Federal Register / Vol. 65, No. 106 / Thursday, June 1, 2000 / Rules and Regulations 34959

physicians’ assistants, naturopaths,

chiropractors, audiologists, and

therapists);

(2) Educational personnel (for

example, school teachers, counselors,

early intervention team members,

developmental center workers, and

daycare center workers);

(3) Public and private social welfare

agency personnel; and

(4) Other non-medical sources (for

example, spouses, parents and other

caregivers, siblings, other relatives,

friends, neighbors, and clergy).

(e) Completeness. The evidence in

your case record, including the medical

evidence from acceptable medical

sources (containing the clinical and

laboratory findings) and other medical

sources not listed in paragraph (a) of

this section, information you give us

about your medical condition(s) and

how it affects you, and other evidence

from other sources, must be complete

and detailed enough to allow us to make

a determination or decision about

whether you are disabled or blind. It

must allow us to determine—

(1) The nature and severity of your

impairment(s) for any period in

question;

(2) Whether the duration requirement

described in § 416.909 is met; and

(3) Your residual functional capacity

to do work-related physical and mental

activities, when the evaluation steps

described in § 416.920(e) or (f)(1) apply,

or, if you are a child, your functioning.

* * * * *

13. Section 416.926 is amended by

revising the second and fourth

sentences of paragraph (c) to read as

follows:

§ 416.926 Medical equivalence for adults

and children.

* * * * *

(c) Who is a designated medical or

psychological consultant. * * * A

medical consultant must be an

acceptable medical source identified in

§ 416.913(a)(1) or (a)(3) through (a)(5).

* * * (See § 416.1016 for limitations on

what medical consultants who are not

physicians can evaluate and the

qualifications we consider necessary for

a psychologist to be a consultant.)

* * * * *

Subpart J—[Amended]

14. The authority citation for subpart

J of part 416 continues to read as

follows:

Authority: Secs. 702(a)(5), 1614, 1631, and

1633 of the Social Security Act (42 U.S.C.

902(a)(5), 1382c, 1383, and 1383b).

§ 416.1015 [Amended]

15. Section 416.1015 is amended by

removing the last sentence of paragraph

(d).

16. Section 416.1016 is revised to read

as follows:

§ 416.1016 Medical or psychological

consultants.

(a) What is a medical consultant? A

medical consultant is a person who is a

member of a team that makes disability

determinations in a State agency, as

explained in § 416.1015, or who is a

member of a team that makes disability

determinations for us when we make

disability determinations ourselves.

(b) What qualifications must a

medical consultant have? A medical

consultant must be an acceptable

medical source identified in

§ 416.913(a)(1) or (a)(3) through (a)(5);

that is, a licensed physician (medical or

osteopathic), a licensed optometrist, a

licensed podiatrist, or a qualified

speech-language pathologist. The

medical consultant must meet any

appropriate qualifications for his or her

specialty as explained in § 416.913(a).

(c) Are there any limitations on what

medical consultants who are not

physicians can evaluate? Medical

consultants who are not physicians are

limited to evaluating the impairments

for which they are qualified, as

described in § 416.913(a). Medical

consultants who are not physicians also

are limited as to when they may serve

as a member of a team that makes a

disability determination. For example, a

speech-language pathologist who is a

medical consultant in a State agency

may be a member of a team that makes

a disability determination in a claim

only if a speech or language impairment

is the only impairment in the claim or

if there is a combination of a speech or

language impairment with another

impairment but the speech or language

impairment alone would justify a

finding of disability. In all other cases,

a physician will be a member of the

team that makes a disability

determination, except in cases in which

this function may be performed by a

psychological consultant as discussed in

paragraph (f) of this section and

§ 416.1015(d).

(d) What is a psychological

consultant? A psychological consultant

is a psychologist who has the same

responsibilities as a medical consultant

explained in paragraph (a) of this

section, but who can evaluate only

mental impairments.

(e) What qualifications must a

psychological consultant have? A

psychological consultant used in cases

where there is evidence of a mental

impairment must be a qualified

psychologist. For disability program

purposes, a psychologist will not be

considered qualified unless he or she:

(1) Is licensed or certified as a

psychologist at the independent practice

level of psychology by the State in

which he or she practices; and

(2)(i) Possesses a doctorate degree in

psychology from a program in clinical

psychology of an educational institution

accredited by an organization

recognized by the Council on PostSecondary Accreditation; or

(ii) Is listed in a national register of

health service providers in psychology

which the Commissioner of Social

Security deems appropriate; and

(3) Possesses 2 years of supervised

clinical experience as a psychologist in

health service, at least 1 year of which

is post masters degree.

(f) Are there any limitations on what

a psychological consultant can

evaluate? Psychological consultants are

limited to the evaluation of mental

impairments, as explained in

§ 416.1015(d). Psychological consultants

also are limited as to when they can

serve as a member of a team that makes

a disability determination. They may do

so only when a mental impairment is

the only impairment in the claim or

when there is a combination of a mental

impairment with another impairment

but the mental impairment alone would

justify a finding of disability.

[FR Doc. 00–13607 Filed 5–31–00; 8:45 am]

BILLING CODE 4191–02–U

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

21 CFR Part 5

Delegations of Authority and

Organization; Food and Drug

Administration

AGENCY: Food and Drug Administration,

HHS.

ACTION: Final rule.

SUMMARY: The Food and Drug

Administration (FDA) is amending the

general redelegations of authority from

the Commissioner of Food and Drugs to

other officers of FDA. On June 20, 1999,

the Commissioner of Food and Drugs

restructured FDA ‘‘to create a more

streamlined and efficient Office of the

Commissioner that will provide

leadership without compromising

programmatic effectiveness.’’ In this

restructuring, organizational

34960 Federal Register / Vol. 65, No. 106 / Thursday, June 1, 2000 / Rules and Regulations

components were abolished and

established and functions and personnel

were transferred. Therefore, FDA is

updating the delegations of authority

regulations to reflect these changes and

to delegate authority to positions in

newly established components. FDA is

also updating some position titles that

may have been affected by previous

reorganizations.

DATES: This rule is effective June 1,

2000.

FOR FURTHER INFORMATION CONTACT:

Donna G. Page, Division of Management

Programs (HFA–330), Food and Drug

Administration, 5600 Fishers Lane,

Rockville, MD 20857, 301–827–4816.

SUPPLEMENTARY INFORMATION: FDA is

amending the delegations of authority

regulations in various sections of 21

CFR part 5, subpart B, Redelegations of

Authority from the Commissioner of

Food and Drugs, to reflect the most

significant changes that resulted from

the June 20, 1999, restructuring. (See 64

FR 36361–36368, July 6, 1999, and 64

FR 38675, July 19, 1999.) The changes

are as follows:

1. Updating the order of succession

and who may perform all of the

functions of the Commissioner of Food

and Drugs.

2. Clarifying certain delegations of

authority to appropriately reflect the

Deputy Commissioners’ authorities—

there will be one principal Deputy

Commissioner; however, two other

Deputy Commissioner titles

(International and Constituent Relations

and Management and Systems) will be

retained for incumbents only.

3. Amending certain delegations of

authority and associated position titles

to reflect the establishment of the Office

of the Senior Associate Commissioner

and the transfer of the Ombudsman,

Executive Secretariat, Advisory

Committee Oversight, Public Affairs,

and Orphan Products Development

functions to that component.

4. Removing position titles and

delegations of authority associated with

the abolished Office of Operations.

5. Removing references to the

abolished Offices of Policy and External

Affairs and updating position titles and

associated delegations of authority,

where appropriate, to reflect their

conversions to the Office of Policy,

Planning, and Legislation and the Office

of International and Constituent

Relations, respectively.

6. Updating position titles and

associated delegations of authority to

reflect the transfer of the health

assessment, patent term extension, and

scheduling controlled substances

functions to the Center for Drug

Evaluation and Research.

7. Updating position titles and

associated delegations of authority to

reflect the transfer of 21 CFR part 16

hearings functions; and to reflect the

delegation of authority to make due

diligence determinations, which pertain

to patent term extensions, to the Office

of the Ombudsman.

Unless stated otherwise, these

authorities may not be further

redelegated. Authority delegated to a

position by title may be exercised by a

person officially designated to serve in

such position in an acting capacity or on

a temporary basis, unless prohibited by

a restriction in the document

designating him/her as ‘‘acting’’ or

unless not legally permissible.

List of Subjects in 21 CFR Part 5

Authority delegations (Government

agencies), Imports, Organization and

functions (Government agencies).

Therefore, under the Federal Food,

Drug, and Cosmetic Act and under

authority delegated to the Commissioner

of Food and Drugs, 21 CFR part 5 is

amended as follows:

PART 5—DELEGATIONS OF

AUTHORITY AND ORGANIZATION

1. The authority citation for part 5

continues to read as follows:

Authority: 5 U.S.C. 504, 552, App. 2; 7

U.S.C. 138a, 2271; 15 U.S.C. 638, 1261–1282,

3701–3711a; 15 U.S.C. 1451–1461; 21 U.S.C.

41–50, 61–63, 141–149, 321–394, 467f,

679(b), 801–886, 1031–1309; 35 U.S.C. 156;

42 U.S.C. 241, 242, 242a, 242l, 242n 243, 262,

263, 264, 265, 300u–300u–5, 300aa–1; 1395y,

3246b, 4332, 4831(a), 10007–10008; E.O.

11921, 41 FR 24294, 3 CFR, 1977 Comp., p.

124–131; E.O. 12591, 52 FR 13414, 3 CFR,

1988 Comp., p. 220–223.

2. Section 5.20 is amended by revising

paragraphs (b), (c), (e), (f), and (g); by

redesignating paragraph (i) as paragraph

(j); and by adding a new paragraph (i)

to read as follows:

§ 5.20 General redelegations of authority

from the Commissioner to other officers of

the Food and Drug Administration.

* * * * *

(b) The following officials are

authorized to perform all of the

functions of the Commissioner of Food

and Drugs and this authority may not be

further redelegated:

(1) Deputy Commissioner;

(2) Associate Commissioner for

Regulatory Affairs;

(3) Senior Associate Commissioner;

(4) Deputy Commissioner for

Management and Systems;

(5) Senior Associate Commissioner for

Policy, Planning, and Legislation; and

(6) Deputy Commissioner for

International and Constituent Relations.

(c)(1) During the absence or disability

of the Commissioner, or in the event of

a vacancy in that position, the first

official who is available in the following

positions, or who has been designated

by the Commissioner to act in such

position, shall act as Commissioner:

(i) Deputy Commissioner;

(ii) Associate Commissioner for

Regulatory Affairs; or

(iii) Senior Associate Commissioner.

(2) This authority may not be further

redelegated. However, for a planned

period of absence, the Commissioner of

Food and Drugs (or someone ‘‘acting’’

on his/her behalf) may specify a

different order of succession.

* * * * *

(e)(1) The Senior Associate

Commissioner is authorized to make

determinations that advisory committee

meetings are concerned with matters

listed in 5 U.S.C. 552(b) and therefore

may be closed to the public in

accordance with § 5.10(a)(18). This

authority may not be further

redelegated.

(2) The Senior Associate

Commissioner is authorized to perform

other associated advisory committee

functions (e.g., establishing technical

and scientific review groups (advisory

committees)); appointing and paying

members; approving waivers to appoint

members to established advisory

committees; renewing and rechartering

of established advisory committees;

amending charters of established

advisory committees; and terminating

established advisory committees. This

authority may not be further

redelegated.

(3) The Senior Associate

Commissioner is authorized to approve

conflict of interest waivers for special

Government employees serving on

advisory committees in accordance with

18 U.S.C. 208(b)(3), as amended. This

authority may not be further

redelegated.

(4) The Senior Associate

Commissioner is authorized to select

temporary members to advisory

committees if such voting members are

serving on an advisory committee

managed by another center. This

authority may not be further

redelegated.

(f)(1) The Senior Associate

Commissioner for Policy, Planning, and

Legislation and the Associate

Commissioner for Policy are authorized

to perform any of the functions of the

Commissioner of Food and Drugs with

respect to the issuance of Federal

Register notices and proposed and final

Federal Register / Vol. 65, No. 106 / Thursday, June 1, 2000 / Rules and Regulations 34961

regulations of the Food and Drug

Administration. This authority may not

be further redelegated.

(2) The Senior Associate

Commissioner for Policy, Planning, and

Legislation and the Associate

Commissioner for Policy are authorized

to issue responses to the following

matters under part 10 of this chapter as

follows, and this authority may not be

further redelegated:

(i) Requests for waiver, suspension, or

modification of procedural requirements

under § 10.19 of this chapter;

(ii) Citizen petitions under § 10.30 of

this chapter;

(iii) Petitions for reconsideration

under § 10.33 of this chapter;

(iv) Petitions for stay under § 10.35 of

this chapter; or

(v) Requests for advisory opinions

under § 10.85 of this chapter.

(3) With respect to any matter

delegated to the Senior Associate

Commissioner for Policy, Planning, and

Legislation and the Associate

Commissioner for Policy under

paragraph (f) of this section, the Senior

Associate Commissioner for Policy,

Planning, and Legislation and the

Associate Commissioner for Policy are

authorized to perform the function of

the Commissioner of Food and Drugs

under §§ 10.40, 10.45, 10.50, 10.55,

10.60, 10.65, 10.80, 10.90, and 10.95 of

this chapter and of the Deputy

Commissioner under § 10.206(g) and (h)

of this chapter. This authority may not

be further redelegated.

(4) The Senior Associate

Commissioner for Policy, Planning, and

Legislation and the Associate

Commissioner for Policy are authorized

under the Regulatory Flexibility Act (5

U.S.C. 605(b)) to certify that a proposed

or final rule, if issued, will not have a

significant economic impact on a

substantial number of small entities.

This authority may be further

redelegated.

(g) The following officials are

authorized to perform all of the

functions of the officials under them in

their respective offices, and this

authority may not be further

redelegated:

(1) Senior Associate Commissioner;

(2) Deputy Commissioner for

International and Constituent Relations;

(3) Deputy Commissioner for

Management and Systems; or

(4) Senior Associate Commissioner for

Policy, Planning, and Legislation.

* * * * *

(i) The Deputy Commissioner is

authorized to perform the due diligence

determinations and informal hearings

functions under 35 U.S.C.

156(d)(2)(B)(ii), as amended, relative to

patent term extensions. This authority

may not be further redelegated.

* * * * *

3. Section 5.22 is amended by revising

paragraphs (a)(1), (a)(2), (a)(3), (a)(6),

(a)(7), (a)(10)(ii), (a)(11)(ii), (a)(12)(ii),

(b)(1), (b)(2), and (b)(3); by redesignating

paragraph (c) as paragraph (d) and

revising newly redesignated paragraph

(d); and by adding new paragraph (c) to

read as follows:

§ 5.22 Certification of true copies and use

of Department seal.

(a) * * *

(1) The Deputy Commissioner, the

Deputy Commissioner for International

and Constituent Relations, and the

Deputy Commissioner for Management

and Systems.

(2) The Senior Associate

Commissioners, the Associate and

Deputy Associate Commissioners, and

the Chief Counsel and Deputies.

(3) The Director, Office of the

Executive Secretariat, Office of the

Senior Associate Commissioner, Office

of the Commissioner.

* * * * *

(6)(i) The Director, Office of Human

Resources and Management Services,

Office of Management and Systems,

Office of the Commissioner.

(ii) The Director, Division of

Management Programs, Office of Human

Resources and Management Services,

Office of Management and Systems,

Office of the Commissioner.

(iii) The Chief, Dockets Management

Branch, Division of Management

Programs, Office of Human Resources

and Management Services, Office of

Management and Systems, Office of the

Commissioner.

(7)(i) The Associate Commissioner for

Public Affairs, Office of Public Affairs,

Office of the Senior Associate

Commissioner, Office of the

Commissioner.

(ii) The Director, Freedom of

Information Staff, Office of Public

Affairs, Office of the Senior Associate

Commissioner, Office of the

Commissioner.

* * * * *

(10) * * *

(ii) The Director and Deputy Director,

Office of Management and

Communications, Center for Veterinary

Medicine (CVM).

* * * * *

(11) * * *

(ii) The Director and Deputy Director,

Office of Management and

Communications, CVM.

* * * * *

(12) * * *

(ii) The Director, Office of

Management, Facilities, and Research

Support, NCTR.

* * * * *

(b) * * *

(1) The Deputy Commissioner, the

Deputy Commissioner for International

and Constituent Relations, and the

Deputy Commissioner for Management

and Systems.

(2) The Senior Associate

Commissioners, the Associate and

Deputy Associate Commissioners, and

the Chief Counsel and Deputies.

(3) The Director, Office of Human

Resources and Management Services,

Office of Management and Systems,

Office of the Commissioner.

(c) The authorities under § 5.22 (a)

and (b), where appropriate, may be

further redelegated by the Deputy

Commissioners; Senior Associate

Commissioners; Associate

Commissioner for Regulatory Affairs

and Deputy; Chief Counsel and

Deputies; Center Directors and Deputies;

and Executive Officers (i.e., Executive

Assistant, Office of the Commissioner;

Director, Office of Management, CBER;

Director, Office of Management, CDER;

Director, Office of Management and

Systems, CFSAN; Director, Office of

Systems and Management, CDRH;

Director, Office of Management and

Communications, CVM; Director, Office

of Management, Facilities, and Research

Support, NCTR; and the Director, Office

of Resource Management, ORA).

(d) The Chief, Regulations Editorial

Section; Regulations Policy and

Management Staff; Office of Policy,

Planning, and Legislation; Office of the

Commissioner, and his/her alternates

are authorized to certify true copies of

Federal Register documents. The Chief,

Regulations Editorial Section;

Regulations Policy and Management

Staff; Office of Policy, Planning, and

Legislation; and the Office of the

Commissioner may designate alternates

as required.

4. Section 5.23 is amended by revising

paragraphs (a)(1), (a)(2), (a)(4), and (d).

§ 5.23 Disclosure of official records.

(a) * * *

(1) The Deputy Commissioner, the

Deputy Commissioner for International

and Constituent Relations, the Deputy

Commissioner for Management and

Systems, Senior Associate

Commissioners, Associate and Deputy

Associate Commissioners.

(2)(i) The Executive Assistant to the

Commissioner, Office of the

Commissioner.

(ii) The Director, Office of the

Executive Secretariat, Office of the

34962 Federal Register / Vol. 65, No. 106 / Thursday, June 1, 2000 / Rules and Regulations

Senior Associate Commissioner, Office

of the Commissioner.

* * * * *

(4)(i) The Director, Office of Human

Resources and Management Services,

Office of Management and Systems,

Office of the Commissioner.

(ii) The Director, Division of

Management Programs, Office of Human

Resources and Management Services,

Office of Management and Systems,

Office of the Commissioner.

(iii) The Chief, Dockets Management

Branch, Division of Management

Programs; Office of Human Resources

and Management Services, Office of

Management Services, Office of the

Commissioner.

* * * * *

(d) The Director, Office of Resource

Management, Office of Regulatory

Affairs is authorized to sign affidavits

regarding the presence or absence of

records in the files of that office.

* * * * *

5. Section 5.25 is amended by revising

paragraphs (a)(7) and (c) to read as

follows:

§ 5.25 Research, investigation, and testing

programs and health information and health

promotion programs.

(a) * * *

(7) The Director, Office of Orphan

Products Development, Office of the

Senior Associate Commissioner, Office

of the Commissioner.

* * * * *

(c) The Deputy Commissioner for

Management and Systems, Office of

Management and Systems, Office of the

Commissioner; the Director and Deputy

Director, Office of Facilities,

Acquisitions, and Central Services,

Office of Management and Systems,

Office of the Commissioner; the

Director, Division of Contracts and

Procurement Management, Office of

Facilities, Acquisitions, and Central

Services, Office of Management and

Systems, Office of the Commissioner;

and the Chief Grants Management

Officer and the Grants Management

Officer, Division of Contracts and

Procurement Management, Office of

Facilities, Acquisitions, and Central

Services, Office of Management

Systems, Office of the Commissioner are

authorized to sign and issue all notices

of grant awards and amendments

thereto and sign and issue notices of

suspension and termination thereof for

grants approved under the authority

delegated in paragraphs (a) and (b) of

this section.

* * * * *

6. Section 5.27 is revised to read as

follows:

§ 5.27 Patent term extensions for human

drug products, medical devices, and food

and color additives; and due diligence

determinations.

(a) The Director, Center for Drug

Evaluation and Research (CDER) and the

Associate Director for Policy, CDER, are

authorized to perform the functions

delegated to the Commissioner of Food

and Drugs under 35 U.S.C. 156, as

amended, except for making due

diligence determinations and holding of

informal hearings under 35 U.S.C.

156(d)(2)(B).

(b) The Chief Mediator and

Ombudsman, Office of the Ombudsman,

Office of the Senior Associate

Commissioner, Office of the

Commissioner, is authorized to perform

the functions delegated to the

Commissioner to make due diligence

determinations under 35 U.S.C.

156(d)(2)(B), as amended, except for

holding of informal hearings under 35

U.S.C. 156(d)(2)(B)(ii).

7. Section 5.30 is amended by revising

paragraph (c)(1) to read as follows:

§ 5.30 Hearings.

* * * * *

(c) * * *

(1) The Chief Mediator and

Ombudsman, Office of the Ombudsman,

Office of the Senior Associate

Commissioner, Office of the

Commissioner.

* * * * *

8. Section 5.32 is revised to read as

follows:

§ 5.32 Authority relating to determination

of product classification and assignment of

primary jurisdiction.

The Chief Mediator and Ombudsman,

Office of the Ombudsman, Office of the

Senior Associate Commissioner, Office

of the Commissioner, as product

jurisdiction officer is authorized to

make a determination under section 563

of the Federal Food, Drug, and Cosmetic

Act (the act) respecting the classification

of a product as a drug, biological

product, device, or a combination

product subject to section 503(g) of the

act, and to assign primary responsibility

respecting the organizational

component of the Food and Drug

Administration that will regulate the

product.

9. Section 5.34 is amended by revising

paragraph (a) to read as follows:

§ 5.34 Authority to select temporary voting

members for advisory committees and

authority to sign conflict of interest waivers.

(a) Each center director is authorized

to select members of, and consultants to,

scientific and technical FDA advisory

committees under that center’s

management to serve temporarily as

voting members on another advisory

committee under that center’s

management when expertise is required

that is not available among current

voting standing members of a committee

or to comprise a quorum when, because

of unforeseen circumstances, a quorum

will be lacking. When additional voting

members are added to a committee to

provide needed expertise not available

among current voting standing members

of a committee, a quorum will be based

on the total of regular and added

members. Authority to select temporary

voting members to advisory committees

if such voting members are serving on

an advisory committee managed by

another center has not been redelegated.

This authority will continue to be

exercised by the Commissioner or the

Senior Associate Commissioner, Office

of the Commissioner.

* * * * *

10. Section 5.58 is amended by

revising introductory text of paragraphs

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

§ 5.58 Orphan products.

(a) The Director, Office of Orphan

Products Development, Office of the

Senior Associate Commissioner, Office

of the Commissioner, is authorized to

issue notices, and amendments thereto,

inviting sponsorship for orphan

products (human and animal drugs,

biological products, and medical

devices) and submission of:

* * * * *

(b) The Director, Office of Orphan

Products Development, Office of the

Senior Associate Commissioner, Office

of the Commissioner, is authorized:

* * * * *

11. Section 5.81 is revised to read as

follows:

§ 5.81 Responses to Drug Enforcement

Administration temporary scheduling

notices.

The Director, Center for Drug

Evaluation and Research (CDER) and the

Director, Executive Operations Staff,

Office of the Center Director, CDER are

authorized to provide responses to the

Drug Enforcement Administration’s

temporary scheduling notices under the

Controlled Substances Act, as amended

(Title II of the Comprehensive Drug

Abuse Prevention and Control Act of

1970, 21 U.S.C. 811(h)(4), as amended

hereafter). The delegation excludes the

authority to submit reports to Congress.

Further redelegation may only be

authorized with the Commissioner of

Food and Drugs’ approval.

Federal Register / Vol. 65, No. 106 / Thursday, June 1, 2000 / Rules and Regulations 34963

Dated: May 17, 2000.

Margaret M. Dotzel,

Acting Associate Commissioner for Policy.

[FR Doc. 00–13586 Filed 5–31–00; 8:45 am]

BILLING CODE 4160–01–F

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

21 CFR Part 312

[Docket No. 97N–0030]

Investigational New Drug Applications;

Amendment to Clinical Hold

Regulations for Products Intended for

Life-Threatening Diseases and

Conditions

AGENCY: Food and Drug Administration,

HHS.

ACTION: Final rule.

SUMMARY: The Food and Drug

Administration (FDA) is amending the

regulations governing investigational

new drug applications (IND’s) to permit

FDA to place a clinical hold on one or

more studies under an IND involving a

drug that is intended to treat a lifethreatening disease or condition

affecting both genders. The amendments

permit the agency to place a clinical

hold on such studies if men or women

with reproductive potential who have

the disease or condition are otherwise

eligible but are categorically excluded

from participation solely because of a

perceived risk or potential risk of

reproductive or developmental toxicity

from use of the investigational drug.

This rule was developed in response to

the past practice of excluding women

with reproductive potential from early

clinical trials because of a perceived risk

or potential risk of reproductive or

developmental toxicity. The final rule

does not impose requirements to enroll

or recruit a specific number of men or

women with reproductive potential.

DATES: The regulation is effective July

31, 2000.

FOR FURTHER INFORMATION CONTACT:

Andrea C. Masciale, Center for Drug

Evaluation and Research (HFD–7), Food

and Drug Administration, 5600 Fishers

Lane, Rockville, MD 20857, 301–594–

2041.

SUPPLEMENTARY INFORMATION:

I. Background

In the Federal Register of September

24, 1997 (62 FR 49946), FDA proposed

to amend its regulations in § 312.42 (21

CFR 312.42) governing clinical holds. A

clinical hold is an order that FDA may

issue to a sponsor to delay a proposed

clinical investigation or to suspend an

ongoing investigation for the

development of a new drug or biological

product (§ 312.42(a)). Under the

proposed amendments, FDA could

impose a clinical hold on any proposed

or ongoing clinical trial for a lifethreatening disease or condition that

affects both genders if men or women

with reproductive potential who have

the disease or condition being studied

were excluded from eligibility in any

phase of the clinical investigation solely

because of a risk or potential risk of

reproductive toxicity or developmental

toxicity from use of the investigational

drug. As explained in the preamble to

the proposed rule (62 FR 49946 at

49947), the amendments address the

exclusion from clinical trials of

members of either gender who have a

life-threatening disease or condition.

Because such exclusions have in the

past been applied primarily to women,

however, it is expected that the impact

of the amendments will be to ensure

that women who have a life-threatening

disease or condition are not

categorically excluded from

investigational trials of drug products

for that disease or condition solely

because of a perceived risk or potential

risk of reproductive or developmental

toxicity from the use of the

investigational drug. FDA provided 90

days for public comment on the

proposed rule.

II. Description of the Final Rule

FDA regulations identify the grounds

for placing a clinical hold on proposed

or ongoing phase 1 studies

(§ 312.42(b)(1)) and on proposed or

ongoing phase 2 or phase 3 studies

(§ 312.42(b)(2)). FDA is amending these

clinical hold regulations to provide an

additional ground for placing a phase 1,

phase 2, or phase 3 study on clinical

hold. Under these amendments, FDA

may impose a clinical hold on any

proposed or ongoing clinical trial for a

life-threatening disease or condition that

affects both genders if men or women

with reproductive potential who have

the disease being studied are excluded

from eligibility in any phase of the

investigation because of a risk or

potential risk of reproductive or

developmental toxicity from use of the

investigational drug.

The proposed rule refers to studies

under an IND involving a drug that is

intended to treat a life-threatening

illness or disease affecting both genders.

As stated in the proposal (62 FR 49946

at 49951 ), the definition of lifethreatening illness or disease is

intended to be consistent with the

agency’s IND regulations

(§ 312.81(a)(1)). Under the IND

regulations, the term life-threatening is

applied to ‘‘conditions’’ or ‘‘diseases.’’

To remain consistent with current

terminology, the agency is amending the

final rule to refer to ‘‘life-threatening

diseases or conditions.’’

The clinical hold under these

amendments would not apply to clinical

studies conducted under special

circumstances, such as studies pertinent

to only one gender (e.g., to evaluate the

excretion of a drug in semen or its

effects on menstrual function).

As described in the proposed rule, a

clinical hold would not be applied to a

clinical study conducted in men, as long

as a study that does not exclude subjects

with reproductive potential has been

planned or is being conducted in

women. The agency expects that in an

active IND, studies that do not exclude

women or men with reproductive

potential will be underway or will

commence in a timely manner. To

clarify this expectation, the final rule

has been modified to state that a clinical

hold would not be ordered for a study

conducted only in men or only in

women, as long as a study that does not

exclude members of the other gender

with reproductive potential is being

conducted concurrently or will take

place within a reasonable time agreed

upon by the agency

(§ 312.42(b)(1)(v)(B)). FDA expects that a

discussion between the sponsor and the

agency concerning a reasonable time for

carrying out the study would take place

at a pre-IND meeting or with the

submission of the IND.

As stated in the proposed rule, this

amendment to the IND regulations

would not apply to clinical studies

conducted exclusively in healthy

volunteers (62 FR 49946 at 49951). The

final rule has been modified in

§ 312.42(b)(1)(v) by adding paragraph

(C) to clarify that the rule applies to

clinical investigations that are

conducted only in subjects who have

the disease or condition that the drug is

intended to treat.

III. Comments on the Proposed Rule

FDA received 26 letters, including

letters from manufacturers, individuals,

advocacy groups, and trade associations,

commenting on the proposed rule. The

majority of comments supported FDA’s

proposal to prohibit the exclusion of

women from investigational studies

through the clinical hold mechanism.

Many comments suggested changes that

would have narrowed or broadened the

proposal.