Federal Register / Vol. 66, No. 78 / Monday, April 23, 2001 / Notices 20469

(the act) (21 U.S.C. 352(n)). This section

of the act requires that advertisements

for prescription drugs and biological

products include a true statement of

information ‘‘in brief summary’’ about

the benefits and risks of using the

advertised product. This is often called

the ‘‘brief summary’’ requirement. The

prescription drug advertising

regulations (21 CFR 202.1(e)(3)(iii))

specify that the information about risks

include every risk in the advertised

drug’s approved product labeling.

Some prescription drug and biological

products have FDA-approved patient

labeling that contains information that

is most important for the safe and

effective use of these products in

language consumers are likely to

understand. The draft guidance

specifies that FDA does not intend to

object to the use of certain FDAapproved patient labeling, reprinted

exactly as approved, to fulfill the brief

summary requirement for DTC print

advertisements. The draft guidance

describes the characteristics that such

patient labeling should have to be used

to fulfill the brief summary requirement.

This draft guidance is being issued as

a level 1 guidance, consistent with

FDA’s good guidance practices

regulations (21 CFR 10.115; 65 FR

56468, September 19, 2000). The draft

guidance represents the agency’s current

thinking on using FDA-approved patient

labeling in DTC print advertisements. It

does not create or confer any rights for

or on any person and does not operate

to bind FDA or the public. An

alternative approach may be used if

such approach satisfies the

requirements of the applicable statutes

and regulations.

II. Comments

Interested persons may submit to the

Dockets Management Branch (address

above) written comments on the draft

guidance. 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. The draft

guidance and received comments are

available for public examination in the

Dockets Management Branch between 9

a.m. and 4 p.m., Monday through

Friday.

III. Electronic Access

Persons with access to the Internet

may obtain the document at http://

www.fda.gov/cder/guidance/index.htm

and at http://www.fda.gov/cber/

guidelines.

Dated: April 17, 2001.

Ann M. Witt,

Acting Associate Commissioner for Policy.

[FR Doc. 01–9948 Filed 4–20–01; 8:45 am]

BILLING CODE 4160–01–S

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

[Docket No. 99D–2638]

Extra-Label Use of Medicated Feeds

for Minor Species; Compliance Policy

Guide; Availability

AGENCY: Food and Drug Administration,

HHS.

ACTION: Notice.

SUMMARY: The Food and Drug

Administration (FDA) is announcing the

availability of a new compliance policy

guide (CPG) section 615.115 entitled

‘‘Extra-Label Use of Medicated Feeds for

Minor Species.’’ The purpose of this

CPG is to provide guidance to FDA

personnel concerning the agency’s

exercise of regulatory discretion with

regard to the extra-label use of

medicated feeds for minor species. This

CPG has been revised in response to

comments received on the draft.

DATES: Submit written comments at any

time.

ADDRESSES: Submit written requests for

single copies of the CPG to the

Communications Staff (HFV–12), Center

for Veterinary Medicine, Food and Drug

Administration, 7500 Standish Pl.,

Rockville, MD 20855. Send one selfaddressed adhesive label to assist that

office in processing your requests.

Submit written comments on the CPG to

the Dockets Management Branch (HFA–

305), Food and Drug Administration,

5630 Fishers Lane, rm. 1061, Rockville,

MD 20852. Comments should be

identified with the full title of the CPG

and the docket number found in

brackets in the heading of this

document. See the SUPPLEMENTARY

INFORMATION section for the electronic

access to the CPG section 615.115

entitled ‘‘Extra-Label Use of Medicated

Feeds for Minor Species.’’

FOR FURTHER INFORMATION CONTACT:

Frances M. Pell, Center for Veterinary

Medicine (HFV–235), Food and Drug

Administration, 7500 Standish Pl.,

Rockville, MD 20855, 301–827–0188, email: fpell@cvm.fda.gov.

SUPPLEMENTARY INFORMATION:

I. Background

In the Federal Register of August 25,

1999 (64 FR 46400), FDA published a

notice of availability of a draft CPG

entitled ‘‘Use of Medicated Feeds for

Minor Species.’’ This CPG was issued as

a level 1 draft guidance consistent with

FDA’s good guidance practices

regulation (21 CFR 10.115; 65 FR 56468,

September, 2000). The purpose of this

CPG is to provide guidance to FDA staff

concerning the agency’s exercise of

regulatory discretion with regard to the

extra-label use of medicated feeds for

minor species. The CPG represents the

agency’s current thinking on this

subject. It does not create or confer any

rights for or on any person and does not

operate to bind FDA or the public.

The agency received comments

regarding this CPG and has revised the

CPG in response to the comments.

Following is a discussion of the issues

raised by the comments.

II. The Final Guidance

The agency received 21 comments on

the draft CPG. When finalizing the CPG,

the agency considered the comments

and, as appropriate, incorporated them

into the final guidance. The final

version of the CPG differs from the draft

only in three areas. The first is a change

in the minor species definition to reflect

a corresponding change to the new

animal drug regulations at 21 CFR

514.1. Sheep are now considered a

minor species for all data collection

purposes (see 65 FR 47668, August 3,

2000).

The second change is a minor

clarification of existing provisions. The

medicated feed must be manufactured

and labeled in accordance with the

approved conditions of use. This means

that the feed cannot be reformulated in

dosage, in form, or nutritional content

such that it would no longer be

appropriate as a feed for the species for

which it is approved. For example, a

medicated feed approved for chickens

may not be pelleted for use in laboratory

animals. An approved swine medicated

feed may not be made to correspond to

the nutrient requirements of pheasants

or deer. All labeling must be truthful

and in accordance with the approved

conditions of use.

The third change is further

clarification of limitations on the

agency’s intent to exercise regulatory

discretion with regard to extra-label use

of medicated feeds. If the medicated

feed is to be used in a food-producing

minor species, the product must be

approved in a food-producing major

species. The agency intends to exercise

regulatory discretion only for farmed or

confined species not for unconfined

wildlife. In aquaculture, the agency

intends to exercise regulatory discretion

only for extra-label use of medicated

20470 Federal Register / Vol. 66, No. 78 / Monday, April 23, 2001 / Notices

feeds already approved for an aquatic

use because factors in the aquatic

environment that may affect the safety

and/or effectiveness of the medicated

feed are so varied.

III. Availability of Medicated Feeds for

Minor Species

FDA plans to continue to address the

issue of lack of availability of medicated

feeds for minor species. There are

serious shortcomings in the legal

availability of medicated feeds for minor

species. These include the need for

specially formulated feeds for laboratory

and zoo animals and the needs of

species raised in aquaculture. Future

guidance will be directed specifically at

these needs.

IV. Electronic Access

Persons with access to the Internet

may obtain the CPG at http://

www.fda.gov/cvm and http://

www.fda.gov/ora.

V. Comments

As with all of FDA’s guidances, the

public is encouraged to submit written

comments with new data or other new

information pertinent to this CPG. FDA

will periodically review the comments

and, where appropriate, the CPG will be

amended. The public will be notified of

any such amendments through a notice

in the Federal Register.

Dated: April 18, 2001.

Dennis E. Baker,

Associate Commissioner for Regulatory

Affairs.

[FR Doc. 01–10164 Filed 4–19–01; 3:10 pm]

BILLING CODE 4160–01–S

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

National Institutes of Health

National Cancer Institute: Opportunity

for a Cooperative Research and

Development Agreement (CRADA) for

the Clinical Development of a

Biologically Active, Epitope-Tagged

Transforming Growth Factor Beta

(TGF–β) Protein

The National Cancer Institute’s

Laboratory of Cell Regulation and

Carcinogenesis (LCRC) has created and

characterized a recombinant

transforming growth factor-beta (TGF–β)

ligand that contains the FLAG epitope

tag and yet retains full biological

activity.

AGENCY: National Institutes of Health,

PHS, DHHS.

ACTION: Notice.

SUMMARY: The National Cancer Institute

(NCI) seeks a Cooperative Research and

Development Agreement (CRADA)

Collaborator to aid NCI in the

preclinical and clinical development of

a tagged form of the TGF–β protein.

Initial studies from LCRC demonstrate

that a specific, eight-amino acid tag

(known as FLAG) can be inserted in at

least three different sites in the TGF–β1

molecule, without interfering with its

biological activity. LCRC has made three

FLAG-tagged porcine TGF–β1

constructs and the identical murine

FLAG–TGF–β1 cDNAs. Each construct

differs only in the location of insertion

of the FLAG tag, and these include

either insertion immediately following

the cleavage site N-terminal in the

mature, processed TGF–β molecule, or

between amino acids 4 and 5 or 11 and

12 of the mature TGF–β molecule. The

tagged molecule can detected by using

a number of different techniques,

including: Immunohistochemistry,

immunoprecipitation, flow cytometry,

immunofluorescence microscopy,

ELISA, immunoblotting (‘‘western’’),

and affinity chromatography.

DATES: Interested parties should notify

NCI in writing of their interest in filing

a formal proposal no later than June 22,

2001. Potential CRADA Collaborators

will then have an additional thirty (30)

days to submit a formal proposal.

Additional proposals will be considered

after the posted deadline in the event

that a CRADA partner is not found

during the initial posted timeperiod.

ADDRESSES: Inquiries and proposals

regarding this opportunity should be

addressed to Holly Symonds Clark,

PhD., Technology Development

Specialist (Tel. # 301–496–0477, FAX #

301–402–2117), Technology

Development and Commercialization

Branch, National Cancer Institute, 6120

Executive Blvd., Suite 450, Rockville,

MD 20852. Inquiries directed to

obtaining a patent license(s) needed for

participation in the CRADA opportunity

should be addressed to John Rambosek,

PhD., Technology Licensing Specialist,

Office of Technology Transfer, National

Institutes of Health, 6011 Executive

Blvd., Suite 325, Rockville, MD 20852,

(Tel. 301–496–7056, ext. 270; FAX 301–

402–0220).

SUPPLEMENTARY INFORMATION: A

Cooperative Research and Development

Agreement (CRADA) is the anticipated

joint agreement to be entered into with

NCI pursuant to the Federal Technology

Act of 1986, NCI seeks a CRADA

Collaborator to aid LCRC in the

preclinical and clinical studies of a

tagged form of the TGF–β protein. The

expected duration of the CRADA would

be from one (1) to five (5) years.

Background Information

NCI’s LCRC has produced the first

epitope-tagged, biologically active

version of a member of the transforming

growth factor-β (TGF–β) family of

proteins. Transforming growth factor-β1

(TGF–β1) is the prototype for a large

family of secreted polypeptides

including the three mammalian TGF–β

isoforms (TGF–β1, TGF–β2, TGF–β3),

the bone morphogenetic proteins

(BMPs), the activins and several more

distantly related factors that regulate

cell growth and function. The various

members of the TGF–β superfamily play

roles in development, immune

homeostasis, cancer progression,

autoimmune disorders and wound

repair. TGF–βs are produced and

secreted from the cell as large latent

(inactive) molecules (pro-proteins). The

Latency Associated Peptide (LAP)

encompasses amino acids 1 through 279

(porcine TGF–β1) of the pro-protein.

Association of LAP through disulfide

bonds with the mature TGF–β1

sequence keeps TGF–β in a biologically

inactive form. Conversion of this propeptide to a biologically active form can

be achieved in several ways. These

include disruption of the disulfide

bonds (for example, mutation of two

cysteine residues involved in forming

this bond), cleavage of the protein to

release the smaller biologically active

TGF–β (amino acids 280 through 391 in

TGF–β1), or denaturation of the

associated LAP by acidification or heat.

The ability to track the distribution of

any exogenously administered,

recombinant forms of these proteins has

been restricted by the inability to

distinguish between the endogenous

forms of the protein produced in treated

cells or tissues, and because most

available antibodies exhibit some degree

of cross-reactivity with related family

members. LCRC’s invention

demonstrates a successful approach to

adding an opitope tag to the mature

TGF–β1 molecule. Epitope tags are short

stretches of amino acids to which a

specific antibody can be raised,

allowing one to directly identify and

track the tagged protein that has been

added to a living organism or to

cultured cells. Examples of useful

epitope tags include FLAG, HA

(hemagglutinin) and myc. In principle,

any of these epitope tags could be used

to tag TGF–β family members, but NCI’s

LCRC has been the first to identify a

way to retain biological function of the

molecule following addition of the tag.

Thus, it will be possible to track LCRC’s

tagged TGF–β molecule when used in