52138 Federal Register / Vol. 62, No. 193 / Monday, October 6, 1997 / Notices

withdrawn from sale for reasons of

safety or effectiveness (§ 314.162 (21

CFR 314.162)).

FDA regulations provide that any

person may petition the agency for a

determination as to whether a listed

drug has been voluntarily withdrawn

from sale for reasons of safety

effectiveness (§ 314.161(b) (21 CFR

314.161(b))). Richard A. Hamer

submitted a citizen petition dated May

24, 1996, under 21 CFR 10.25(a), 10.30,

and 314.122(a), requesting that the

agency determine whether

chlorhexidine gluconate topical tincture

0.5% (Hibitane) was withdrawn from

sale for reasons of safety or

effectiveness. Zeneca Pharmaceuticals

(formerly Steuart Pharmaceuticals and

ICI Americas) obtained approval of NDA

18–049 for chlorhexidine gluconate

topical tincture 0.5% on December 18,

1978, as a patient preoperative skin

preparation. The product was

withdrawn from sale by the sponsor in

early 1984. Because the sponsor

discontinued marketing of the product,

the agency currently lists chlorhexidine

gluconate topical tincture 0.5% in the

Orange Book’s ‘‘Discontinued Drug

Product List.’’

FDA has reviewed its records and,

under §§ 314.161 and 314.162(a)(2), has

determined that chlorhexidine

gluconate topical tincture 0.5% was

withdrawn from sale for reasons of

safety. Specifically, the product was

withdrawn because of the significant

number of reports received concerning

chemical and thermal burns associated

with the use of the product. Therefore,

chlorhexidine gluconate topical tincture

0.5% will be removed from the list of

drug products with effective approvals

published in FDA’s publication,

‘‘Approved Drug Products with

Therapeutic Equivalence Evaluations.’’

FDA will not accept ANDA’s that refer

to this drug product.

Dated: September 26, 1997.

William K. Hubbard,

Associate Commissioner for Policy

Coordination.

[FR Doc. 97–26353 Filed 10–3–97; 8:45 am]

BILLING CODE 4160–01–F

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

[Docket No. 97D–0410]

Guidance for Industry on SUPAC–MR,

Modified Release Solid Oral Dosage

Forms; Scale-Up and Postapproval

Changes for Chemistry,

Manufacturing, and Controls;

Availability

AGENCY: Food and Drug Administration,

HHS.

ACTION: Notice.

SUMMARY: The Food and Drug

Administration (FDA) is announcing the

availability of a guidance for industry

entitled ‘‘SUPAC–MR: Modified Release

Solid Oral Dosage Forms; Scale-Up and

Postapproval Changes: Chemistry,

Manufacturing, and Controls; In Vitro

Dissolution Testing and In Vivo

Bioequivalence Documentation.’’ The

purpose of this guidance document is to

provide insight and recommendations to

pharmaceutical sponsors of new drug

applications (NDA’s), abbreviated new

drug applications (ANDA’s), and

abbreviated antibiotic applications

(AADA’s) who intend to change the

components or composition, the

manufacturing (process or equipment),

the scale-up/scale-down of manufacture,

and/or the site of manufacture of a

modified release solid oral formulation

during the postapproval period. This

guidance document represents the

agency’s current thinking on scale-up

and postapproval changes (SUPAC) for

modified release solid oral dosage forms

regulated by the Center for Drug

Evaluation and Research (CDER).

DATES: Written comments may be

submitted at any time.

ADDRESSES: Submit written requests for

single copies of ‘‘SUPAC–MR: Modified

Release Solid Oral Dosage Forms; ScaleUp and Postapproval Changes:

Chemistry, Manufacturing, and

Controls; In Vitro Dissolution Testing

and In Vivo Bioequivalence

Documentation’’ to the Drug

Information Branch (HFD–210), Center

for Drug Evaluation and Research, Food

and Drug Administration, 5600 Fishers

Lane, Rockville, MD 20857. Send two

self-addressed adhesive labels to assist

that office in processing your requests.

Submit written comments on the

guidance document to the Dockets

Management Branch (HFA–305), Food

and Drug Administration, 12420

Parklawn Dr., rm. 1–23, Rockville, MD

20857.

FOR FURTHER INFORMATION CONTACT:

Mehul U. Mehta, Center for Drug

Evaluation and Research (HFD–860),

Food and Drug Administration, 5600

Fishers Lane, Rockville, MD 20857,

301–594–0501.

SUPPLEMENTARY INFORMATION: FDA is

announcing the availability of a

guidance for industry entitled ‘‘SUPAC–

MR: Modified Release Solid Oral Dosage

Forms; Scale-Up and Postapproval

Changes: Chemistry, Manufacturing,

and Controls; In Vitro Dissolution

Testing and In Vivo Bioequivalence

Documentation.’’ The purpose of this

guidance document is to provide insight

and recommendations to

pharmaceutical sponsors of NDA’s,

ANDA’s, and AADA’s who intend to

change: (1) The components or

composition; (2) the manufacturing

(process or equipment); (3) the scale-up/

scale-down of manufacture; and/or (4)

the site of manufacture of a modified

release solid oral formulation during the

postapproval period. The guidance

document defines the following: (1)

Levels of change; (2) recommended

chemistry, manufacturing, and controls

(CMC) tests to support each level of

change; (3) recommended in vitro

dissolution release tests and/or in vivo

bioequivalence tests to support each

level of change; and (4) documentation

to support the change.

For postapproval changes for

modified release dosage forms that

affect components and composition,

manufacturing process or equipment

changes, scale-up, and site change, this

guidance supersedes the

recommendations in section 4.G of the

Office of Generic Drugs Policy and

Procedure Guide 22–90 (FDA,

September 11, 1990). For all other

dosage forms and changes, this guidance

does not affect the recommendations in

Guide 22–90.

This guidance document represents

the agency’s current thinking on SUPAC

for modified release solid oral dosage

forms regulated by CDER. It does not

create or confer any rights for or on any

person and does not operate to bind

FDA or the public. An alternative

approach may be used if such approach

satisfies the requirements of the

applicable statute, regulations, or both.

Interested persons may, at any time,

submit written comments on the

guidance document to the Dockets

Management Branch (address above).

Two copies of any comments are to be

submitted, except that individuals may

submit one copy. Comments are to be

identified with the docket number

found in brackets in the heading of this

document. A copy of the guidance
Federal Register / Vol. 62, No. 193 / Monday, October 6, 1997 / Notices 52139

document and received comments may

be seen in the office above between 9

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

Friday.

An electronic version of this guidance

is also available on the Internet at http:/

/www.fda.gov/cder/guidance/

index.htm.

Dated: September 29, 1997.

William K. Hubbard,

Associate Commissioner for Policy

Coordination.

[FR Doc. 97–26412 Filed 10–3–97; 8:45 am]

BILLING CODE 4160–01–F

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Substance Abuse and Mental Health

Services Administration

Estimation Methodology for Children

With a Serious Emotional Disturbance

(SED)

AGENCY: Center for Mental Health

Services, Substance Abuse and Mental

Health Services Administration, HHS.

ACTION: Solicitation of comments.

SUMMARY: This notice describes the

proposed methodology for identifying

and estimating the number of children

with a serious emotional disturbance

(SED) within each State. This notice is

being served as part of the requirement

of Public Law 102–321, the ADAMHA

Reorganization Act of 1992.

COMMENT PERIOD: The Administrator is

requesting written comments which

must be received on or before December

5, 1997.

ADDRESSES: Comments should be sent to

Judith Katz-Leavy, M.Ed., Senior Policy

Analyst, Office of Policy, Planning, and

Administration, Center for Mental

Health Services, Parklawn Building

Room 15–87, 5600 Fishers Lane,

Rockville, MD 20857. (301) 443–1563

fax.

FOR FURTHER INFORMATION CONTACT: A

detailed paper outlining the estimation

methodology described here is available

from: Judith Katz-Leavy M.Ed., Senior

Policy Analyst, Office of Policy,

Planning, and Administration, Center

for Mental Health Services, Parklawn

Building Room 15–87, 5600 Fishers

Lane, Rockville, MD 20857. (301)443–

1563 fax.

Background

Public Law 102–321, the ADAMHA

Reorganization Act of 1992, amended

the Public Health Service Act and

created the Substance Abuse and Mental

Health Services Administration

(SAMHSA). The Center for Mental

Health Services (CMHS) was established

within SAMHSA to coordinate Federal

efforts in the prevention, treatment, and

promotion of mental health. Title II of

Public Law 102–321 establishes a Block

Grant for Community Mental Health

Services (Block Grant) administered by

CMHS, which permits the allocation of

funds to States for the provision of

community mental health services to

children with a serious emotional

disturbance and adults with a serious

mental illness. Public Law 102–321

stipulates that States estimate the

incidence (number of new cases) and

prevalence (total number of cases in a

year) in their applications for Block

Grant funds, see 42 U.S.C. 300 (2). The

statute also requires the Secretary to

establish definitions for adults with a

serious mental illness and children with

a serious emotional disturbance. In

addition, the Secretary is required to

develop standardized methods for the

states to use in providing the estimates

required as part of their block grant

applications. See 42 U.S.C. 300 (2). As

part of the process of implementing this

new block grant, definitions of the terms

‘‘children with a serious emotional

disturbance’’ and ‘‘adults with a serious

mental illness’’ were announced on May

20, 1993, in Federal Register Volume

58, No 96, p. 29422. Subsequently, a

group of technical experts was

convened by CMHS to develop an

estimation methodology to

‘‘operationalize the key concepts’’ in the

definition of children with a serious

emotional disturbance. A similar group

has prepared an estimation

methodology for adults with a serious

mental illness.

Serious Emotional Disturbance (SED)

The CMHS definition is that

‘‘children with serious emotional

disturbance’’ are persons:

—From birth up to age 18;

—Who currently or at any time during

the past year;

—Have had a diagnosable mental,

behavioral, or emotional disorder of

sufficient duration to meet diagnostic

criteria specified within DSM–III–R

—That resulted in functional

impairment which substantially

interferes with or limits the child’s

role or functioning in family, school,

or community activities (p.29425).

The definition goes on to indicate

that, ‘‘these disorders include any

mental disorder (including those of

biological etiology) listed in DSM–III–R

or their ICD–9–CM equivalent (and

subsequent revisions) with the

exception of DSM–III–R ‘V’ codes,

substance use, and developmental

disorders, which are excluded, unless

they co-occur with another diagnosable

serious emotional disturbance’’ (p.

29425).

Further, the definition indicates that,

‘‘Functional impairment is defined as

difficulties that substantially interfere

with or limit a child or adolescent from

achieving or maintaining one or more

developmentally-appropriate social,

behavioral, cognitive, communicative,

or adaptive skills. Functional

impairments of episodic, recurrent, and

continuous duration are included unless

they are temporary and expected

responses to stressful events in their

environment. Children who would have

met functional impairment criteria

during the referenced year without the

benefit of treatment or other support

services are included in this definition’’

(p. 29425).

The first decision that was made was

to focus on community epidemiological

studies done in the United States that

used either the DSM–III–R, or its

predecessor, the DSM–III, and that

provided information on the prevalence

of mental disorders using a structured

interview procedure. The group decided

that given the relatively small number of

community epidemiological studies that

had been conducted in the United

States, it would be a mistake to exclude

those few studies that had used the

DSM–III, given its considerable

similarity to the DSM–III–R.

The most frequently used structured

interview procedure was the Diagnostic

Interview Schedule for Children (DISC),

originally developed by A. Costello and

his colleagues (A. Costello, Edelbrock,

Dulcan, Kalas, & Klaric, l984), which

includes both child and parent versions.

Other interview procedures include the

Diagnostic Interview for Children and

Adolescents (DICA, Herjanic & Reich,

l982), the Child and Adolescent

Psychiatric Assessment (CAPA, Angold

& E. Costello, l995), and the Composite

International Diagnostic Interview (CIDI,

Kessler et al, 1994).

The group elected to consider that a

child met the criteria of a diagnosable

disorder either if a diagnosis was

obtained from his/her own report on the

structured interview, or from the

parent’s report on the structured

interview, or from the combination of

the youth’s report and the parent’s

report, even if neither one met the

criteria separately. While there are other

approaches to combining data from two

or more sources that were considered

and have been used (Cohen, Velez, &

Kohn, l987; Reich & Earls, 1987), the

group chose to use this ‘‘either/or’’

approach because it was believed that