oversight

Food and Drug Administration's Regulation of Antibiotics Used in Animal Feeds

Published by the Government Accountability Office on 1977-09-19.

Below is a raw (and likely hideous) rendition of the original report. (PDF)

                           DOCUMENT RESUM
 03386 - [A2653862]

 Food and Drug Administration's Regulation of Antibiotics
 Animal Feeds. September 19, 1977. 1( pp.                 Used in

 Testimony before the House Committee on Interstate and
 Ccmmerce: Oversight and Investigations Subcommittee;   Foreign
                                                      by Gregory
 J. Ahart, Director, Human Resources Div.

Issue Area: Consumer and Worker Protection (900).
Contact: Human Resources Div.
Pudget Function: Commerce and Transportation: Other Advancement
     and Regulation of Commerce (403).
COrganization Concerned: Food and Drug Administraticn.
Congressional Relevance: House Committee on Interstate
                                                       and
    Foreign Commerce: Oversight and Investigations Subcommittee.
Authority: Federal Food, Drug, and Cosmetic Act.

          The Food and Drug Administration (FDA) needs
 establish the safety and effectiveness of antibiotics to
 animal feeds. The safety of several antibiotics has notused in
                                                          been
 decided, and FDA has not established regulations specifying
 and how most antibiotics used in animal feeds prevent         when
                                                        animal
diseases and stimulate growth. FDA established criteria
 determining whether use of an antibiotic in animal feeds for
subtherapeutic levels created a hazard to human or animal at
and whether such use was effective for its intended purpose. health
Although sc entists have determined that several antibiotics
failed to meet one or more of the safety criteria, and
                                                         although
many antibiotics have not been proven effective under
                                                       the
approved conditions of use, FDA has permitted the continued
of subtherapeutic levels of these antibiotics in animal        use
                                                          feeds.
Only three antibiotics met all safety criteria for low-level
in one or more animal species. FDA has not yet published        use
Register notices specifying the conditions under which     Federal
                                                         most
antibiotics used in animal feeds are effective. The
Commissioner should take appropriate steps to insure FDA
                                                      that policy
advisory committees are used to review cnly broad policy
in accordance with FA regulations and that their members matters
fully aware of their responsibilities. (SC)                 are
       United States General Accounting Office
               Washington, D.C. 20548



dF




                                   FOR RELEASE ON DELIVERY
                                   Expected at 10 a.m., EST
                                   Monday, September 19, 1977




                        Statement of
     Gregory  . Ahart, Director, Human Resources Division
                         before the
          Subcommittee on Oversight and Investigations
      House Committee on Interstate and Foreign Commerce
                            on
                Food and Drug Administration's
        Regulation of Antibiotics Used in Animal Feeds
     Mr. Chairman and Members of the Subcommittee, we are

pleased to appear here today to discuss our report on the

Food and Drug Administration's (FDA's) need to establish the

safety and effectiveness of antibiotics used in animal feeds,

which was    ssued to the Subcommittee on June 27, 1977.
     The Federal Food, Drug, and Cosmetic Act requires that

an animal drug be approved as safe and effective by FDA before it

is introduced into interstate commerce.

     Antibiotics are used in veterinary medicine not only at

therapeutic levels to treat animal diseases, but also at

subtherapeutic levels to promote growth and prevent or control

disease.    Subtherapeutic levels of antibiotics are administered

to food-producing animals including swine, poultry, and

beef cattle through the use of medicated feeds.

     Between 1960 and 1970 the use of antibiotics in animal

feeds increased   pproximatelv sixfold.   In 1970 antibiotics
used in animal feeds represented about 43    percent of the
approximately 17 million pounds used for all purposes.     It
was estimated that almost 100 percent of the chickens and

turkeys, about 90 percent of the swine and veal calves,

anc about 60 percent of the cattle raised in the United States

during 1970 received antibiotics in their feed.

ADVISORY PANEL REVIEWS OF ANTIBIOTIC
SAFETY AND EFFECTIVENESS

     Since about 1960 there has been increasing concern

that use of low levels of antibiotics in animal feeds may
lead to the developmer.t of antibiotic-resi',tant bacteria

and that this resistance may be transferred betweel animals

and man.   Because many of the antibiotics used in animal

feeds are also used to treat disease ir man or animals, the

development of antibiotic resistance ray lessen the

effectiveness of those drugs in treating disease.

     Expert advisory panels have reviewed t-     public health
aspects of the use of antibiotics in animal feeds as well as

the effectiveness of the use of antibiotics to     romote
growth and prevent disease in animals.

     Several advisory panels hav    recommended restrictions on the
use of antibiotics in animal feeds because of the potential

human health hazard resulting from such use.

National Academy of Sciences

     In June 1969 the National Academy of Sciences' Committee
on Salmonella recon.mended that only minimal levels of anti-

biotics be used in animal feeds and water to promote growth

and that antibiotics not be used routinely for disease prevention.

Swann Commission

     In November 1969 England's Joint Commmission on the Use of

Antibiotics in Animal Husbandry and Veterinary Medicine,

commonly referred to as the Swann Commission, recommended

that permission to use antibiotics in animal feeds without

prescription be restricted to those which (1) are of

economic value in livestock production, (2) have little or

                               -2
no use in treating disease in humans or animals, and

(3) will not impair the effectiveness of other antibiotics

in treating disease.    The Commission specifically recommended
that legislation permitting the supply and use of tetra-

cyclines and penicillin without prescription be revoked.

     On the basis of the Swann Commission's recommendations,

England, in 1971, restricted tc veterinarian's prescription

the subtherapeutic use of certain antibiotics in animal

feeds including penicillin and tetracyclines.   Antibiotics
which have little or no use in treating   isease in man or
animals and will not lead to the development of resistance

to an antibiotic used to treat disease remained available

without prescription.

FDA Task Force

     In January 1972 the FDA Task Force cn the Use of

Artioiotics in Animal Feeds noted that:

     -- The feeding of certain antibiotics to animals has led

       to tne development of antibiotic-resistant bacteria

       ii food animals that may be transmitted to humans.

     --The continuous feeding of certain antibiotics to

      animals has been reported to compromise the treatment

      of certain animal diseases.

    -- Limiting the types of antibiotics used in animal

      feeds is a step toward controlling the resistance

      problem.

                             -3-
      -- The safety and efficacy of long-term subtherapeutic

         feeding of antibiotics for disease   revention and
         control have not ban adequately demonstrated.

     The task force established safety and effectiveness

guidelines for antibiotics and recommended    tlat anti-
biotics used in human medicine be prohibited from use in

animals for growth promotion and disease prevention if they

fail t   meet the task force's guidelines.    FDA established
regulations implementing the task force recommendations in

Arril 1973.   The regulations provided that approval of sub-
therapeutic uses of antibiotics in animal feeds would be

revoked as of April 20, 1975, unless manufacturers or other

'interested parties submitted data which resolved conclusively

their safety and effectiveness under spec:fic FDA criteria.

World Health Organization

     In October 1973 the World Health Organization's Working

Group on the Public Health Aspects of Antibiotics in Feedstuffs

recommended that only those antibiotics without terapeutic

value be used for growth promotion.   Specifically, the
Working Group recommended that penicillins, tetracyclines,

sulfonamides, streptomycin, and neomycin not be used for

growth promotion purposes.

National Advisory Committee

     In June 1975 FDA established an Antibiotics in Animal
Feeds Subccmmittee of its National Avjsory Food and Drug
 Committee, a broad policy advisory committee, to review
                                                         the
 evidence developed in response to the FDA's April 1973

 regulations.   The subcommittee reviewed data on three
 antibiotics used in animal feeds--penicillin, tetracyclines,

and sulfaquinoxaline--and, in January 1977, recommended

 to the parent committee that:

      --All growth promotion and feed efficiency uses of

       penicillin be discontinued.

     -- Growth promotion and feed efficiency uses of

        tetracyclines be discontinued where effective

       substitutes are available.
     -- Disease prevention use of penicillin be discontinued

       when effective substitutes are available.

     -- All disease prevention uses of sulfaquinoxaline and
                                                            those
       disease prevention uses of tetracyclines for which effec-

       tive substitutes are not available continue, but that

       their use be limited to those periods of time when there

       is the greatest threat of animal diseases.
There are currently no approved growth promotion and feed

efficiency uses of sullaquinoxaline.

     On January 24, 1977, the National Advisory Food and
                                                         Drug
Committee voted to accept the subcommittee's recommendations
with respect to penicillin and sulfaquinoxaline, but voted
                                                           to
recommend that tetracyclines remain available for growth

promotion and disease prevention uses.

                             - 5 -
       Contrary to the position taken by the committee, on

April 15, 1977, FDA announced that it plans to restrict

the use of penicillin, tetracyclines, and sulfaquinoxaline

used in animal feeds.      will further discuss FDh's proposed
restrictions later.

ANTIBIOTICS NOT MEETING
SAFETY AND EFFECTIVENESS
CRITERIA REMAIN ON THE MARKET

       The safety of   everal antibiotics has not been decided.
In addition, FDA has not established regulations specifying

when    nd how most antibiotics used in animal feeds prevent

animal diseases and stimulate growth.

       The Federal Food, Drug, and Cosmetic Act requires that

FDA withdraw approval to market an animal drug if experience

or new scientific data shows that the drug is unsafe or if

the drug has not proven to be effective under its approved

conditions of use.

       Based on guidelines established by FDA's task force,

FDA established criteria for determining whether use of an

antibiotic in animal feeds at subtherapeutic levels created a

hazard to human or animal health, and whether such use was

effective for its intended purposes.    The criteria we:e
developed in consultation with industry representatives,

OA task force members, and Canadian health officials.




                              - 6 -
Antibi;tics not meeting thp criteria were to be withdrawn

from the market.

Criteria

      FDA's human and animal health safety criteria provide

that a human or animal health nazard exists if an antibiotic

en   a,ices the capability of bacteria to cause disease.   In
addition the criteria stated that the use of subtherapeutic

levels of an antibiotic in animal feeds can be considered

a hazard if such use creates:

     -- A significant adverse effect on the relative quantity,

       prevalence, and shedding or excretion of salmonella

       organisms in animals.

     --A significant increase of salmonella organisms ih the

       animal resistant to antibiotics used therpeuticaly

       in man or animals.

     -- A significant increase of coliforms (intestinal

       bacteria) resistant to antibiotics used thera-

       peutically i.n man or animals.

     -- A condition in which disease is more difficult to treat.

     ---A continuing increase in the amount of antibiotic

       necessary to achieve the desired response.

     The effectiveness criteria require that labels of

antibiotics for which disease prevention or control claims

are made be qualified as to the situations in which the drug

offers beneficial effects.     The criteria also require that

                               - 7 -
controlled studies be conducted to determine whether claimed

disease prevention uses of antibiotics in animal feeds

af'od protection that is      t least as effective as the
recognized therapeutic use administered at the tme clinical

signs of disease become evident.

Antibiotics fail to meet criteria
        FDA scientists have determined that several antibiotics,

including penicillin and tetracyciines, failed to meet one or

more of the safety criteria and thus create a hazard to

human and animal health when used at low levels in animal

feed.     In addition, many antibiotics have not been proven

effective under the approved conditions of use.     FDA, however,
has permitted the continued use of subzherapeutic levels of

these antibiotics in animal feeds.
        The Bureau of Veterinary Medicine found that the use of

penicillin in animal feeds causes (1) a significant increase

in the percentage of salmonella organisms resistant to ampicillin,

an antibiotic used in human and animal therapy, and (2) an

increase in the percentage of intestinal bacteria resistant

to more than one antibiotic and capable of transferring

resistance to man.

        No data has been submitted to FDA to support the effectiveness

of subtherapeutic use of penicillin in animals for disease

prevention and control.



                               - 8 -
     With respect to tetracyclines, the Bureau of Veterinary

Medicine found that (1) there was a significant increase in

the percentage of salmonella resistant to tetracyclines,

(2) there was an increase in salmonella shedding     n medicated

versus nonmedicated animals when there were     .igh numbers of

drug resistant bacteria, and (3) data were available indicating

a trend toward compromise of subsequent therapy of

salmonellosis, the infection caused by the salmonella organism.

     A Bureau of Veterinary Medicine official recommended that

Federal Register notices be published specifying acceptable

claims and dosages for use of tetracyclines in animal feeds.

Any claims not specifically covered by the Federal Register

noti:es would be disallowed.    The notices would not include

most of the current claims for disease prevention and control.

The notice:,   however, have not teen issued.
     At the conclusion of our review FDA had determined that

only three antibiotics--bacitracin, flavomycin, and oleandomycin--

had met all safety criteria for low-level use in one or more

animal species. Also FDA has not published Federal Register

notices specifying the conditions under which most antibiotics

used in animal feeds are effective. According to an FDA

official many of the antibiotics for which a safety determination

has not been made are not used as human drugs and were

not given the same priority for review as penicillin

and tetracyclines.

                               - 9-
GAO RECOMMENDATION
AND AGENCY COMMENTS

     We recommended that the Secretary of the Department

of Health, Education, and Welfare (HEW) direct the FDA

Commissioner to promptly make a final determination as

to the safety and effectiveness of antibiotics used in

animal feeds based on available data and take appropriate

steps to withdraw approval for subtherapeutic use in animal

feeds of any antibiotic not shown to be safe and effective

under the approved conditions of use.

     HEW agreed with our recommenration and on April 15, 1977,
FDA announced its decision to restrict the use of three

antibiotics--penicillin, tetracyclines, and sulfaquinoxaline--

used in animal feeds.   HEW said that FDA will issue a Notice
of Opportunity for Hearing proposing to:

     -- Withdraw approval of penicillin fcr growth promotion

      purposes.

     -- Discontinue use of penicillin for disease prevention

      when effective substitutes are available.

     -- Restrict the use of tetracyclines for growth promotion

      to certain minor animal species.

    -- Restrict the use of tetracyclines for disease

      prevention to uses for which effective substitutes are

      not available.




                            -   10 -
     -- Continue the present uses of sulfaquinoxaline, but limit

       its use to those periods of time when there is a threat
       of disease.

HEW further said that FDA will propose that penicillin and

tetracyclines be available for use only upon the written

order of a licensed veterinarian.

     On August 30, 1977, FDA published in the Federal Register

a Notice of Opportunity for Hearing proposing to withdraw

approval for all animal feed uses of penicillin on the grounds

that they have not been shown to be safe and lack substantial

evidence of effectiveness for therapeutic use.   Interested

persons have been given 30 days to file objections to the

proposal and request a public hearing.

     At the same time, FDA announced that a Federal Register

notice proposing to withdraw approval for certain sub-

therapeutic uses of tetracyclines will be issued shortly.

QUESTIONABLE USE OF
ADVISORY COMMITTEE

     The National Advisory Food and Drug Committee was established

to review and evaluate agency programs and provide advice on

policy matters of national significance.   According to FDA

regulations, such policy advisory committees deal with broad

policy issues and should not get involved with specific

regulatory matters.




                             -11    -
     However, FDA has sought and obtained advice from the

National Advisory Food and Drug Committee on an issue concerning

the use of antibiotics in animal feeds which, in our opinion,

concerned regulation, not policy.

     Such use of a policy advisory committee seems questionable

in that the committee did not have sufficient expertise to

adequately consider the highly complex regulatory issue.

     FDA regulations differentiate between policy advisory

committees which advise the Commissioner on broad, general

matte'rs, and technical advisory committees which advise on

specific regulatory issues.    Members of technical advisory

committees are required to possess specific expertise in the

subject matter to be addressed by the committee; policy advisory

committee members are not.

     FDA's Special Assistant for Review of Antibiotics in

Animal Feeds advised us that the National Advisory Food and

Drug Committee had several physicians who had some limited

training in antibiotic resistance, but only one member who

might be considered an expert.
     Also, one committee member, the president of an animal
feedlot, voted on the continued use of antibiotics in animal
feeds although he had a definite interest in such use.     This
raised a question of whether a conflict of interest existed.
     Under FDA regulations, advisory committee members are
special Government employees and are subject to the conflict
                              -12-
of interest laws and regulations.       HEW regulations instruct

that a special Government employee should not participate in

a matter which will have a "direct and predictable effect" on

his financial interest.

     The president of Farr Farms, a Colorado Feedlot, took

an active role in committee deliberations on pencillin, tetra-

cyclines, and sulfaquinoxaline and seconded a motion which

overturned a subcommittee's recommendation that the use of

tetracyclines be restricted.

     The president of Farr Farms advised us that FDA had not

discussed the restrictions of conflict of interest laws and

regulations with him prior to his involvement in the committee's

deliberations, and, that had FDA so advised him, he would not

have participated.     He also said that because all feedlots

would be affected by restrictions on the use of antibiotics

in animal feeds, he would not gain a ccmpetitive advantage

over other feedlots.

AGENCY COMMENTS
AND OUR EVALUATION

     In a draft of our report submitted to HEW for comment,

we proposed that the Secretary of HEW direct the FDA

Commissioner to promptly resolve the question of whether

the president of Farr Farms was involved in a conflict of

interest and determine whether participation of other members




                               - 13 -
of the National Advisory Food and Drug Committee in the review

of antibiotics used in animal feeds created conflicts.

     HEW advised us that FDA has reviewed the participation

of the president of Farr Farms in the January 24, 1977,

National Advisory Food and Drug Committee discussion of the

use of antibiotics in animal feed and has determined that

there was no conflict of interest created Ly his contributions.

HEW said that FDA believes the participation of all committee

members in the discussion to have been proper.

     With respect to use of the National Advisory Food and

Drug Committee to review the use of antibiotics in animal

feeds, HEW said that FDA is of the opinion that the committee

was addressing a broad policy matter in accordance with FDA

regulations.

     HEW believed that we questioned the advisory committee's

use because we assumed that the National Advisory Food and

Drug Committee was addressing a "particular" matter in the

context of the Federal statutes relating to conflict of interest.

HEW said that FDA does not believe the committee was addressing

a particular matter because (1) antibiotics encompass a number

of individual products. (2) there are multiple manufacturers

of these products, and (3) the use of antibiotics in animal

feeds is widespread throughout the United States.




                            - 14 -
     We believe that the appropriateness of subjects reviewed

by FDA advisory committees is determined not by its conflict

of interest regulations, but by its regulations concerning

the use of advisory committees although review of purely

regulatory matters would necessarily entail application

of the conflict of interest regulations.   HEW assumes that an

issue is a broad policy issue appropriate for review by a

policy advisory committee if it does not involve a particular

matter.   FDA regulations concerning the use of policy and

technical advisory committees, however, are based not on whether

the issue discussed is a particular matter in the context of is

conflict of interest regulations, but on whether the issue

is a policy or a regulatory issue.

     HEW also noted that the Antibiotics in Animal Feeds

Subcommittee of the National Advisory Food and Drug

Committee performed an indepth review of the use of antibiotics

in animal feeds.   According to FDA's Chief Counsel this

review gave a clearer regulatory focus to the committee's

final recommendations than FDA had initially anticipated.

As a result, we believe that the committee members should

have met all qualifications foc membership on a technical

advisory committee, qualifications that differ greatly

from those of policy advisory committee members.




                             - 15 -
RECOMMENDATION

     We recommended that the Secretary of HEW direct the FDA

Commissioner to take appropriate steps to insure that

(1) policy advisory committees are used to review only broad

policy matters in accordance with FDA regulations and

(2) that their members are fully aware of their responsibilities
with regard to and the restrictions of conflict of interest
laws and regulations.


     Mr. Chairman, that concludes my prepared statement.
We will be pleased to answer any   uestions that you or other
members of the Subcommittee may have.




                             - 16 -