48840 Federal Register / Vol. 71, No. 162 / Tuesday, August 22, 2006 / Proposed Rules 

A320–111 airplanes; Model A320–211, –212, 

–214, –231, 232, and –233 airplanes; and 

Model A321–111, –112, and –131 airplanes; 

except those on which Airbus Modification 

26495 has been accomplished in production: 

Within 18 months after January 8, 2001 (the 

effective date of AD 2000–24–02, amendment 

39–12009), modify the sliding panel driving 

mechanism of the flap drive trunnions, in 

accordance with Airbus Service Bulletin 

A320–27–1117, Revision 02, dated January 

18, 2000. 

Note 1: Accomplishment of the 

modification required by paragraph (f) of this 

AD before January 8, 2001, in accordance 

with Airbus Service Bulletin A320–27–1117, 

dated July 31, 1997; or Revision 01, dated 

June 25, 1999, is acceptable for compliance 

with that paragraph. 

Detailed Inspections 

(g) For Model A318–111 and –112 

airplanes; Model A319–111, –112, –113, 

–114, –115, –131, –132, and –133 airplanes; 

Model A320–211, –212, –214, –231, –232, 

and –233 airplanes; and Model A321–111, 

–112, and –131 airplanes; on which Airbus 

Modification 26495 has been incorporated in 

production: At the latest of the times 

specified in paragraphs (g)(1), (g)(2), and 

(g)(3) of this AD, do a detailed inspection of 

the inboard flap trunnions for any wear 

marks and of the sliding panels for any 

cracking at the long edges, and do any 

corrective actions, as applicable, by 

accomplishing all of the applicable actions 

specified in the Accomplishment 

Instructions of Airbus Service Bulletin A320–

57–1133, dated July 28, 2005; except as 

provided by paragraph (m) of this AD. Any 

corrective actions must be done at the 

compliance times specified in Figures 5 and 

6, as applicable, of the service bulletin; 

except as provided by paragraphs (j), (k), and 

(l) of this AD. Repeat the inspection 

thereafter at intervals not to exceed 4,000 

flight hours until the inspection required by 

paragraph (i) of this AD is done. 

Note 2: For the purposes of this AD, a 

detailed inspection is: ‘‘An intensive 

examination of a specific item, installation, 

or assembly to detect damage, failure, or 

irregularity. Available lighting is normally 

supplemented with a direct source of good 

lighting at an intensity deemed appropriate. 

Inspection aids such as mirror, magnifying 

lenses, etc., may be necessary. Surface 

cleaning and elaborate procedures may be 

required.’’

(1) Before accumulating 4,000 total flight 

hours on the inboard flap trunnion since 

new. 

(2) Within 4,000 flight hours after 

accomplishing paragraph (f) of this AD. 

(3) Within 600 flight hours after March 24, 

2006 (the effective date of AD 2006–04–06). 

New Requirements of This AD 

Modification 

(h) For Model A321–211 and –231 

airplanes, except those on which Airbus 

Modification 26495 has been accomplished 

in production: Within 18 months after the 

effective date of this AD, modify the sliding 

panel driving mechanism of the flap drive 

trunnions, in accordance with Airbus Service 

Bulletin A320–27–1117, Revision 02, dated 

January 18, 2000. 

Note 3: Accomplishment of the 

modification required by paragraph (h) of 

this AD before the effective date of this AD, 

in accordance with Airbus Service Bulletin 

A320–27–1117, dated July 31, 1997; or 

Revision 01, dated June 25, 1999, is 

acceptable for compliance with that 

paragraph. 

General Visual Inspections 

(i) For all airplanes: At the time specified 

in paragraph (i)(1) or (i)(2) of this AD, as 

applicable, do a general visual inspection of 

the inboard flap trunnions for any wear 

marks and of the sliding panels for any 

cracking at the long edges, and do all 

applicable corrective actions, by 

accomplishing all of the applicable actions 

specified in the Accomplishment 

Instructions of Airbus Service Bulletin A320–

57–1133, dated July 28, 2005; except as 

provided by paragraph (m) of this AD. All 

corrective actions must be done at the 

compliance times specified in Figures 5 and 

6, as applicable, of the service bulletin; 

except as provided by paragraphs (j), (k), and 

(l) of this AD. Repeat the inspection 

thereafter at intervals not to exceed 4,000 

flight hours. Accomplishment of the general 

visual inspection required by this paragraph 

terminates the detailed inspection 

requirement of paragraph (g) of this AD. 

Note 4: For the purposes of this AD, a 

general visual inspection is: ‘‘A visual 

examination of an interior or exterior area, 

installation, or assembly to detect obvious 

damage, failure, or irregularity. This level of 

inspection is made from within touching 

distance unless otherwise specified. A mirror 

may be necessary to ensure visual access to 

all surfaces in the inspection area. This level 

of inspection is made under normally 

available lighting conditions such as 

daylight, hangar lighting, flashlight, or 

droplight and may require removal or 

opening of access panels or doors. Stands, 

ladders, or platforms may be required to gain 

proximity to the area being checked.’’

(1) For airplanes on which the detailed 

inspection required by paragraph (g) of this 

AD has been done before the effective date 

of this AD: Inspect before accumulating 4,000 

total flight hours on the inboard flap 

trunnion since new, or within 4,000 flight 

hours after accomplishing the most recent 

inspection required by paragraph (g) of this 

AD, whichever occurs later. 

(2) For airplanes other than those 

identified in paragraph (i)(1) of this AD: 

Inspect at the latest of the times specified in 

paragraphs (i)(2)(i), (i)(2)(ii), and (i)(2)(iii) of 

this AD. 

(i) Before accumulating 4,000 total flight 

hours on the inboard flap trunnion since 

new. 

(ii) Within 4,000 flight hours after 

accomplishing paragraph (f) of this AD. 

(iii) Within 600 flight hours after the 

effective date of this AD. 

Compliance Times 

(j) Where Airbus Service Bulletin A320–

57–1133, dated July 28, 2005, specifies 

replacing the sliding panel at the next 

opportunity if damaged, replace it within 600 

flight hours after the inspection required by 

paragraph (g) or (i) of this AD, as applicable. 

(k) If any damage to the trunnion is found 

during any inspection required by paragraph 

(g) or (i) of this AD, do the corrective actions 

specified in the service bulletin before 

further flight. 

Grace Period Assessment 

(l) Where the service bulletin specifies 

contacting the manufacturer for a grace 

period assessment after replacing the 

trunnion or flap, contact the Manager, 

International Branch, ANM–116, Transport 

Airplane Directorate, FAA; or the European 

Aviation Safety Agency (EASA) (or its 

delegated agent) for the grace period 

assessment. 

No Reporting Requirement 

(m) Although Airbus Service Bulletin 

A320–57–1133, dated July 28, 2005, specifies 

to submit certain information to the 

manufacturer, this AD does not include that 

requirement. 

Alternative Methods of Compliance 

(AMOCs) 

(n)(1) The Manager, International Branch, 

ANM–116, has the authority to approve 

AMOCs for this AD, if requested in 

accordance with the procedures found in 14 

CFR 39.19. 

(2) Before using any AMOC approved in 

accordance with 14 CFR 39.19 on any 

airplane to which the AMOC applies, notify 

the appropriate principal inspector in the 

FAA Flight Standards Certificate Holding 

District Office. 

Related Information 

(o) French airworthiness directive F–2005–

139, dated August 3, 2005, also addresses the 

subject of this AD. 

Issued in Renton, Washington, on August 

14, 2006. 

Ali Bahrami, 

Manager, Transport Airplane Directorate, 

Aircraft Certification Service. 

[FR Doc. E6–13826 Filed 8–21–06; 8:45 am] 

BILLING CODE 4910–13–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

21 CFR Parts 20, 25, 201, 202, 207, 225, 

226, 500, 510, 511, 515, 516, 558, and 

589 

[Docket No. 2006N–0067] 

RIN 0910–AF67 

Index of Legally Marketed Unapproved 

New Animal Drugs for Minor Species 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Proposed rule. 


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Federal Register / Vol. 71, No. 162 / Tuesday, August 22, 2006 / Proposed Rules 48841 

SUMMARY: The Minor Use and Minor 

Species Animal Health Act of 2004 

(MUMS act) amended the Federal Food, 

Drug, and Cosmetic Act (the act) to 

authorize the U.S. Food and Drug 

Administration (FDA, the agency) to 

establish new regulatory procedures that 

provide incentives intended to make 

more drugs legally available to 

veterinarians and animal owners for the 

treatment of minor animal species and 

uncommon diseases in major animal 

species. At this time, FDA is issuing 

proposed regulations to implement 

section 572 of the act entitled ‘‘Index of 

Legally Marketed Unapproved New 

Animal Drugs for Minor Species.’’ These 

regulations propose administrative 

procedures and criteria for index listing 

a new animal drug for use in a minor 

species. Such indexing provides a basis 

for legally marketing an unapproved 

new animal drug intended for use in a 

minor species. 

DATES: Submit written or electronic 

comments on this document by 

November 20, 2006. Interested persons 

are requested to submit comments on 

the information collection provisions by 

September 21, 2006. 

ADDRESSES: You may submit comments, 

identified by [Docket No. 2006N–0067 

and/RIN number 0910–AF67], by any of 

the following methods: 

Electronic Submissions 

Submit electronic comments in the 

following ways: 

• Federal eRulemaking Portal: http:// 

www.regulations.gov. Follow the 

instructions for submitting comments. 

• Agency Web site: http:// 

www.fda.gov/dockets/ecomments. 

Follow the instructions for submitting 

comments on the agency Web site. 

Written Submissions 

Submit written submissions in the 

following ways: 

• FAX: 301–827–6870. 

• Mail/Hand delivery/Courier [For 

paper, disk, or CD–ROM submissions]: 

Division of Dockets Management (HFA–

305), Food and Drug Administration, 

5630 Fishers Lane, rm. 1061, Rockville, 

MD 20852. 

To ensure more timely processing of 

comments, FDA is no longer accepting 

comments submitted to the agency by email. FDA encourages you to continue 

to submit electronic comments by using 

the Federal eRulemaking Portal or the 

agency Web site, as described in the 

Electronic Submissions portion of this 

paragraph. 

Instructions: All submissions received 

must include the agency name and 

Docket No(s). and Regulatory 

Information Number (RIN) for this 

rulemaking. All comments received may 

be posted without change to http:// 

www.fda.gov/ohrms/dockets/ 

default.htm, including any personal 

information provided. For detailed 

instructions on submitting comments 

and additional information on the 

rulemaking process, see the 

‘‘Comments’’ heading of the 

SUPPLEMENTARY INFORMATION section of 

this document. 

Docket: For access to the docket to 

read background documents or 

comments received, go to http:// 

www.fda.gov/ohrms/dockets/ 

default.htm and insert the docket 

number(s), found in brackets in the 

heading of this document, into the 

‘‘Search’’ box and follow the prompts 

and/or go to the Division of Dockets 

Management, 5630 Fishers Lane, rm. 

1061, Rockville, MD 20852. 

To ensure that comments on the 

information collection are received, 

OMB recommends that written 

comments be faxed to the Office of 

Information and Regulatory Affairs, 

OMB, Attn: FDA Desk Officer, FAX: 

202–395–6974. 

FOR FURTHER INFORMATION CONTACT: 

Andrew Beaulieu, Center for Veterinary 

Medicine (HFV–50), Food and Drug 

Administration, 7519 Standish Pl., 

Rockville, MD 20855, 240–276–9090, email: Andrew.Beaulieu@fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: 

I. Background 

In enacting the MUMS act (Pub. L. 

108–282), Congress sought to encourage 

the development of animal drugs that 

are currently unavailable to minor 

species (species other than cattle, 

horses, swine, chickens, turkeys, dogs, 

and cats) in the United States or to 

major species afflicted with uncommon 

diseases or conditions (minor use). 

Congress recognized that the markets for 

drugs intended to treat these species, 

diseases, or conditions, are so small that 

there are often insufficient economic 

incentives to motivate sponsors to 

develop data to support approvals. 

Further, Congress recognized that some 

minor species populations are too small 

or their management systems too 

diverse to make it practical to conduct 

traditional studies to demonstrate safety 

and effectiveness of animal drugs for 

such uses. As a result of these 

limitations, sponsors have generally not 

been willing or able to collect data to 

support legal marketing of drugs for 

these species, diseases, or conditions. 

Consequently, Congress enacted the 

MUMS act, which amended the Federal 

Food, Drug, and Cosmetic Act to 

provide incentives to develop new 

animal drugs for minor species and 

minor use, while still ensuring 

appropriate safeguards for animal and 

human health. 

The major incentives of the MUMS 

act include the following: 

(1) Designation, established by section 

573 of the act (21 U.S.C. 360ccc–2), 

which provides for eligibility for grants 

and contracts to defray the costs of 

qualified safety and effectiveness testing 

expenses and manufacturing expenses 

incurred in the development of 

designated new animal drugs. 

Designation also provides for eligibility 

for a 7-year period of exclusive 

marketing rights to enable sponsors to 

recover costs of drug development 

without competition. FDA proposed 

regulations to implement the 

designation provision of the act on 

September 27, 2005 (70 FR 56394) (the 

designation proposed rule). 

(2) Conditional approval, established 

by section 571 of the act (21 U.S.C. 

360ccc), which provides for animal drug 

marketing after all safety and 

manufacturing components of a new 

animal drug approval have met the 

standards of section 512 of the act (21 

U.S.C. 360b). For the effectiveness 

component, a reasonable expectation of 

effectiveness must be established, after 

which sponsors have up to 5 years to 

complete the demonstration of 

effectiveness by the standards of section 

512 of the act and achieve a full 

approval. Regulations to implement the 

conditional approval provision will be 

proposed in the future. 

(3) Indexing, established under 

section 572 of the act (21 U.S.C. 360ccc–

1), which provides for the legal 

marketing of unapproved new animal 

drugs intended for use in a minor 

species through an integrated process of 

agency and expert panel review. 

At this time, FDA is issuing proposed 

regulations to implement the indexing 

provisions of the MUMS act. These 

regulations propose procedures and 

criteria for index listing a new animal 

drug for use in a minor species. They 

describe a process whereby the agency 

makes a determination regarding the 

following: (1) The eligibility of a new 

animal drug, (2) the selection of a 

qualified expert panel, and (3) the 

findings of the qualified expert panel. 

II. Proposed Regulations 

A. Definitions (proposed § 516.115). 

Most of the proposed definitions are 

straightforward. The proposed 

definition of ‘‘qualified expert panel’’ is 

drawn from the statutory definition, 

given in section 572(d)(3) of the act. The 

proposed definition of ‘‘transgenic 

animal’’ comes from the statutory 


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48842 Federal Register / Vol. 71, No. 162 / Tuesday, August 22, 2006 / Proposed Rules 

definition, given in section 571(j) of the 

act (21 U.S.C. 360ccc). The proposed 

definition of ‘‘intended use’’ is identical 

to one proposed with respect to the 

designation proposed rule of September 

27, 2005 (70 FR 56394). The designation 

proposed rule also included definitions 

for the phrases ‘‘same intended use,’’

‘‘same drug,’’ and ‘‘same dosage form’’

that would be applicable to all subparts 

of part 516, including the indexing 

regulations. 

B. Permanent-resident U.S. agent for a 

foreign requestor (proposed § 516.119). 

The proposed rule would require a 

foreign requestor or holder to name a 

permanent-resident U.S. agent so that 

the agency may ensure that notifications 

of decisions regarding indexing and all 

other communications with the 

requestor or holder are legally and 

effectively made. 

C. Meetings (proposed § 516.121) 

The act provides that any person 

intending to file a request for eligibility 

or a request for addition to the index 

may have an opportunity to meet with 

the agency to discuss the requirements 

for indexing a new animal drug. 

D. Informal conferences regarding 

agency administrative actions (proposed 

§ 516.123) 

The act also provides that a requestor 

or holder be offered an informal 

conference in association with an 

agency decision to deny a request for a 

determination of eligibility to index, to 

deny a request for index listing or to 

remove an index listing. Proposed 

§ 516.123 establishes the nature of and 

the procedures for requesting and 

conducting such conferences. FDA 

would give notice of the grounds for the 

initial decision and provide an 

opportunity to respond to that decision. 

As proposed, the conference’s presiding 

officer would not have significantly 

participated in the initial decision, 

would prepare a written summary of the 

informal conference to share with the 

participants, and would issue a written 

report describing the basis for his or her 

findings. The proposed regulation also 

provides for an informal conference 

associated with a decision to terminate 

an investigational exemption for a new 

animal drug proposed for indexing or a 

decision not to affirm an expert panel 

because it does not meet the selection 

criteria of § 516.141. In the case of 

conferences associated with adverse 

agency decisions, the proposed 

regulation establishes that decisions to 

deny, remove, terminate, or not affirm 

will be made by the Director, Office of 

Minor Use and Minor Species Animal 

Drug Development (OMUMS) and a 

subsequent conference, if requested, 

will be conducted by the Director, 

Center for Veterinary Medicine or his 

designee, other than the Director, 

OMUMS. These procedures were 

adapted from the process for holding 

regulatory hearings before the agency 

under 21 CFR part 16. 

E. Investigational use of new animal 

drugs to support indexing (proposed 

§ 516.125). 

As required by section 512(a)(1) of the 

act, a new animal drug may not be 

legally marketed unless it is the subject 

of an approved New Animal Drug 

Application (NADA), the subject of a 

conditionally approved NADA, or on 

FDA’s list of legally marketed 

unapproved new animal drugs. The act 

contains two exemptions for drugs 

intended solely for investigational use 

by experts qualified by scientific 

training and experience to investigate 

the safety and effectiveness of drugs. 

The first, in section 512(j) of the act, 

applies to new animal drugs generally, 

including animal feeds bearing or 

containing new animal drugs. FDA’s 

regulations implementing this 

investigational use exemption are at part 

511 (21 CFR part 511). The second, in 

section 572(g) of the act, is parallel to 

the first exemption but is for the 

purposes of indexing and applies only 

to minor species new animal drugs, 

including animal feeds bearing or 

containing such new animal drugs. Note 

that the coverage of these exemptions 

overlaps and, therefore, in some 

circumstances an investigational use 

might qualify for an exemption under 

either section 512(j) of the act or section 

572(g) of the act. 

Proposed § 516.125 would implement 

section 572(g) of the act. It states that 

certain investigational uses, although 

they involve a minor species new 

animal drug, are nonetheless subject to 

part 511. Such uses include 

investigations to demonstrate safety 

with respect to individuals exposed to 

the new animal drug through its 

manufacture and use under section 

572(c)(1)(F) of the act, to conduct an 

environmental assessment under section 

572(c)(1)(E) of the act, or to obtain 

approval of a new animal drug 

application or abbreviated new animal 

drug application under section 512(b) of 

the act. These investigational uses 

would be required to be conducted 

under part 511 because, whether these 

types of studies are conducted to 

support indexing or approval, the 

agency would evaluate the study results 

using the same standards. Thus, the 

agency believes it should apply the 

same substantive and procedural 

requirements for these investigational 

uses for minor species new animal 

drugs as it does for new animal drugs 

generally. 

For other types of investigational 

uses, proposed § 516.125 establishes 

separate exemption regulations, 

although they are very similar to part 

511. The agency believes the regulations 

should be similar because of the 

similarity of the purpose and the 

language of the two investigational use 

exemptions in the act. Proposed 

§ 516.125 states that, with certain 

modifications, part 511 applies to minor 

species new animal drugs or animal 

feeds bearing or containing such new 

animal drugs intended for 

investigational use for all other 

purposes in support of a drug index 

listing (such as to demonstrate target 

animal safety and effectiveness). Among 

the proposed modifications is the need 

to specifically identify that the 

investigational use is in support of 

index listing, which would be done 

when labeling the drugs involved and 

when notifying the agency of the 

claimed investigational exemption. 

Another modification is that FDA would 

provide notice and an opportunity for 

an informal conference before 

terminating an investigational use 

exemption. While part 511 provides for 

notice and an opportunity for a hearing 

under 21 CFR part 16 concerning 

whether the exemption should be 

terminated, the administrative process 

in the proposed regulations reflects the 

fact that section 572 of the act provides 

for an informal conference with respect 

to other agency decisions regarding 

indexing, such as removal of a new 

animal drug from the index. FDA does 

not believe it should have an 

administrative process for terminating 

an investigational use exemption 

relating to indexing that is different 

from the informal conference process for 

other decisions relating to indexing. 

F. Content and format of a request for 

determination of eligibility for indexing 

(proposed § 516.129). 

To be added to the index, a new 

animal drug must meet certain criteria. 

The act establishes what can be 

described as a two-part regulatory 

decision-making process for 

determining whether these criteria have 

been met. The first part in this 

regulatory process is FDA’s 

determination of whether the new 

animal drug is eligible for indexing. 

This involves an evaluation of most of 

the indexing criteria, with the major 

exceptions being target animal safety 

and effectiveness. The second part 


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Federal Register / Vol. 71, No. 162 / Tuesday, August 22, 2006 / Proposed Rules 48843 

includes the agency’s determination of 

the suitability of the qualified expert 

panel and a review of whether the new 

animal drug meets the statutory criteria 

regarding target animal safety and 

effectiveness. 

The determination of eligibility for 

indexing is initiated by a request to the 

agency that must be accompanied by 

sufficient information to permit the 

agency to make an informed decision 

regarding the request. The information 

proposed by the agency to determine 

eligibility for indexing, described in 

proposed § 516.129(c), is based on the 

requirements of 572(c)(1) of the act. The 

categories of information are described 

below: 

1. Food safety 

The act allows the indexing of new 

animal drugs that are intended for use 

in food-producing animals only in 

limited circumstances. The new animal 

drug must be for use in an early, nonfood life stage of a minor species; it 

must be intended for use only in a 

hatchery, tank, pond, or other similar 

contained man-made structure; and 

there must be sufficient information to 

demonstrate food safety in accordance 

with the standards of section 512(d) of 

the act (including, for an antimicrobial 

new animal drug, with respect to 

antimicrobial resistance). 

When a new animal drug proposed for 

indexing is not intended for use in an 

early life stage of a food-producing 

minor species animal, the requestor 

must demonstrate that there is a 

reasonable certainty that the minor 

species or edible products from the 

minor species will not be consumed by 

humans or food-producing animals. For 

many minor species, this should be as 

straightforward as an affirmation that 

the species has never been traditionally 

consumed by humans and is not subject 

to being used in the feed of foodproducing animals. A new animal drug 

intended for use in a wildlife species 

might be eligible for indexing if it could 

be demonstrated that there is a 

reasonable certainty that treated animals 

would not be subsequently harvested 

and consumed by humans or foodproducing animals. 

Under the proposed rule, FDA would 

rely on its existing regulations regarding 

the food safety standards of section 

512(d) of the act, which are in part 514 

(21 CFR part 514) at § 514.111, and be 

guided by relevant policies and 

guidance such as FDA’s Guidance for 

Industry (GFI) #152. 

2. Environmental assessments 

Under the proposal, a request for 

eligibility would be required to contain 

either an environmental assessment or 

sufficient information to support a 

categorical exclusion from the 

requirement to prepare an 

environmental assessment. The 

proposal would rely on the process and 

the standards for environmental 

assessments that are already defined in 

part 25 (21 CFR part 25). It would also 

amend part 25 to have categorical 

exclusions relating to indexing that 

parallel those relating to new animal 

drug approvals. 

3. Occupational and user safety 

As with new animal drug approvals, 

indexing includes a provision for a 

demonstration of safety to individuals 

exposed to the new animal drug during 

the drug’s manufacture and use. FDA 

intends to rely on the same user safety 

standards for both drug approval and 

drug indexing. 

4. Chemistry, manufacturing, and 

control information 

The required chemistry, 

manufacturing, and control information, 

and the agency’s review of that 

information, are much different for 

indexing than they are for approval. 

A request for a determination of 

eligibility for a new animal drug for 

indexing must include ‘‘information 

regarding’’ the components and 

composition of the involved drug 

(section 572(c)(1)(C) of the act) and must 

also include ‘‘a description’’ of the 

methods used in, and the facilities and 

controls used for, the manufacture, 

processing, and packing of the new 

animal drug (section 572(c)(1)(D) of the 

act) for the purpose of determining 

whether the requestor has an 

understanding of current Good 

Manufacturing Practices (cGMPs) and 

has established appropriate 

specifications for the manufacture and 

control of the new animal drug (section 

572(c)(2)(C) of the act). In addition, 

before a new animal drug can be added 

to the index, the requestor must make a 

commitment that the indexed drug will 

be manufactured in compliance with 

cGMPs (section 572(d)(1)(F) of the act). 

In contrast, an NADA must include a 

‘‘full list’’ of the articles used as 

components of the drug and ‘‘a full 

statement’’ of the composition of the 

drug (section 512(b)(1)(B), (C) of the act) 

as well as ‘‘a full description’’ of the 

methods used in, and the facilities and 

controls used for, the manufacture, 

processing, and packing of the new 

animal drug (section 512(b)(1)(D) of the 

act). These statutory requirements, as 

implemented by regulation (21 CFR 

514.1(b)(4), (5)), result in a highly 

detailed NADA submission which must 

contain sufficient information to permit 

FDA to determine the adequacy of the 

‘‘full description’’ with respect to 

preserving the identity, strength, 

quality, and purity of the subject new 

animal drug (see section 512(d)(1)(C) of 

the act). 

As previously stated, FDA believes 

that the submission of chemistry, 

manufacturing, and control information 

for a new animal drug proposed for 

indexing that would meet the relevant 

statutory standard would consist of a 

comprehensive summary of the 

manufacturing process that is sufficient 

to permit a determination that the 

requestor understands cGMPs and has 

established appropriate specifications in 

accordance with that understanding. 

FDA believes that the ‘‘full description’’

and underlying confirmatory 

information that are required in an 

NADA would not be necessary in a 

request for determination of eligibility 

for indexing. 

5. Other Information 

Proposed 21 CFR 516.129 also 

requires that a request for determination 

of eligibility contain the following: (1) 

Identification of the minor species or 

groups of minor species for which 

indexing is sought; (2) a statement of the 

intended use(s) in those species; (3) a 

statement of the conditions of use, such 

as dosage, route of administration, 

warnings, contraindications or other 

significant limitations associated with 

the intended use(s); (4) a brief 

discussion of the need for the drug for 

the intended use(s); and (5) an estimate 

of the anticipated annual distribution 

after indexing. 

Additionally, the regulation provides 

that a single request for eligibility may 

involve only one drug (or combination 

of drugs) in one dosage form, may 

involve multiple intended uses or 

multiple minor species, may not involve 

a new animal drug that is contained in 

or a product of a transgenic animal, and 

may not involve the same drug in the 

same dosage form for the same intended 

use as a new animal drug that is already 

approved or conditionally approved. 

G. Granting and denying requests for a 

determination of eligibility and 

notification thereof (proposed § 516.133, 

§ 516.135, and § 516.137). 

FDA will deny a request for 

determination of eligibility if a requestor 

fails to submit information required by 

section 572(c)(1) of the act, or the 

submitted information, evaluated 

together with other information 

available to the agency, is insufficient to 

support a decision to grant a request in 


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48844 Federal Register / Vol. 71, No. 162 / Tuesday, August 22, 2006 / Proposed Rules 

accordance with section 572(c)(2) of the 

act. 

The new animal drug that is the 

subject of the request must be 

sufficiently characterized to enable the 

agency to determine whether the same 

drug in the same dosage form for the 

same intended use is already approved 

or conditionally approved. The 

proposed designation rule contains a 

definition of sameness regarding these 

three elements that would also apply to 

indexing (see proposed § 516.3 

published in the Federal Register of 

September 27, 2005 (70 FR 56394)). 

FDA believes that the estimate of the 

quantity of the indexed drug likely to be 

distributed on an annual basis following 

indexing is primarily required because 

of concern over extralabel use of 

indexed drugs, which is statutorily 

prohibited. The anticipated quantity to 

be distributed for the intended 

purpose(s) can serve as a baseline 

against which actual distribution can be 

measured. Significant differences 

between expected and actual 

distribution may indicate that an 

indexed drug is being used for other 

than its intended purposes. An 

estimation of the quantity of drug likely 

to be distributed may also inform 

decisions associated with the extent of 

environmental or user exposure 

following indexing. 

As previously noted, a new animal 

drug which is contained in or is the 

product of a transgenic animal may not 

be indexed. A transgenic animal is 

defined, in section 571(j) of the act, as 

an animal whose genome contains a 

nucleotide sequence that has been 

intentionally modified in vitro, and the 

progeny of such an animal; provided 

that the term ‘‘transgenic animal’’ does 

not include an animal of which the 

nucleotide sequence of the genome has 

been modified solely by selective 

breeding. 

Under the proposal, FDA cannot 

determine a drug to be eligible for 

indexing if the information submitted in 

support of the request evaluated 

together with other information 

available to the agency is insufficient to 

do the following: (1) Demonstrate food 

safety in an early, non-food life stage of 

a food-producing minor species animal 

or demonstrate that there is a reasonable 

certainty that treated animals will not be 

consumed by humans or food-producing 

animals, (2) determine that the requestor 

has established appropriate 

specifications for the manufacture and 

control of the new animal drug, (3) 

demonstrate that the requestor has an 

understanding of current good 

manufacturing practices, or (4) 

determine that the new animal drug is 

safe with respect to individuals exposed 

to the new animal drug during 

manufacture or use; or the request fails 

to include an adequate environmental 

assessment or sufficient information to 

support a categorical exclusion from the 

requirement to prepare an 

environmental assessment. 

In addition, under the proposal a 

request for a determination of eligibility 

for indexing may be denied if it contains 

any untrue statement of a material fact 

or omits material information. 

Within 90 days after the submission 

of a request for a determination of 

eligibility for a non food-producing 

animal, or 180 days for a request for an 

early, non-food life stage of a foodproducing animal, FDA must grant or 

deny the request and notify the 

requestor of its decision in writing. If 

FDA denies the request, the agency will 

provide due notice and an opportunity 

for an informal conference regarding its 

decision. A decision of FDA to deny a 

request for determination of eligibility 

for indexing following an informal 

conference would constitute the final 

agency action subject to judicial review. 

H. Qualified expert panels (proposed 

§ 516.141). 

Once a requestor has received a letter 

granting eligibility for indexing, as the 

first step in the process of requesting an 

index listing, it can propose a qualified 

expert panel. The panel, which operates 

external to FDA, plays a central role in 

the indexing process—evaluating target 

animal safety and effectiveness 

information and making a 

recommendation to FDA based on its 

evaluation. Section 572(d) of the act 

requires the agency to ‘‘define the 

criteria for selection of a qualified 

expert panel and the procedures for the 

operation of the panel.’’ The same 

section states that the panel is not 

subject to the Federal Advisory 

Committee Act, also known as FACA. 

Section 516.141 of the proposed 

implementing regulations describes the 

process for selecting the qualified expert 

panel and describes how the panel 

operates. It does this by stating the 

responsibilities of each of the parties 

involved—the requestor, FDA, the panel 

members, and the panel leader. 

Because of the diverse nature of the 

products that are subject to indexing 

and anticipated differences in the 

availability and accessibility of experts 

qualified to review different product 

classes, the proposed rule does not 

specify the day-to-day operations of a 

qualified expert panel other than to 

require that the activities of the panel be 

conducted in accordance with generally 

accepted professional and ethical 

business practices and that one member 

of the panel be identified to serve as the 

‘‘leader’’ of the review process. The 

leader would serve as the principal 

spokesperson for the panel and be 

responsible for submitting the panel’s 

final written report to the requestor and 

maintaining records of the final report. 

In addition, the agency plans to issue 

guidance documents regarding other 

aspects of the operation of expert panels 

and the preparation of written reports. 

In developing the selection criteria for 

the qualified expert panel, FDA adapted 

some aspects of the agency’s 

implementation of section 523 of the act 

(21 U.S.C. 360m). That provision deals 

with FDA accreditation of persons in 

the private sector to conduct the initial 

pre-market review for certain medical 

devices. FDA also considered its use of 

advisory committees that review 

information and make recommendations 

to FDA on various technical and 

scientific issues relating to product 

approval. In addition, FDA tried to 

minimize the burden on the potential 

members to help ensure that qualified 

individuals will be willing to participate 

while still establishing adequate 

controls to help ensure that FDA obtains 

objective, high quality evaluations and 

recommendations. 

To maintain the integrity of the 

review process, one proposed selection 

criterion is that a qualified expert panel 

member must not have a conflict of 

interest or the appearance of a conflict 

of interest, unless FDA makes a 

determination to allow participation 

notwithstanding an otherwise 

disqualifying financial interest. The 

proposed rule describes the factors that 

are, and are not, relevant to determining 

whether there is a conflict of interest or 

the appearance of a conflict of interest 

and identifies the information needed 

from potential panel members to 

support this determination by the 

agency. Proposed § 516.141(e)(7) 

requires qualified expert panel members 

to immediately notify the requestor and 

FDA of any change in conflict of interest 

status. For purposes of this regulation, 

the agency believes that this generally 

requires a panelist to report changes in 

his conflict of interest status within 30 

days. 

In selecting members for the qualified 

expert panel, the person requesting the 

index listing would be required to 

ensure that the members have the 

requisite scientific training and 

experience to evaluate the target animal 

safety and effectiveness of the new 

animal drug at issue for the proposed 

intended use. The group of identified 

experts would also be required to 


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represent an adequate range of expertise 

to fully evaluate the product. 

After identifying potential panel 

members, the requestor would be 

required to provide their names and 

addresses to FDA, along with sufficient 

information about each proposed 

member for FDA to determine whether 

the panel meets the selection criteria 

other than with respect to potential 

conflicts of interest. Each proposed 

panel member would provide 

information regarding potential conflicts 

of interest directly to the agency. If the 

agency determines that the qualified 

expert panel does not meet the selection 

criteria, it will provide information to 

the requestor so that a suitable panel 

can be proposed. For example, FDA may 

decline some candidates and request 

replacements or request that the panel 

include additional members to provide 

needed expertise. If the requestor 

disagrees with FDA’s determination 

regarding the panel, under the proposal 

it may request review through an 

informal conference. 

The work of the expert panel centers 

around its primary task, which is to 

prepare a written report that describes 

the panel’s evaluation of all available 

target animal safety and effectiveness 

information relevant to the proposed 

use of the new animal drug and the 

panel’s conclusions based on its 

evaluation. In preparing the written 

report, panel members would be 

required to review all relevant 

information provided by the requestor 

and should also consider any other 

relevant information otherwise known 

by panel members, including anecdotal 

information. Panel members would be 

required to participate in the 

preparation of the written report. 

Members could be paid a reasonable fee 

to serve on expert panels by the 

requestor. 

I. Written report (proposed § 516.143). 

The qualified expert panel’s written 

report must meet the requirements of 

section 572(d)(2) of the act. Under 

proposed § 516.143, which would 

implement this provision, the report 

must describe the panel’s evaluation of 

all available target animal safety and 

effectiveness information relevant to the 

proposed use of the new animal drug; 

provide citations of all literature 

reviewed and summaries of 

unpublished information considered; 

and state the panel’s opinion regarding 

whether the benefits of using the new 

animal drug for the proposed use in a 

minor species outweigh its risks to the 

target animal, taking into account the 

harm being caused by the absence of an 

approved or conditionally approved 

new animal drug for the minor species 

in question. The purpose of these 

requirements is to provide sufficient 

information to permit the agency to 

assess the quality and quantity of the 

information relating to target animal 

safety and effectiveness of the new 

animal drug assessed by the panel. 

Therefore, the panel’s evaluation should 

be such that FDA can understand the 

basis for the panel’s conclusion 

regarding the drug’s benefits and risks. 

If the expert panel concludes that the 

benefits of using the drug outweigh its 

risks, it would also be required to 

provide as part of the report either draft 

labeling, which includes all conditions 

of use deemed necessary by the expert 

panel to assure that the benefits of the 

drug will outweigh its risks, or narrative 

information on the basis of which such 

labeling can be drafted by the requestor. 

All panel members would be required to 

sign the report or otherwise approve it 

in writing. 

J. Content and format of a request for 

addition to the index (proposed 

§ 516.145). 

As noted previously, the second part 

of the indexing regulatory process 

involves FDA’s review of whether the 

new animal drug meets the statutory 

criteria regarding target animal safety 

and effectiveness information. FDA’s 

review is based on the qualified expert 

panel’s written report and 

recommendation. The agency’s review 

begins with the requestor’s submission 

asking for addition of the new animal 

drug to the index. This submission must 

contain the information required by 

section 572(d)(1) of the act. FDA’s 

decision to grant or deny the request for 

indexing is governed by section 

572(d)(4) of the act. Therefore, the 

request for addition to the index needs 

to contain sufficient information to 

permit FDA to grant the request. The 

sections of the proposed rule that 

implement these statutory provisions 

are sections 516.145 and 516.149, 

respectively. 

K. Refusal to file and review a request 

for addition to the index (proposed 

§ 516.147). 

The agency proposes that if a request 

for indexing fails to contain information 

required by § 516.145, FDA will not file 

or review it and will so notify the 

requestor within 30 days of receiving 

the request. 

L. Granting or denying a request for 

addition to the index and notification 

thereof (proposed § 516.149, § 516.151, 

and § 516.153). 

FDA must deny a request for indexing 

if the same drug in the same dosage 

form for the same intended use is 

approved or conditionally approved. 

While this is also a basis for denying 

eligibility for indexing, it is possible 

that a new animal drug may be 

approved or conditionally approved 

between the time that a determination 

for eligibility is made and the request 

for indexing is submitted, thus 

preventing the indexing of a new animal 

drug previously determined to be 

eligible. 

It is also possible that new scientific 

information may arise between the time 

of a determination of eligibility and 

submission of a request for indexing. 

Section 572(d)(4) of the act (by reference 

to section 572(a) of the act) and 

proposed § 516.151 require the agency 

in reviewing a request for index listing 

to evaluate any new information 

together with the information available 

at the time of a determination of 

eligibility to determine whether the new 

animal drug is still eligible for indexing. 

If a request for indexing fails to 

contain, or appropriately reference, 

information required by the statute, as 

implemented by proposed § 516.145, the 

agency would be required to deny the 

request. 

In general, FDA intends to rely 

heavily on the recommendations of the 

qualified expert panel regarding target 

animal safety and effectiveness, 

including the necessary conditions of 

use. However, the written report of a 

qualified expert panel may not be 

sufficiently clear or complete with 

respect to the basis for a panel 

recommendation to index a new animal 

drug to permit FDA to make an 

informed decision regarding whether it 

agrees with the recommendation. In this 

case, FDA would either deny the request 

for indexing or, under proposed 

§ 516.145(c), require that the requestor 

submit the information provided to the 

panel. It is also possible that, in some 

cases, the written report of an expert 

panel may be sufficiently clear and 

complete for the agency to make a 

decision regarding the panel 

recommendations, but the agency may 

disagree in whole or in part with the 

recommendations. Such disagreement 

may be based on the written report itself 

or the report along with additional 

information available to the agency. In 

such a case, FDA would deny the 

request. If FDA denies a request for 

addition to the index, the requestor 


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could submit another request, which 

contains information to overcome the 

agency’s grounds for denial. 

One of the grounds for denying a 

request for addition to the index is that 

the qualified expert panel failed to meet 

one or more of the selection criteria. 

Proposed § 516.141 would require panel 

members to submit any new information 

regarding conflicts of interest to the 

agency so that FDA can determine 

whether a disqualifying conflict has 

arisen since the agency’s initial review. 

Under the proposal, and consistent 

with FDA’s regulations governing new 

animal drug applications, FDA may also 

deny a request for addition to the index 

if it contains any untrue statement of a 

material fact or omits material 

information. 

Within 180 days after the filing of a 

request for addition of a new animal 

drug to the index, FDA will grant or 

deny the request, and notify the person 

requesting indexing of FDA’s decision 

in writing. If FDA denies the request for 

indexing of a new animal drug, the 

agency will provide due notice and an 

opportunity for an informal conference. 

A decision by FDA to deny a request to 

index a new animal drug following an 

informal conference will constitute final 

agency action subject to judicial review. 

M. Publication of the index and content 

of an index listing (proposed § 516.157). 

FDA proposes to meet the 

requirement of section 572(e)(2) of the 

act by maintaining and updating, at 

least annually, a publicly available list 

of indexed drugs. Each index listing 

would contain the following: (1) The 

name and address of the person who 

holds the index listing, (2) the name of 

the new animal drug and the intended 

use and conditions of use for which it 

is indexed, (3) product labeling, and (4) 

conditions and any limitations that the 

agency deems necessary regarding the 

use of the new animal drug. 

N. Modifications to indexed drugs 

(proposed § 516.161). 

As with approved new animal drugs, 

and as provided for by section 572(e)(3) 

of the act, there will almost certainly be 

a need to change the conditions under 

which a new animal drug is indexed or 

other aspects of an indexed drug at 

some point after indexing. The proposed 

regulations for making such changes are 

based on those governing new animal 

drug applications, although the 

proposed regulations are generally less 

burdensome than the regulatory 

requirements of the corresponding 

section of 21 CFR part 514. 

Proposed § 516.161 provides for three 

classes of changes to indexed drugs. 

The first class of changes involves the 

following: (1) The addition to labeling 

or prescription drug advertising of 

additional warning, contraindication, 

side effect, or cautionary information, 

(2) the deletion from labeling or 

prescription drug advertising of false, 

misleading, or unsupported indications 

for use or claims of effectiveness, or (3) 

changes in manufacturing methods or 

controls required to correct product or 

manufacturing defects that may result in 

serious adverse drug events. Changes of 

this nature should be made as soon as 

possible and a request for modification 

of an index listing containing 

information describing the need for the 

change should be concurrently 

submitted to the agency. 

The second class of changes involves 

the following: (1) Addition of an 

intended use, (2) addition of a species, 

(3) addition or alteration of an active 

ingredient, (4) alteration of the 

concentration of an active ingredient, (5) 

alteration of the dose or dosage regimen, 

or (6) alteration of prescription or overthe-counter status. Changes of this 

nature can be made only after a request 

to make such a change has been granted 

by FDA. Each such change must go 

through the same review process as the 

original index listing. Therefore, the 

initial submission to FDA relating to 

such a change should be a request for 

a determination of eligibility for 

indexing that relates specifically to the 

proposed change. However, while the 

process for modifications to index 

listings of this kind follows the same 

process as a new index listing, much of 

the work to support the initial listing 

might also support the change to the 

listing and so would not have to be 

duplicated. Likewise, the panel that 

reviewed the original request for listing 

would likely be acceptable to review the 

proposed change as well. The agency 

notes, however, that the nature of the 

change or new information about, for 

example, the product’s safety or 

effectiveness, may mean that previous 

work would no longer be adequate to 

support the change. 

The third class of changes involves 

any change to the conditions established 

in labeling or otherwise described in the 

request for determination of eligibility 

or request for indexing at the time a new 

animal drug was indexed other than 

those noted above. Information 

describing such changes would be 

required to be submitted as part of the 

annual indexed drug experience report. 

These changes include changes to the 

formulation of the product or to the 

manufacturing methods or controls 

other than those to correct defects that 

may cause serious adverse drug events. 

Changes to the formulation or 

manufacturing process would be 

required to be reported at the same level 

of detail as the level of detail at which 

the formulation or manufacturing 

process were initially described in the 

request for determination of eligibility 

for indexing. 

The proposed provisions under 

§ 516.161 would apply only to 

modifications to the indexed drug. 

Regardless of which class of changes is 

requested, these provisions would not 

apply to changes that would cause an 

indexed drug to be a different drug (or 

different combination of drugs) or a 

different dosage form. In the case of 

such a submission, the agency would 

deny the request for modification and 

notify the holder that a new index 

listing is required for the new drug or 

dosage form. The designation proposed 

rule (September 27, 2005, 70 FR 56394) 

contains proposed definitions for ‘‘same 

drug’’ and ‘‘same dosage form.’’ The 

holder could then initiate the new 

listing by submitting a request for 

eligibility for the new drug or dosage 

form. 

O. Change in ownership of an index file 

(proposed § 516.163). 

The agency proposes that, in order to 

meet the requirement of section 

572(e)(1)(A) of the act, the owner of an 

index file supporting an index listing 

may transfer ownership of the file 

provided that the agency is 

appropriately notified of this. The 

agency would then update the index 

listing accordingly. 

P. Records and reports (proposed 

§ 516.165). 

Section 572(i) of the act requires the 

maintenance of records and the 

submission of reports sufficient to 

permit a determination of whether an 

indexed drug should be removed from 

the index. The information FDA 

believes is necessary to make this 

determination is described in proposed 

§ 516.165. This information would be 

similar in nature but less extensive than 

the information required with respect to 

approved new animal drugs. Most of the 

information required would be 

submitted annually, on, or within 60 

days of, the anniversary date of the 

letter granting the request for indexing. 

Under the proposed regulation, 

product or manufacturing defects that 

may result in serious adverse drug 

experiences must be reported to the 

appropriate FDA District Office or 

resident post within three working days 

of their discovery. Serious and 

unexpected adverse drug experiences 

must be reported to the Director, 


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OMUMS within 15 working days of the 

index holder first receiving the 

information. 

Distribution of an indexed drug by a 

distributor would be permissible 

provided that the holder of the index 

listing submits a special report at the 

time of initial distribution by the 

distributor containing the information 

required under proposed § 516.165. This 

includes a signed statement from the 

distributor that the indexed drug will be 

distributed and promoted only in 

accordance with the index listing. 

The agency proposes that all other 

required information be submitted 

annually. This includes the following: 

The quantity of the drug distributed 

(domestically and for export), holder 

and distributor current package labeling 

with a summary of any changes in 

labeling since the previous annual 

report, a summary of changes in the 

manufacturing process (at the level of 

detail that the manufacturing process 

was described in the request for 

determination of eligibility) not already 

reported under proposed § 516.161, any 

pertinent safety or effectiveness 

information not previously reported, 

and any adverse drug experience 

information not previously reported. 

Q. Removal from the index (proposed 

§ 516.167). 

Proposed § 516.167 provides for 

removal of a new animal drug from the 

index, after due notice to the holder of 

the index listing and an opportunity for 

an informal conference. 

The proposed grounds for removal, 

which track those in the act, include 

that the same drug in the same dosage 

form for the same intended use has been 

approved or conditionally approved. 

In accordance with section 572(f)(1) of 

the act, if FDA determines, subsequent 

to the indexing of a new animal drug, 

that the qualified expert panel failed to 

meet its applicable requirements, FDA 

would remove the drug from the index. 

In light of the purpose of the MUMS 

act to increase the availability of legally 

marketed new animal drugs to treat 

minor species, the agency proposes to 

only partially remove an index listing if 

it believes that doing so would 

satisfactorily resolve a safety or 

effectiveness issue otherwise warranting 

complete removal of the drug from the 

index. For example, if an index listing 

provides for the use of a new animal 

drug in several minor species and new 

information indicates that the benefits 

of using the drug in one of those minor 

species does not outweigh its risks to 

that species, the agency may remove 

only the use of the new animal drug in 

that minor species from the index 

listing. 

In accordance with section 572(f)(2) of 

the act, the regulation proposes that 

FDA may immediately suspend a new 

animal drug from the index if it 

determines that there is a reasonable 

probability that the use of the drug 

would present a risk to the health of 

humans or other animals. The agency 

would subsequently offer the holder of 

the index listing an opportunity for an 

informal conference. 

A decision by FDA to remove a new 

animal drug from the index following an 

informal conference would constitute 

final agency action subject to judicial 

review. 

R. Confidentiality of data and 

information in an index file (proposed 

§ 516.171). 

This proposed regulation is based on 

§ 514.11, which applies to new animal 

drug application files. It would apply to 

index files, which would encompass all 

data and information submitted to or 

incorporated by reference into the index 

file including requests for determination 

of eligibility for indexing, information 

supporting selection of expert panel 

members, requests for addition to the 

index, claimed investigational 

exemptions under proposed § 516.125, 

requests for modification to indexed 

drugs, reports submitted under 

proposed § 516.165, and master files. 

III. Conforming Changes 

FDA is proposing conforming changes 

to certain applicable sections of the 

Code of Federal Regulations (CFR) that 

would add a reference to new animal 

drugs that are index listed under section 

572 of the act. The affected sections in 

title 21 of the CFR are: 

§ 20.100 Applicability; cross-reference 

to other regulations. 

§ 25.33 Animal drugs. 

§ 201.105 Veterinary drugs. 

§ 201.115 New drugs or new animal 

drugs. 

§ 201.122 Drugs for processing, 

repacking, or manufacturing. 

§ 202.1 Prescription-drug 

advertisements. 

§ 207.21 Times for registration and 

drug listing. 

§ 207.35 Notification of registrant; 

drug establishment registration number 

and drug listing number. 

§ 225.1 Current good manufacturing 

practice. 

§ 225.35 Use of work areas, 

equipment, and storage areas for other 

manufacturing and storage purpose. 

§ 225.135 Work and storage areas. 

§ 226.1 Current good manufacturing 

practice. 

§ 500.25 Anthelmintic drugs for use in 

animals. 

§ 500.26 Timed-release dosage form 

drugs. 

§ 510.301 Records and reports 

concerning experience with animal 

feeds bearing or containing new animal 

drugs for which an approved medicated 

feed mill license application is in effect. 

§ 510.305 Maintenance of copies of 

approved medicated feed mill licenses 

to manufacture animal feed bearing or 

containing new animal drugs. 

§ 510.455 Requirements for freechoice medicated feeds. 

§ 511.1 New animal drugs for 

investigational use exempt from section 

512(a) of the act. 

§ 515.10 Medicated feed mill license 

applications. 

§ 515.21 Refusal to approve a 

medicated feed mill license application. 

§ 558.3 Definitions and general 

considerations applicable to this part. 

§ 558.5 Requirements for liquid 

medicated feed. 

§ 558.6 Veterinary feed directive 

drugs. 

§ 589.1000 Gentian violet. 

In § 201.105, FDA is also proposing to 

remove a reference to certification 

requirements applicable to preparations 

of antibiotic drugs. FDA no longer 

certifies or recognizes certification of 

antibiotic drugs. 

In addition, FDA is proposing to 

remove the last sentence in § 500.25(c) 

because it cites § 514.9 which no longer 

exists. Labeling revisions for animal 

feeds bearing or containing anthelmintic 

drugs are now subject to the same 

requirements under 21 CFR 500.25 as 

dosage form drugs. Medicated animal 

feeds covered by approved applications 

are subject to the provisions of § 514.8 

(d) and (e). Medicated animal feeds 

covered by an index listing are subject 

to the provisions of 21 CFR 

516.161(b)(1). 

IV. Legal Authority 

FDA’s authority for issuing this 

proposed rule is provided by the MUMS 

act (21 U.S.C. 360ccc et seq.). When 

Congress passed the MUMS act, it 

directed FDA to publish implementing 

regulations (see 21 U.S.C. 360ccc note). 

In the context of the MUMS act, the 

statutory requirements of section 572 of 

the act, along with section 701(a) of the 

act (21 U.S.C. 371(a)) provide authority 

for this proposed rule. Section 701(a) 

authorizes the agency to issue 

regulations for the efficient enforcement 

of the act. 

V. Analysis of Economic Impacts 

FDA has examined the impacts of the 

proposed rule under Executive Order 


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48848 Federal Register / Vol. 71, No. 162 / Tuesday, August 22, 2006 / Proposed Rules 

12004 National Industry-Specific Occupational 

Employment and Wage Estimates, U.S. Department 

of Labor, Bureau of Labor Statistics (http:// 

www.bls.gov/oes/current/naics4_325400.htm); 

compliance officer wage rate for pharmaceutical 

and medicine manufacturing (NAICS 325400). 

12866, the Regulatory Flexibility Act (5 

U.S.C. 601–612), and the Unfunded 

Mandates Reform Act (Public Law 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 (5 U.S.C. 

601–612) requires agencies to analyze 

regulatory options that would minimize 

any significant impact of a rule on small 

entities. 

FDA tentatively finds that the 

proposed rule does not constitute an 

economically significant regulatory 

action as defined in 3(f)(1) of Executive 

Order 12866. We base this on the 

following analysis that estimates annual 

costs ranging from about $342,000 in the 

first year to about $735,000 in the 10th 

year. Similarly, the administrative costs 

are unlikely to have a significant 

economic impact on a substantial 

number of small entities. 

Section 202(a) of the Unfunded 

Mandates Reform Act requires that 

agencies prepare a written statement, 

which includes 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 million 

(adjusted annually for inflation) in any 

one year.’’ The current threshold after 

adjustment for inflation is $115 million, 

using the most current (2003) implicit 

price deflator for the Gross Domestic 

Product. FDA does not expect this 

proposed rule to result in any 1-year 

expenditure that would meet or exceed 

this amount. As such, no further 

analysis of anticipated costs and 

benefits is required by the Unfunded 

Mandates Reform Act. 

Summary 

The proposed rule is expected to 

result in about 30 requestors, each 

averaging about 2 requests for a 

determination of eligibility for indexing 

of individual animal drugs annually, 

submitting a total of 60 requests 

annually. We estimate that requestors 

for 20 of these products will create and 

convene expert panels to review the 

safety and efficacy data. Further, the 

recommendations of these panels are 

expected to lead to the addition of 20 

animal drug index listings each year. 

Benefit 

This rule intends to create 

administrative practices and procedures 

for index listing a new animal drug for 

use in a minor species, thereby 

providing the benefit of a legal basis for 

marketing an unapproved new animal 

drug intended for use in a minor 

species. The need for the rule arises 

from the existence of some minor 

species populations that are too small to 

support traditional drug approval 

studies. The countervailing risk of this 

rule is that sponsors of animal drugs 

that are marginally economically viable 

could use this system to avoid the 

traditional animal drug approval 

process. Under this proposed rule, 

however, the voluntary indexing of a 

new animal drug for use in a minor 

species would only be allowed when 

the same drug in the same dosage form 

for the same intended use is not already 

approved or conditionally approved, 

thereby reducing this risk. 

Administrative Costs 

This section will describe and 

estimate the annual administrative costs 

by proposed provision for both 

producers of currently unapproved 

drugs that would request an index 

listing and FDA. First, we address the 

efforts required by requestors concerned 

with index listing. The estimates of the 

number of requestors, frequencies of 

responses, and hours per procedure for 

each of the provisions of the proposed 

rule were determined by Center for 

Veterinary Medicine personnel. 

We estimate that, on average, two 

foreign requestors of drug indexing 

would need to hire a permanent 

resident agent to represent them. We 

expect this to require about 1 hour of 

administrative time for a requestor’s 

management employee in regulatory 

affairs. We estimate the loaded wage 

estimate at $42.29 per hour (including a 

30 percent increase for benefits) for 

regulatory affairs personnel.1 This 

provision would cost the two requestors 

a total of about $85. We expect that a 

resident agent would expend only about 

6 hours of administrative effort per year 

per indexed drug. We estimate the wage 

rate of the resident agent at $100 to $150 

per hour, and use the midpoint, $125, 

for our calculations. Total annual costs 

for resident agents are estimated at 

$1,500 (two agents times 6 hours times 

$125 per hour) in the first year. In the 

10th year this is expected to rise to 

about $15,000 as two more resident 

agents each provide 6 more hours of 

administrative effort each additional 

year. Due to the uncertainty in the costs 

for resident agents, we request public 

comment and data on this issue. 

Proposed § 516.121 provides for one 

or more meetings between requestors 

and FDA to discuss the requirements for 

indexing a new animal drug. We 

estimate that 30 requestors will each 

request, on average, 2 meetings 

annually, for a total of 60 meetings. 

Preparation and participation in these 

meetings is estimated at 4 hours each, 

for an annual total of 240 hours. 

Proposed § 516.123 concerns informal 

conferences regarding agency 

administrative actions. These would 

include conferences to discuss a request 

for determination of eligibility that has 

been denied, the removal of an expert 

panel member, a request for indexing 

that was denied or an indexed drug that 

was removed from the list. We estimate 

that about three requestors would 

request one conference with FDA 

annually for any of these reasons. We 

expect that each requestor would 

expend about 8 hours (24 hours total) to 

prepare for and attend each of these 

conferences. The combined efforts for 

preparation and participation in all 

conferences are estimated at 264 hours 

(240 plus 24). At the same loaded wage 

estimate of $42.29 per hour, this 

provision is expected to cost about 

$11,200 annually. 

For proposed § 516.125, we estimate 

that two requestors would each 

annually submit three notices of 

claimed investigational exemptions for 

new animal drugs for index listing. We 

estimate that each submission would 

require about 20 hours for regulatory 

affairs personnel to prepare. At the 

loaded wage estimate of $42.29 per 

hour, the total of 120 hours would cost 

about $5,100. 

We estimate that about 30 requestors 

would each average about 2 requests for 

determination of eligibility for indexing 

of individual animal drugs annually, 

totaling to 60 requests annually for 

proposed § 516.129. At the loaded wage 

estimate of $42.29 per hour, and our 

estimate of 12 hours of preparation for 

each request, this provision would 

require about 720 hours equal to about 

$30,400. Included in this estimate of 60 

requests are any resubmitted requests 

that were previously denied. 

Proposed § 516.141 would require the 

creation of a qualified expert panel to 

review all information, provided by any 

source, relevant to a determination of 

the target animal safety and 

effectiveness of the new animal drug. 

FDA would be required to approve the 

panel members before the panel 

formally convened. We estimate that 

requestors of 20 animal drugs, or about 

one-third of the 60 animal drugs that 


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22002 Economic Census, U.S. Census Bureau, 

Manufacturing Industry Series, Pharmaceutical 

Preparation Manufacturing, Tables 3 and 4. 

annually are determined to be eligible 

for indexing, would create qualified 

expert panels to further study the safety 

and efficacy data. The creation of each 

panel by a requestor is estimated to take 

about 8 hours of effort by regulatory 

affairs personnel. At the same loaded 

wage estimate, these 160 hours would 

cost about $6,800 annually. 

Proposed § 516.143 describes how the 

expert panel would prepare a written 

report for FDA with its findings 

concerning the new animal drug under 

consideration for index listing. The 

review of the relevant information and 

preparation of the report by each panel 

would take an estimated 80 hours. This 

equates to 1,600 hours for 20 panels. 

The proposed rule allows for fees to be 

paid to panel members for their time. 

We estimated the average wage rate for 

panel members at $100 to $150/hr, and 

use the midpoint ($125) in our 

calculations. At this wage, we estimate 

these activities to cost up to $200,000 

annually for the total industry, or 

$10,000 per requestor for each animal 

drug under consideration. An additional 

0.5 hours is estimated for recordkeeping 

of the final written report described in 

proposed § 516.143 by the panel leader. 

This would result in an additional $400 

in costs annually. We request comment 

and data on the range of hourly wage 

rates for qualified panel members. 

We estimate that the formal request 

for addition to the index, provided for 

in proposed § 516.145, would require 

about 12 hours to prepare. This would 

result in another 240 hours of effort (20 

requests times 12 hours) for regulatory 

affairs personnel. We project the 

compliance cost of this effort at $10,200 

annually. 

We only expect to receive one request 

each for a modification to an indexed 

listed drug and a change in ownership 

of an index file annually (provided for 

in proposed §§ 516.161 and 516.163), 

and estimate the preparation of each to 

require 4 and 2 hours, respectively. In 

total, these compliance efforts would 

cost about $250 in the first year. Total 

modification requests and ownership 

change notifications are expected to 

increase by 1 each year so that 10 of 

each would be expected to be submitted 

in year 10. The cost of these provisions 

in year 10 is estimated at about $2,500. 

This proposed rule would require, in 

§ 516.165, that records and reports be 

created, submitted and retained by the 

holder of the indexed drug. These 

records include a 3-day indexed drug 

field alert report, a 15-day indexed drug 

field alert report and an annual indexed 

drug experience report. We expect that 

the vast majority of compliance efforts 

will be associated with the annual 

indexed drug experience report. 

Because the number of expected 

requests that are granted for addition to 

the index is 20 per year (on average, 20 

requestors with 1 request granted each), 

the number of reports to be created, 

submitted and stored is also estimated 

at 20 per year. We estimate the reports 

for each index listing would require 8 

hours annually, totally about 160 hours 

for all 20 listings. At the loaded wage 

estimate of $42.29 per hour, we estimate 

the first-year reporting costs at about 

$6,800. These annual costs will increase 

by an additional $6,800 each year as an 

additional 20 indexed drugs are added 

to the list. In year 10 we estimate the 

cost of this provision at about $67,700. 

Further, we expect that the maintenance 

of these records (recordkeeping) would 

require an additional hour of 

administrative time for each indexed 

drug listing. These additional 20 hours 

would cost about $850 at the same 

loaded wage estimate in the first year, 

and would also increase in succeeding 

years by an additional $850 as 

additional indexed drugs are added to 

the list. We estimate the cost of this 

provision in year 10 at about $8,500. 

For those choosing to seek a MUMS 

index listing of an unapproved animal 

drug, total requestor compliance costs 

are expected to sum to about $273,000 

in the first year. These costs would be 

borne by 30 requestors at an average 

cost per requestor of about $9,100 per 

indexed drug. Costs in succeeding years 

would be expected to increase slightly 

due to the annual reporting 

requirements for all indexed drugs 

resulting in year-10 costs of about 

$358,000. 

Costs to Government 

The Government would also incur 

costs for this proposed rule. We expect 

that about 60 percent of a full-time 

equivalent employee at a GS–14 salary 

would be needed to handle the 

administrative work of the indexing of 

MUMS drugs in the first year. This 

would include all administrative efforts 

from responding to requests for 

presubmission meetings to making 

changes to approved indexed drugs. We 

estimate Government costs (including a 

30 percent adjustment for benefits) of 

this provision at about $69,000 in the 

first year. In year 10 we estimate that up 

to four full time equivalent employees 

(one GS–14 position, two GS–13 

positions and one GS–11 position) 

would be needed to administer the 

program. Including a 30 percent 

adjustment for benefits, we estimate that 

the cost to Government in year 10 could 

increase to about $378,000. 

Total costs for this proposed rule 

would be the sum of private 

administrative and Government costs. 

Total costs are estimated to increase 

from $342,000 in the first year up to 

$735,000 in the 10th year. 

Regulatory Flexibility Analysis 

1. Small Business Impacts 

The Regulatory Flexibility Act 

requires agencies to prepare a regulatory 

flexibility analysis if a rule is expected 

to have a significant economic impact 

on a substantial number of small 

entities. Although we believe it is 

unlikely that significant economic 

impacts would occur, the following 

constitutes the initial regulatory 

flexibility analysis. 

One requirement of the Regulatory 

Flexibility Act is a succinct statement of 

any objectives of the rule. As stated 

previously in this analysis, with this 

rule the agency intends to create an 

administrative system, provided for by 

statute, that would allow for the legal 

marketing of unapproved animal drugs 

for intended uses in minor species in 

the U.S. that would otherwise not be 

economically viable under current 

market conditions. 

The Regulatory Flexibility Act also 

requires a description of the small 

entities that would be affected by the 

rule, and an estimate of the number of 

small entities to which the rule would 

apply. The Small Business 

Administration (SBA) defines the 

criteria for small businesses using the 

North American Industrial 

Classification System (NAICS). For 

pharmaceutical preparation 

manufacturers (NAICS number 325412), 

SBA defines small businesses as those 

with less than 750 employees. Census 

data shows that 723 companies with 901 

establishments represent this category.2

While about two-thirds of the 

establishments would be considered 

small using the SBA criteria, the agency 

acknowledges that many requests for 

MUMS index listing would likely be 

received from multi-establishment 

companies that exceed the 750- 

employee limit on small businesses. 

Nonetheless, the average cost for a 

requestor that has two meetings with us, 

requests a determination of eligibility 

for indexing, creates and convenes a 

qualified panel of experts resulting in a 

written report, requests an addition to 

the index and keeps all necessary 

records, would be about $12,600. This 

cost per request represents about 1.5 

percent of the revenues of the smallest 

set of establishments (those with one to 

four employees), and less than 0.4 


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percent of revenues of all larger 

establishments. These costs would not 

represent a significant economic impact 

on these firms, especially in light of the 

fact that they incur these expenses in 

order to realize increased sales revenue 

from the indexing. The firms submitting 

requests for index listing are expected to 

already have the necessary 

administrative personnel with the skills 

required to prepare the requests and 

fulfill reporting requirements as 

identified above. 

2. Analysis of Alternatives 

The Regulatory Flexibility Act 

requires that the agency consider any 

alternatives to the proposed rule that 

would accomplish the objective while 

minimizing significant impacts of the 

rule. As stated previously, the agency 

believes that the proposed rule, due to 

the relatively small size of the costs, 

would not be likely to impose 

significant economic impacts on a 

substantial number of small businesses. 

The statute that creates this system, 

Pub. L. 108–282, does not provide the 

agency a great deal of flexibility in the 

implementing regulations, such as in 

determining whether or not to use 

independent qualified expert panels to 

review the safety and efficacy data. We 

conclude that the proposed rule 

achieves the objective of increasing drug 

availability for minor species with 

minimal costs to industry while staying 

within the limits set by Pub. L. 108–282. 

VI. Paperwork Reduction Act of 1995 

This proposed rule contains 

information collection provisions that 

are subject to review by the Office of 

Management and Budget (OMB), under 

the Paperwork Reduction Act of 1995 

(the PRA) (44 U.S.C. 3501–3520). A 

description of these provisions is given 

below with an estimate of the annual 

reporting and recordkeeping burden. 

Included in the estimate is the time for 

reviewing instructions, searching 

existing data sources, gathering and 

maintaining the data needed, and 

completing and reviewing each 

collection of information. 

FDA invites comments on these 

topics: (1) Whether the proposed 

collection of information is necessary 

for the 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; (4) ways to minimize the 

burden of the collection of information 

on respondents, including through the 

use of automated collection techniques 

and other forms of information 

technology. 

Title: Index of Legally Marketed 

Unapproved New Animal Drugs for 

Minor Species 21 CFR Part 516 

Description: The Minor Use and 

Minor Species Animal Health Act of 

2004 (MUMS act) amended the Federal 

Food, Drug, and Cosmetic Act (the act) 

to authorize FDA to establish new 

regulatory procedures intended to make 

more medications legally available to 

veterinarians and animal owners for the 

treatment of minor animal species 

(species other than cattle, horses, swine, 

chickens, turkeys, dogs, and cats), as 

well as uncommon diseases in major 

animal species. 

The MUMS act created three new 

sections to the act (section 571, 572, and 

573), and this proposed rule is intended 

to implement section 572 of the act, 

which provides for an index of legally 

marketed unapproved new animal drugs 

for minor species. Participation in any 

part of the MUMS program is optional 

so the associated paperwork only 

applies to those who choose to 

participate. The proposed rule specifies, 

among other things, the criteria and 

procedures for requesting eligibility for 

indexing and for requesting addition to 

the index as well as the annual 

reporting requirements for index 

holders. 

Under the new subpart C of part 516, 

proposed § 516.119 provides 

requirements for naming a permanentresident U.S. agent by foreign drug 

companies, and § 516.121 would 

provide for informational meetings with 

FDA. Section 516.123 provides 

proposed requirements for requesting 

informal conferences regarding agency 

administrative actions and proposed 

§ 516.125 provides for investigational 

use of new animal drugs intended for 

indexing. Provisions for requesting a 

determination of eligibility for indexing 

can be found under proposed § 516.129 

and provisions for subsequent requests 

for addition to the index can be found 

under proposed § 516.145. A 

description of the written report 

required in § 516.145 can be found 

under proposed § 516.143. Under 

proposed § 516.141 are provisions for 

drug companies to nominate a qualified 

expert panel as well as the panel’s 

recordkeeping requirements. This 

section would also call for the 

submission of a written conflict of 

interest statement to FDA by each 

proposed panel member. Index holders 

would be able to modify their index 

listing under proposed § 516.161 or 

change drug ownership under proposed 

§ 516.163. Requirements for records and 

reports are proposed under § 516.165. 

Description of Respondents: 

Pharmaceutical companies that sponsor 

new animal drugs. 

Thus, FDA estimates the burden for 

this collection of information as follows: 

TABLE 1.—ESTIMATED ANNUAL REPORTING BURDEN1

21 CFR Section No. of 

Respondents 

Annual Frequency 

per Response 

Total Annual 

Responses 

Hours per 

Response Total Hours 

516.119 2 1 2 1 2 

516.121 30 2 60 4 240 

516.123 3 1 3 8 24 

516.125 2 3 6 20 120 

516.129 30 2 60 12 720 

516.141 20 1 20 8 160 

516.143 20 1 20 80 1,600 

516.145 20 1 20 12 240 


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TABLE 1.—ESTIMATED ANNUAL REPORTING BURDEN1—Continued 

21 CFR Section No. of 

Respondents 

Annual Frequency 

per Response 

Total Annual 

Responses 

Hours per 

Response Total Hours 

516.161 1 1 1 4 4 

516.163 1 1 1 2 2 

516.165 10 2 20 8 160 

Total 3,272 

1There is no capital or operating and maintenance costs associated with this collection of information. 

TABLE 2.—ESTIMATED ANNUAL RECORDKEEPING BURDEN1

21 CFR Section No. of 

Respondents 

Annual Frequency 

per Response 

Total Annual 

Responses 

Hours per 

Response Total Hours 

516.141 30 2 60 0.5 30 

516.165 10 2 20 1 20 

Total 50 

1There is no capital or operating and maintenance costs associated with this collection of information. 

The burden estimate for this reporting 

requirement was derived by our Office 

of Minor Use and Minor Species Animal 

Drug Development by extrapolating 

from relevant portions of the current 

Investigational New Animal Drug 

(INAD) and NADA reporting 

requirements for similar actions by a 

similar segment of the regulated 

industry and from previous interactions 

with the minor species community. 

In compliance with the Paperwork 

Reduction Act of 1995 (44 U.S.C. 

3507(d)), the agency has submitted the 

information collection provisions of this 

proposed rule to OMB for review. 

VII. Environmental Impact 

We have carefully considered the 

potential environmental impacts of this 

rule and determined under 21 CFR 

25.30(h) that this action is of a type that 

does not individually or cumulatively 

have a significant effect on the human 

environment. Therefore, neither an 

environmental assessment nor an 

environmental impact statement is 

required. 

VIII. Federalism 

We have analyzed this proposed rule 

in accordance with the principles in 

Executive Order 13132. We have 

determined that the proposed rule does 

not contain policies that have 

substantial direct effects on the States, 

on the relationship between the 

National Government and the States, or 

on the distribution of power and 

responsibilities among the various 

levels of government. Accordingly, we 

have tentatively concluded that the 

proposed rule does not contain policies 

that have federalism implications as 

defined in the Executive order and, 

consequently, a federalism summary 

impact statement has not been prepared. 

IX. Comments 

You may submit to the Division of 

Dockets Management (see ADDRESSES) 

written or electronic comments 

regarding this document. Please submit 

a single copy of electronic comments or 

two paper copies of any mailed 

comments, except that individuals may 

submit one paper copy. Identify your 

comments with the docket number 

found in brackets in the heading of this 

document. You may view received 

comments in the Division of Dockets 

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

Monday through Friday. 

List of Subjects 

21 CFR Part 20 

Confidential business information, 

Courts, Freedom of information, 

Government employees. 

21 CFR Part 25 

Environmental impact statements, 

Foreign relations, Reporting and 

recordkeeping requirements. 

21 CFR Part 201 

Drugs, Labeling, Reporting and 

recordkeeping requirements. 

21 CFR Part 202 

Advertising, Prescription drugs. 

21 CFR Part 207 

Drugs, Reporting and recordkeeping 

requirements. 

21 CFR Part 225 

Animal drugs, Animal feeds, 

Labeling, Packaging and containers, 

Reporting and recordkeeping 

requirements. 

21 CFR Part 226 

Animal drugs, Animal feeds, 

Labeling, Packaging and containers, 

Reporting and recordkeeping 

requirements. 

21 CFR Part 500 

Animal drugs, Animal feeds, Cancer, 

Labeling, Packaging and containers, 

Polychlorinated biphenyls (PCBs). 

21 CFR Part 510 

Administrative practice and 

procedure, Animal drugs, Labeling, 

Reporting and recordkeeping 

requirements. 

21 CFR Part 511 

Animal drugs, Medical research, 

Reporting and recordkeeping 

requirements. 

21 CFR Part 515 

Administrative practice and 

procedure, Animal drugs, Confidential 

business information, Reporting and 

recordkeeping requirements. 

21 CFR Part 516 

Administrative practice and 

procedure, Animal drugs, Confidential 

business information, Reporting and 

recordkeeping requirements. 

21 CFR Part 558 

Animal drugs, Animal feeds. 


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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 Chapter I be amended as 

follows: 

PART 20—PUBLIC INFORMATION 

1. The authority citation for 21 CFR 

part 20 continues to read as follows: 

Authority: 5 U.S.C. 552; 18 U.S.C. 1905; 19 

U.S.C. 2531–2582; 21 U.S.C. 321–393, 1401–

1403; 42 U.S.C. 241, 242, 242a, 242l, 242n, 

243, 262, 263, 263b–263n, 264, 265, 300u–

300u–5, 300aa–1. 

2. Amend § 20.100 by adding 

paragraph (c)(44) to read as follows: 

§ 20.100 Applicability; cross-reference to 

other regulations. 

* * * * * 

(c) * * * 

(44) Minor-species drug index 

listings, in § 516.171 of this chapter. 

PART 25—ENVIRONMENTAL IMPACT 

CONSIDERATIONS 

3. The authority citation for 21 CFR 

part 25 continues to read as follows: 

Authority: 21 U.S.C. 321–393; 42 U.S.C. 

262, 263b–264; 42 U.S.C. 4321, 4332; 40 CFR 

parts 1500–1508; E.O. 11514, 35 FR 4247, 3 

CFR, 1971 Comp., p. 531–533 as amended by 

E.O. 11991, 42 FR 26967, 3 CFR, 1978 Comp., 

p. 123–124 and E.O. 12114, 44 FR 1957, 3 

CFR, 1980 Comp., p. 356–360. 

4. Amend § 25.33 by revising 

paragraphs (a) introductory text, (c), (d) 

introductory text, and (g) to read as 

follows: 

§ 25.33 Animal drugs. 

* * * * * 

(a) Action on an NADA, abbreviated 

application, request for determination of 

eligibility for indexing, a supplement to 

such applications, or a modification of 

an index listing, if the action does not 

increase the use of the drug. Actions to 

which this categorical exclusion applies 

may include: 

* * * * * 

(c) Action on an NADA, abbreviated 

application, request for determination of 

eligibility for indexing, a supplement to 

such applications, or a modification of 

an index listing, for substances that 

occur naturally in the environment 

when the action does not alter 

significantly the concentration or 

distribution of the substance, its 

metabolites, or degradation products in 

the environment. 

(d) Action on an NADA, abbreviated 

application, request for determination of 

eligibility for indexing, a supplement to 

such applications, or a modification of 

an index listing, for: 

* * * * * 

(g) Withdrawal of approval of an 

NADA or an abbreviated NADA or 

removal of a new animal drug from the 

index. 

* * * * * 

PART 201—LABELING 

5. The authority citation for 21 CFR 

part 201 continues to read as follows: 

Authority: 21 U.S.C. 321, 331, 351, 352, 

353, 355, 358, 360, 360b, 360gg–360ss, 371, 

374, 379e; 42 U.S.C. 216, 241, 262, 264. 

6. Amend § 201.105 by revising 

paragraphs (c)(2) and (d)(1) to read as 

follows: 

§ 201.105 Veterinary drugs. 

* * * * * 

(c) * * * 

(2) If the article is subject to section 

512 or 572 of the act, the labeling 

bearing such information is the labeling 

authorized by the approved new animal 

drug application or contained in the 

index listing: Provided, however, That 

the information required by paragraph 

(c)(1) of this section may be omitted 

from the dispensing package if, but only 

if, the article is a drug for which 

directions, hazards, warnings, and use 

information are commonly known to 

veterinarians licensed by law to 

administer the drug. Upon written 

request, stating reasonable grounds 

therefore, the Commissioner will offer 

an opinion on a proposal to omit such 

information from the dispensing 

package under this proviso. 

(d) * * * 

(1) Adequate information for such 

use, including indications, effects, 

dosages, routes, methods, and frequency 

and duration of administration, and any 

relevant warnings, hazards, 

contraindications, side effects, and 

precautions, and including information 

relevant to compliance with the new 

animal drug provisions of the act, under 

which veterinarians licensed by law to 

administer the drug can use the drug 

safely and for the purposes for which it 

is intended, including all conditions for 

which it is advertised or represented; 

and if the article is subject to section 

512 or 572 of the act, the parts of the 

labeling providing such information are 

the same in language and emphasis as 

labeling approved, permitted, or 

indexed under the provisions of section 

512 or 572, and any other parts of the 

labeling are consistent with and not 

contrary to such approved, permitted, or 

indexed labeling; and 

* * * * * 

7. Amend § 201.115 by revising 

paragraphs (a) and (b) to read as follows: 

§ 201.115 New drugs or new animal drugs. 

* * * * * 

(a) To the extent to which such 

exemption is claimed in an approved 

application with respect to such drug 

under section 505 or 512 of the act or 

an index listing with respect to such 

drug under section 572 of the act; or 

(b) If no application under section 505 

of the act is approved with respect to 

such drug but it complies with section 

505(i), 512, or 572 of the act and 

regulations thereunder. 

* * * * * 

8. Amend § 201.122 by revising 

paragraphs (a), (b), and (c) to read as 

follows: 

§ 201.122 Drugs for processing, repacking, 

or manufacturing. 

* * * * * 

(a) An approved new drug application 

or new animal drug application or a 

new animal drug index listing covers 

the production and delivery of the drug 

substance to the application or index 

listing holder by persons named in the 

application or in the request for 

determination of eligibility for indexing, 

and, for a new drug substance, the 

export of it by such persons under 

§ 314.410 of this chapter; or 

(b) If no application is approved with 

respect to such new drug or new animal 

drug and it is not listed in the index, the 

label statement ‘‘Caution: For 

manufacturing, processing, or 

repacking’’ is immediately 

supplemented by the words ‘‘in the 

preparation of a new drug or new 

animal drug limited by Federal law to 

investigational use’’, and the delivery is 

made for use only in the manufacture of 

such new drug or new animal drug 

limited to investigational use as 

provided in part 312 or § 511.1 or 

§ 516.125 of this chapter; or 

(c) A new drug application or new 

animal drug application or a request for 

addition to the index covering the use 

of the drug substance in the production 

and marketing of a finished drug 

product has been submitted but not yet 

approved, disapproved, granted, or 

denied, the bulk drug is not exported, 

and the finished drug product is not 

further distributed after it is 

manufactured until after the new drug 

application or new animal drug 

application is approved or the request 

for addition to the index is granted. 

PART 202—PRESCRIPTION DRUG 

ADVERTISING 

9. The authority citation for 21 CFR 

part 202 continues to read as follows: 


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Authority: 21 U.S.C. 321, 331, 352, 355, 

360b, 371. 

10. Amend § 202.1 by revising 

paragraph (e)(4)(i)(a) to read as follows: 

§ 202.1 Prescription-drug advertisements. 

* * * * * 

(e) * * * 

(4) Substance of information to be 

included in brief summary. (i)(a) An 

advertisement for a prescription drug 

covered by a new-drug application 

approved pursuant to section 505 of the 

act after October 10, 1962, or a 

prescription drug covered by a new 

animal drug application approved 

pursuant to section 512 of the act after 

August 1, 1969, or any approved 

supplement thereto, or for a prescription 

drug listed in the index pursuant to 

section 572 of the act, or any granted 

modification thereto, shall not 

recommend or suggest any use that is 

not in the labeling accepted in such 

approved new-drug application or 

supplement, new animal drug 

application or supplement, or new 

animal drug index listing or 

modification. The advertisement shall 

present information from labeling 

required, approved, permitted, or 

granted in a new-drug or new animal 

drug application or new animal drug 

index listing relating to each specific 

side effect and contraindication in such 

labeling that relates to the uses of the 

advertised drug dosage form(s) or shall 

otherwise conform to the provisions of 

paragraph (e)(3)(iii) of this section. 

* * * * * 

PART 207—REGISTRATION OF 

PRODUCERS OF DRUGS AND LISTING 

OF DRUGS IN COMMERCIAL 

DISTRIBUTION 

11. The authority citation for 21 CFR 

part 207 continues to read as follows: 

Authority: 21 U.S.C. 321, 331, 351, 352, 

355, 360, 360b, 371, 374, 381, 393; 42 U.S.C. 

262, 264, 271. 

12. Amend § 207.21 by revising the 

second sentence in paragraph (a) to read 

as follows: 

§ 207.21 Times for registration and drug 

listing. 

(a) * * * If the owner or operator of 

the establishment has not previously 

entered into such an operation, the 

owner or operator shall register within 

5 days after submitting a new drug 

application, abbreviated new drug 

application, new animal drug 

application, abbreviated new animal 

drug application, request for addition to 

the index, medicated feed mill license 

application, or a biologics license 

application. * * * 

* * * * * 

13. Amend § 207.35 by revising 

paragraph (b)(3)(v) to read as follows: 

§ 207.35 Notification of registrant; drug 

establishment registration number and drug 

listing number. 

* * * * * 

(b) * * * 

(3) * * * 

(v) The placing of the assigned NDC 

number on a label or in other labeling 

does not require the submission of a 

supplemental new drug application, 

supplemental new animal drug 

application, or a modification to an 

index listing. 

* * * * * 

PART 225—CURRENT GOOD 

MANUFACTURING PRACTICE FOR 

MEDICATED FEEDS 

14. The authority citation for 21 CFR 

part 225 continues to read as follows: 

Authority: 21 U.S.C. 351, 352, 360b, 371, 

374. 

15. Amend § 225.1 by revising 

paragraph (c) to read as follows: 

§ 225.1 Current good manufacturing 

practice. 

* * * * * 

(c) In addition to the recordkeeping 

requirements in this part, Type B and 

Type C medicated feeds made from 

Type A articles or Type B feeds under 

approved NADAs or indexed listings 

and a medicated feed mill license are 

subject to the requirements of § 510.301 

of this chapter. 

16. Amend § 225.35 by revising 

paragraph (b) to read as follows: 

§ 225.35 Use of work areas, equipment, 

and storage areas for other manufacturing 

and storage purpose. 

* * * * * 

(b) Work areas and equipment used 

for the manufacture or storage of 

medicated feeds or components thereof 

shall not be used for, and shall be 

physically separated from, work areas 

and equipment used for the 

manufacture of fertilizers, herbicides, 

insecticides, fungicides, rodenticides, 

and other pesticides unless such articles 

are approved drugs, indexed drugs, or 

approved food additives intended for 

use in the manufacture of medicated 

feed. 

17. Revise § 225.135 to read as 

follows: 

§ 225.135 Work and storage areas. 

Work areas and equipment used for 

the production or storage of medicated 

feeds or components thereof shall not be 

used for, and shall be physically 

separated from, work areas and 

equipment used for the manufacture 

and storage of fertilizers, herbicides, 

insecticides, fungicides, rodenticides, 

and other pesticides unless such articles 

are approved or index listed for use in 

the manufacture of animal feed. 

PART 226—CURRENT GOOD 

MANUFACTURING PRACTICE FOR 

TYPE A MEDICATED ARTICLES 

18. The authority citation for 21 CFR 

part 226 continues to read as follows: 

Authority: 21 U.S.C. 351, 352, 360b, 371, 

374. 

19. Amend § 226.1 by adding a second 

sentence to paragraph (b) to read as 

follows: 

§ 226.1 Current good manufacturing 

practice. 

* * * * * 

(b) * * * Similarly, Type A medicated 

articles listed in the index are subject to 

the requirements of § 516.165 of this 

chapter. 

PART 500—GENERAL 

20. The authority citation for 21 CFR 

part 500 continues to read as follows: 

Authority: 21 U.S.C. 321, 331, 342, 343, 

348, 351, 352, 353, 360b, 371. 

21. Amend § 500.25 by revising 

paragraph (c) to read as follows: 

§ 500.25 Anthelmintic drugs for use in 

animals. 

* * * * * 

(c) For drugs covered by approved 

new animal drug applications, the 

labeling revisions required for 

compliance with this section may be 

placed into effect without prior 

approval, as provided for in § 514.8 (d) 

and (e) of this chapter. For drugs listed 

in the index, the labeling revisions 

required for compliance with this 

section may be placed into effect 

without prior approval, as provided for 

in § 516.161(b)(1) of this chapter. 

* * * * * 

22. Amend § 500.26 by revising 

paragraph (b) and the second sentence 

in paragraph (c) to read as follows: 

§ 500.26 Timed-release dosage form 

drugs. 

* * * * * 

(b) Timed-release dosage form animal 

drugs that are introduced into interstate 

commerce are deemed to be adulterated 

within the meaning of section 501(a)(5) 

of the act and subject to regulatory 

action, unless such animal drug is the 

subject of an approved new animal drug 

application, or listed in the index, as 

required by paragraph (a) of this section. 


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(c) * * * A new animal drug 

application or index listing is required 

in any such case. 

* * * * * 

PART 510—NEW ANIMAL DRUGS 

23. The authority citation for 21 CFR 

part 510 continues to read as follows: 

Authority: 21 U.S.C. 321, 331, 351, 352, 

353, 360b, 371, 379e. 

24. Amend § 510.301 by revising the 

introductory text, paragraph (a)(2), and 

the second sentence in paragraph (b)(1) 

to read as follows: 

§ 510.301 Records and reports concerning 

experience with animal feeds bearing or 

containing new animal drugs for which an 

approved medicated feed mill license 

application is in effect. 

Records and reports of clinical and 

other experience with the new animal 

drug will be maintained and reported, 

appropriately identified with the new 

animal drug application(s) or index 

listing(s) to which they relate, to the 

Center for Veterinary Medicine in 

duplicate in accordance with the 

following: 

(a) * * * 

(2) Information concerning any 

bacteriological or any significant 

chemical, physical, or other change or 

deterioration in the drug, or any failure 

of one or more distributed batches of the 

drug to meet the specifications 

established for it in the new animal drug 

application or request for determination 

of eligibility for indexing. 

(b) * * * 

(1) * * * Unexpected as used in this 

paragraph refers to conditions or 

developments not previously submitted 

as part of the new animal drug 

application or in support of the index 

listing or not encountered during 

clinical trials of the drug, or conditions 

or developments occurring at a rate 

higher than shown by information 

previously submitted as part of the new 

animal drug application or in support of 

the index listing or at a rate higher than 

encountered during such clinical trials. 

* * * * * 

25. Amend § 510.305 by revising 

paragraph (b) to read as follows: 

§ 510.305 Maintenance of copies of 

approved medicated feed mill licenses to 

manufacture animal feed bearing or 

containing new animal drugs. 

* * * * * 

(b) Approved or index listed labeling 

for each Type B and/or Type C feed 

being manufactured on the premises of 

the manufacturing establishment or the 

facility where the feed labels are 

generated. 

26. Amend § 510.455 by revising 

paragraphs (b) and (c) to read as follows: 

§ 510.455 Requirements for free-choice 

medicated feeds. 

* * * * * 

(b) What is required for new animal 

drugs intended for use in free-choice 

feed? Any new animal drug intended for 

use in free-choice feed must be 

approved for such use under section 512 

of the Federal Food, Drug, and Cosmetic 

Act (the act) (21 U.S.C. 360(b)) or listed 

in the index under section 572 of the act 

(21 U.S.C. 360ccc–1). Such approvals 

under section 512 of the act must be: 

(1) An original new animal drug 

application (NADA), 

(2) A supplemental NADA, or 

(3) An abbreviated NADA. 

(c) What are the approval 

requirements under section 512 of the 

act for new animal drugs intended for 

use in free-choice feed? An approval 

under section 512 of the act for a Type 

A medicated article intended for use in 

free-choice feed must contain the 

following information: 

(1) Data, or reference to data in a 

master file (MF), showing that the target 

animal consumes the new animal drug 

in the Type C free-choice feed in an 

amount that is safe and effective 

(consumption/effectiveness data); and 

(2) Data, or reference to data in an MF, 

showing the relevant ranges of 

conditions under which the drug will be 

chemically and physically stable in the 

Type C free-choice feed under field 

conditions. 

* * * * * 

PART 511—NEW ANIMAL DRUGS FOR 

INVESTIGATIONAL USE 

27. The authority citation for 21 CFR 

part 511 continues to read as follows: 

Authority: 21 U.S.C. 321, 351, 352, 353, 

360b, 371. 

28. Amend § 511.1 by adding a 

paragraph (g) to read as follows: 

§ 511.1 New animal drugs for 

investigational use exempt from section 

512(a) of the act. 

* * * * * 

(g) Index of legally marketed 

unapproved new animal drugs for minor 

species. All provisions of part 511 apply 

to new animal drugs for investigational 

use in support of indexing, as described 

in section 572 of the act, subject to the 

provisions of § 516.125 of this chapter. 

PART 515—MEDICATED FEED MILL 

LICENSE 

29. The authority citation for 21 CFR 

part 515 continues to read as follows: 

Authority: 21 U.S.C. 360b, 371. 

30. Amend § 515.10 by revising 

paragraphs (b)(4) and (b)(7) to read as 

follows: 

§ 515.10 Medicated feed mill license 

applications. 

* * * * * 

(b) * * * 

(4) A certification that the animal 

feeds bearing or containing new animal 

drugs are manufactured and labeled in 

accordance with the applicable 

regulations published under section 

512(i) of the act or in accordance with 

the index listing published under 

section 572(e)(2) of the act. 

* * * * * 

(7) A commitment that current 

approved or index listed Type B and/or 

Type C medicated feed labeling for each 

Type B and/or Type C medicated feed 

to be manufactured will be in the 

possession of the feed manufacturing 

facility prior to receiving the Type A 

medicated article containing such drug. 

* * * * * 

31. Amend § 515.21 by revising 

paragraph (a)(3) to read as follows: 

§ 515.21 Refusal to approve a medicated 

feed mill license application. 

(a) * * * 

(3) The facility manufactures animal 

feeds bearing or containing new animal 

drugs in a manner that does not accord 

with the specifications for manufacture 

or labels animal feeds bearing or 

containing new animal drugs in a 

manner that does not accord with the 

conditions or indications of use that are 

published under section 512(i) or 

572(e)(2) of the act. 

* * * * * 

PART 516—NEW ANIMAL DRUGS FOR 

MINOR USE AND MINOR SPECIES 

32. Part 516 is amended by adding 

subpart C, consisting of §§ 516.111 to 

516.171, to read as follows: 

Subpart C—Index of Legally Marketed 

Unapproved New Animal Drugs for Minor 

Species 

Sec. 

516.111 Scope of this subpart. 

516.115 Definitions. 

516.117 Submission of correspondence 

under this subpart. 

516.119 Permanent-resident U.S. agent for 

foreign requestors and holders. 

516.121 Meetings. 

516.123 Informal conferences regarding 

agency administrative actions. 

516.125 Investigational use of minor 

species new animal drugs to support 

indexing. 

516.129 Content and format of a request for 

determination of eligibility for indexing. 

516.131 Refuse to file a request for 

determination of eligibility for indexing. 


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516.133 Denying a request for 

determination of eligibility for indexing. 

516.135 Granting a request for 

determination of eligibility for indexing. 

516.137 Notification of decision regarding 

eligibility for indexing. 

516.141 Qualified expert panels. 

516.143 Written report. 

516.145 Content and format of a request for 

addition to the index. 

516.147 Refuse to file a request for addition 

to the index. 

516.149 Denying a request for addition to 

the index. 

516.151 Granting a request for addition to 

the index. 

516.153 Notification of decision regarding 

index listing. 

516.155 Labeling of indexed drugs. 

516.157 Publication of the index and 

content of an index listing. 

516.161 Modifications to indexed drugs. 

516.163 Change in ownership of an index 

file. 

516.165 Records and reports. 

516.167 Removal from the index. 

516.171 Confidentiality of data and 

information in an index file. 

Authority: 21 U.S.C. 360ccc–1, 371. 

Subpart C—Index of Legally Marketed 

Unapproved New Animal Drugs for 

Minor Species 

§ 516.111 Scope of this subpart. 

This subpart implements section 572 

of the act and provides standards and 

procedures to establish an index of 

legally marketed unapproved new 

animal drugs. This subpart applies only 

to minor species and not to minor use 

in major species. This index is only 

available for new animal drugs intended 

for use in a minor species for which 

there is a reasonable certainty that the 

animal or edible products from the 

animal will not be consumed by 

humans or food-producing animals and 

for new animal drugs intended for use 

only in a hatchery, tank, pond, or other 

similar contained man-made structure 

in an early, non-food life stage of a foodproducing minor species, where safety 

for humans is demonstrated in 

accordance with the standard of section 

512(d) of the act (including, for an 

antimicrobial new animal drug, with 

respect to antimicrobial resistance). The 

index shall not include a new animal 

drug that is contained in, or a product 

of, a transgenic animal. Among its 

topics, this subpart sets forth the 

standards and procedures for: 

(a) Investigational exemptions for 

indexing purposes; 

(b) Submissions to FDA of requests for 

determination of eligibility of a new 

animal drug for indexing; 

(c) Establishment and operation of 

expert panels; 

(d) Submissions to FDA of requests 

for addition of a new animal drug to the 

index; 

(e) Modifications to index listings; 

(f) Publication of the index; and 

(g) Records and reports. 

§ 516.115 Definitions. 

(a) The following definitions of terms 

apply only in the context of subpart C 

of this part: 

Director means the Director of the 

Office of Minor Use and Minor Species 

Animal Drug Development of the FDA 

Center for Veterinary Medicine. 

Holder means the requestor of an 

index listing after the request is granted 

and the new animal drug is added to the 

index. 

Index means FDA’s list of legally 

marketed unapproved new animal drugs 

for minor species. 

Intended use means the intended 

treatment, control or prevention of a 

disease or condition, or the intention to 

affect the structure or function of the 

body of animals within an identified 

species, subpopulation of a species, or 

collection of species. 

Qualified expert panel means a panel 

that is composed of experts qualified by 

scientific training and experience to 

evaluate the target animal safety and 

effectiveness of a new animal drug 

under consideration for indexing. 

Requestor means the person making a 

request for determination of eligibility 

for indexing or a request for addition to 

the index. 

Transgenic animal means an animal 

whose genome contains a nucleotide 

sequence that has been intentionally 

modified in vitro, and the progeny of 

such an animal, provided that the term 

‘transgenic animal’ does not include an 

animal of which the nucleotide 

sequence of the genome has been 

modified solely by selective breeding. 

(b) The definitions of the following 

terms are given in § 514.3 of this 

chapter: 

Adverse drug experience. 

Product defect/manufacturing defect. 

Serious adverse drug experience. 

Unexpected adverse drug experience. 

§ 516.117 Submission of correspondence 

under this subpart. 

Unless directed otherwise by FDA, all 

correspondence relating to any aspect of 

the new animal drug indexing process 

described in this subpart must be 

addressed to the Director of the Office 

of Minor Use and Minor Species Animal 

Drug Development. The initial 

correspondence for a particular index 

listing should include the name and 

address of the authorized contact 

person. Notifications of changes in such 

person or changes of address of such 

person should be provided in a timely 

manner. 

§ 516.119 Permanent-resident U.S. agent 

for foreign requestors and holders. 

Every foreign requestor and holder 

shall name a permanent resident of the 

United States as their agent upon whom 

service of all processes, notices, orders, 

decisions, requirements, and other 

communications may be made on behalf 

of the requestor or holder. Notifications 

of changes in such agents or changes of 

address of agents should preferably be 

provided in advance, but not later than 

60 days after the effective date of such 

changes. The permanent-resident U.S. 

agent may be an individual, firm, or 

domestic corporation and may represent 

any number of requestors or holders. 

The name and address of the 

permanent-resident U.S. agent shall be 

submitted to the Director of the Office 

of Minor Use and Minor Species Animal 

Drug Development and included in the 

index file. 

§ 516.121 Meetings. 

(a) A requestor or potential requestor 

is entitled to one or more meetings to 

discuss the requirements for indexing a 

new animal drug. 

(b) Requests for such meetings should 

be in writing, be addressed to the 

Director, specify the participants 

attending on behalf of the requestor or 

potential requestor, and contain a 

proposed agenda for the meeting. 

(c) Within 30 days of receiving a 

request for a meeting, FDA will attempt 

to schedule the meeting at a time 

agreeable to both FDA and the person 

making the request. 

§ 516.123 Informal conferences regarding 

agency administrative actions. 

(a) Should FDA make an initial 

decision denying a request for 

determination of eligibility for indexing, 

terminating an investigational 

exemption, determining that a qualified 

expert panel does not meet the selection 

criteria, denying a request for addition 

to the index, or removing a new animal 

drug from the index, FDA will give 

written notice that specifies the grounds 

for the initial decision and provides an 

opportunity for an informal conference 

for review of the decision. 

(b) The written notice will include 

information for scheduling the informal 

conference and state that a written 

request for a conference must be made 

within 30 calendar days of the date FDA 

sends its notice. 

(c) Within 30 days of receiving a 

request for an informal conference, FDA 

will attempt to schedule the meeting at 


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a time agreeable to both FDA and the 

person making the request. 

(d) Such an informal conference will 

be conducted by a presiding officer who 

will be the Director of the Center for 

Veterinary Medicine or his or her 

designee, excluding the Director of the 

Office of Minor Use and Minor Species 

Animal Drug Development and other 

persons significantly involved in the 

initial decision. 

(e) The person requesting an informal 

conference must provide a written 

response to FDA’s initial decision at 

least 2 weeks prior to the date of the 

scheduled meeting. Generally, this 

written response would be attached to 

the request for an informal conference. 

At the option of the person requesting 

an informal conference, such written 

response to FDA’s initial decision may 

act in lieu of a face-to-face meeting. In 

this case, the informal conference will 

consist of a review by the presiding 

officer of the submitted written 

response. 

(f) The purpose of an informal 

conference is to discuss scientific and 

factual issues. It will involve a 

discussion of FDA’s initial decision and 

any written response to that decision. 

(g) Internal agency review of a 

decision must be based on the 

information in the administrative file. If 

the person requesting an informal 

conference presents new information 

not in the file, the matter will be 

returned to the appropriate lower level 

in the agency for reevaluation based on 

the new information. 

(h) Informal conferences under this 

part are not subject to the separation of 

functions rules in § 10.55 of this 

chapter. 

(i) The rules of evidence do not apply 

to informal conferences. No motions or 

objections relating to the admissibility 

of information and views will be made 

or considered, but any party to the 

conference may comment upon or rebut 

all such data, information and views. 

(j) The presiding officer will prepare 

a written summary of the informal 

conference and share it with the parties 

to the conference. 

(k) The presiding officer will prepare 

a written report regarding the subject of 

the informal conference that states and 

describes the basis for his or her 

findings. 

(l) The administrative record of the 

informal conference will consist of: 

(1) The notice providing an 

opportunity for an informal conference 

and the written response to the notice. 

(2) All written information and views 

submitted to the presiding officer at the 

conference or, at the discretion of the 

presiding officer, thereafter. 

(3) The written summary of the 

informal conference. 

(4) The presiding officer’s written 

report. 

(5) All correspondence and 

memoranda of any and all meetings 

between the participants and the 

presiding officer. 

(m) The administrative record of the 

informal conference is closed to the 

submission of information and views at 

the close of the conference, unless the 

presiding officer specifically permits 

additional time for further submission. 

(n) The administrative record of the 

informal conference specified herein 

constitutes the exclusive record for 

decision. 

§ 516.125 Investigational use of minor 

species new animal drugs to support 

indexing. 

(a) The investigational use of a new 

animal drug or animal feed bearing or 

containing a new animal drug intended 

solely for investigational use in minor 

species shall meet the requirements of 

part 511 of this chapter if the 

investigational use is for the purpose of: 

(1) Demonstrating human food safety 

under section 572(a)(1)(B) of the act; 

(2) Demonstrating safety with respect 

to individuals exposed to the new 

animal drug through its manufacture 

and use under section 572(c)(1)(F) of the 

act; 

(3) Conducting an environmental 

assessment under section 572(c)(1)(E) of 

the act; or 

(4) Obtaining approval of a new 

animal drug application or abbreviated 

new animal drug application under 

section 512(b) of the act. 

(b) Correspondence and information 

associated with investigations described 

in paragraph (a) of this section shall not 

be sent to the Director, OMUMS, but 

shall be submitted to FDA in accordance 

with the provisions of part 511 of this 

chapter. 

(c) The investigational use of a new 

animal drug or animal feed bearing or 

containing a new animal drug intended 

solely for investigational use in minor 

species, other than for an investigational 

use described in paragraph (a) of this 

section, shall meet the requirements of 

this section. For such investigations, all 

provisions of part 511 of this chapter 

apply with the following modifications: 

(1) Under § 511.1(a)(1) of this chapter, 

the label statement is as follows: 

‘‘Caution. Contains a new animal drug 

for investigational use only in laboratory 

animals or for tests in vitro in support 

of index listing. Not for use in humans.’’

(2) Under § 511.1(b)(1) of this chapter, 

the label statement is as follows: 

‘‘Caution. Contains a new animal drug 

for use only in investigational animals 

in clinical trials in support of index 

listing. Not for use in humans. Edible 

products of investigational animals are 

not to be used for food for humans or 

other animals unless authorization has 

been granted by the U.S. Food and Drug 

Administration or by the U.S. 

Department of Agriculture.’’

(3) Under § 511.1(b)(4) of this chapter, 

the notice is titled ‘‘Notice of Claimed 

Investigational Exemption for a New 

Animal Drug for Index Listing’’ and is 

submitted in duplicate to the Director. 

(4) Under § 511.1(c)(3) of this chapter, 

if an investigator is determined to be 

ineligible to receive new animal drugs, 

each ‘‘Notice of Claimed Investigational 

Exemption for a New Animal Drug for 

Index Listing’’ and each request for 

indexing shall be examined with respect 

to the reliability of information 

submitted by the investigator. 

(5) Under § 511.1(c)(4) and (d)(2) of 

this chapter, with respect to termination 

of exemptions, the sponsor of an 

investigation shall not be granted an 

opportunity for a regulatory hearing 

before FDA pursuant to part 16 of this 

chapter. Instead, the sponsor shall have 

an opportunity for an informal 

conference as described in § 516.123. 

(6) Under § 511.1(c)(5) of this chapter, 

if the Commissioner of Food and Drugs 

determines, after the unreliable data 

submitted by the investigator are 

eliminated from consideration, that the 

data remaining are such that a request 

for addition to the index would have 

been denied, FDA will remove the new 

animal drug from the index in 

accordance with § 516.167. 

(d) The investigational use of a new 

animal drug or animal feed bearing or 

containing a new animal drug subject to 

paragraph (c) of this section shall not be 

subject to the good laboratory practice 

requirements in part 58 of this chapter. 

(e) Correspondence and information 

associated with investigations described 

in paragraph (c) of this section shall be 

sent to the Director of the Office of 

Minor Use and Minor Species in 

accordance with the provisions of this 

section. 

§ 516.129 Content and format of a request 

for determination of eligibility for indexing. 

(a) Each request for determination of 

eligibility: 

(1) May involve only one drug (or one 

combination of drugs) in one dosage 

form; 

(2) May not involve a new animal 

drug that is contained in or a product of 

a transgenic animal; 

(3) May not involve the same drug in 

the same dosage form for the same 

intended use as a drug that is already 


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approved or conditionally approved; 

and 

(4) Must be submitted separately. 

(b) A request for determination of 

eligibility for indexing may involve 

multiple intended uses and/or multiple 

minor species. However, if a request for 

determination of eligibility for indexing 

that contains multiple intended uses 

and/or multiple minor species cannot be 

granted in any part, the entire request 

will be denied. 

(c) A requestor must submit two 

copies of a dated request signed by the 

authorized contact person for 

determination of eligibility for indexing 

that contains the following: 

(1) Identification of the minor species 

or groups of minor species for which the 

new animal drug is intended; 

(2) Information regarding drug 

components and composition; 

(3) A statement of the intended use(s) 

of the new animal drug in the identified 

minor species or groups of minor 

species; 

(4) A statement of the proposed 

conditions of use associated with the 

stated intended use(s) of the new animal 

drug, including the proposed dosage, 

route of administration, 

contraindications, warnings, and any 

other significant limitations associated 

with the intended use(s) of the new 

animal drug; 

(5) A brief discussion of the need for 

the new animal drug for the intended 

use(s); 

(6) An estimate of the anticipated 

annual distribution of the new animal 

drug, in terms of the total quantity of 

active ingredient, after indexing; 

(7) Information to establish that the 

new animal drug is intended for use: 

(i) In a minor species for which there 

is a reasonable certainty that the animal 

or edible products from the animal will 

not be consumed by humans or foodproducing animals; or 

(ii) In a hatchery, tank, pond, or other 

similar contained man-made structure 

in (which includes on) an early, nonfood life stage of a food-producing 

minor species, and information to 

demonstrate food safety in accordance 

with the standards of section 512(d) of 

the act and § 514.111 of this chapter 

(including, for an antimicrobial new 

animal drug, with respect to 

antimicrobial resistance); 

(8) A description of the methods used 

in, and the facilities and controls used 

for, the manufacture, processing and 

packing of the new animal drug 

sufficient to demonstrate that the 

requestor has established appropriate 

specifications for the manufacture and 

control of the new animal drug and that 

the requestor has an understanding of 

current good manufacturing practices; 

(9) Either a claim for categorical 

exclusion under § 25.30 or § 25.33 of 

this chapter or an environmental 

assessment under § 25.40 of this 

chapter; 

(10) Information sufficient to support 

the conclusion that the new animal drug 

is safe under section 512(d) of the act 

with respect to individuals exposed to 

the new animal drug through its 

manufacture and use; and 

(11) The name and address of the 

contact person or permanent-resident 

U.S. agent. 

§ 516.131 Refuse to file a request for 

determination of eligibility for indexing. 

(a) If a request for determination of 

eligibility for indexing contains all of 

the information required by § 516.129, 

FDA shall file it, and the filing date 

shall be the date FDA receives the 

request. 

(b) If a request for a determination of 

eligibility lacks any of the information 

required by § 516.129, FDA will not file 

it, but will inform the requestor in 

writing within 30 days of receiving the 

request as to what information is 

lacking. 

§ 516.133 Denying a request for 

determination of eligibility for indexing. 

(a) FDA will deny a request for 

determination of eligibility for indexing 

if it determines upon the basis of the 

request evaluated together with any 

other information before it with respect 

to the new animal drug that: 

(1) The same drug in the same dosage 

form for the same intended use is 

already approved or conditionally 

approved; 

(2) There is insufficient information to 

demonstrate that the new animal drug is 

intended for use: 

(i) In a minor species for which there 

is a reasonable certainty that the animal 

or edible products from the animal will 

not be consumed by humans or foodproducing animals, or 

(ii) In a hatchery, tank, pond, or other 

similar contained man-made structure 

in (which includes on) an early, nonfood life stage of a food-producing 

minor species, and there is insufficient 

evidence to demonstrate safety for 

humans in accordance with the 

standard of section 512(d) of the act and 

§ 514.111 of this chapter (including, for 

an antimicrobial new animal drug, with 

respect to antimicrobial resistance); 

(3) The new animal drug is contained 

in or is a product of a transgenic animal; 

(4) There is insufficient information to 

demonstrate that the requestor has 

established appropriate specifications 

for the manufacture and control of the 

new animal drug and that the requestor 

has an understanding of current good 

manufacturing practices; 

(5) The requester fails to submit an 

adequate environmental assessment 

under § 25.40 of this chapter or fails to 

provide sufficient information to 

establish that the requested action is 

subject to categorical exclusion under 

§ 25.30 or § 25.33 of this chapter; 

(6) There is insufficient information to 

determine that the new animal drug is 

safe with respect to individuals exposed 

to the new animal drug through its 

manufacture or use; or 

(7) The request for determination of 

eligibility for indexing fails to contain 

any other information required under 

the provisions of § 516.129. 

(b) FDA may deny a request for 

determination of eligibility for indexing 

if it contains any untrue statement of a 

material fact or omits material 

information. 

(c) When a request for determination 

of eligibility for indexing is denied, FDA 

will notify the requestor in accordance 

with § 516.137. 

§ 516.135 Granting a request for 

determination of eligibility for indexing. 

(a) FDA will grant the request for 

determination of eligibility for indexing 

if none of the reasons described in 

§ 516.133 for denying such a request 

applies. 

(b) When a request for determination 

of eligibility for indexing is granted, 

FDA will notify the requestor in 

accordance with § 516.137. 

§ 516.137 Notification of decision 

regarding eligibility for indexing. 

(a) Within 90 days after the filing of 

a request for a determination of 

eligibility for indexing based on 

§ 516.129(c)(7)(i), or 180 days for a 

request based on § 516.129(c)(7)(ii), FDA 

shall grant or deny the request, and 

notify the requestor of FDA’s decision in 

writing. 

(b) If FDA denies the request, FDA 

shall provide due notice and an 

opportunity for an informal conference 

as described in § 516.123 regarding its 

decision. A decision of FDA to deny a 

request for determination of eligibility 

for indexing following an informal 

conference shall constitute final agency 

action subject to judicial review. 

§ 516.141 Qualified expert panels. 

(a) Establishment of a qualified expert 

panel. Establishing a qualified expert 

panel is the first step in the process of 

requesting the addition of a new animal 

drug to the index. A qualified expert 

panel may not be established until FDA 


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has determined that the new animal 

drug is eligible for indexing. The 

requestor must choose members for the 

qualified expert panel in accordance 

with selection criteria listed in 

paragraph (b) of this section and submit 

information about these proposed 

members to FDA. FDA must determine 

whether the proposed qualified expert 

panel meets the selection criteria prior 

to the panel beginning its work. 

Qualified expert panels operate external 

to FDA and are not subject to the 

Federal Advisory Committee Act, as 

amended, 5 U.S.C. App. 

(b) Criteria for the selection of a 

qualified expert panel. (1) A qualified 

expert panel member must be an expert 

qualified by training and experience to 

evaluate the target animal safety and 

effectiveness of the new animal drug 

under consideration. 

(2) A qualified expert panel member 

must certify that he or she has a working 

knowledge of section 572 of the act (the 

indexing provisions of the statute) and 

this subpart, and that he or she has also 

read and understood a clear written 

statement provided by the requestor 

stating his or her duties and 

responsibilities with respect to 

reviewing the new animal drug 

proposed for addition to the index. 

(3) A qualified expert panel member 

may not be an FDA employee. 

(4) A qualified expert panel must have 

at least three members. 

(5) A qualified expert panel must have 

members with a range of expertise such 

that the panel, as a whole, is qualified 

by training and experience to evaluate 

the target animal safety and 

effectiveness of the new animal drug 

under consideration. 

(6) Unless FDA makes a 

determination to allow participation 

notwithstanding an otherwise 

disqualifying financial interest, a 

qualified expert panel member must not 

have a conflict of interest or the 

appearance of a conflict of interest, as 

described in paragraph (g) of this 

section. 

(c) Requestor responsibilities. (1) The 

requestor must: 

(i) Choose members for the qualified 

expert panel in accordance with 

selection criteria listed in paragraph (b) 

of this section. 

(ii) Provide each potential expert 

panel member a copy of section 572 of 

the act (the indexing provisions of the 

statute) and this subpart and obtain 

certification that he or she has a 

working knowledge of the information. 

(iii) Provide each potential expert 

panel member a written statement 

describing the purpose and scope of his 

or her participation on the qualified 

expert panel and obtain certification 

that he or she has read and understood 

the information. The written statement 

should describe the duties and 

responsibilities of qualified expert 

panels and their members established 

by paragraphs (e) and (f) of this section, 

including the need to prepare a written 

report under § 516.143. 

(iv) Obtain information from each 

potential expert panel member 

demonstrating that he or she is qualified 

by training and experience to evaluate 

the target animal safety and 

effectiveness of the new animal drug 

under consideration. This information 

can be obtained from a comprehensive 

curriculum vitae or similar document. 

(v) Notify each potential expert panel 

member that he or she must submit 

information relating to potential conflict 

of interest directly to FDA in a timely 

manner, as required in paragraph (e)(6) 

of this section. 

(2) The requestor must submit, in 

writing, the names and addresses of the 

proposed qualified expert panel 

members and sufficient information 

about each proposed member for FDA to 

determine whether the panel meets the 

selection criteria listed in paragraphs 

(b)(1) through (b)(5) of this section. 

(3) After FDA has determined that the 

qualified expert panel meets the 

selection criteria, the requestor must 

provide to the panel all information 

known by the requestor that is relevant 

to a determination of the target animal 

safety and the effectiveness of the new 

animal drug at issue. In addition, the 

requestor must notify FDA of the name 

of the qualified expert panel leader. 

(4) The requestor must immediately 

notify FDA if it believes a qualified 

expert panel member no longer meets 

the selection criteria listed in paragraph 

(b) of this section or is otherwise not in 

compliance with the requirements of 

this section. 

(5) If a qualified expert panel member 

cannot complete the review for which 

he or she was selected, the requestor 

must either choose a replacement or 

justify the continued work of the panel 

in the absence of the lost panelist. In 

either case, the requestor must submit 

sufficient information for FDA to 

determine whether the proposed revised 

qualified expert panel meets the 

selection criteria listed in paragraphs 

(b)(1) through (b)(5) of this section. 

(6) The requestor must keep copies of 

all information provided to, or received 

from, qualified expert panel members, 

including the written report, for 2 years 

after the completion of the report, or the 

product is added to the index, 

whichever occurs later, and make them 

available to a duly authorized employee 

of the agency at all reasonable times. 

(d) FDA responsibilities. (1) FDA will 

determine whether the requestor’s 

proposed qualified expert panel meets 

the selection criteria listed in paragraph 

(b) of this section. FDA will 

expeditiously inform the requestor, in 

writing, of its determination. If FDA 

determines that the qualified expert 

panel does not meet the selection 

criteria, FDA will provide due notice 

and an opportunity for an informal 

conference as described in § 516.123. A 

determination by FDA that a proposed 

qualified expert panel does not meet the 

selection criteria following an informal 

conference shall constitute final agency 

action subject to judicial review. 

(2) If FDA determines that a qualified 

expert panel no longer meets the 

selection criteria listed in paragraph (b) 

of this section or that the panel or its 

members are not in compliance with the 

requirements of this section, the agency 

will expeditiously inform the requestor, 

in writing, of this determination and 

provide due notice and an opportunity 

for an informal conference as described 

in § 516.123. A determination by FDA, 

following an informal conference, that a 

qualified expert panel no longer meets 

the selection criteria listed in paragraph 

(b) of this section or that the panel or 

its members are not in compliance with 

the requirements of this section shall 

constitute final agency action subject to 

judicial review. 

(e) Responsibilities of a qualified 

expert panel member. A qualified expert 

panel member must do the following: 

(1) Continue to meet all selection 

criteria described in paragraph (b) of 

this section. 

(2) Act in accordance with generally 

accepted professional and ethical 

business practices. 

(3) Review all information relevant to 

a determination of the target animal 

safety and effectiveness of the new 

animal drug provided by the requestor. 

The panel should also consider all 

relevant information otherwise known 

by the panel members, including 

anecdotal information. 

(4) Participate in the preparation of 

the written report of the findings of the 

qualified expert panel, described in 

§ 516.143. 

(5) Sign, or otherwise approve in 

writing, the written report. Such 

signature or other written approval will 

serve as certification that the written 

report meets the requirements of the 

written report in § 516.143. 

(6) Provide the information relating to 

potential conflict of interest described 

in paragraph (g) of this section to FDA 

for its consideration. Such information 


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should be submitted directly to the 

Director when notified by the requestor. 

(7) Immediately notify the requestor 

and FDA of any change in conflict of 

interest status. 

(8) Certify at the time of submission 

of the written report that there has been 

no change in conflict of interest status, 

or identify and document to FDA any 

such change. 

(f) Additional responsibilities of a 

qualified expert panel leader. (1) The 

qualified expert panel leader must 

ensure that the activities of the panel are 

performed efficiently and in accordance 

with generally accepted professional 

and ethical business practices. 

(2) The qualified expert panel leader 

serves as the principal point of contact 

between representatives of the agency 

and the panel. 

(3) The qualified expert panel leader 

is responsible for submitting the written 

report and all notes or minutes relating 

to panel deliberations to the requestor. 

(4) The qualified expert panel leader 

must maintain a copy of the written 

report and all notes or minutes relating 

to panel deliberations that are submitted 

to the requestor for 2 years after the 

report is submitted. Such records must 

be made available to a duly authorized 

employee of the agency for inspection at 

all reasonable times. 

(g) Prevention of conflicts of interest. 

(1) For the purposes of this subpart, 

FDA will consider a conflict of interest 

to be any financial or other interest that 

could impair a person’s objectivity in 

serving on the qualified expert panel or 

could create an unfair competitive 

advantage for a person or organization. 

(2) Factors relevant to whether there 

is a conflict of interest or the appearance 

of a conflict of interest include whether 

the qualified expert panel member, their 

spouse, their minor children, their 

general partners, or any organizations in 

which they serve as an officer, director, 

trustee, general partner or employee: 

(i) Is currently receiving or seeking 

funding from the requestor through a 

contract or research grant (either 

directly or indirectly through another 

entity, such as a university). 

(ii) Has any employment, contractual, 

or other financial arrangement with the 

requestor other than receiving a 

reasonable fee for serving as a member 

of the qualified expert panel. 

(iii) Has any ownership or financial 

interest in any drug, drug manufacturer, 

or drug distributor which will benefit 

from either a favorable or unfavorable 

evaluation or opinion. 

(iv) Has any ownership or financial 

interest in the new animal drug being 

reviewed by the qualified expert panel. 

(v) Has participated in the design, 

manufacture, or distribution of any drug 

that will benefit from either a favorable 

or unfavorable opinion of the qualified 

expert panel. 

(vi) Has provided within 1 year any 

consultative services regarding the new 

animal drug being reviewed by the 

qualified expert panel. 

(vii) Has entered into an agreement in 

which fees charged or accepted are 

contingent upon the panel member 

making a favorable evaluation or 

opinion. 

(viii) Receives payment for services 

related to preparing information the 

requestor presents to the qualified 

expert panel, other than for services 

related to the written report described in 

§ 516.143. 

(3) To permit FDA to make a decision 

regarding potential conflict of interest, a 

potential qualified expert panel member 

must submit to the Director of the Office 

of Minor Use and Minor Species the 

following information relating to 

themselves, their spouse, their minor 

children, their general partners, or any 

organizations in which they serve as an 

officer, director, trustee, general partner 

or employee, regarding the following 

issues to the extent that they are, in any 

way, relevant to the subject of the 

review of the qualified expert panel: 

(i) Investments (for example, stocks, 

bonds, retirement plans, trusts, 

partnerships, sector funds, etc.), 

including for each the following: Name 

of the firm, type of investment, owner 

(self, spouse, etc.), number of shares / 

current value. 

(ii) Employment (full or part time, 

current or under negotiation), including 

for each the following: Name of the firm, 

relationship (self, spouse, etc.), position 

in firm, date employment or negotiation 

began. 

(iii) Consultant/advisor (current or 

under negotiation), including for each 

the following: Name of the firm, topic/ 

issue, amount received, date initiated. 

(iv) Contracts, grants, Cooperation 

Research and Development Agreement 

(CRADAs) (current or under 

negotiation), including for each the 

following: Type of agreement, product 

under study and indications, amount of 

remuneration (institution/self), time 

period, sponsor (government, firm, 

institution, individual), role of the 

person (site investigator, principal 

investigator, co-investigator, partner, no 

involvement, other), awardee. 

(v) Patents/royalties/trademarks, 

including for each the following: 

Description, name of firm involved, 

income received. 

(vi) Expert witness (last 12 months or 

under negotiation), including for each 

the following: For or against, name of 

firm, issue, amount received. 

(vii) Speaking/writing (last 12 months 

or under negotiation), including for each 

the following: Firm, topic/issue, amount 

received (honorarium/travel), date. 

(viii) Whether the potential qualified 

expert panel member, their spouse, their 

minor children, their general partners or 

any organizations in which they serve as 

an officer, director, trustee, general 

partner or employee, have had, at any 

time in the past, involvement of the 

kind noted in paragraph (g)(3)(i) through 

(g)(3)(vii) of this section with respect to 

the animal drug that is the subject of the 

qualified expert panel review. 

(ix) Whether there are any other 

involvements (other kinds of 

relationships) that would give the 

appearance of a conflict of interest 

which have not been described in 

paragraph (g)(3)(i) through (g)(3)(viii) of 

this section. 

(x) In all cases, a response of ‘‘no,’’

‘‘none,’’ or ‘‘not applicable’’ is 

satisfactory when there is no relevant 

information to submit. 

(xi) A certification statement signed 

by the potential qualified expert panel 

member to the effect that all information 

submitted is true and complete to the 

best of their knowledge, that they have 

read and understood their obligations as 

an expert panel member, and that they 

will notify FDA and the requestor of any 

change in their conflict of interest 

status. 

(4) The fact that a qualified expert 

panel member receives a reasonable fee 

for services as a member of the qualified 

expert panel, provided that the fee is no 

more than commensurate with the value 

of the time that the member devotes to 

the review process, does not constitute 

a conflict of interest or the appearance 

of a conflict of interest. 

§ 516.143 Written report. 

The written report required in 

§ 516.145(b)(3) shall: 

(a) Be written in English by a 

qualified expert panel meeting the 

requirements of § 516.141; 

(b) Describe the panel’s evaluation of 

all available target animal safety and 

effectiveness information relevant to the 

proposed use of the new animal drug, 

including anecdotal information; 

(c) For all information considered, 

including anecdotal information, 

include either a citation to published 

literature or a summary of the 

information; 

(d) State the panel’s opinion regarding 

whether the benefits of using the new 

animal drug for the proposed use in a 

minor species outweigh its risks to the 

target animal, taking into account the 


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harm being caused by the absence of an 

approved or conditionally-approved 

new animal drug for the minor species 

in question; 

(e) Be signed, or otherwise approved 

in writing, by all panel members, in 

accordance with § 516.141; and 

(f) If the panel unanimously 

concludes that the benefits of using the 

new animal drug for the proposed use 

in a minor species outweigh its risks to 

the target animal, taking into account 

the harm being caused by the absence of 

an approved or conditionally-approved 

new animal drug for the minor species 

in question, the written report shall: 

(1) Provide draft labeling that 

includes all conditions of use and 

limitations of use of the new animal 

drug deemed necessary by the panel to 

assure that the benefits of use of the new 

animal drug outweigh the risks, or 

provide narrative information from 

which such labeling can be written by 

the requestor; and 

(2) Include a recommendation 

regarding whether the new animal drug 

should be limited to use under the 

professional supervision of a licensed 

veterinarian. 

§ 516.145 Content and format of a request 

for addition to the index. 

(a) A requestor may request addition 

of a new animal drug to the index only 

after the new animal drug has been 

granted eligibility for indexing. 

(b) A requestor shall submit two 

copies of a dated request signed by the 

authorized contact for addition of a new 

animal drug to the index that contains 

the following: 

(1) A copy of FDA’s determination of 

eligibility issued under § 516.137; 

(2) A copy of FDA’s written 

determination that the proposed 

qualified expert panel meets the 

selection criteria provided for in 

§ 516.141(b); 

(3) A written report that meets the 

requirements of § 516.143; 

(4) A proposed index entry that 

contains the information described in 

§ 516.157; 

(5) Proposed labeling, including 

representative labeling proposed to be 

used for Type B and Type C medicated 

feeds if the drug is intended for use in 

the manufacture of medicated feeds; 

(6) Anticipated annual distribution of 

the new animal drug, in terms of the 

total quantity of active ingredient, after 

indexing; 

(7) A written commitment to 

manufacture the new animal drug and 

animal feeds bearing or containing such 

new animal drug according to current 

good manufacturing practices; 

(8) A written commitment to label, 

distribute, and promote the new animal 

drug only in accordance with the index 

entry; 

(9) The name and address of the 

contact person or permanent-resident 

U.S. agent; and 

(10) A draft Freedom of Information 

summary which includes the following 

information: 

(i) A general information section that 

contains the name and address of the 

requestor and a description of the drug, 

route of administration, indications, and 

recommended dosage. 

(ii) A list of the names and affiliations 

of the members of the qualified expert 

panel, not including their addresses or 

other contact information. 

(iii) A summary of the findings of the 

qualified expert panel concerning the 

target animal safety and effectiveness of 

the drug. 

(iv) Citations of all publicly-available 

literature considered by the qualified 

expert panel. 

(v) For an early life stage of a foodproducing minor species animal, a 

human food safety summary. 

(c) Upon specific request by FDA, the 

requestor shall submit the information 

described in § 516.141 that it submitted 

to the qualified expert panel. Any such 

information not in English should be 

accompanied by an English translation. 

§ 516.147 Refuse to file a request for 

addition to the index. 

(a) If a request for addition to the 

index contains all of the information 

required by § 516.145(b), FDA shall file 

it, and the filing date shall be the date 

FDA receives the request. 

(b) If a request for addition to the 

index lacks any of the information 

required by § 516.145, FDA will not file 

it, but will inform the requestor in 

writing within 30 days of receiving the 

request as to what information is 

lacking. 

§ 516.149 Denying a request for addition to 

the index. 

(a) FDA will deny a request for 

addition to the index if it finds the 

following: 

(1) The same drug in the same dosage 

form for the same intended use is 

already approved or conditionally 

approved; 

(2) On the basis of new information, 

the new animal drug no longer meets 

the conditions for eligibility for 

indexing; 

(3) The request for indexing fails to 

contain information required under the 

provisions of § 516.145; 

(4) The qualified expert panel fails to 

meet any of the selection criteria listed 

in § 516.141(b); 

(5) The written report of the qualified 

expert panel and other information 

available to FDA is insufficient to 

permit FDA to determine that the 

benefits of using the new animal drug 

for the proposed use in a minor species 

outweigh its risks to the target animal, 

taking into account the harm caused by 

the absence of an approved or 

conditionally-approved new animal 

drug for the minor species in question; 

(6) On the basis of the report of the 

qualified expert panel and other 

information available to FDA, the 

benefits of using the new animal drug 

for the proposed use in a minor species 

do not outweigh its risks to the target 

animal, taking into account the harm 

caused by the absence of an approved or 

conditionally-approved new animal 

drug for the minor species in question; 

or 

(7) The request contains any untrue 

statement of a material fact or omits 

material information. 

(b) When a request for addition to the 

index is denied, FDA will notify the 

requestor in accordance with § 516.153. 

§ 516.151 Granting a request for addition 

to the index. 

(a) FDA will grant the request for 

addition of a new animal drug to the 

index if none of the reasons described 

in § 516.149 for denying such a request 

applies. 

(b) When a request for addition of a 

new animal drug to the index is granted, 

FDA will notify the requestor in 

accordance with § 516.153. 

§ 516.153 Notification of decision 

regarding index listing. 

(a) Within 180 days after the filing of 

a request for addition of a new animal 

drug to the index, FDA shall grant or 

deny the request and notify the 

requestor of FDA’s decision in writing. 

(b) If FDA denies the request for 

addition of a new animal drug to the 

index, FDA shall provide due notice 

and an opportunity for an informal 

conference as described in § 516.123. A 

decision of FDA to deny a request to 

index a new animal drug following an 

informal conference shall constitute 

final agency action subject to judicial 

review. 

§ 516.155 Labeling of indexed drugs. 

(a) The labeling of an indexed drug 

that is found to be eligible for indexing 

under § 516.129(c)(7)(i) shall state, 

prominently and conspicuously: ‘‘NOT 

APPROVED BY FDA.—Legally marketed 

as an FDA indexed product. Extra-label 

use is prohibited.’’ ‘‘This product is not 

to be used in animals intended for use 

as food for humans or other animals.’’

(b) The labeling of an indexed drug 

that was found to be eligible for 


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indexing for use in an early, non-food 

life stage of a food-producing minor 

species animal, under § 516.129(c)(7)(ii), 

shall state, prominently and 

conspicuously: ‘‘NOT APPROVED BY 

FDA.—Legally marketed as an FDA 

indexed product. Extra-label use is 

prohibited.’’

(c) The labeling of an indexed drug 

shall contain such other information as 

may be prescribed in the index listing. 

§ 516.157 Publication of the index and 

content of an index listing. 

(a) FDA will make the list of indexed 

drugs available through the FDA Web 

site. A printed copy can be obtained by 

writing to the FDA Freedom of 

Information Staff or by visiting the FDA 

Freedom of Information Public Reading 

Room. 

(b) The list will contain the following 

information for each indexed drug: 

(1) The name and address of the 

person who holds the index listing; 

(2) The name of the drug and the 

intended use and conditions of use for 

which it is indexed; 

(3) Product labeling; and 

(4) Conditions and any limitations 

that FDA deems necessary regarding use 

of the drug. 

§ 516.161 Modifications to indexed drugs. 

(a) After a drug is listed in the index, 

certain modifications to the index 

listing may be requested. Any 

modification of an index listing may not 

cause an indexed drug to be a different 

drug (or different combination of drugs) 

or a different dosage form. If such 

modification is requested, FDA will 

notify the holder that a new index 

listing is required for the new drug or 

dosage form. 

(b) Modifications to the indexed drug 

will fall under one of three categories 

and must be submitted as follows: 

(1) Urgent changes. (i) The following 

modifications to an indexed drug or its 

labeling should be made as soon as 

possible and a request to modify the 

indexed drug should be concurrently 

submitted: 

(A) The addition to package labeling, 

promotional labeling, or prescription 

drug advertising of additional warning, 

contraindication, side effect, or 

cautionary information. 

(B) The deletion from package 

labeling, promotional labeling, and drug 

advertising of false, misleading, or 

unsupported indications for use or 

claims for effectiveness. 

(C) Changes in manufacturing 

methods or controls required to correct 

product or manufacturing defects that 

may result in serious adverse drug 

events. 

(ii) The modifications described in 

paragraph (b)(1)(i) of this section must 

be submitted to the Director, Office of 

Minor Use and Minor Species Animal 

Drug Development in the form of a 

request for modification of an indexed 

drug, and must contain sufficient 

information to permit FDA to determine 

the need for the modification and 

whether the modification appropriately 

addresses the need. 

(iii) FDA will take no action against 

an indexed drug or index holder solely 

because modifications of the kinds 

described in paragraph (b)(1)(i) of this 

section are placed into effect by the 

holder prior to receipt of a written 

notice granting the request if all the 

following conditions are met: 

(A) A request to modify the indexed 

drug providing a full explanation of the 

basis for the modifications has been 

submitted, plainly marked on the 

mailing cover and on the request as 

follows: ‘‘Special indexing request—

modifications being effected;’’

(B) The holder specifically informs 

FDA of the date on which such 

modifications are to be effected and 

submits two printed copies of any 

revised labeling to be placed in use, and 

(C) All promotional labeling and all 

drug advertising are promptly revised 

consistent with modifications made in 

the labeling on or within the indexed 

drug package. 

(2) Significant changes. (i) The 

following modifications to an indexed 

drug or its labeling may be made only 

after a request has been submitted to 

and subsequently granted by FDA: 

(A) Addition of an intended use. 

(B) Addition of a species. 

(C) Addition or alteration of an active 

ingredient. 

(D) Alteration of the concentration of 

an active ingredient. 

(E) Alteration of dose or dosage 

regimen. 

(F) Alteration of prescription or overthe-counter status. 

(ii) Each modification described in 

paragraph (b)(2)(i) of this section must 

go through the same review process as 

an original index listing and is subject 

to the same standards for review. 

(iii) Each submission of a request for 

a modification described in paragraph 

(b)(2)(i) of this section should contain 

only one type of modification unless 

one modification is actually 

necessitated by another, such as a 

modification of dose necessitated by a 

modification of the concentration of an 

active ingredient. Submissions relating 

to addition of an intended use for an 

existing species or addition of a species 

should be submitted separately, but 

each such submission may include 

multiple additional intended uses and/ 

or multiple additional species. 

(3) Minor changes. All modifications 

other than those described in 

paragraphs (b)(1) and (b)(2) of this 

section including, but not limited to, 

formulation, labeling, and 

manufacturing methods and controls (at 

the same level of detail that these were 

described in the request for 

determination of eligibility for indexing) 

must be submitted as part of the annual 

indexed drug experience report or as 

otherwise required by § 516.165. 

(c) When changes affect the index 

listing, it will be updated accordingly. 

§ 516.163 Change in ownership of an index 

file. 

(a) A holder may transfer ownership 

of a drug’s index file to another person. 

(1) The former owner shall submit in 

writing to FDA a statement that all 

rights in the index file have been 

transferred, giving the name and address 

of the new owner and the date of the 

transfer. The former owner shall also 

certify that a complete copy of the 

following, to the extent that they exist 

at the time of the transfer of ownership, 

has been provided to the new owner: 

(i) The request for determination of 

eligibility; 

(ii) The request for addition to the 

index; 

(iii) Any modifications to the index 

listing; 

(iv) Any records and reports under 

§ 516.165; and 

(v) All correspondence with FDA 

relevant to the indexed drug and its 

index listing. 

(2) The new owner shall submit the 

following information in writing to 

FDA: 

(i) The date that the change in 

ownership is effective; 

(ii) A statement that the new owner 

has a complete copy of all documents 

listed in paragraph (a)(1) of this section 

to the extent that they exist at the time 

of the transfer of ownership; 

(iii) A statement that the new owner 

understands and accepts the 

responsibilities of a holder of an 

indexed drug; 

(iv) The name and address of a new 

primary contact person or permanentresident U.S. agent; and 

(v) A list of labeling changes 

associated with the change of ownership 

(e.g., a new trade name) as draft 

labeling, with complete final printed 

labeling to be submitted in the indexed 

drug annual report in accordance with 

§§ 516.161 and 516.165. 

(b) Upon receiving the necessary 

information to support a change of 

ownership of a drug’s index file, FDA 


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48862 Federal Register / Vol. 71, No. 162 / Tuesday, August 22, 2006 / Proposed Rules 

will update its publicly-available listing 

in accordance with § 516.157. 

§ 516.165 Records and reports. 

(a) Scope and purpose. (1) The 

recordkeeping and reporting 

requirements of this section apply to all 

holders of indexed drugs, including 

indexed drugs intended for use in 

medicated feeds. 

(2) A holder is not required to report 

information under this section if the 

holder has reported the same 

information under § 514.80 of this 

chapter. 

(3) The records and reports referred to 

in this section are in addition to those 

required by the current good 

manufacturing practice regulations in 

parts 211, 225, and 226 of this chapter. 

(4) FDA will review the records and 

reports required in this section to 

determine, or facilitate a determination, 

whether there may be grounds for 

removing a drug from the index under 

section 572(f) of the act. 

(b) Recordkeeping requirements. (1) 

Each holder of an indexed drug must 

establish and maintain complete files 

containing full records of all 

information pertinent to the safety or 

effectiveness of the indexed drug. Such 

records must include information from 

foreign and domestic sources. 

(2) The holder must, upon request 

from any authorized FDA officer or 

employee, at all reasonable times, 

permit such officer or employee to have 

access to copy and to verify all such 

records. 

(c) Reporting requirements. (1) Threeday indexed drug field alert report. The 

holder must inform the appropriate FDA 

District Office or local FDA resident 

post of any product or manufacturing 

defects that may result in serious 

adverse drug events within 3 working 

days of first becoming aware that such 

a defect may exist. The holder may 

initially provide this information by 

telephone or other electronic 

communication means, with prompt 

written follow up. The mailing cover 

must be plainly marked ‘‘3–Day Indexed 

Drug Field Alert Report.’’

(2) Fifteen-day indexed drug alert 

report. The holder must submit a report 

on each serious, unexpected adverse 

drug event, regardless of the source of 

the information. The holder must 

submit the report within 15 working 

days of first receiving the information. 

The mailing cover must be plainly 

marked ‘‘15-Day Indexed Drug Alert 

Report.’’

(3) Annual indexed drug experience 

report. The holder must submit this 

report every year on the anniversary 

date of the letter granting the request for 

addition of the new animal drug to the 

index, or within 60 days thereafter. The 

report must contain data and 

information for the full reporting period. 

Any previously submitted information 

contained in the report must be 

identified as such. The holder may ask 

FDA to change the date of submission 

and, after approval of such request, file 

such reports by the new filing date. The 

report must contain the following: 

(i) The number of distributed units of 

each size, strength, or potency (e.g., 

100,000 bottles of 100 5-milligram 

tablets; 50,000 10-milliliter vials of 5- 

percent solution) distributed during the 

reporting period. This information must 

be presented in two categories: 

quantities distributed domestically and 

quantities exported. This information 

must include any distributor-labeled 

product. 

(ii) If the labeling has changed since 

the last report, include a summary of 

those changes and the holder’s and 

distributor’s current package labeling, 

including any package inserts. For largesize package labeling or large shipping 

cartons, submit a representative copy 

(e.g., a photocopy of pertinent areas of 

large feed bags). If the labeling has not 

changed since the last report, include a 

statement of such fact. 

(iii) A summary of any changes made 

during the reporting period in the 

methods used in, and facilities and 

controls used for, manufacture, 

processing, and packing. This 

information must be presented in the 

same level of detail that it was 

presented in the request for 

determination of eligibility for indexing. 

Do not include changes that have 

already been submitted under § 516.161. 

(iv) Nonclinical laboratory studies 

and clinical data not previously 

reported under this section. 

(v) Adverse drug experiences not 

previously reported under this section. 

(vi) Any other information pertinent 

to safety or effectiveness of the indexed 

drug not previously reported under this 

section. 

(4) Distributor’s statement. At the time 

of initial distribution of an indexed drug 

by a distributor, the holder must submit 

a report containing the following: 

(i) The distributor’s current product 

labeling. This must be identical to that 

in the index listing except for a different 

and suitable proprietary name (if used) 

and the name and address of the 

distributor. The name and address of the 

distributor must be preceded by an 

appropriate qualifying phrase such as 

‘‘manufactured for’’ or ‘‘distributed by.’’

(ii) A signed statement by the 

distributor stating: 

(A) The category of the distributor’s 

operations (e.g., wholesale or retail); 

(B) That the distributor will distribute 

the drug only under the indexed drug 

labeling; 

(C) That the distributor will promote 

the indexed drug only for use under the 

conditions stated in the index listing; 

and 

(D) If the indexed drug is a 

prescription new animal drug, that the 

distributor is regularly and lawfully 

engaged in the distribution or 

dispensing of prescription products. 

(5) Other reporting. FDA may by order 

require that a holder submit information 

in addition to that required by this 

section or that the holder submit the 

same information but at different times 

or reporting periods. 

§ 516.167 Removal from the index. 

(a) After due notice to the holder of 

the index listing and an opportunity for 

an informal conference as described in 

§ 516.123, FDA shall remove a new 

animal drug from the index if FDA finds 

that: 

(1) The same drug in the same dosage 

form for the same intended use has been 

approved or conditionally approved; 

(2) The expert panel failed to meet the 

requirements in § 516.141; 

(3) On the basis of new information 

before FDA, evaluated together with the 

evidence available to FDA when the 

new animal drug was listed in the 

index, the benefits of using the new 

animal drug for the indexed use do not 

outweigh its risks to the target animal, 

taking into account the harm caused by 

the absence of an approved or 

conditionally-approved new animal 

drug for the minor species in question; 

(4) Any of the conditions in 

§ 516.133(a)(2), (5), or (6) are present; 

(5) The manufacture of the new 

animal drug is not in accordance with 

current good manufacturing practices; 

(6) The labeling, distribution, or 

promotion of the new animal drug is not 

in accordance with the index listing; 

(7) The conditions and limitations of 

use associated with the index listing 

have not been followed; or 

(8) Any information used to support 

the request for addition to the index 

contains any untrue statement of 

material fact. 

(b) The agency may partially remove 

an indexing listing if, in the opinion of 

the agency, such partial removal would 

satisfactorily resolve a safety or 

effectiveness issue otherwise warranting 

removal of the listing under section 

572(f)(1)(B) of the act. 

(c) FDA may immediately suspend a 

new animal drug from the index if FDA 

determines that there is a reasonable 


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Federal Register / Vol. 71, No. 162 / Tuesday, August 22, 2006 / Proposed Rules 48863 

probability that the use of the drug 

would present a risk to the health of 

humans or other animals. The agency 

will subsequently provide due notice 

and an opportunity for an informal 

conference as described in § 516.123. 

(d) A decision of FDA to remove a 

new animal drug from the index 

following an informal conference, if 

any, shall constitute final agency action 

subject to judicial review. 

§ 516.171 Confidentiality of data and 

information in an index file. 

(a) For purposes of this section, the 

index file includes all data and 

information submitted to or 

incorporated by reference into the index 

file, such as data and information 

related to investigational use 

exemptions under § 516.125, requests 

for determination of eligibility for 

indexing, requests for addition to the 

index, modifications to indexed drugs, 

changes in ownership, reports 

submitted under § 516.165, and master 

files. The availability for public 

disclosure of any record in the index file 

shall be handled in accordance with the 

provisions of this section. 

(b) The existence of an index file will 

not be disclosed by FDA before an index 

listing has been made public by FDA, 

unless it has previously been publicly 

disclosed or acknowledged by the 

requestor. 

(c) If the existence of an index file has 

not been publicly disclosed or 

acknowledged, no data or information 

in the index file are available for public 

disclosure. 

(d) If the existence of an index file has 

been publicly disclosed or 

acknowledged before an index listing 

has been made public by FDA, no data 

or information contained in the file will 

be available for public disclosure before 

such index listing is made public, but 

the agency may, at its discretion, 

disclose a brief summary of such 

selected portions of the safety and 

effectiveness data as are appropriate for 

public consideration of a specific 

pending issue, e.g., at an open session 

of a Food and Drug Administration 

advisory committee or pursuant to an 

exchange of important regulatory 

information with a foreign government. 

(e) After FDA sends a written notice 

to the requestor granting a request for 

addition to the index, the following data 

and information in the index file are 

available for public disclosure unless 

extraordinary circumstances are shown: 

(1) All safety and effectiveness data 

and information previously disclosed to 

the public, as defined in § 20.81 of this 

chapter. 

(2) A summary or summaries of the 

safety and effectiveness data and 

information submitted with or 

incorporated by reference in the index 

file. Such summaries do not constitute 

the full information described under 

section 572(c) and (d) of the act on 

which the safety or effectiveness of the 

drug may be determined. Such 

summaries will be based on the draft 

Freedom of Information summary 

submitted under § 516.145, which will 

be reviewed and, where appropriate, 

revised by FDA. 

(3) A protocol for a test or study, 

unless it is shown to fall within the 

exemption established for trade secrets 

and confidential commercial 

information in § 20.61 of this chapter. 

(4) Adverse reaction reports, product 

experience reports, consumer 

complaints, and other similar data and 

information, after deletion of the 

following: 

(i) Names and any information that 

would identify the person using the 

product. 

(ii) Names and any information that 

would identify any third party involved 

with the report, such as a veterinarian. 

(5) A list of all active ingredients and 

any inactive ingredients previously 

disclosed to the public as defined in 

§ 20.81 of this chapter. 

(6) An assay method or other 

analytical method, unless it serves no 

regulatory or compliance purpose and is 

shown to fall within the exemption 

established in § 20.61 of this chapter. 

(7) All correspondence and written 

summaries of oral discussions relating 

to the index file, in accordance with the 

provisions of part 20 of this chapter. 

(f) The following data and information 

in an index file are not available for 

public disclosure unless they have been 

previously disclosed to the public as 

defined in § 20.81 of this chapter or they 

relate to a product or ingredient that has 

been abandoned and they no longer 

represent a trade secret or confidential 

commercial or financial information as 

defined in § 20.61 of this chapter: 

(1) Manufacturing methods or 

processes, including quality control 

procedures. 

(2) Production, sales, distribution, and 

similar data and information, except 

that any compilation of such data and 

information aggregated and prepared in 

a way that does not reveal data or 

information which is not available for 

public disclosure under this provision is 

available for public disclosure. 

(3) Quantitative or semiquantitative 

formulas. 

(g) Subject to the disclosure 

provisions of this section, the agency 

shall regard the contents of an index file 

as confidential information unless 

specifically notified in writing by the 

holder of the right to disclose, to 

reference, or otherwise utilize such 

information on behalf of another named 

person. 

(h) For purposes of this regulation, 

safety and effectiveness data include all 

studies and tests of an animal drug on 

animals and all studies and tests on the 

animal drug for identity, stability, 

purity, potency, and bioavailability. 

(i) Safety and effectiveness data and 

information that have not been 

previously disclosed to the public are 

available for public disclosure at the 

time any of the following events occurs 

unless extraordinary circumstances are 

shown: 

(1) No work is being or will be 

undertaken to have the drug indexed in 

accordance with the request. 

(2) A final determination is made that 

the drug cannot be indexed and all legal 

appeals have been exhausted. 

(3) The drug has been removed from 

the index and all legal appeals have 

been exhausted. 

(4) A final determination has been 

made that the animal drug is not a new 

animal drug. 

PART 558—NEW ANIMAL DRUGS FOR 

USE IN ANIMAL FEEDS 

33. The authority citation for 21 CFR 

part 558 continues to read as follows: 

Authority: 21 U.S.C. 360b, 371. 

34. Amend § 558.3 by revising the last 

sentence of paragraph (b)(2) and 

revising paragraphs (b)(5), (b)(6), and 

(b)(7) to read as follows: 

§ 558.3 Definitions and general 

considerations applicable to this part. 

* * * * * 

(b) * * * 

(2) * * * The manufacture of a Type 

A medicated article requires an 

application approved under § 514.105 of 

this chapter or an index listing granted 

under § 516.151 of this chapter. 

* * * * * 

(5) A Type B or Type C medicated 

feed manufactured from a drug 

component (bulk or ‘‘drum-run’’ (dried 

crude fermentation product)) requires 

an application approved under 

§ 514.105 of this chapter or an index 

listing granted under § 516.151 of this 

chapter. 

(6) A ‘‘veterinary feed directive (VFD) 

drug’’ is a new animal drug approved 

under section 512(b) or listed in the 

index under section 572 of the Federal 

Food, Drug, and Cosmetic Act (the act) 

for use in or on animal feed. Use of a 

VFD drug must be under the 

professional supervision of a licensed 

veterinarian. 


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48864 Federal Register / Vol. 71, No. 162 / Tuesday, August 22, 2006 / Proposed Rules 

(7) A ‘‘veterinary feed directive’’ is a 

written statement issued by a licensed 

veterinarian in the course of the 

veterinarian’s professional practice that 

orders the use of a veterinary feed 

directive (VFD) drug in or on an animal 

feed. This written statement authorizes 

the client (the owner of the animal or 

animals or other caretaker) to obtain and 

use the VFD drug in or on an animal 

feed to treat the client’s animals only in 

accordance with the directions for use 

approved or indexed by the Food and 

Drug Administration (FDA). A 

veterinarian may issue a VFD only if a 

valid veterinarian-client-patient 

relationship exists, as defined in 

§ 530.3(i) of this chapter. 

* * * * * 

35. Amend § 558.5 by revising 

paragraphs (c) and (d) to read as follows: 

§ 558.5 Requirements for liquid medicated 

feed. 

* * * * * 

(c) What is required for new animal 

drugs intended for use in liquid feed? 

Any new animal drug intended for use 

in liquid feed must be approved for 

such use under section 512 of the act or 

index listed under section 572 of the 

act. Such approvals under section 512 of 

the act must be: 

(1) An original NADA, 

(2) A supplemental NADA, or 

(3) An abbreviated NADA. 

(d) What are the approval 

requirements under section 512 of the 

act for new animal drugs intended for 

use in liquid feed? An approval under 

section 512 of the act for a new animal 

drug intended for use in liquid feed 

must contain the following information: 

(1) Data, or a reference to data in a 

master file (MF), that shows the relevant 

ranges of conditions under which the 

drug will be chemically stable in liquid 

feed under field use conditions; and 

(2) Data, or a reference to data in an 

MF, that shows that the drug is 

physically stable in liquid feed under 

field conditions; or 

(3) Feed labeling with recirculation or 

agitation directions as follows: 

(i) For liquid feeds stored in 

recirculating tank systems: Recirculate 

immediately prior to use for not less 

than 10 minutes, moving not less than 

1 percent of the tank contents per 

minute from the bottom of the tank to 

the top. Recirculate daily as described 

even when not used. 

(ii) For liquid feeds stored in 

mechanical, air, or other agitation-type 

tank systems: Agitate immediately prior 

to use for not less than 10 minutes, 

creating a turbulence at the bottom of 

the tank that is visible at the top. Agitate 

daily as described even when not used. 

* * * * * 

36. Amend § 558.6 by revising 

paragraphs (a)(4)(iv) and (a)(6) to read as 

follows: 

§ 558.6 Veterinary feed directive drugs. 

(a) * * * 

(4) * * * 

(iv) Approved or index listed 

indications for use. 

* * * * * 

(6) You must issue a VFD only for the 

approved or indexed conditions and 

indications for use of the VFD drug. 

* * * * * 

PART 589—SUBSTANCES 

PROHIBITED FROM USE IN ANIMAL 

FOOD OR FEED 

37. The authority citation for 21 CFR 

part 589 continues to read as follows: 

Authority: 21 U.S.C. 321, 342, 343, 348, 

371. 

38. Revise § 589.1000 to read as 

follows: 

§ 589.1000 Gentian violet. 

The Food and Drug Administration 

has determined that gentian violet has 

not been shown by adequate scientific 

data to be safe for use in animal feed. 

Use of gentian violet in animal feed 

causes the feed to be adulterated and in 

violation 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, unless it is subject to an effective 

notice of claimed investigational 

exemption for a food additive under 

§ 570.17 of this chapter, or unless the 

substance is intended for use as a new 

animal drug and is subject to an 

approved application under section 512 

of the act, or an index listing under 

section 572 of the act, or an effective 

notice of claimed investigational 

exemption for a new animal drug under 

part 511 of this chapter or § 516.125 of 

this chapter. 

Dated: June 15, 2006. 

Jeffrey Shuren, 

Assistant Commissioner for Policy. 

[FR Doc. 06–7070 Filed 8–21–06; 8:45 am] 

BILLING CODE 4160–01–S 

DEPARTMENT OF DEFENSE 

Office of the Secretary 

32 CFR Part 199 

[DOD–2006–OS–0091] 

RIN 0720–AB00 

TRICARE; Reserve and Guard Family 

Member Benefits 

ACTION: Proposed rule. 

SUMMARY: This proposed rule would 

implement sections 704 and 705 of the 

Ronald W. Reagan National Defense 

Authorization Act for Fiscal Year 2005. 

These provisions would apply to 

eligible family members who become 

eligible for TRICARE as a result of their 

Reserve Component (RC) sponsor 

(including those with delayed effective 

date orders up to 90 days) being called 

or ordered to active duty for more than 

30 days in support of a federal/ 

contingency operation and choose to 

participate in TRICARE Standard or 

Extra, rather than enroll in TRICARE 

Prime. The first provision would 

provide the Secretary the authority to 

waive the annual TRICARE Standard (or 

Extra) deductible, which is set by law 

(10 U.S.C. 1079(b)) at $150 per 

individual and $300 per family ($50/ 

$150 for families of members in pay 

grades E–4 and below). The second 

provision would provide the Secretary 

the authority to increase TRICARE 

payments up to 115 percent of the 

TRICARE maximum allowable charge, 

less the applicable patient cost share if 

not previously waived under the first 

provision, for covered outpatient health 

services received from a provider that 

does not participate (accept assignment) 

with TRICARE. These provisions would 

help ensure timely access to health care 

and maintain clinically appropriate 

continuity of health care to family 

members of Reservists and Guardsmen 

activated in support of a federal/ 

contingency operation; limit the out-ofpocket health care expenses for those 

family members; and remove potential 

barriers to health care access by Guard 

and Reserve families. 

DATES: Written comments received at 

the address indicated below by October 

23, 2006. 

ADDRESSES: You may submit comments, 

identified by docket number and or RIN 

number and title, by any of the 

following methods: 

• Federal eRulemaking Portal: http:// 

www.regulations.gov. Follow the 

instructions for submitting comments. 


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