958 use. (See United

States v. Naremco, 553 F.2d 1138 (8th

Cir. 1977); compare United States v.

Western Serum, 666 F.2d 335 (9th Cir.

1982).) A recognition of safety through

common use is ordinarily to be based on

generally available data and information

(§ 570.30(c)). An ingredient that was not

in common use in food prior to January

1, 1958, may achieve general

recognition of safety only through

scientific procedures.

General recognition of safety based

upon scientific procedures requires the

same quantity and quality of scientific

evidence as is required to obtain

approval of a food additive regulation

for the ingredient (§ 570.30(b)). (See

United States v. Naremco, 553 F.2d at

1143.) A substance is not GRAS if there

is a genuine dispute among experts as

to its recognition (An Article of Drug

* * * Furestrol Vaginal Suppositories,

251 F. Supp. 1307 (N.D. Ga. 1968), aff’d

415 F.2d 390 (5th Cir. 1969).) Further,

general recognition of safety through

scientific procedures must be based

upon published studies (United States

v. Articles of Food and Drug Colitrol 80

Medicated, 372 F. Supp. 915 (N.D. Ga.

1974), aff’d, 518 F.2d 743, 747 (5th Cir.

1975)), so that the results are generally

available to experts. It is not enough, in

attempting to establish that a substance

is GRAS, to establish that there is an

absence of scientific studies that

demonstrate the substance to be unsafe;

there must be studies that show the

substance to be safe (United States v. An

Article of Food * * * Co Co Rico,

supra.)

Conversely, a substance may be

ineligible for GRAS status if studies

show that the substance is, or may be,

unsafe. This is true whether the studies

are published or unpublished (50 FR

27294 at 27296, July 2, 1985). If there

are studies that tend to support a

finding that a particular substance is

GRAS, but also studies that tend to

support a contrary position, the conflict

in the studies, just as a conflict in expert

opinion, may prevent the general

recognition of the safe use of the

substance.

B. Prior Sanction

Under section 201(s) of the act, the

term ‘‘food additive’’ does not apply to

any substance used in accordance with

a sanction or approval granted prior to

enactment of section 201(s) of the act

and granted under the act, the Poultry

Products Inspection Act (21 U.S.C. 451

et seq.), or the Federal Meat Inspection

Act (21 U.S.C. 601 et seq.). Section

570.38(d) provides that if the

Commissioner of Food and Drugs is

aware of any prior sanction for use of a

substance, he will, concurrently with a

notice determining that a substance is

not GRAS and is a food additive subject

to section 409 of the act, propose a

separate regulation covering such use of

the substance.

In the case of the materials subject to

this proposed rule, FDA has determined

that it is unaware of any applicable

prior sanction. Any person who intends

to assert or rely on such sanction is

required to submit proof of the existence

of the applicable prior sanction. The

failure of any person to come forward

with proof of such an applicable prior

sanction in response to this notice will

constitute a waiver of the right to assert

or rely on such sanction at any later

time.

C. Food Additive Status of Ruminant

Tissues

The agency recognizes that processed

ruminant byproducts have a long

history of use in animal feeds without

known adverse effects. However, the

evidence as discussed in sections I and

II.A. through II.D. of this document, for

the development of a new pattern of

disease transmission, now indicates that

these ingredients can no longer be

categorically regarded as safe. The

agency tentatively concludes that, based

on this evidence, use of such products

in ruminant feed is not GRAS. The

agency is proposing this regulation in

light of the findings and conclusions

described in sections I and II in this

notice. Nor is the agency aware of a

prior sanction for any feed products that

contain these tissues. Therefore, FDA is

proposing that the addition of protein

derived from ruminant tissues to

ruminant feed would constitute the use

of an unapproved food additive because

no regulation is in effect providing for

such use. Any ruminant feed that

contains protein derived from ruminant

and mink tissues would be adulterated.

Accordingly, FDA is proposing to list

protein derived from ruminant tissues

in part 589.

IV. Comments

FDA’s May 1996 ANPRM requested

public comment and information on all

aspects of TSE’s, including BSE, and the

potential consequences of a prohibition

on the feeding of ruminant protein to

ruminants. The agency received nearly

600 comments, including many that

were submitted long after the comment

period ended. The agency has attempted

to address the comments in this

proposal. If there are any significant

concerns that the agency has not

addressed, these concerns should be

brought to the agency’s attention in

timely comments on this proposal.

Comments that were specific to the

topics covered by the other sections of

this preamble were considered in the

preamble as written. Comments are

discussed in the text of some of these

sections. The following is a general

discussion of the comments received.

Many comments, especially from

renderers, meat packers, feed companies

and farmers, opposed the prohibition of

ruminant protein being fed to

ruminants. The main reasons offered

were the lack of evidence of BSE in the

United States, lack of scientific data to

support the proposal in the absence of
Federal Register / Vol. 62, No. 2 / Friday, January 3, 1997 / Proposed Rules 567

BSE, environmental concerns, lack of an

assay or other practical means to

support enforcement, and the economic

hardship that would fall upon the

animal producers, slaughter facilities,

renderers, feed manufacturers, and

packers. Support for such a prohibition

from consumer groups, pharmaceutical

firms, scientists and veterinarians, and

some livestock organizations,

emphasized a potential effect on human

health, the experience and data from the

United Kingdom, and significant

economic detriment if a BSE epidemic

were to occur in this country. Other

comments described a need to ensure

that exported U.S. bovine-derived

products met international standards

and guidelines, and to maintain

consumer confidence in the beef and

dairy industries even though those

comments acknowledged that there is a

minimal potential risk of infectivity to

animals and humans.

The agency requested scientific

information regarding the occurrence,

transmission, etiology, pathogenesis,

epidemiology, and inactivation of TSE

agents. Many comments were received

that contained useful scientific

information that was considered in the

preparation of this proposed rule, as

described in this preamble and

supporting documents.

Three comments suggested that the

documented existence of nonBSE TSE’s,

and the presence of ‘‘downer’’ cows

(cows unable to walk) in the United

States is evidence that BSE is present in

this country. Three comments stated

that the BSE surveillance in the United

States provides sufficient assurance that

BSE does not exist in this country. A

number of persons commented on

whether specific tissues, such as milk,

blood, and gelatin, should be excluded

from any prohibition, with nearly all

supporting such exclusion.

The agency requested information on

the economic impact of the described

action. Numerous comments provided

data on volume of product impacted,

potential economic benefits, and cost of

compliance to affected persons. The

data were used to develop the

preliminary economic assessment

supporting this proposed rule.

The agency requested information on

the environmental impact and potential

mitigating factors of the described

action. Many comments stated that

alternative disposal of the prohibited

carcasses would be less environmentally

safe than rendering. These and other

comments were considered in the

development of the environmental

assessment.

Numerous comments were received

regarding the need to prohibit only

tissues that have been demonstrated to

be infective. Generally, the comments

stated that tissues that have been proven

to be noninfective should be exempted.

Although the agency is proposing a rule

that would prohibit the use of all

ruminant-derived protein in ruminant

feeds, the agency will, as explained

elsewhere in this document, consider a

partial ruminant-to-ruminant

prohibition as well as a mammalian-toruminant prohibition.

Many comments supported

establishment of Hazard Analysis

Critical Control Points (HACCP) for the

rendering industry, often with

concurrent support for current good

manufacturing practices (CGMP’s) for

animal-derived proteins. For example,

the American Feed Industry Association

proposed a specific set of Good

Manufacturing Practices for the

producers of animal protein products,

and the National Renderers Association

proposed a specific HACCP regulation

for rendering operations. The agency

agrees that the need for HACCP, perhaps

supported by CGMP’s, for animalderived proteins could be considered in

future rulemaking. Several comments

were received regarding labeling

requirements for animal-derived

proteins. The majority of the comments

supported a statement of the origin of

animal-derived protein. The agency has

included a labeling requirement in the

proposed rule.

V. Analysis of Alternatives

A. Overview

In addition to the proposed ruminantto-ruminant rule, the agency is

considering alternative approaches. The

alternatives include: (1) excluding from

ruminant feed all ruminant and mink

materials except those that have not

been found to present a risk of

transmitting spongiform

encephalopathy (partial ruminant-toruminant prohibition); (2) prohibiting

the use in ruminant feed of all

mammalian protein (mammalian-toruminant prohibition); (3) prohibiting

the feeding of materials from species in

which TSE’s have been diagnosed in the

United States (sheep, goats, mink, deer,

and elk); (4) prohibiting the feeding of

specified sheep and goat offal, as

proposed by the agency in 1994; (5)

other alternatives that might be

proposed by the comments; and (6) no

action.

Analysis of the advantages and

disadvantages of the options follows.

Analysis of costs and benefits, including

detailed economic analysis, also appears

in section IX. of this document.

Environmental consequences are

discussed in section VIII. of this

document.

In determining the scope of the final

rule, the agency will weigh carefully the

comments received, along with material

contained in the administrative record

for this proposal and the comments

submitted in response to the ANPRM.

Comments regarding the scope of the

rule, including those comments

supporting other options other than the

proposed option, should be addressed

accordingly.

B. Ruminant-to-Ruminant Prohibition

Advantages of this option, compared

with the ‘‘no action’’ option, are

discussed in detail in section I. of this

document. The advantages of this

option that are discussed in that section

would apply if BSE were to occur in this

country. As discussed in separate

sections that follow, there would also be

environmental and economic

advantages to the ruminant-to-ruminant

option, if BSE were to occur in this

country. Disadvantages of the ruminantto-ruminant option, compared to the

‘‘no action’’ option, would be relevant

primarily if BSE did not occur in the

United States. These disadvantages

would include the time and expense

required to comply with the provisions

of the regulation, and the limited, short

term environmental effects described in

section VIII. of this document.

Compared with the mammalian-toruminant option, the ruminant-toruminant option has the advantages of

being tailored more precisely to the

identified scientific concerns, and less

burdensome on the affected industries.

Economic and environmental costs

would be less. The major disadvantage

is that the ruminant-to-ruminant option

results in more complexity for the

regulated industries, and thereby

provides less assurance of compliance.

This is explained further in the

discussion of the mammalian-toruminant option, in section V.D. of this

document.

Compared to the other remaining

options, which are less restrictive, the

ruminant-to-ruminant option provides

greater assurance of protection of the

public health and, if BSE were to occur

in the United States, lower economic

and environmental costs. The

disadvantages relate generally to the

greater economic and environmental

costs that would be incurred if BSE did

not occur in the United States.

C. Partial Ruminant-to-Ruminant

Prohibition

As an alternative to the proposed

ruminant-to-ruminant prohibition, the

agency is considering a partial
568 Federal Register / Vol. 62, No. 2 / Friday, January 3, 1997 / Proposed Rules

ruminant-to-ruminant prohibition

which would exclude from ruminant

feed all ruminant and mink materials

except those that have not been found

to present a risk of transmitting

spongiform encephalopathy. The

exclusions would be in addition to milk

products, gelatin and bovine blood,

which are excluded in the proposed

rule. Possible exclusions include

slaughter byproducts from bovine that

have been inspected and passed in

inspected slaughter facilities, except the

brain, eyes, spinal cord, and distal

ileum. The four named tissues would be

prohibited because they have been

shown through experimental trials and

bioassays to transmit spongiform

encephalopathy. The remaining tissues

have not been demonstrated to transmit

spongiform encephalopathy.

This option has the advantage of

having its prohibitions based primarily

on scientific information related to

infectivity of specific tissues. A number

of persons who commented on the

ANPRM urged the agency to base its

regulation entirely on such scientific

information. In addition, this option

would likely involve lower lost sales

revenues to the affected industries, and

could have fewer adverse economic

effects, than would the other options.

However, the agency has three

concerns with regard to the adequacy of

this option in providing sufficient

protection for the public health. First,

FDA recognizes that it may be

impractical in the slaughter and

rendering processes to segregate and

exclude the bovine tissues that have not

been found to present a risk. For

example, USDA has expressed

reservations that separating the distal

ileum from the other intestinal offal

could jeopardize a slaughter plant’s

ability to meet pathogen reduction goals

required under USDA’s HACCP

regulations. Furthermore, regulatory

enforcement of a prohibition affecting

only specified bovine tissues may be

impractical in the absence of specific

diagnostic methods for identifying

protein derived from such tissues. If a

partial prohibition were adopted, it

would be based on a finding that

practical methods can be implemented

for segregating, processing, storing, and

identifying feed materials derived from

tissues that have not been found to

present a risk.

Second, this option would be

inconsistent with actions taken in a

number of other nations. For example,

CDC has commented that any

prohibition of lesser scope than a

ruminant-to-ruminant prohibition

would place the United States out of

step with the international public health

community.

Third, limiting the prohibition of

tissues to those that have been shown to

be infective would not address the risk

that may be presented by other tissues.

Definitive assays using methods more

sensitive than currently available

methods might identify such additional

tissues as infective. The possibility of

undetected low dose exposure cannot be

eliminated, particularly for tissues such

as lymph nodes and spleens which

would be expected to be infective (Ref.

1).

These issues raise a substantial

question as to whether the tissues could

be GRAS. To achieve the highest level

of public health protection, the agency

believes that it may be reasonable to

assume that, in the absence of scientific

data definitively establishing that each

tissue does not transmit spongiform

encephalopathy, all ruminant tissues

present a risk of infectivity.

The agency nevertheless welcomes

comments on this alternative to the

proposed ruminant-to-ruminant

prohibition and especially invites

comments on possible practical means

of separating the distal ileum in

compliance with USDA and industry

standards, as well as the practicality of

the removal of brain, spinal cord, and

eye and the segregation of these tissues

from others in the slaughter plant.

D. Mammal-to-Ruminant Prohibition

The agency received comments in

support of a rule that would prohibit the

use in ruminant feed of all mammalianderived protein. For instance, the

American Feed Industry Association,

NRA, and APPI expressed concerns that

segregating certain mammalian derived

proteins from others would not be

feasible because of regular commingling

of protein products at feed mills and

rendering facilities. A mammalian-toruminant prohibition would provide

greater assurance of industry

compliance than either a partial or total

ruminant-to-ruminant prohibition

because practical analytical methods

exist for distinguishing mammalian

from nonmammalian proteins.

Implementation of a mammal-toruminant prohibition by the regulated

industries would be less complex, and

would reduce the potential for

contamination of cattle feeds with

material intended for feeding

monogastric animals. Contamination of

cattle feeds with material intended for

feeding nonruminants was the primary

reason that the United Kingdom has

prohibited mammalian proteins in the

rations of cattle. A mammal-to-ruminant

prohibition would enable the continued

use of Association of American Feed

Control Officials definitions for the

purpose of identifying and labeling

products covered by the prohibition,

and would not require additional or

new labeling. Finally, concerns were

expressed that allowing certain products

containing meat and bone meal to be

used in ruminant feeds while

prohibiting others would lead to

instability in financially sensitive

commodity markets for animal protein.

On the other hand, the agency is not

aware of any scientific data that

establish or suggest TSE infectivity in

nonruminant mammals except in mink.

Thus, excluding nonruminant tissues

from ruminant feed would be based

primarily on the view that the

possibility of infection of nonruminant

tissue through cross-contamination or

commingling with ruminant tissue is

sufficient to preclude GRAS status for

the nonruminant tissue. However, FDA

is aware that some portions of the

affected industries would prefer to

segregate ruminant from nonruminant

tissues, and believe that such separation

is practical. Accordingly, the agency

invites comments on the relative merits

and disadvantages of a mammal-toruminant prohibition compared with a

total or partial ruminant-to-ruminant

prohibition.

E. Prohibition of Materials From U.S.

Species Diagnosed With TSE’s (Sheep,

Goats, Mink, Deer, and Elk)

This option would involve requiring

that ruminants not be fed any proteins

derived from any U.S. animal species in

which a TSE has been diagnosed. This

includes sheep, goats, mink, deer, and

elk. This approach would eliminate the

scrapie agent, along with TME and

CWD, from ruminant feed, and thereby

reduce the risk of BSE in cattle caused

by TSE transmission from other species.

However, it would not prevent the

spread of BSE among cattle if BSE

occurred for some other reasons, e.g., by

a spontaneous mutation in cattle or

importation of animals with BSE, and

the animals were processed and

subsequently included in ruminant

feed. As explained in section IX. of this

document, this option involves lower

economic costs than the three options

previously described, in the absence of

a BSE outbreak.

F. Sheep-Specified Offal Prohibition

The option of prohibiting only protein

from specified offal from sheep and

goats for use in ruminant feed would

eliminate the scrapie agent from bovine

feed. However, it would not prevent the

spread of BSE among cattle if BSE

occurred for some other reason, e.g., by
Federal Register / Vol. 62, No. 2 / Friday, January 3, 1997 / Proposed Rules 569

a spontaneous mutation in cattle or

importation of animals with BSE, and

the animals were processed and

subsequently included in ruminant

feed. The agency notes that if it were to

select this option, it would reconsider

its statement in the 1994 proposed rule

that sheep less than 12 months of age

presented a minimal risk. Cases of

scrapie in sheep as young as 7 months

have been reported (Ref. 113). Although

the risk presented by young animals

may be minimal, excluding them may

provide inadequate protection to the

public health. As explained in section

IX. of this document, this option

involves lower economic costs than the

options described previously, in the

absence of a BSE outbreak.

G. No Action

The advantages and disadvantages of

this option, in relation to the other

options, are discussed in detail in

section I. of this document and in the

preceding subsections of this section, as

well as the environmental and economic

sections. In general, this option offers

lower economic and environmental

costs if BSE does not occur in the

United States, and higher such costs (in

addition to public health implications)

if BSE does occur.

VI. Description of the Proposed Rule

A. Introduction

1. Regulatory Alternatives

Typically, FDA regulates products

that are of public health concern

through a combination of regulatory

tools including: labeling for appropriate

use; CGMP regulations and, recently,

HACCP regulations; specifications for

the product or its manufacture; and

testing to determine the presence or

level of the agent of concern. Use of two

or more of these means provides for

appropriate reinforcement to ensure that

the public is protected.

The agency’s choice of readily

available approaches for regulating

animal protein products derived from

ruminant and mink tissues is limited.

For example, there are no practical tests

for the presence of the TSE agent or of

ruminant protein in animal feed. No

commercial method of deactivating the

TSE agent in animal protein products

has been scientifically validated as

effective. None of the agency’s CGMP or

HACCP regulations apply to this

situation. Labeling requirements can be

used but, by themselves, do not meet

the agency’s regulatory objectives.

2. The Regulated Industry

Often, the industry that manufactures

and distributes an FDA-regulated

product is fairly easily characterized.

This facilitates regulation. That is not

the case for animal protein products, as

the following brief overview makes

clear.

Renderers collect animal tissues from

a variety of sources, and process these

tissues into both protein and nonprotein

products. The renderers may be

specialized (packer/renderer) or

independent. The packer/renderer,

which involves a renderer associated

with a large slaughter operation,

specializes in one species—primarily

cattle, swine, or poultry. Thus, whether

the packer/renderer handles ruminant

materials is fairly easily determined.

The independent renderer, on the other

hand, obtains a variety of raw materials

ranging from restaurant scraps to

byproducts from multi-species

slaughtering operations to dead animals

obtained from farmers. Typically, the

independent renderer does not have a

practical method to separate incoming

ruminant from nonruminant materials,

and thus commingles both ruminant

and nonruminant materials in the

rendering process. The rendered

product is typically designated ‘‘meat

and bone meal,’’ but rendering

operations produce a variety of other

products. Renderers sell their products

to animal protein blenders, animal feed

manufacturers or pet food

manufacturers. Virtually all rendered

material at present is used ultimately for

pet food or the feed of livestock or

poultry.

Animal protein blenders mix animal

and plant protein materials to meet a

protein guarantee stated on the label,

and to make a balanced nutritional

product. Typically, the blender does not

separate ruminant from nonruminant

animal protein in its blending operation,

although it may keep mammalian,

poultry, fish and soybean meal protein

separate at least in the initial stages. The

blender sells its products to feed or pet

food manufacturers. Some renderers

also blend animal protein products.

Feed manufacturers use the protein

material to make a complete feed (ready

to be feed to animals), or a concentrated

feed that needs to be further diluted

(blended) before it can be fed to

animals. The feed may be manufactured

by an off-farm miller, or on the farm.

Feed that is manufactured off-farm may

be sold to one or more persons (for

blending and/or further distribution)

before reaching the farm.

Farmers that feed animals typically

raise one species, but may have more

than one (including both ruminants and

nonruminants). Only about 10 percent

of all animal protein products are fed to

ruminants (mainly cattle) but

approximately half of all animal protein

products comes from ruminants.

3. Enforcement Considerations

The industry scenario described in

the preceding section presents unique

enforcement challenges. The agency is

aware, from the comments to the

ANPRM and other sources, of concerns

that the regulatory impact be

minimized. The agency is also aware of

the need to provide incentive for

innovation, e.g., in testing methodology

and manufacturing technology, that

would reduce the need for regulation.

Finally, the agency is aware of the need,

in designing a regulatory program, to

acknowledge the different

circumstances that exist in the

industries previously described.

Therefore, the agency has designed a

proposed regulatory scheme using the

following principles. First, the agency

has identified minimally necessary

requirements to meet its regulatory

objectives. The agency’s goal is to apply

risk management principles that

minimize risk. Second, the proposed

regulation applies greater restriction

where the risk is greater—for example,

where a firm handles both ruminant and

nonruminant materials and intends to

keep them separated. Third, the agency

intends to rely on normal business

records for much of the documentation

it needs.

A fourth and most important

principle concerns the related objectives

of flexibility and providing incentives to

reduce recordkeeping and labeling

requirements. The proposed regulation

provides for the reduction or

elimination of recordkeeping and

labeling requirements, upon the

development of methods for detection,

deactivation, or verification of product

identity. These provisions are described

further in the discussion that follows.

Industry-wide adoption of scientific

advances including, or in addition to,

those specified in the regulation, could

ultimately lead to amendment or

revocation of any final regulation. An

example of an additional method would

be the development of a practical

method to detect the presence of

ruminant protein in animal protein

products or feed, which could be used

for quality control by firms that separate

ruminant from nonruminant protein,

and by firms downstream from

renderers.

Similarly, research leading to

identification of the TSE causative agent

and the etiology of BSE, and the

characterization of the zoonotic nature

of animal TSE’s, could also lead to

amendment or revocation of any final

regulation.
570 Federal Register / Vol. 62, No. 2 / Friday, January 3, 1997 / Proposed Rules

The agency has tentatively decided

not to place any record keeping, labeling

or other specific requirement on firms

that handle only protein materials from

nonruminant sources. An example

would be a rendering operation that is

part of a swine slaughter operation.

However, if these firms would use or

intend to use animal protein products

containing ruminant tissues in ruminant

feed, or caused such use or intended

use, the feed would be adulterated

under the act.

The agency has also tentatively

decided to require farmers (those

responsible for feeding ruminant

animals) only to make available copies

of invoices and labeling for feed

purchases. Farmers would not be

required to maintain written procedures

for handling animal protein products.

These minimal requirements would

apply even if the farmers were feeding

both ruminant and nonruminant

animals. Purchase records would be

used primarily for traceback purposes.

Because only minimal requirements

would be placed on farmers, the

proposed rules require that labeling for

the animal protein and feed products

caution against feeding the products to

ruminants. Comments on these two

tentative decisions are encouraged.

B. Outline of the Proposed Regulation

The proposed regulation places two

general requirements on persons that

manufacture, blend, process, and

distribute animal protein products and

feeds made from such products. The

first requirement is to place cautionary

labeling on the protein and feed

products. The second is a requirement

to provide FDA with access to sales and

purchase invoices, for compliance

purposes. For example, an invoice

obtained from a feed manufacturer for a

protein product not labeled with the

cautionary statement could be used to

trace back to the supplying renderer to

ensure that it manufactures and

distributes animal protein product from

nonruminant sources.

Firms (renderers, blenders, and feed

manufacturers and distributors) that

handle animal protein products from

both ruminant and nonruminant

sources, and that intend to keep the

products separate, would have certain

additional requirements related to their

source of nonruminant material; the

need for separate facilities or cleanout

procedures; and the need for SOP’s. The

same requirements would apply to firms

that handle feeds containing animal

protein products from both ruminant

and nonruminant sources, and that

intend to keep the feeds separate.

Requirements would be greater for these

operations because of the greater risk

they would present for the possibility of

ruminant protein being fed to

ruminants.

The proposed rule provides that some

or all of the regulatory requirements

would not apply if innovations such as

development of test methods and

deactivation processes for TSE agents

were scientifically validated and put

into commercial use. Provisions for use

of such methods do not imply that the

agency believes that such agents are or

will be in the animal protein products.

The objective is to minimize the risk

that the agent would occur in the

products, regardless of the level of risk.

Certain minimal but additional

requirements would be imposed in such

circumstances. For example, because

the innovations likely would be applied

by renderers, the renderers would need

to certify to downstream customers that

the methods were being utilized.

Section 589.2000(a) presents

definitions of certain words used in the

regulation. The definition of ‘‘protein

derived from ruminant and mink

tissues’’ excludes blood from bovines,

milk proteins, and gelatins. Thus, those

products are not subject to the

regulatory provisions of the regulation.

The proposed rule does not apply to any

nonprotein animal tissues such as

tallow or other fats. ‘‘Renderer’’

includes firms, not traditionally

considered to be included within the

definition of that term, but that collect

animal tissues from various sources and

subject them to minimal processing

before offering the materials for use in

animal feed. Also, ‘‘feed manufacturers’’

is defined to include both off-farm and

on-farm feed manufacturing operations.

Section 589.2000(b) declares that

protein derived from ruminant and

mink tissues is not GRAS when

intended for use in the feed of ruminant

animals. The use or intended use of

such material in ruminant animal feed

causes the feed to be adulterated.

Section 589.2000(c) establishes

regulatory requirements for renderers

that manufacture products that contain

or may contain protein derived from

ruminant and mink tissues. (‘‘May

contain’’ allows for the fact that the

renderer may not be able to determine

the species of some incoming material).

These renderers typically process both

ruminant and nonruminant materials,

but do not attempt to separate ruminant

from nonruminant materials. Section

589.2000(e) covers renderers that intend

to separate such materials. As

mentioned, renderers that process

exclusively nonruminant materials are

not covered by the specific requirements

of the regulation. Section 589.2000(c)

applies to animal protein products

intended for use in animal feeds, as well

as animal feeds containing such

products.

Two requirements would be placed

on renderers covered by § 589.2000(c).

First, they would be required to label

their products to indicate that they

contain (or may contain) protein derived

from ruminant and mink tissues, and

that the materials should not be fed to

ruminant animals or used to

manufacture feed for ruminants.

Second, the renderers would be

required to maintain copies of sales

invoices for all their animal protein

products, and to make those copies

readily available for inspection. As an

example, FDA would use the invoices to

follow up with customers to verify that

the customers are not using the products

to manufacture ruminant feed. Because

sales invoices are normal business

records, the agency believes that the

additional burden imposed by this

requirement would be minimal.

Section 589.2000(c) renderers would

be exempted from the labeling and

record requirements if they used a

manufacturing method that deactivates

the agent that causes TSE’s, or a test

method that detects the presence of the

agent that causes TSE’s. Both methods

would have to be validated by FDA, and

made available to the public. The

regulation would require ‘‘routine’’ use.

That is, renderers would be required to

use the test method on all incoming

material or in each batch it

manufactures.

Section 589.2000(c) renderers would

be exempted from the record

requirements (but not the labeling

requirement) if they used a safe method

to mark the presence of the materials.

The marking could be visible to the

naked eye, e.g., through use of a dye, or

by a nonvisual means. One ANPRM

comment recommended use of a colored

uniform fine iron product to identify

specific feed ingredients. If the marking

is not visible, the marking agent must be

detectable by a method that has been

validated by FDA, and made available to

the public. The mark must be

permanent, i.e., it must be visible in

mixed feed as used on the farm.

Section 589.2000(d) establishes

regulatory requirements for persons

other than renderers and persons

responsible for feeding ruminants that

handle animal protein products or feeds

containing such products. This includes

protein blenders, and feed

manufacturers and distributors.

However, as in the case of renderers,

those firms that would otherwise be

included in § 589.2000(d) but that

handle both ruminant and nonruminant
Federal Register / Vol. 62, No. 2 / Friday, January 3, 1997 / Proposed Rules 571

materials and intend to separate the

materials would be covered by

§ 589.2000(e) instead. Protein blenders,

and feed manufacturers and

distributors, that handle only

nonruminant materials are excluded

from the regulatory requirements of the

proposed rule.

Persons covered by § 589.2000(d)

would be subject to the same

requirements as renderers, i.e., labeling

and records. The records would include

invoices both to cover purchases and

sales of animal protein products and

feeds containing those products. For onfarm mixers, production records could

be substituted for sales invoices.

Section 589.2000(d) firms would be

exempt from the labeling and record

requirements if they purchased

materials from renderers that certified

the use of deactivation or detection

methods as described in § 589.2000(c).

They would also be exempt from the

labeling and record requirements if they

purchased materials from persons other

than renderers who certified that they

purchased materials from renderers who

certified the use of deactivation and

detection methods as described in

§ 589.2000(c). Paragraph (d) firms would

also be exempt if they used the

deactivation or detection methods

described in § 589.2000(c), where use of

such method is appropriate for the

particular firm.

Paragraph (d) firms would be exempt

from the record requirements if they

purchased visibly-marked materials, or

purchased from renderers that certified

the use of marking methods as described

in § 589.2000(c). They would also be

exempt from the record requirements if

they used the marking methods as

described in § 589.2000(c).

Section 589.2000(e) establishes

regulatory requirements for renderers,

protein blenders, feed manufacturers

and distributors, and independent

haulers that handle both ruminant and

nonruminant materials, and intend to

keep the products separate. Section

589.2000(e) establishes four kinds of

requirements. First, the firms would

have the same labeling and

recordkeeping requirements as specified

in paragraphs (c) and (d) of § 589.2000,

except that the labeling requirement

would apply only to the ruminant and

mink materials. Second, a renderer’s

source of nonruminant protein materials

would be limited to single-species

facilities, i.e., facilities slaughtering only

swine. A renderer could purchase

nonruminant protein from more than

one single-species facility. The agency

believes that this restriction is necessary

because of its understanding that it is

not likely to be feasible for mixed

species slaughterhouses to undertake

the additional compliance costs, and

possibly additional facility costs, that

would be required to assure separation

of ruminant and nonruminant materials.

The restriction would therefore help

assure that enforcement of § 589.2000(e)

would be practicable. However, the

agency specifically requests comments

on this provision.

Third, the firms would be required to

establish separate equipment and

facilities for the two kinds of materials,

or cleanout procedures to prevent cross

contamination. Fourth, the firms would

need to establish written SOP’s

specifying the cleanout procedures, if

used, and specifying procedures for

separating the materials from the time of

receipt until the time of shipment.

Although § 589.2000(e) applies to

several different kinds of firms, the

agency’s preliminary expectation is that

only feed manufacturers and

distributors will find it feasible to

separate ruminant and nonruminant

materials. As an example, a feed

manufacturer might obtain ruminant

materials from an independent renderer

and swine materials from a packer/

renderer, and use these materials to

manufacture feed both for ruminants

and nonruminants. The feed

manufacturer would be required to meet

the criteria listed previously, including

the use of separate equipment and

facilities or cleanout procedures, and

the establishment of SOP’s. The

requirements of § 589.2000(e) would be

applicable in the transportation process,

whether the material is hauled by the

feed manufacturer or another party such

as an independent hauler. The

requirement for separate facilities,

procedures or SOP’s would not apply to

a firm, e.g., a feed mill or hauler, that

handles only nonruminant materials, or

only ruminant materials. Nor would it

apply to a firm that handles both

ruminant and nonruminant materials

but does not attempt to separate the two

kinds of materials.

The paragraph (e) firms would be

exempted from the labeling and/or

record keeping requirements, and the

requirements related to sourcing,

facilities and SOP’s, if they meet the

appropriate criteria for exemption. That

is, renderers covered by § 589.2000(e)

would be exempt from the labeling and

recordkeeping requirements if they used

deactivation or detection methods, and

from the recordkeeping requirements if

they used marking methods. Blenders

and feed manufacturers and distributors

would be exempt in a similar manner.

Section 589.2000(f) establishes

requirements for those who are

responsible for feeding ruminant

animals. The only requirement

contained in this paragraph is that those

persons make available to FDA copies of

purchase invoices and labeling for all

incoming feeds. However, § 589.2000(f)

does not apply to the feed

manufacturing portion of farms and

feedlots that have on-farm feed

manufacturing operations. Section

589.2000 (d) and (e) would apply in

those instances. Furthermore, persons

who feed or intend to feed ruminant

protein to ruminant animals would be

subject to regulatory action for using or

intending to use an unapproved feed

additive as established in § 589.2000 (b).

Section 589.2000(g) establishes that

violations of § 589.2000 (c) through (f)

would cause animal protein products or

feed containing animal protein products

to be adulterated under sections

402(a)(4) or 402(a)(2)(d) of the act, or

misbranded under section 403(a)(1).

Section 589.2000(h) establishes

inspection and records retention

requirements for persons covered by

section 589.2000 (c) through (f). Records

that are required under those paragraphs

would need to be kept for a minimum

of 2 years. The agency believes that this

time period is adequate for purposes of

verifying compliance with the

regulation’s procedural requirements.

The agency invites comments on the

need for a longer retention period

related to the BSE incubation period,

especially the practicality of using such

records for epidemiologic investigation.

Section 589.2000(h) also requires that

written procedures required by the

regulation be made available for

inspection and copying by FDA. The

written procedures referred to are those

specified in § 589.2000(e)(3). Affected

firms would be required to have a copy

of the current procedures available at all

times.

VII. Specific Protein Sources

A number of comments discussed the

exemption of certain tissues, including

fluids, from any prohibitory rule. Most

commentors favored the exemption of

one or more tissues, including milk

products; blood products; skeletal

muscle and gelatin; and a variety of

other tissues including both protein and

nonprotein materials. Most of the

comments cited published studies as

well as positions taken by the European

Union, European Commission, WHO

and the government of France. The

agency’s comments on the status of

milk, gelatin and blood follow. In

addition, we discuss a comment on the

use of canine and feline derived protein.
572 Federal Register / Vol. 62, No. 2 / Friday, January 3, 1997 / Proposed Rules

A. Milk Proteins

Data available to the agency suggests

that milk proteins do not transmit the

TSE agent. Research with oral exposure,

intracerebral, and intraperitoneal

administration of milk or mammary

glands from BSE-infected bovine to

normal and BSE-sensitive mice has not

demonstrated the development of TSE’s

(Refs. 42 and 52). An expert group

under the auspices of WHO

recommended that all countries prohibit

the use of ruminant tissues in ruminant

feed. The WHO expert group also

declared that milk and milk products,

including such products from the

United Kingdom, are safe for human

consumption. In addition, OIE has

recommended, because of lack of

infectivity, that restriction of import or

transit of milk products from healthy

animals from BSE countries need not be

instituted. Therefore, the proposed rules

provide that protein derived from

ruminant tissues does not include milk

proteins derived from bovine, ovine,

caprine, and cervine.

B. Gelatin Proteins

Data available to the agency suggest

that gelatin does not transmit the TSE

agent. The WHO has concluded that

gelatin in the food chain is considered

to be safe, as the conventional

manufacturing process for gelatin has

been demonstrated to significantly

inactivate any residual infective activity

that may have been present in source

tissues (Ref. 2). FDA concurs with this

statement and the scientific information

on which it is based. Thus, the proposed

rule excludes gelatin from protein

derived from ruminant tissues.

C. Blood Meal Proteins

Data available to the agency suggests

that bovine blood components do not

transmit the TSE agent (Refs. 56, 78, and

94). Therefore, the proposed rule does

not include blood meal from bovine as

a protein derived from ruminant tissues.

D. Canine and Feline Derived Proteins

One comment suggesting that canineand feline-derived proteins should not

be fed to ruminants because of the

finding of FSE in domestic cats in the

United Kingdom. The agency is also

aware of an ethically-based objection by

some to the rendering of the carcasses

of pet animals. TSE has not been

diagnosed in dogs or other canines. FSE

has not been diagnosed in the United

States. The agency has considered the

information provided by the comments

and the published scientific literature

(Refs. 26 and 27), and has preliminarily

determined that there is no measurable

risk of the spread of TSE’s from canineor feline-derived proteins to ruminants

in the United States. However, the

agency is inviting further comment on

this issue.

VIII. Environmental Impact

FDA has carefully considered the

potential environmental effects of this

proposed rule and of five possible

alternative actions. In doing so, the

agency reviewed ANPRM comments

submitted by a number of organizations

and individuals. The comments were

mostly concerned with the volume of

material (e.g., dead animals and

slaughter byproducts) that would be

affected, and the nonrendering or

rendering alternative means by which

these materials could be disposed of, or

utilized, safely. Comments suggested a

number of uses for the processed

materials, other than ruminant feed,

including use in nonruminant animal

feed and fertilizers, and disposal

methods such as on-farm burial,

landfilling, and incineration.

In the environmental assessment that

accompanies this proposed rule, FDA

evaluated the environmental

consequences of six different options.

These included: No action; ruminant

and mink-to-ruminant prohibition (the

proposed action); partial ruminant and

mink-to-ruminant prohibition;

mammalian-to-ruminant prohibition;

prohibition of feeding tissues from any

animal species in which TSE has been

detected in the United States; and sheep

and goat specified offal prohibition.

The environmental assessment

considered each of the alternatives in

the context of two scenarios. The first

assumes that BSE does not occur in the

United States, regardless of the

alternative selected. The second

scenario assumes that BSE does occur in

the United States, again regardless of the

alternative selected. In the first scenario,

the assessment considered

environmental impacts related to onfarm disposal, landfill, incineration, and

industry wastes produced. The second

scenario considered environmental

impacts related to production losses and

impacts, wildlife exposure, on-farm

disposal, landfill, and incineration.

In the first scenario (no BSE), the ‘‘no

action’’ alternative does not have

environmental consequences because it

is the ‘‘status quo’’ or baseline

alternative. Environmental impacts for

the other alternatives ranged from slight

to moderate increases in environmental

effects. For the proposed option

(ruminant-to-ruminant) there would be

moderate increases in environmental

effects from on-farm disposal and

landfill use, and slight increases in the

other effects. Increases in waste disposal

(on-farm, landfill, etc.) are anticipated to

be temporary, however, as the markets

are expected to adjust quickly to the

more restricted uses of the ruminant

materials.

In the second scenario (occurrence of

BSE), the greatest negative

environmental effect would occur in the

case of the ‘‘no action’’ alternative. This

is because the likely spread of the BSE

agent through animal feed before the

first BSE case is diagnosed would result

in disposal of large numbers of animals

by means other than rendering. Similar

large impacts would occur with the

sheep and goat, and TSE animal,

options. Minimum environmental

consequences would occur with the

proposed option (ruminant-toruminant), because the spread of the

BSE agent would have been controlled.

Minimum to small effects would result

from the remaining two options, partial

ruminant prohibition and mammalianto-ruminant prohibition.

The agency has concluded that the

proposed rule will not have a significant

impact on the human environment, and

that an environmental impact statement

is not required. FDA’s finding of no

significant impact (FONSI) and the

evidence supporting that finding,

contained in an environmental

assessment (EA) prepared under 21 CFR

25.31, may be seen in the Dockets

Management Branch (address above)

between 9 a.m. and 4 p.m., Monday

through Friday. FDA invites comments

and submission of data concerning the

EA and FONSI.

IX. Analysis of Impacts

FDA has examined the impacts of the

proposed rule under Executive Order

12866, under the Regulatory Flexibility

Act (5 U.S.C. 601–612), and under the

Unfunded Mandates Reform Act (Pub.

L. 104–4). Executive Order 12866

directs agencies to assess all costs and

benefits of available regulatory

alternatives and, when regulation is

necessary, to select regulatory

approaches that maximize net benefits

(including potential economic,

environmental, public health and safety,

and other advantages; and distributive

impacts and equity). The Regulatory

Flexibility Act requires agencies to

analyze regulatory options that would

minimize any significant impact of a

rule on small entities. The Unfunded

Mandates Reform Act requires that

agencies prepare an assessment of

anticipated costs and benefits before

proposing any rule that may result in an

annual expenditure by State, local, and

tribal governments, in the aggregate, or

by the private sector, of $100,000,000

(adjusted annually for inflation). FDA
Federal Register / Vol. 62, No. 2 / Friday, January 3, 1997 / Proposed Rules 573

concludes that this proposed rule is

consistent with the principles set forth

in the Executive Order and in these two

statutes.

A study of the impacts on industry of

the proposed rule (on file with the

Docket Management Branch (Ref. 114))

conducted for FDA by the Eastern

Research Group (ERG), a private

consulting firm, and the discussion in

the remainder of this section,

demonstrate that the proposed rule

constitutes an economically significant

rule as described in the Executive

Order. The agency has further

determined that the proposed rule will

have a significant impact on a

substantial number of small entities.

The proposal makes no mandates on

government entities and is estimated to

result in aggregate net annual costs

ranging from $21.4 to $48.2 million to

the private sector.

A. The Need for Regulation

Although BSE has not been diagnosed

in the United States, the need for

regulatory action is based on a need to

protect U.S. livestock from the risk of

contracting BSE. In its guidelines for the

preparation of Economic Impact

Analyses, the Office of Management and

Budget (OMB) directs Federal regulatory

agencies to determine whether a market

failure exists, and if so, whether that

market failure could be resolved by

measures other than new Federal

regulation. In this instance, private

incentive systems for both suppliers and

purchasers may fail in markets for

cattle, rendering, and ruminant feed.

The potential for market failure among

the suppliers in these sectors results

from the externality that could be

created by individual suppliers

imposing economic hardships on other

suppliers within the industry. The

potential for market failure among the

purchasers results from the inadequate

information that would be available to

purchasers of potentially infective

products.

Any renderer, feed manufacturer, or

cattle producer that permits animal

protein derived from ruminants and

mink to be placed in ruminant feed

increases the risk that other renderers,

feed manufacturers, or cattle producers

will suffer the severe economic

consequences that would follow an

outbreak of BSE in the United States.

The industry is aware of this risk, as

evidenced by the existence of voluntary

programs aimed at reducing the

transmission of the infectious agent.

These include an adult sheep rendering

ban recommended by the NRA, a

recommended ban on the feeding of

rendered ruminant protein to ruminants

by the NCBA and others, and scrapiefree certification programs by individual

sheep producers. Although the benefits

of such programs—the reduction or

elimination of the risk of an outbreak of

BSE and the increased consumer

confidence in the safety of the

industries’ products—accrue to all

members of these industries,

compliance with these measures is

incomplete, because individual

noncomplying members can avoid the

costs of risk reduction measures while

still enjoying the benefits of compliance

by others in the industry.

If purchasers could easily identify the

risks of infective agent contamination

associated with products from specific

suppliers, they could more easily take

defensive actions to reduce these risks

(e.g., refusing products from cattle

known to have consumed specified

ruminant proteins). Purchasers are

unlikely to obtain the information they

need, however, for several reasons.

First, the long incubation period for BSE

creates a lag between the actual onset

and the recognition of the disease and

could lead to a suboptimal level of risk

prevention by the concerned parties

during the incubation period. By the

time the first signs of disease are

observed, many animals may have been

already exposed. Moreover, renderers

sell their product to feed manufacturers

who frequently combine proteins from

many different plant sources and animal

species to produce cattle feed. Ruminant

producers, therefore, have no sure way

of knowing whether a particular batch

of feed is free from potentially infective

proteins and cannot easily avoid

purchasing risky feed. Finally, if

renderers or feed manufacturers do not

believe that BSE is an important threat

they may choose not to take preventive

action, regardless of the risk levels

perceived by epidemiological experts or

consumers.

B. Benefits

The proposed rule would reduce the

risk of an outbreak and subsequent

proliferation of BSE disease in the

United States. It may also forestall the

loss of consumer confidence in the U.S.

beef market due to concerns about BSE

and its implications. Thus, the benefits

of this proposal would include the value

of reduced risks to human and animal

health and to the economic stability of

the U.S. livestock and livestock

dependent industries compared to the

‘‘no action’’ option. In technical terms,

these benefits measure the expected

value of the future disease-related costs

that might be averted by the proposed

rule. Specifically, they are calculated as

a product of three factors: (1) The

probability that, in the absence of this

rule, BSE would be introduced and

proliferate in the United States, (2) the

costs, both direct and indirect, that

would be associated with the spread of

BSE in the United States, and (3) the

extent to which the proposed rule

would reduce the likelihood of BSE

proliferation.

BSE has not been detected in the

United States and the probability that it

currently exists is remote. Nevertheless,

it is possible that BSE could develop in

the future. Once developed, BSE could

remain undetected for several years

because of its long incubation period

and because, at present, it can be

diagnosed reliably only by microscopic

brain examination after death. During

the period between introduction and

diagnosis, the disease could spread as it

apparently did in the U.K. via intake of

infective feed. If regulation was delayed

until after discovery, the costs would be

substantial. By addressing the central

risk factors associated with BSE, FDA

believes that the proposed rule would

eliminate the vast majority of the BSErelated risks and costs.

BSE was first detected in the U.K. in

November 1986, and a ban on ruminant

offal in ruminant feed was imposed in

the U.K. in July 1988 (Ref. 115). An

analysis of cattle born before and after

the feed ban went into effect suggests

that the feed ban significantly decreased

disease transmission (Ref. 116). This

analysis found that the incidence of

confirmed BSE roughly doubled each

year for animals born between July 1985

and July 1988, but declined

precipitously in animals born in August

1988 compared to the previous year and

continued to fall thereafter. Because

BSE has a long incubation period,

however, a decrease in the incidence

was not evident until several years after

the initial feed ban was implemented.

The incidence of BSE peaked in 1992 at

36,681 detected cases, or approximately

0.3 percent of the UK’s 11.5 million

cattle. Despite a sharp decrease in the

incidence rate since then, by the end of

1996, more than 165,000 cases of BSE

will have been detected, with one-third

of all U.K. cattle herds infected (Refs.

115 and 117).

The likelihood that BSE will someday

be developed in the United States

cannot be estimated with any

confidence, although U.S. risk factors

are believed to be significantly smaller

than existed in the United Kingdom of

the early 1980’s. As described

previously, the various remaining

modes include transmission from

scrapie-infected sheep or other animals

with TSE, e.g., through meat and bone

meal; introduction via imported
574 Federal Register / Vol. 62, No. 2 / Friday, January 3, 1997 / Proposed Rules

animals; and spontaneous introduction

(which in some TSE’s has been

hypothesized to occur at a rate of about

1 case per million per year). USDA

import controls and the voluntary bans

on sheep offal and ruminant tissues in

ruminant foods reduce the risk of

disease introduction but cannot

completely eliminate it.

Although FDA cannot quantitatively

estimate the risk of a significant BSE

outbreak in the United States, the

agency has used the U.K. experience,

modified to account for major

differences in circumstances, to assess

the consequences of the potential spread

of the disease within the United States.

If BSE were introduced in this country,

the pattern of disease spread would

presumably be similar to that in the

United Kingdom, with most

symptomatic disease appearing in older

cattle (the average time for BSE

symptoms is approximately 5 years after

infection (Ref. 115)). The rate of spread

of symptomatic disease would probably

differ, however, because compared with

the pre-BSE U.K. dairy industry, U.S.

dairy cows are younger and are exposed

to meat and bone meal in feed later in

life than was true in the United

Kingdom (Ref. 118). United Kingdom

dairy animals were historically fed meat

and bone meal as calves, whereas U.S.

dairy cows ingest meat and bone meal

primarily as adults.

1. Methodology

To develop an illustrative estimate of

the number of cattle that might be lost

to BSE infection if the disease were to

occur in the United States in the

absence of regulation, FDA extrapolated

from the experience in the United

Kingdom, but adjusted for the

differences in cattle age and potential

age of exposure to meat and bone meal.

This extrapolation assumes that the

detection of BSE in this country would

quickly lead to a ruminant-to-ruminant

feed prohibition but that, as in the

United Kingdom, BSE incidence would

nonetheless continue to increase for 6

years due to the disease’s long

incubation time (hence several years of

disease spread before the diagnosis of

the first case). To account for the

difference in cattle age-related risk

factors, FDA assumed that, if BSE

occurred in the United States, the

affected animals would be

predominately dairy cows of age 4 or

more, rather than age 3 and up as in the

U.K. (due to the differences in age of

exposure.) The difference of 1 year is

based on the agency’s estimate that U.S.

cattle are first exposed to meat and bone

meal 1 year later than U.K. cattle.

Therefore, the onset of the clinical

disease is estimated to start 1 year later.

Accordingly, only 47 percent of U.S.

dairy cows are age 4 and up (about 4.8

million cows), while 90 percent of

United Kingdom cows are age 3 and up

(about 2.6 million cows). Thus, a lower

percentage of U.S. cattle were assumed

to be at risk of symptomatic BSE, and

the projected rate of death was

proportionately lower. Based on the

relative size of the U.S. and U.K. dairy

cattle populations, these projections

suggest that if BSE were introduced in

the United States and spread in a

similar manner, the disease would

destroy 299,000 U.S. cattle over 11 years

(4.8 x 2.6 x 162,000 U.K. BSE deaths).

(These calculations assume that a feed

prohibition would be implemented very

soon after the first case is diagnosed,

and that the prohibition would

immediately begin to affect the

underlying rate of new infection. If a

feed prohibition were not implemented

at that time, the number of cattle deaths

would be much higher.)

Other adjustments could be made to

this estimate, but their effect on the

direction of the results would be

uncertain. For example, compared with

U.K. practices before 1988, U.S. dairy

cattle consume a higher proportion of

concentrated feed that contains meat

and bone meal. On the other hand, most

U.S. concentrate contains a lower

percentage of meat and bone meal (and

a higher percentage of vegetable-based

proteins). If BSE infectivity in feed is

highly dose-dependent, these factors

could cause FDA’s cost estimate to be

either too high or too low, if one of the

factors is dominant over the other.

The risks and costs associated with

BSE when it occurs are primarily of

three types. First, there is the possible

risk and associated cost of ruminant-tohuman transmission of TSE disease. The

proposed rule would reduce this risk by

eliminating the main routes by which

ruminants might acquire transmissible

TSE, greatly reducing any risk incurred

by the human consumption of

ruminant-derived products. Thus, the

proposed rule would reduce the risk of

future mortality, morbidity, and health

care costs due to human TSE. Second,

there is the risk of livestock losses.

These losses include not only the deaths

of BSE-infected animals, but also the

loss and disposal costs of other animals

that would be destroyed, either to

contain the immediate spread of disease

or to restore consumer confidence in the

safety of beef and dairy products. Third,

there are the costs associated with

decreased domestic sales and exports of

beef and other bovine-derived products

until consumer and international

confidence could be restored.

2. Reduced Risk to Public Health

As discussed earlier, scientists believe

that the nv-CJD cases identified in the

U.K. may have been associated with the

BSE epidemic. If indeed there were such

an association, and if BSE were to occur

in this country, there would be a risk of

spreading BSE-related human TSE in

the United States The proposed rule

therefore might avert human deaths in

the United States, although the number

of deaths cannot be estimated. The

proposed rule would also save the

health care and other costs associated

with treating individuals with the

disease.

3. Reduced Risk of Direct Livestock

Losses

For estimating the present value of

livestock losses if BSE occurred in the

United States, FDA assumed that the

first case of BSE would not be

detected—even in the absence of the

proposed rule—for 4 years. Based on an

estimated value of $502 per animal (Ref.

119) and disposal costs of $4 per

animal, direct losses from the death of

299,000 BSE-infected cattle would reach

$151 million over 11 years (starting 4

years from now). At a discount rate of

7 percent, the total present value of

these losses is $75 million.

In addition to the animal losses from

direct infection, a significant outbreak

would probably lead to the eradication

of high-risk animals to restore consumer

confidence. Switzerland, for example,

has proposed slaughtering all cattle born

before that country implemented a feed

ban, or approximately one-eighth of its

national herd (Ref. 120). The United

Kingdom has begun a program to

destroy and incinerate all animals over

age 30 months as they reach the end of

their useful life, or about 1 million

animals in 1996 and a total of 4.7

million over 6 years. In addition, the

United Kingdom has a program to

slaughter some unmarketable male dairy

calves (126,000 had been slaughtered as

of August 1996) and up to 147,000

additional ‘‘high-risk’’ animals (Refs.

115 and 121). Even if the U.K.

eradication of animals were limited to a

one-time total of 1 million cattle (about

8.7 percent of their cattle stock), similar

measures in the United States, if they

occurred immediately upon detection of

the disease, would result in the onetime destruction of $4.58 billion worth

of cattle, with a present value of $3.49

billion.

4. Costs of Future Regulation

Moreover, the ability to control a BSE

outbreak once it occurred would require

putting in place restrictions on the use
Federal Register / Vol. 62, No. 2 / Friday, January 3, 1997 / Proposed Rules 575

of ruminant proteins in ruminant feeds

that would be at least as restrictive as

the measure under this proposed rule.

Presumably, the total costs of

implementing a ruminant-to-ruminant

feed prohibition at that point would be

at least as great as the low estimates for

this proposed rule, or $21.4 million per

year. The present value of these future

regulatory costs would total

approximately $240 million. Moreover,

this estimate may vastly understate the

economic impact because the market

value of ruminant-derived proteins

could disappear if there were an actual

outbreak.

5. Reduced Risk of Losses in Domestic

Sales and Exports

If BSE were to emerge in the United

States, the news could greatly reduce

both domestic sales and exports of

bovine products. In the United

Kingdom, domestic consumption fell by

more than 20 percent between 1988 and

1990 and has not yet fully recovered

(Ref. 122), presumably due to

continuing concerns about possible

links between BSE and CJD. If U.S.

consumers acted similarly, U.S.

producers of beef products could lose

over $9 billion in annual sales (Ref.

123). Alternatively, U.S. consumers

might demonstrate considerably less

concern, as the U.K. experience may

have improved the ability of U.S. risk

managers to communicate both the

extent of the risk of contracting CJD

from the consumption of beef and the

responsiveness of the government’s

safety policies. Nonetheless, it remains

probable that the uncertainty

surrounding a serious BSE outbreak

would lead U.S. consumers to reduce

their consumption and spending on beef

by a significant amount. Also, at the

same time that U.K. domestic sales of

beef were declining due to the fear of

BSE, the volume of U.K. exported beef

fell by nearly 16 percent (Ref. 122).

Based on U.S. beef exports in 1994 of

approximately $2.2 billion (Ref. 109), a

proportional decline of this magnitude

would reduce U.S. exports by up to $0.3

billion per year.

While the values of such lost

domestic and international sales would

reduce the profits of the U.S. beef

industry and the enjoyment of some

U.S. consumers of beef, they do not

provide an accurate measure of societal

costs, because competitor industries,

such as poultry, pork, and seafood,

would gain new profits. Thus, the net

costs that would result from such

potential shifts in consumer spending

cannot be precisely discerned without

extensive economic modeling. While

FDA examined a partial equilibrium

model for projecting the approximate

losses of consumer and producer

surplus within the market for beef

products, the agency could not

adequately quantify the likely effects on

the markets for substitutes of beef.

Consequently, FDA could not estimate

the net economic cost of these lost sales.

Nevertheless, the magnitude of these

potential costs could be substantial and

the agency requests public comment on

how the appropriate measurement

methodologies could be developed and

applied.

Finally, even in the absence of

evidence of BSE in the United States,

consumer concern about BSE could

affect beef consumption and

expenditures. Thus, one benefit of

implementing the proposed rule now is

that it might prevent a loss of consumer

confidence in the beef market,

irrespective of the actual risk of BSE.

FDA did not attempt to quantify this

potential loss, but believes that it also

may be substantial, particularly in light

of the recent increased U.S. publicity of

BSE and its hypothesized links to CJD.

6. Total Losses Averted

In summary, the losses averted by the

proposed rule include the expected

value of the costs associated with BSE

itself, and the potential value of

forestalling a drop in domestic and

international demand for U.S. beef due

to BSE-related causes. The first

component largely reflects the statistical

probability that BSE could occur and

spread within the United States and the

potential $3.7 billion cost of destroying

BSE-exposed livestock. The second

primarily measures the expected loss to

U.S. consumers and producers that

would result from reduced sales. While

FDA has not quantified these latter

costs, plausible scenarios indicate that

they could reach billions of dollars.

Moreover, these figures have not

included the possibility of lost lives and

treatment costs associated with treating

human TSE.

Finally, the expected benefits of the

proposed rule are slightly lower than

the sum of the expected value of all the

costs associated with BSE, because the

rule would not totally eliminate all of

the related risk (e.g., due to the

possibility of spontaneous introduction

of disease and the possible incomplete

compliance with the rule). FDA

believes, however, that any remaining

risk would be extremely small. In

addition, because the rate of BSE

infection and the associated costs would

probably vary geographically (as scrapie

does now) (Ref. 98) , the benefits would

vary across regions of the country.

7. Comparison of Alternatives

As described elsewhere in this

document, FDA is considering five

alternatives to the proposed rule, in

addition to other options that might be

offered in the comments. The first three

of these alternatives are: (1) No action

(relying on voluntary industry

activities), (2) prohibit only materials

from U.S. species in which TSE has

been diagnosed, and (3) a prohibition on

proteins from specified sheep and goat

offal in ruminant feed. Compared with

the proposed action, prohibiting

proteins from all U.S. TSE species

provides similar reductions in the risk

that BSE might be introduced, with a

sheep/goat specified offal protein ban

and no action providing progressively

less risk reduction. The TSE species

alternative, however, would be

significantly less effective in limiting

the spread of BSE (e.g., after

spontaneous introduction) until BSE

was diagnosed and cattle were added to

the list of TSE species. Likewise, the

two other alternatives would be

significantly less effective in inhibiting

the spread of ruminant-to-ruminant

transmission of disease once BSE is

introduced. Thus, the expected value of

the benefits of each of the three rejected

options is substantially lower than the

proposed rule, although the amount of

difference cannot be estimated

precisely.

The agency is also considering two

other alternatives: (1) A mammalianprotein-to-ruminant prohibition, and (2)

a partial ruminant-to-ruminant

prohibition which would exclude all

ruminant and mink tissues except

certain bovine tissues. Compared with

the proposed rule, both alternatives

offer similar benefits in substantially

inhibiting the initial introduction of

BSE. The extent of inhibition of the

spread of disease (and associated costs),

however, would be different.

The mammalian protein alternative

would further reduce the spread of

disease compared with the proposed

rule, by reducing the risk of crosscontamination within rendering and

processing plants. Thus, this alternative

would bring the expected value of the

BSE-related costs even closer to zero

than would the proposed measure.

However, the incremental benefit is

small if cross- contamination under the

proposed measure does not pose a

substantial risk.

The partial ruminant-to-ruminant

prohibition would be less effective than

the proposed measure, because it would

be more administratively difficult to

enforce. Thus, this alternative would

not reduce the expected value of the
576 Federal Register / Vol. 62, No. 2 / Friday, January 3, 1997 / Proposed Rules

BSE-related costs as much as the

proposal. Again, however, the exact

difference cannot be estimated, but

would vary depending on the likely

level of compliance under the

alternative.

C. Industry Impacts

The ERG study examines the

composition, size, and scale of

economic activity for the various

affected industry sectors and provides

estimates of the cost and high and low

market impacts (depending on the size

of the price change for restricted meat

and bone meal of five regulatory options

(see Table 1).

TABLE 1.—ESTIMATED COSTS OF ALTERNATIVE REGULATORY PROHIBITIONS 1

Mammalianto-ruminant

Ruminantto-ruminant

(proposal)

Partial ruminant-to-ruminantSheep/

Mink-to-ruminant

Sheep/

Goat-to-ruminant

Annualized Impacts ($ million)

Low Market Impact Scenario ($25/ton)

Capital Costs ............................................................................................ 8.8 1.0 3.2 0.0 0.0

Operating/Disposal Costs ......................................................................... 10.1 0.1 14.4 5.1 0.2

Transportation ........................................................................................... 10.7 7.6 5.3 0.0 0.0

Documentation .......................................................................................... 1.9 1.5 0.5 0.0 0.0

Substitution Costs ..................................................................................... 9.7 8.0 3.7 0.0 0.0

Renderer Revenue Losses ....................................................................... 76.4 63.2 28.8 4.2 0.1

Nonruminant Gains ................................................................................... (72.6) (60.0) (27.4) 0.0 0.0

Totals ............................................................................................. 45.0 21.4 28.5 9.3 0.3

High Market Impact Scenario ($100/ton)

Capital Costs ............................................................................................ 8.8 8.2 4.9 0.0 0.0

Operating/Disposal Costs ......................................................................... 10.1 10.1 16.9 5.1 0.2

Transportation ........................................................................................... 10.7 7.6 5.3 0.0 0.0

Documentation .......................................................................................... 1.9 1.8 0.7 0.0 0.0

Substitution Costs ..................................................................................... 9.7 8.0 3.7 0.0 0.0

Renderer Revenue Losses ....................................................................... 305.6 252.8 115.4 4.2 0.1

Nonruminant Gains ................................................................................... (290.3) (240.2) (109.6) 0.0 0.0

Totals ............................................................................................. 56.5 48.3 37.3 9.3 0.3

1Totals may not match text due to rounding error.

1. The Proposed Rule

The proposed alternative would

prohibit the use of ruminant and mink

protein in ruminant feeds. Currently,

only about 10 percent of the meat and

bone meal supply is used in ruminant

feed, but over 80 percent of the meat

and bone meal contains some ruminant

material. ERG forecast that because no

mixed-species slaughtering or rendering

establishments would find it profitable

to separate ruminant from nonruminant

offal, most would continue to contain

ruminant material. ERG estimated that

affected renderers and feedmills would

incur total direct compliance costs

ranging from $10.2 to $27.6 million per

year. Renderers would bear annual costs

of about $6.3 million and feed mills

would bear annual costs of from $3.8 to

$21.3 million. Arrayed by compliance

category, transportation costs were

estimated at $7.6 million;

documentation costs for activities to

ensure control of ruminant feed

constituents ranged from $1.5 to $1.8

million; and capital costs and operating

costs ranged from $1.0 to $8.2 million

and $0.1 to $10.1 million, respectively,

due primarily to the need for some

feedmills to expand their capacity to

offer both ruminant and nonruminant

feed products under a high market

impact scenario.

Because consumer response to the

rule is uncertain, ERG could not

develop a precise projection of future

meat and bone meal prices. ERG

estimated, however, that the regulatory

prohibition of marketing ruminant meat

and bone meal to ruminants would

lower the price of this product by from

$25 to $100 per ton, decreasing

rendering industry revenues by from

$63.2 to $252.8 million per year. In

contrast, a lower MBM price would

increase sales of meat and bone meal to

the nonruminant sector and the

resulting increased profits for that sector

would offset, at an aggregate level, most

revenue losses. Although ERG did not

quantify this effect, FDA determined

that the assumption of a fixed supply of

meat and bone meal and a linear

demand for nonruminant feed implies

that purchasers of mixed-species meat

and bone meal for nonruminant uses

would save from $60.0 to $240.2 million

annually, because of the lower meat and

bone meal costs. This estimate assumes

a total meat and bone meal supply of 2.5

million tons, changes in price ranging

from $25 to $100 per ton, and an

increase in nonruminant consumption

of meat and bone meal of about 250,000

tons. In addition, manufacturers of

ruminant feed would incur higher costs

if they could not use ruminant proteins.

In an analysis prepared for the feed

industry, protein substitutes, such as

soybean meal and other minerals

necessary to provide the same

nutritional level as that provided by the

meat and bone meal, were estimated to

cost approximately $31.75 per ton more

than meat and bone meal (Ref. 125).

FDA believes that this estimate is

overstated, because it assumes that

soybean meal alone sells for $20 per ton

more than meat and bone meal. In fact,

their respective market prices are

currently similar. Nevertheless, FDA

used the reported $31.75 per ton

differential to estimate that the higher

price of alternative proteins would

increase ruminant feed costs by about

$8.0 million per year.

As a result, FDA estimates that the

aggregated annualized costs of this

proposal, comprised of both the direct

compliance costs and the various

indirect gains and losses, would total
Federal Register / Vol. 62, No. 2 / Friday, January 3, 1997 / Proposed Rules 577

from $21.4 to $48.2 million. Although

the greatest initial burden would fall on

the rendering and feed manufacturing

sectors, ERG noted that the final

distribution of these impacts would

shift; renderers would pass back the

economic impacts to slaughterers, who,

in turn, would pass them back to cattle

producers. FDA judged, however, that of

the small renderers dependent upon

farmers’ and ranchers’ dead stock for

their raw materials, 20 to 25 would be

likely to close. ERG also forecast that

these impacts would cause a decline in

prices for slaughter-weight cattle of $1

to $5 per head. In the long run, ERG

foresaw a modest reduction in the size

of the U.S. cattle herd.

In response to its ANPRM, FDA

received comments on the possible

impacts of the proposal from both

individuals and industry. The

submission from the American Feed

Industry Association (AFIA) contained

an analysis of the animal feed market

that was based on the assumption that

the proposal would taint the safety of all

meat and bone meal (both ruminant and

nonruminant), to the extent that even

nonruminant animal producers would

refuse to purchase the product. This loss

of wholesale value was estimated at

$523 million. Further, the AFIA

comment estimated the cost for

disposing of this meat and bone meal at

$349 million and for substituting to

higher priced feeds at $74 million

annually.

FDA questions the conclusions of the

AFIA report, largely because the

proposed rule does not prohibit the use

of ruminant proteins in nonruminant

feeds and there is no evidence that this

market would disappear. As noted

earlier, nonruminant feed use currently

constitutes about 90 percent of the meat

and bone meal market. While some

nonruminant producers may be wary of

ruminant MBM after the proposal

becomes final, the broad media coverage

of BSE in the United Kingdom and the

voluntary prohibition of ruminant MBM

in ruminant feeds have already

provided nonruminant producers with

substantial information on the relevant

risks. The implications of the ERG study

are that most of the major nonruminant

sectors that use ruminant meat and bone

meal in their feeds would continue this

practice, particularly at sharply lower

MBM prices. Because ERG believed that

all stocks of meat and bone meal would

find a commercial outlet within the

nonruminant feed sector, they projected

no additional disposal costs and far

smaller revenue losses than AFIA.

2. Partial Ruminant-to-Ruminant

Prohibition

ERG also estimated the economic

impact of a partial ruminant-toruminant prohibition, which would

prohibit only the use of proteins from

designated ruminant tissues in ruminant

feeds. ERG projected that cattle packer/

renderers and approximately one-half of

the large cattle packers would choose to

separate the designated and

nondesignated tissues. As shown in

Table 1, this change in processing

would lead to increased costs from

capital investments, increases in

operating and transportation expenses,

training, and documentation activities.

Further, ERG projected, under the high

market impact scenario, that some

feedmills would expand their facilities

to offer both restricted and nonrestricted

meat and bone meal. They estimated the

annualized direct compliance costs for

this option at from $23.5 to $27.9

million. In addition, ERG projected that

this option would cause price declines

of from $25 to $100 per ton for the meat

and bone meal derived from designated

tissues, leading to decreases in renderer

revenues of from $28.8 to $115.4 million

per year. As discussed previously, FDA

again assumed a fixed supply of meat

and bone meal and a linear demand for

nonruminant feed to calculate that

purchasers of mixed-species meat and

bone meal for nonruminant uses would

save from $27.4 million to $109.6

million annually because of the lower

meat and bone meal costs. Adding

additional protein substitution costs of

$3.7 million and other indirect costs

raises the estimated net aggregate costs

for this alternative to $28.6 to $37.4

million.

3. Mammalian-to-Ruminant Prohibition

The third option assessed was the

prohibition of mammalian protein in

ruminant feeds. ERG projected that

slaughtering and rendering

establishments would have no reason to

separate offal because very few of these

establishments process both mammals

and nonmammals. They estimated

annualized direct compliance costs for

this option at $31.6 million. ERG

forecast that, regardless of the size of the

price decline for restricted meat and

bone meal, some feedmills would

expand their capacity to offer both

restricted and nonrestricted meat and

bone meal, resulting in increased capital

and plant operating costs. The majority

of the remaining regulatory costs are

composed of documentation costs.

Assuming that a regulatory prohibition

on marketing restricted meat and bone

meal to ruminants would cause the

price of the restricted meat and bone

meal to fall by from $25 to $100 per ton,

ERG projected that this option would

reduce renderer revenues by from $76.4

to $305.6 million per year.

Alternatively, under the same

assumptions as applied above, FDA

found that purchasers of mixed-species

meat and bone meal for nonruminant

uses would save from $72.6 million to

$290.3 million annually, because of the

lower meat and bone meal costs. Adding

additional protein substitution costs of

$9.7 million and other indirect costs

raises the estimated net aggregate costs

for this third option to from $45.1 to

$56.6 million.

4. Other Regulatory Alternatives

FDA also considered two less

restrictive options for controlling the

spread of an outbreak of BSE in the

United States: A prohibition of all

sheep, goat, mink, deer, and elk proteins

in ruminant feed; and a prohibition of

sheep and goat proteins in ruminant

feed. The first of these alternatives

would require that ruminants not be fed

proteins from any species in which a

TSE was diagnosed in the United States,

which includes sheep, goats, mink,

deer, and elk. ERG anticipated minimal

regulatory impacts for sheep, lamb, and

goat producers because most renderers

already require that sheep, lamb, and

goat offal be excluded from mixed

species meat and bone meal. ERG

estimated that this alternative could

restrict the use of up to 34,150 tons of

offal annually from the various species,

or about 0.3 percent of all mammalian

offal rendered. Using an estimated cost

of $150/ton for landfill disposal, ERG

calculated that the disposal costs for

this alternative could equal $5.1

million. Furthermore, ERG estimated

that the meat and bone meal and tallow

manufactured from offal generates

revenues of about $500/ton of processed

material. Under this option, meat and

bone meal production would fall by

8,450 tons per year, reducing industry

revenues by an estimated $4.2 million

annually.

The final alternative would restrict

only sheep and goat protein from use in

ruminant feed. This alternative is

similar to the agency’s 1994 proposal,

which pertained only to adult sheep and

goats. Most sheep and goats are

currently excluded by renderers from

being rendered into mixed species meat

and bone meal. ERG estimated that this

alternative would restrict the use of up

to 1,200 tons of offal, or about 0.01

percent of all mammalian offal

rendered. At $150/ton for landfill

disposal, the disposal costs would equal

$0.2 million. ERG calculated that
578 Federal Register / Vol. 62, No. 2 / Friday, January 3, 1997 / Proposed Rules

production of meat and bone meal

under this option would be restricted by

only 300 tons per year, leading to

revenue losses of about $0.1 million.

ERG noted that the disposal costs

presented for the latter two alternatives

are high-end estimates because of the

likelihood of onsite disposal for deer

and elk taken by hunters. Further, these

alternatives were not expected to have

a measurable effect on the price of meat

and bone meal because they would

affect only 0.3 percent and 0.01 percent

of the meat and bone meal markets,

respectively. In contrast to the first three

options, these rules would not change

the demand for meat and bone meal, but

would restrict the supply of meat and

bone meal. Any postregulation increase

in price, therefore, would increase

revenues of renderers and costs of

purchasers of meat and bone meal by an

almost equal amount. ERG reported that

this decrease in supply would have a

negligible effect on meat and bone meal

prices.

D. Small Business Impacts

The Regulatory Flexibility Act

requires agencies to prepare a regulatory

flexibility analysis if a rule would have

a significant impact on a substantial

number of small entities. The discussion

in this section, as well as in other

sections of this document, and the ERG

report, constitute the agency’s

compliance with this requirement.

The Regulatory Flexibility Act asks

for a succinct statement of the purpose

and objectives of the rule. As explained

previously in this document, FDA is

proposing this measure to address the

risk to U.S. livestock associated with

feeding ruminant proteins to ruminants.

Existing epidemiological evidence

suggests a link between an outbreak of

BSE in the United Kingdom and the

practice of feeding products to cattle

that included ruminant proteins. This

rule would prohibit that practice. Thus,

the need for regulatory action is based

on the need to prevent the spread of

BSE and thereby to protect the health of

animals and to minimize any risk that

might be posed to humans from BSE.

The Regulatory Flexibility Act also

requires a description of the affected

small entities. The ERG study includes

counts of entities in each class of

industry that are involved in ruminant

production and meat preparation. The

vast majority of all of these firms are

considered small businesses according

to size standards set by the Small

Business Administration. There are 282

rendering plants, of which 204 have

fewer than 500 employees, including all

of the 152 independent renderers. ERG

also estimated that 30,000 feedmills, all

with fewer than 500 employees, could

be affected by this rule. An estimated

1.4 million enterprises are engaged in

ruminant production. These include

businesses engaged in the production of

beef and dairy cattle, including farmers

and ranchers, stocker operators, and

cattle feeders, and other ruminant

producers. The slaughtering industry

contains more than 4,000

establishments. Of this total, however,

only 130 are packer/renderers that could

have compliance requirements and

about 52 of these establishments have

fewer than 500 employees. ERG

estimated that almost 300,000 small

establishments are engaged in meat

processing. These businesses would

have no direct compliance activities, but

could be affected indirectly by altered

renderer practices. Also, about 150,000

small producers of nonruminant

animals could gain from lower feed

costs.

The RFA also requires a description of

the recordkeeping requirements of the

proposed rule. The ERG report presents

detailed estimates of these costs. ERG

found that the rule would require

certain feed manufacturers to develop

new written operating procedures. In

addition, affected firms would have to

retain invoices but FDA believes this

activity is already generally accepted

business practice.

Finally, the Regulatory Flexibility Act

asks for an evaluation of any regulatory

overlaps and regulatory alternatives that

would minimize costs to small entities.

FDA is unaware of any significant

regulatory conflicts with other Federal

rules. FDA examined five regulatory

alternatives in addition to no action: (1)

The ruminant-to-ruminant prohibition;

(2) the partial ruminant-to-ruminant

prohibition; (3) the mammalian-toruminant prohibition; (4) the

prohibition of all sheep, goat, mink,

deer, and elk proteins in ruminant feed;

and (5) the prohibition of specified

sheep and goat proteins in ruminant

feed. The ERG report provides a detailed

comparison of the respective impacts of

these alternatives and found that the

estimated direct compliance costs are

lower under the proposed rule ($10.2 to

$27.6 million) than under two of the

alternative rules ($23.5 to $27.9 million

for the partial ruminant-to-ruminant

option, $31.6 million for the

mammalian-to-ruminant option). The

other alternatives would not be nearly

as effective at reducing the risk of an

outbreak and spread of BSE, but are

considerably less costly. As many of the

above projections are uncertain, FDA

particularly invites additional data or

comment on the effects of the proposed

and alternative rules on any group of

small businesses.

E. Unfunded Mandates Analysis

Based on the ERG study, FDA

estimated that aggregate expenditures by

the private sector that result from the

proposed rule, issued under 21 CFR

589.2000, will range from $10.2 to $27.6

million per year. As described in section

IX.B. of this document, the benefits of

this measure accrue both to the general

public (through decreased risks to

health) and to the livestock and

associated industries. The costs of the

measure are borne by the private sector,

primarily the rendering and animal feed

industries. Because FDA anticipates no

significant additional costs to State,

local, or tribal governments, this

regulatory action does not require an

assessment under the Unfunded

Mandates Reform Act.

X. The Paperwork Reduction Act of

1995

This proposed rule contains

recordkeeping requirements that are

subject to public comment and review

by OMB under the Paperwork

Reduction Act of 1995 (Pub. L. 104–13).

Therefore, in accordance with 5 CFR

part 1320, a description of reporting

requirements is given in Table 2 of this

document, with an estimate of the

annual collection of information

burden. Included in the estimate is the

time for reviewing instructions,

gathering and maintaining the data

needed, and completing and reviewing

the collection of information.

With respect to the following

collection of information, FDA is

soliciting comments on: (1) Whether the

proposed collection of information is

necessary for proper performance of

FDA’s functions, including whether the

information will have practical utility;

(2) the accuracy of FDA’s estimate of the

burden of the proposed collection of

information, including the validity of

the methodology and assumptions used;

(3) ways to enhance the quality, utility,

and clarity of the information to be

collected; and (4) ways to minimize the

burden of the collection of information

on those who are to respond, including

through the use of automated collection

techniques or other forms of information

technology, when appropriate.

Title: Substances Prohibited from Use

in Animal Food or Feed; Animal

Proteins Prohibited in Ruminant Feed.

Description: The proposed rule

(§ 589.2000) provides that protein

derived from ruminant and mink tissues

is not GRAS for use in ruminant feed

and is a food additive subject to section

409 of the act. Proteins derived from
Federal Register / Vol. 62, No. 2 / Friday, January 3, 1997 / Proposed Rules 579

animal tissues contained in such feed

ingredients in distribution cannot be

readily determined by recipients

engaged in the manufacture, processing

and distribution, and use of animal

feeds and feed ingredients. To achieve

the public and animal health objectives

of this proposed rule, the agency

believes that manufacturers, processors,

distributors, and users must be

responsible for ensuring and

appropriately maintaining the identity

of the specific nature of the components

of animal protein products and animal

feeds containing these products.

Thus, under the agency’s authority in

section 701(a) (21 U.S.C. 371(a)) of the

act to issue regulations for the efficient

enforcement of the act, this proposed

rule places three general requirements

on persons that manufacture, blend,

process and distribute products that

contain or may contain protein derived

from ruminant and mink tissues, and

feeds made from such products. The

first requirement is for cautionary

labeling of these products with direct

language developed by FDA. The

second requirement is for these

establishments to provide FDA with

access to their purchase and sales

invoices for compliance purposes. FDA

believes that maintenance of such

records is a usual and customary part of

normal business activities for such

firms. These two requirements are not

within the scope of the Paperwork

Reduction Act. The third requirement is

recordkeeping which requires that the

firms develop standard operating

procedures if they intend to keep

ruminant and mink material separate

from nonruminant material. The agency

is aware that the certification

procedures provided in § 589.2000(d) of

the regulation could be interpreted as

imposing a paperwork burden on

certain industry segments. However, the

agency notes that the certification

procedures apply only where new

technology (e.g., a deactivation method)

is developed. The agency was unable to

estimate when such technology might

be developed, what its characteristics

and costs would be, and other essential

information needed to make realistic

estimates of any paperwork burden.

Therefore, such costs are not included

in this proposed rule. However, the

agency specifically requests comments

and information related to the factors

that would determine the extent of any

paperwork burden.

The recordkeeping burden in Table 2

has been estimated using the typical

average size establishment that is

expected to handle animal protein from

both ruminant and nonruminant

sources, or feeds containing these

products, and intend to keep them

separate. FDA’s preliminary estimate is

that only a fraction of feed

manufacturers and distributors will

separate their products. Independent

renderers were excluded from the

burden estimates based on information

provided for the economic estimate.

Packer/renderers were excluded because

they are single species processors.

Under these recordkeeping

requirements, for which records must be

made available for FDA inspection, an

estimated 2,000 feed mills would

handle both restricted and nonrestricted

products and would develop standard

operating procedures for keeping

ruminant and mink material separate

from nonruminant material from the

time of receipt to time of shipment. The

estimate in the burden chart is based on

the time required to develop and

establish the written procedures and is

a one time requirement. The 2,000 firms

will also incur annual operating cost

estimated at $10 million, because of the

flushing, sequencing and other

procedures that will be required. It is

estimated that 1,000 of the firms may

incur capital cost for the construction of

separate facilities. These costs have

been annualized for 10 years, at $7.119

million per year. The remaining firms

are expected to be able to meet the

regulation’s requirements without

incurring capital cost.

The agency has submitted copies of

the proposed rule to OMB for its review

of these requirements. Interested

persons are requested to send comments

regarding this collection of information

by February 18, 1997, but not later than

March 4, 1997 to the Office of

Information and Regulatory Affairs,

OMB (address above), Attn: Desk Officer

for FDA.

Description of Respondents:

Distributors, feed manufacturers,

blenders and renderers.

TABLE 2.—ESTIMATED ANNUAL RECORDKEEPING BURDEN 1

21 CFR section

No. of

record

keepers/

firms

Frequency Total annual

records

Hours per

record Total hours Capital cost(annualized)

Operating cost

(yearly)

589.2000 (e)(1)(iv) ............................ 2,000 1 2,000 14 28,000 $7,119,000 $10,000,000

1 Costs are only incurred under the high-impact scenario.

XI. Federalism

FDA has analyzed this proposal in

accordance with the principles and

criteria set forth in Executive Order

12612 and has determined that this

proposal does not warrant the

preparation of a Federalism Assessment.

XII. References

The following references have been

placed on display in the Dockets

Management Branch (address above)

and may be seen by interested persons

between 9 a.m. and 4 p.m., Monday

through Friday.

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77. Hunter, N., W. Goldmann, G. Smith

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79. Schmerr, et al., Journal of

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81. Banissi-Sabourdy, C., et al.,

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83. Schreuder, B. E. C., et al, ‘‘Preclinical

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84. Hsich, g., et al, ‘‘The 14–3–3 Brain

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88. Fraser, H., et al., ‘‘Transmission of

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89. Robinson, M. M., ‘‘Bovine Spongiform

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pp. 134–138, 1992.

90. Spongiform Encephalopathy Advisory

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91. WHO, ‘‘Scientific Consultation on

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Transmission to Macaques,’’ Nature, 381:743,

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93. Collinge, J., et al., ‘‘Molecular analysis

of prion strain variation and the aetiology of

‘new variant’ CJD,’’ Nature, 383:685, 1996.

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PH/95.145, 1995.

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communication, 1996.

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Program,’’ in Foreign Animal Disease Report,

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at U.S. Animal Health Association annual

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States,’’ 1993.

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the Emergence of a New Variant of

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1996.

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March 29, 1996.

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American Feed Industry Association.

Comments submitted to FDA Docket No.

96N–0135.

XIII. Request for Comments

Interested persons may, on or before

February 18, 1997, submit to the

Dockets Management Branch (address

above) written comments regarding this

proposal. Two copies of any comments

are to be submitted, except that

individuals may submit one copy.

Comments are to be identified with the

docket number found in brackets in the

heading of this document. Received

comments may be seen in the office

above between 9 a.m. and 4 p.m.,

Monday through Friday.

List of Subjects in 21 CFR Part 589

Animal feeds, Animal foods, Food

additives.

Therefore, under the Federal Food,

Drug, and Cosmetic Act and under

authority delegated to the Commissioner

of Food and Drugs, it is proposed that

21 CFR part 589 be amended as follows:

PART 589—SUBSTANCES

PROHIBITED FROM USE IN ANIMAL

FOOD OR FEED

1. The authority citation for 21 CFR

part 589 continues to read as follows:

Authority: Secs. 201, 402, 409, 701 of the

Federal Food, Drug, and Cosmetic Act (21

U.S.C. 321, 342, 348, 371).

2. New § 589.2000 is added to subpart

B to read as follows:

§ 589.2000 Animal proteins prohibited in

ruminant feed.

(a) Definitions. (1) Protein derived

from ruminant and mink tissues means

any protein-containing portion of

ruminant animals or mink, excluding

blood from bovines, milk proteins and

gelatin.

(2) Renderer means any firm or

individual that processes slaughter

byproducts, animals unfit for human

consumption, meat scraps or food

waste. The term includes persons who

collect such materials and subject them

to minimal processing, or distribute

them to firms other than renderers

whose intended use for the products

may include animal feed. The term

includes renderers that also blend

animal protein products.

(3) Blender means any firm or

individual which obtains processed

animal protein from more than one

source or from more than one species,

and subsequently mixes (blends) or

redistributes an animal protein product.

(4) Feed manufacturer and distributor

includes manufacturers and distributors

of complete and intermediate feeds

intended for animals, and includes onfarm in addition to off-farm feed

manufacturing and mixing operations.

(5) Nonruminant protein includes

protein from nonruminant animals and

from vegetable sources.

(b) Food additive status. The Food

and Drug Administration has

determined that protein derived from

ruminant and mink tissues is not

generally recognized as safe for use in

ruminant feed because it may contain

transmissible spongiform

encephalopathy (TSE)-infective

material, and is a food additive subject

to section 409 of the Federal Food, Drug,

and Cosmetic Act (the act). In the

absence of a regulation providing for its

safe use as a food additive under section

409 of the act, the use or intended use

in ruminant feed of any material that

contains protein derived from ruminant

and mink tissues causes the feed to be

adulterated and in violation of the act,

unless it is the subject of an effective

notice of claimed investigational

exemption for a food additive under

§ 570.17 of this chapter. The Food and

Drug Administration has determined

that ruminant and mink derived protein

is not prior sanctioned for use in

ruminant feeds.

(c) Requirements for renderers that

are not included in paragraph (e) of this

section. (1) Renderers that manufacture

products that contain or may contain

protein derived from ruminant and

mink tissues and that are intended for

use in animal feed shall take the

following measures to ensure that

materials identified in paragraph (b) of

this section are not used in the feed of

ruminants:

(i) Label the materials as follows:

‘‘Contains (or may contain) protein

derived from ruminant and mink

tissues. Do not feed to ruminant

animals, and do not use to manufacture

feed intended for ruminant animals’’;

and

(ii) Maintain copies of sales invoices

for the materials, and make the copies

available for inspection and copying by

the Food and Drug Administration.

(2) Renderers described in paragraph

(c)(1) of this section will be exempted

from the requirements of paragraphs

(c)(1)(i) and (c)(1)(ii) of this section if

they:

(i) Use exclusively a manufacturing

method that has been validated by the

Food and Drug Administration to

deactivate the agent that causes TSE’s

and whose design has been made

available to the public; or

(ii) Use routinely a test method that

has been validated by the Food and

Drug Administration to detect the

presence of the agent that causes TSE’s

and whose design has been made

available to the public. Products found

to contain the agent that causes TSE’s

shall be labeled ‘‘Not for Use in Animal

Feed.’’ Records of the test results shall

be made available for inspection by the

Food and Drug Administration.

(3) Renderers described in paragraph

(c)(1) of this section who are not

exempted under paragraph (c)(2)(i) or

paragraph (c)(2)(ii) of this section will

be exempted from the requirements of

paragraph (c)(1)(ii) of this section if they

use a permanent method, approved by

FDA, to mark the presence of the

materials. If the marking is by the use

of an agent that cannot be detected on

visual inspection, the renderer must use

an agent whose presence can be

detected by a method that has been

validated by the Food and Drug

Administration and whose design has

been made available to the public.

(d) Requirements for protein blenders,

and feed manufacturers and

distributors, that are not included in

paragraph (e) of this section. (1) Protein

blenders, and feed manufacturers and

distributors, that manufacture, blend,

process and distribute products that

contain or may contain protein derived

from ruminant and mink tissues shall:

(i) Comply with paragraph (c)(1) of

this section, and

(ii) Maintain copies of invoices for

purchase of animal protein products or

feeds containing such products, and

make copies available for inspection

and copying by the Food and Drug

Administration.

(2) Protein blenders, and feed

manufacturers and distributors, shall be

exempt from paragraphs (d)(1)(i) and

(d)(1)(ii) of this section if they:

(i) Purchase animal protein products

from renderers that certified compliance

with paragraph (c)(2) of this section or

purchase such materials from parties
Federal Register / Vol. 62, No. 2 / Friday, January 3, 1997 / Proposed Rules 583

that certify that the materials were

purchased from renderers that certified

compliance with paragraph (c)(2); or

(ii) Comply with the requirements of

paragraph (c)(2) of this section where

appropriate.

(3) Protein blenders, and feed

manufacturers and distributors, shall be

exempt from paragraph (c)(1)(ii) of this

section if they:

(i) Purchase animal protein products

that are marked or purchase such

materials from renderers that certified

compliance with paragraph (c)(3) of this

section, or purchase such materials from

parties that certify that the materials

were purchased from renderers that

certified compliance with paragraph

(c)(3) of this section; or

(ii) Comply with the requirements of

paragraph (c)(3) of this section where

appropriate.

(4) Copies of certifications as

described in paragraphs (d)(2) and (d)(3)

of this section, shall be made available

for inspection and copying by the Food

and Drug Administration.

(e) Requirements for persons that

intend to separate ruminant/mink and

nonruminant/mink materials. (1)

Renderers, protein blenders, feed

manufacturers and distributors, haulers

and others that manufacture, process,

blend and distribute both protein

products derived from ruminant and

mink tissues or feeds containing such

products, and protein products from

other animal tissues or feeds containing

such products, and that intend to keep

those products separate shall:

(i) Comply with paragraphs (c)(1) or

(d)(1) of this section as appropriate

except that the labeling requirement

shall apply only to products derived

from ruminant and mink tissues or feeds

containing such products;

(ii) In the case of a renderer, obtain

nonruminant (excluding mink)

materials only from single-species

facilities;

(iii) Provide for measures to avoid

commingling or cross-contamination:

(A) Maintain separate equipment or

facilities for the manufacture,

processing, or blending of such

materials; or

(B) Use clean-out procedures or other

means adequate to prevent carry-over of

ruminant and mink derived protein into

animal protein products or feeds that

may be used for ruminants; and

(iv) Maintain written procedures

specifying the clean-out procedures or

other means, and specifying the

procedures for separating ruminant and

mink materials from nonruminant

materials (excluding mink) from the

time of receipt until the time of

shipment.

(2) Renderers, blenders, and feed

manufacturers and distributors will be

exempted from appropriate

requirements of paragraph (e)(1) of this

section, if they meet the appropriate

criteria for exemption under paragraphs

(c)(2) or (c)(3), and (d)(2) or (d)(3) of this

section.

(f) Requirements for establishments

and individuals that are responsible for

feeding ruminant animals.

Establishments and individuals that are

responsible for feeding ruminant

animals shall maintain copies of

purchase invoices and labeling for all

feeds received, and make the copies

available for inspection and copying by

the Food and Drug Administration.

(g) Adulteration and misbranding. (1)

Animal protein products, and feeds

containing such products, that are not in

compliance with paragraphs (c) through

(f) of this section, excluding labeling

requirements, will be deemed

adulterated under section 402(a)(2)(C) or

402(a)(4) of the act.

(2) Animal protein products, and

feeds containing such products, that are

not in compliance with the labeling

requirements of paragraphs (c) through

(f) of this section will be deemed

misbranded under section 403(a)(1) of

the act.

(h) Inspection; records retention. (1)

Records that are to be made available for

inspection and copying, as required by

this section, shall be kept for a

minimum of 2 years.

(2) Written procedures required by

this section shall be made available for

inspection and copying by the Food and

Drug Administration.

Dated: December 27, 1996.

David A. Kessler,

Commissioner of Food and Drugs.

Donna E. Shalala,

Secretary of Health and Human Services.

[FR Doc. 97–37 Filed 1–2–97; 8:45 am]

BILLING CODE 4160–01–F