Viruses, Serums, Toxins, and Analogous Products; Packaging and Labeling

DEPARTMENT OF AGRICULTURE

Animal and Plant Health Inspection Service

9 CFR Part 112

[Docket No. 92-098-2]

Viruses, Serums, Toxins, and Analogous Products; Packaging and

Labeling

AGENCY: Animal and Plant Health Inspection Service, USDA.

ACTION: Final rule.

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SUMMARY: This rule amends the regulations pertaining to packaging and

labeling of veterinary biological products by prohibiting final

containers of product that are imported or that are packaged at

licensed establishments in cartons or other containers from being

repackaged and relabeled for sale or distribution. The rule also

clarifies that, unless otherwise authorized, labeling may only be

performed at a licensed establishment or by the producer of an imported

product, and amends the ``Applicability'' statement in the regulations

on packaging and labeling to clarify its intent.

The action is necessary in order to ensure that veterinary

biological products are not rendered worthless, contaminated,

dangerous, or harmful because of incomplete, unclear, misleading, or

inappropriate labeling. The effect of the final rule is to ensure that

product integrity is maintained and that the purchasers of biological

products are provided with appropriate and accurate labeling which

complies with the pertinent rules and regulations.

EFFECTIVE DATE: February 21, 1995.

FOR FURTHER INFORMATION CONTACT: Dr. David A. Espeseth, Deputy

Director, Veterinary Biologics, BBEP, APHIS, USDA, room 838, Federal

Building, 6505 Belcrest Road, Hyattsville, MD 20782, (301) 436-8245.

SUPPLEMENTARY INFORMATION:

Background

The Virus-Serum-Toxin Act (21 U.S.C. 151-159; hereinafter the Act),

as amended by the 1985 Food Security Act, prohibits the shipment of

veterinary biological products anywhere in or from the United States

that are worthless, contaminated, dangerous or harmful. It also

prohibits such shipment of products unless they are prepared pursuant

to USDA regulations in an establishment licensed by USDA. The term

``preparation'', as it is defined in the regulations, includes

packaging and labeling. The 1985 amendments granted additional

rulemaking authority to implement the purposes of the Act. Under the

Act and regulations, the Animal and Plant Health Inspection Service

(APHIS) of the U.S. Department of Agriculture grants licenses for

veterinary biological products which are pure, safe, potent, and

efficacious when used according to label instructions. Complete

labeling (either on the product or accompanying the product) must be

reviewed and approved by APHIS in accordance with 9 CFR 112.5 prior to

its use.

On April 28, 1993, we published in the Federal Register a proposed

rule on packaging and labeling of veterinary biologics (see Docket No.

92-098-1, 58 FR 25786-25788). We proposed to amend the regulations

pertaining to packaging and labeling of veterinary biological products

by prohibiting final containers of product packaged at licensed

establishments in cartons or other containers from being repackaged for

sale or distribution. We also proposed to clarify that, unless

otherwise authorized, labeling may only be performed at a licensed

establishment and to amend the ``Applicability'' statement in the

regulations on packaging and labeling to clarify its intent.

We solicited comments concerning our proposal during a 60-day

comment period ending June 28, 1993. We received 39 comments by that

date. Comments were received from biologics manufacturers, State and

national professional associations, a trade association, an educational

institution, animal hospitals and clinics, veterinarians, a registered

pharmacist, a practicing attorney, and private citizens.

Thirty-six commenters were in support of the rule as proposed.

Three commenters were in opposition to the rule.

The issues raised by the commenters were: (1) The perceived higher

cost of animal vaccinations resulting from the proposed rule; (2) the

inclusion of a provision to allow repackaging if each repackaged

product includes a complete copy of a package insert; (3) a question

whether the proposed rule provides an adequate remedy concerning the

problem of incorrect labeling; (4) the effect of the proposed rule on

the ability of consumers to vaccinate their own animals; (5) the impact

of the rule on veterinarians who dispense their own biologics; (6)

whether licensed veterinary biologics are in compliance with the U.S.

Department of Transportation's regulations; and (7) other issues

related to the proposed rule.

After the close of the comment period on June 28, 1993, APHIS

received a significant number of additional comment letters. These

additional comment letters were read, but since they were late, they

were not included as part of this rulemaking. The additional comments,

however, generally expressed opinions similar to those of commenters

who submitted letters before the close of the comment period.

Analysis of Comments and APHIS' Response

Thirty-six commenters were in agreement with the rule as proposed.

It was the general opinion of commenters supporting the rule that it

should be implemented in order to protect the health and safety of

animals and animal owners. They expressed the belief that unauthorized

repackaging and relabeling of licensed veterinary biologics contributes

to improper handling and storage of these products, which could render

them worthless and ineffective. Many also stated that unauthorized

repackaging and relabeling contributes to the improper administration

of vaccines and to the use of improper diluents resulting in liability

problems for the manufacturer of the original product. Additionally,

the commenters believe that manufacturers have a proprietary interest

in the packaging and labeling of their products and in the integrity of

the products that they manufacture, and that these interests are

compromised by unauthorized repackaging and relabeling.

Three commenters disagreed with the rule. Their comments are

discussed below.

1. The Increased Cost of Vaccinations Resulting From the Proposed Rule

One commenter stated that prohibiting repackaging would force pet

owners to seek vaccination from veterinarians and thus raise the cost

of vaccinations. Alternatively the increased cost would cause many pets

to go unvaccinated. In the commenter's opinion, the resulting increase

in unvaccinated pets would pose a much greater health risk than any

minute danger brought about by the possible mispackaging of ``home

administered vaccines.'' According to the commenter, the rule would

also restrict competition and threaten small businesses that repackage

non-prescription pet vaccines.

APHIS does not agree with these arguments in opposition to the

proposed rule. One purpose of the amendments is to clarify the intent

of the packaging and labeling provisions of the regulations which is to

regulate such activities in a comprehensive manner. Allowing the

repackaging and relabeling of products once they have left the licensed

establishment is not consistent with such intent. The rule will help to

eliminate the problem of improper or unauthorized packaging and

labeling after the product has left the producer's establishment. It

should be noted, however, that the rule does not prohibit over-the-

counter (OTC) sales of veterinary biologics. Pet owners may still

purchase vaccines for their own use, so long as they are packaged and

labeled according to regulations.

The rule makes it clear that persons who currently repackage

multiple vial cartons or containers for further sale would no longer be

able to do so. This does not mean that they could not continue to

operate as distributors or to sell single dose or individual products

for consumer use if such products were so packaged and labeled

according to regulations. As a matter of fact, APHIS has recently

approved a number of applications for such products. If there is any

additional cost to the consumer as a result of this rule, it is

outweighed by the risk to animal health posed by the improper packaging

and labeling of veterinary biological products after they have left the

licensed establishment. Therefore, no change is made to the regulations

in response to this commenter.

2. Commenter's Proposal to Allow Repackaging if Each Repackaged Product

Includes a Complete Copy of a Package Insert

A commenter proposed a compromise solution to allow repackaging if

every sale of a repackaged product includes a complete copy of a

package insert which contains complete product information and all

relevant data as to the method of administration.

APHIS does not agree with the proposed solution. Allowing

repackaging in this manner could cause a number of problems and would

raise many questions. For example, would the Agency need to issue a new

set of regulations to regulate repackagers in order to assure that

labeling and packaging inserts are consistent with regulations and that

the repackaging is adequately controlled and supervised to prevent

errors, and to assure that labels are legible? Would repackagers have

to be licensed, since packaging and labeling is included in the

regulatory definition of the term ``preparation''? How would the

integrity of the product be assured? And finally, who would bear the

responsibility in the event of damage caused by error or mislabeling?

As a matter of fact, just recently, the inclusion of wrong package

inserts with repackaged products has caused death and injury to dogs.

Considering these questions and the potential problems which could

arise, the most practical and logical solution concerning repackaging

is to issue the rule as proposed and to leave to the licensees the

option of producing and offering to the distributors individually

packaged or single dose products for resale.

APHIS explained in the preamble of the proposed rule that it would

prohibit the repackaging of final containers of product (either single

or multiple dose containers) packed in multiple container cartons if

the carton label or enclosure is required to complete the labeling for

the container (see 58 FR 25787, column 2, Docket No. 92-098-1, April

28, 1993). Therefore, APHIS proposed in Sec. 112.6(e) that biological

products in cartons or other containers shall not be removed from such

cartons or containers and repackaged for sale or distribution unless

each final container of product bears or is accompanied by complete and

approved labeling, which is affixed to or included with each final

container by the licensed establishment or producer of an imported

product.

This rule is intended to explicitly prohibit repackaging so that

mislabeling cannot occur. The final rule is slightly modified to

clarify the purpose of the provision.

Final containers of a product need not be packaged one per carton

when these products are distributed and sold in a multiple container

carton (see current Sec. 112.6(b)). When these products are distributed

and sold as individual final containers, however, such containers of a

product must be packaged and fully labeled in individual cartons with

the appropriate amount of diluent, if required, in order to be in

compliance with the regulations.

Section 112.1(a) of this rule requires that before they are removed

from a licensed establishment or offered for importation, biological

products must be packaged and labeled according to regulations. The

section further provides that packaging and labeling may only be

performed in a licensed establishment under an approved Outline of

Production. Therefore, the removal, from a multiple container carton,

of a final container of product for resale is prohibited. Labeling may

not be added or removed after the product has left the licensed

establishment or has been imported.

The effect of the final rule is to prohibit the unauthorized

repackaging and relabeling, for sale or distribution, of final

containers of veterinary biological products that are packaged in

multiple container cartons or other containers, and which do not bear a

complete, approved labeling affixed or included with each final

container by the licensed establishment producing the product. In the

case of imported products, a similar prohibition applies. In response

to a comment that imports should be included under the amendments,

proposed Sec. 112.6(e) is modified to provide for this. The

modification also makes the section consistent with Sec. 112.1(a).

In addition, we are making nonsubstantive changes in Sec. 112.6(e)

in order to clarify the fact that packaging and labeling should be an

integral part of product production and that final containers should

bear or be packaged, in a carton with, complete and approved labeling

which is affixed to or included with each container by the licensed

establishment or producer of an imported product. No other amendment to

the regulations is made in response to this commenter.

3. Whether the Proposed Rule Provides an Adequate Remedy to the Problem

of Incorrect Labeling

In response to the statement concerning enforcement under the

current regulations and the lack of an adequate remedy, APHIS notes

that the current regulations prohibit false and misleading labeling

and, although Sec. 112.5 provides for the review and approval of

labeling prior to use, it is not clear that repackaging and relabeling

after the products have left the licensed establishment is prohibited.

The explicit prohibition of repackaging and relabeling in this rule

directly addresses those activities after the product has left the

licensed establishment or has been imported and is intended to prevent

unapproved labeling.

The commenter was also concerned that the proposed rule would

unnecessarily restrict contract labeling. Labeling of licensed products

is required to be performed at licensed establishments. APHIS has not

allowed establishments to contract with others to apply labeling to

products (see 7 CFR 112.4(c)). This rule does not change this practice

and explicitly provides that all licensed products must be packaged and

labeled at licensed establishments or by the producer of an imported

product. This rule would not, however, prohibit the production of

biological products having a distributor's label.

4. The effect of the proposed rule on the ability of consumers to

vaccinate their own animals

A commenter indicated that the consumer should have the opportunity

to immunize his or her own animals. The rule does not deprive the

consumer of the option to immunize his or her own animals. As stated

previously, the rule does not prohibit OTC sales of veterinary

biologics. Animal owners will still be able to purchase single dose or

individual packages of vaccines that have been prepared in licensed

establishments in accordance with the regulations. Manufacturers may

continue to provide products for sale OTC, so long as the products

comply with the labeling and packaging requirements. Thus, the consumer

is still free to immunize his or her own animals. No change to the

regulations is made in response to this commenter.

5. The impact of the rule on veterinarians who dispense their own

biologics

Another commenter requested clarification of the impact of the rule

on products dispensed by a veterinarian.

It should be noted that the rule is not intended to interfere with

the practice of veterinary medicine. The practitioner may dispense

biological products under a veterinarian-client-patient relationship

(VCPR) as that term is described in Sec. 107.1 of the regulations.

Therefore, in response to the comments, proposed Sec. 112.6(e), is

modified to clarify its intended scope of coverage. Veterinarians

engaged solely in the mail order sale of veterinary biologics would not

meet the requirements that establish a valid VCPR exemption under 9 CFR

107.1.

6. Comments concerning Department of Transportation regulations

A commenter raised the issue of compliance with the regulations of

the U. S. Department of Transportation (DOT) pertaining to the shipment

of hazardous materials, including infectious agents.

In response to this commenter, APHIS notes that the DOT regulations

cited by the commenter provide a special exclusion for veterinary

biological products prepared according to regulations. These licensed

or permitted veterinary biological products are specifically exempted

from the requirements for the shipment of a hazardous substance (see

DOT regulations at 49 CFR 173.196(h)(2)). No change to the regulations

is made in response to this commenter.

7. Consumer responsibility for used syringes and needles

Several commenters stated that individual users of veterinary

biologics that require a syringe should be held responsible for the

proper disposal of syringes. We are making no changes based on these

comments, as the disposal of syringes is outside the scope of this

rule.

8. Other comments related to the proposed rule

One commenter stated that packaging and labeling requirements in

Sec. 112.1 should apply to any person, not just the licensee, making

changes to packaging and labeling. This is the intent of the rule. For

example, the preamble of the proposed rule (see 58 FR 25787, column 2,

Docket No. 92-098-1, April 28, 1993) stated that:

The regulations under proposed paragraphs (a) through (d) of

Sec. 112.1 would be applicable generally to any person and would not be

restricted to licensees.

No change to the regulations is made in response to this comment.

The commenter also stated that any changes to packaging or labeling

must be done by the licensed establishment and approved by APHIS. APHIS

agrees with this comment. In that regard, it should be noted that

Sec. 112.1(a) provides that packaging and labeling may only be

performed in a licensed establishment under an approved Outline of

Production or by the producer of an imported product. No change to the

regulations is made in response to this comment.

The commenter further stated that the rule should not apply to

certain products that are exempted by statute and thus not subject to

product licensure. APHIS agrees with this comment. This is true, since

products that are exempted by statute are not required to be made in a

licensed establishment, they are not subject to the provisions of this

rule. No change to the regulations is made in response to this

commenter.

It was the commenter's opinion that Secs. 112.1, 112.4, and 112.6

should not apply to the ultimate purchaser. APHIS also agrees with this

comment.

With reference to the heading of Sec. 112.5, the commenter

recommended that it should be changed from ``labeling'' to ``labels''.

APHIS does not agree with this comment. The term ``labeling'' under the

definitions of labeling terminology in 9 CFR 101.4(b) includes ``all

labels''. Thus the term ``labeling'' is retained in the title of

Sec. 112.5.

The commenter also stated that the regulations should not prohibit

the manufacture and sale of single dose licensed products. APHIS agrees

with this comment. APHIS notes that the final rule does not prohibit

the manufacture or sale of single dose or individual final containers

of licensed products. No change to the regulations has been made in

response to this comment.

The commenter concluded his comments with the statement that the

proposed amendments to 9 CFR 112 reflect a concern on the part of

licensed manufacturers that unauthorized repackaging and relabeling of

licensed products was tantamount to product tampering, which adversely

affects the integrity of such products and puts manufacturers at risk

of damage to their reputations as a consequence of such actions.

180-day transition period

In order to provide for a reasonable transition period before this

rule takes effect, we are making this rule effective 180 days after the

date of publication in the Federal Register. APHIS believes that this

transition period will allow needed time for manufacturers and

distributors that wish to prepare and distribute single-dose packages

of veterinary biologics to reach agreement and begin to implement the

manufacture and distribution of these products.

Other changes

In order to reflect organizational changes within APHIS, the

introductory paragraph of Sec. 112.5 is amended by removing the words

``Veterinary Services'' and adding the words ``Animal and Plant Health

Inspection Service'' in their place.

Based on the rationale set forth in the proposed rule and in this

document, we are adopting the provisions of the proposed rule as a

final rule, with the changes discussed in this document.

Executive Order 12866 and Regulatory Flexibility Act

This final rule has been reviewed under Executive Order 12866. The

rule has been determined to be not significant for purposes of

Executive Order 12866, and, therefore has not been reviewed by the

Office of Management and Budget.

The rule prohibits the repackaging of veterinary biologics packaged

in multiple container cartons or other containers. Such repackaging can

result in the preparation, including labeling, of a veterinary

biological product in violation of the Act and regulations, and in the

removal or alteration of approved labeling, thereby compromising the

safety and efficacy of the biological product. In the absence of

approved labeling, the safe and effective use of the veterinary

biological product cannot be assured. This action benefits users in

that it helps ensure that users are provided with a product that is

properly labeled with approved directions, indications, and cautions

for use.

This action will provide greater assurance to consumers that

licensed veterinary biological products are prepared only with approved

labeling with adequate directions for use. The prohibition against

repackaging and relabeling outside of licensed facilities ensures that

cases involving unapproved labeling of biological products such as

those which resulted in the recent death and injury of dogs are avoided

in the future. APHIS believes that safety to animal health is best

assured by restricting to licensed facilities and producers of imported

products the preparation, which includes packaging and labeling, of

veterinary biological products.

Distributors who are currently in the business of breaking apart

multiple container cartons and repackaging and relabeling them for sale

as individual final containers of product are provided notice that

their actions will be in violation of the Act and regulations on the

effective date of this rule. Distributors may still purchase from

licensed manufacturers products that are already individually packaged

and labeled in accordance with part 112 rather than purchasing multiple

container cartons that must be broken apart and repackaged to provide a

single dose final container package for distribution. This action does

not prohibit the OTC distribution of products as long as the product is

produced in a licensed establishment under an approved Outline of

Production with approved labeling. Thus, persons currently repackaging

and distributing a licensed product can seek to have a licensee produce

a single dose or an individual container product for distribution. If

desired, such product may be labeled with a distributor label that

includes the name and address of the distributor. Based on information

available to APHIS, several licensed manufacturers already have

approved labeling to produce single dose veterinary biological

products.

Under these circumstances, the Administrator of the Animal and

Plant Health Inspection Service has determined that this action will

not have a significant economic impact on a substantial number of small

entities.

Executive Order 12778

This final rule has been reviewed under Executive Order 12778,

Civil Justice Reform. This rule: (1) Preempts all State and local laws

and regulations that are in conflict with this rule; (2) has no

retroactive effect; and (3) does not require administrative proceedings

before parties may file suit in court challenging this rule.

Paperwork Reduction Act

This rule contains no new information collection or recordkeeping

requirements under the Paperwork Reduction Act of 1980 (44 U.S.C. 3501

et seq.).

Executive Order 12372

This program/activity is listed in the Catalog of Federal Domestic

Assistance under No. 10.025 and is subject to Executive Order 12372,

which requires intergovernmental consultation with State and local

officials. (See 7 CFR part 3015, subpart V).

List of Subjects in 9 CFR part 112

Animal biologics, Exports, Imports, Labeling, Packaging and

containers, Reporting and recordkeeping requirements.

Accordingly, 9 CFR part 112 is amended as follows:

PART 112--PACKAGING AND LABELING

1. The authority citation for 9 CFR part 112 continues to read as

follows:

Authority: 21 U.S.C. 151-159; 7 CFR 2.17, 2.51, and 371.2(d).

2. Section 112.1 is revised to read as follows:

Sec. 112.1 General.

(a) Unless otherwise authorized or directed by the Administrator,

each biological product prepared at a licensed establishment, or

imported, shall be packaged and labeled as prescribed in this part

before it is removed from the licensed establishment or presented for

importation: Provided, That biological products to be imported for

research and evaluation shall be subject to packaging and labeling

requirements in Sec. 112.9. Provided further, That, unless otherwise

exempted, all preparation, including packaging and labeling, of

biological products shall only be performed in a licensed establishment

under an approved Outline of Production.

(b) No person shall apply or affix to or include with, or cause to

be applied or affixed to or included with, any carton or final

container of a biological product, any label, stamp, mark or statement

that is false or misleading in any particular, is not in compliance

with the regulations, or is not approved by APHIS.

(c) No person shall alter, mark or remove any approved labeling

affixed to or included with any biological product prior to selling or

otherwise distributing such product. In addition, no person shall mark

any carton, other container, or final container of a biological product

so as to falsify the labeling, make it misleading, or cause it to be

illegible.

(d) Labels that are stamped, printed or glued directly on cartons,

other containers, or final containers shall be legible throughout the

dating period. Biological products bearing labels, which have been

altered, mutilated, destroyed, obliterated or removed, shall be

withheld from the market.

3. In Sec. 112.4, the introductory paragraph is revised to read as

follows:

Sec. 112.4 Subsidiaries, divisions, distributors, and permittees.

Labels used by subsidiaries, divisions, distributors, and

permittees shall be affixed by the licensee in a licensed establishment

where the product is produced. Such labels shall comply with

requirements for their review, approval, and filing as provided in the

regulations.

* * * * *

4. In Sec. 112.5, the introductory paragraph, the words

``Veterinary Services'' are removed and the words ``Animal and Plant

Health Inspection Service'' are added in their place.

5. In Sec. 112.6, new paragraphs (e) and (f) are added to read as

follows:

Sec. 112.6 Packaging biological products.

* * * * *

(e) Final containers of biological product prepared at a licensed

establishment, or imported, in cartons or other containers shall not be

removed from such cartons or containers for sale or distribution,

unless each final container bears, or is packaged in a carton with,

complete and approved labeling which is affixed to or included with

each container by the licensed establishment producing the product or

by the producer in the case of imported product: Provided, That this

paragraph is not intended to apply to licensed veterinary practitioners

administering or dispensing biological products in the course of their

practice under a veterinary-client-patient-relationship as that term is

used in Sec. 107.1.

(f) Labels which are affixed to or included with a biological

product shall not be removed or altered in any manner.

Done in Washington, DC, this 17th day of August 1994.

Terry L. Medley,

Acting Administrator, Animal and Plant Health Inspection Service.

[FR Doc. 94-20640 Filed 8-23-94; 8:45 am]

BILLING CODE 3410-34-P