27094 Federal Register / Vol. 63, No. 94 / Friday, May 15, 1998 / Notices

Drug, and Cosmetic Act (the act) (21

U.S.C. 355(d)) to clarify that FDA, at its

discretion, may make exception to the

general requirement that there must be

more than one adequate and wellcontrolled investigation to support an

effectiveness determination. Section 115

of the Modernization Act provides in

relevant part that ‘‘[i]f the [agency]

determines, based on relevant science,

that data from one adequate and wellcontrolled clinical investigation and

confirmatory evidence (obtained prior to

or after such investigation) are sufficient

to establish effectiveness, the [agency]

may consider such data and evidence to

constitute substantial evidence [of

effectiveness].’’

In clarifying the standard for

substantial evidence, Congress

acknowledged the agency’s position that

there have been major advances in the

science and practice of clinical drug

development since the effectiveness

requirement was added to the act in

1962, and confirmed FDA’s

interpretation of the substantial

evidence of effectiveness standard, as

explained in the draft guidance

document.

In addition to the provision on the

evidence standard, the Modernization

Act included section 403, ‘‘Approval of

Supplemental Applications for

Approved Products.’’ Section 403(a) of

the Modernization Act requires FDA to

publish in the Federal Register, within

180 days of enactment, standards for the

prompt review of supplemental

applications for drugs and biological

products. These standards are included

in a guidance document for which a

notice of availability is published

elsewhere in this issue of the Federal

Register.

Section 403(b) of the Modernization

Act requires that FDA, within 180 days

of enactment, issue final guidances to

clarify the requirements for, and

facilitate the submission of data to

support, the approval of supplemental

applications for drugs and biologics.

The guidance issued today fulfills this

statutory requirement as it addresses the

data requirements for both original drug

and biological product applications and

supplements to those applications.

In addition, section 403(b)(1) of the

Modernization Act requires that FDA

provide guidance to ‘‘clarify

circumstances in which published

matter may be the basis for approval of

a supplemental application.’’ Section III

of the guidance describes the

circumstances in which a sponsor may

rely in part, or entirely, on published

reports of studies to support approval of

a supplemental application.

Section 403(b)(2) of the

Modernization Act requires that FDA

provide guidance to ‘‘specify data

requirements that will avoid duplication

of previously submitted data by

recognizing the availability of data

previously submitted in support of an

original application.’’ Section II of the

guidance describes a range of

circumstances in which existing data,

whether or not previously submitted to

an original application, may be used to

support an application for a

supplemental indication, thus

permitting a sponsor to avoid

developing unnecessary additional data.

The agency received 13 submissions

commenting on the draft guidance,

including comments from

pharmaceutical and biological products

companies and their trade associations,

individuals and organizations in

academic medicine and clinical

pharmacology, patient advocacy

organizations, and a consumer. The

response to the draft guidance was

generally favorable. The guidance was

viewed as a significant step forward by

the agency in clarifying and better

articulating its quantitative and

qualitative evidentiary standards for

evidence of effectiveness. Comments

observed that the principles espoused

were scientifically reasonable, practical,

and appropriately flexible. The agency

has considered all of the comments in

making revisions to the guidance

document.

This guidance document is being

issued as a Level 1 guidance consistent

with FDA’s good guidance practices (62

FR 8961, February 27, 1997). It

represents the agency’s current thinking

on clinical evidence of effectiveness for

human drug and biological products. 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.

Submit written requests for single

copies of the guidance for industry

entitled ‘‘Providing Clinical Evidence of

Effectiveness for Human Drug and

Biological Products’’ to the Drug

Information Branch (HFD–210), Center

for Drug Evaluation and Research, Food

and Drug Administration, 5600 Fishers

Lane, Rockville, MD 20857; or the Office

of Communication, Training and

Manufacturers Assistance (HFM–40),

Center for Biologics Evaluation and

Research (CBER), Food and Drug

Administration, 1401 Rockville Pike,

Rockville, MD 20852–1448. Please send

one self-addressed adhesive label to

assist the offices in processing your

request. The document may also be

obtained by mail by calling the CBER

Voice Information System at 1–800–

835–4709 or 301–827–1800, or by fax by

calling the CBER FAX Information

System at 1–888–CBERFAX or 301–

827–3844.

Interested persons may at any time

submit written comments on the

guidance to the Dockets Management

Branch (address above). Requests and

comments should be identified with the

docket number found in brackets in the

heading of this notice. A copy of the

guidance and received comments may

be seen in the office above between 9

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

Friday.

Dated: May 8, 1998.

William B. Schultz,

Deputy Commissioner for Policy.

[FR Doc. 98–12901 Filed 5–14–98; 8:45 am]

BILLING CODE 4160–01–F

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

[Docket No. 97D–0214]

Guidance for Industry on

Pharmacokinetics in Patients with

Impaired Renal Function—Study

Design, Data Analysis, and Impact on

Dosing and Labeling; 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 ‘‘Pharmacokinetics in Patients

with Impaired Renal Function—Study

Design, Data Analysis, and Impact on

Dosing and Labeling.’’ The guidance is

intended for sponsors planning to

conduct studies to assess the influence

of renal impairment on the

pharmacokinetics of an investigational

drug.

DATES: General comments on agency

guidance documents are welcome at any

time.

ADDRESSES: Copies of this guidance are

available on the Internet at ‘‘http://

www.fda.gov/cder/guidance/

index.htm’’, or ‘‘http://www.fda.gov/

cber/guidelines.htm’’. Submit written

requests for single copies of

‘‘Pharmacokinetics in Patients with

Impaired Renal Function—Study

Design, Data Analysis, and Impact on

Dosing and Labeling’’ to the Drug

Information Branch (HFD–210), Center

for Drug Evaluation and Research, Food
Federal Register / Vol. 63, No. 94 / Friday, May 15, 1998 / Notices 27095

and Drug Administration, 5600 Fishers

Lane, Rockville, MD 20857, or Office of

Communication, Training and

Manufacturers Assistance (HFM–40),

1401 Rockville Pike, Rockville, MD

20852–1448, or by calling 1–800–835–

4709 or 301–827–1800. Submit written

comments on the guidance to the

Dockets Management Branch (HFA–

305), Food and Drug Administration,

12420 Parklawn Dr., rm. 1–23,

Rockville, MD 20857.

FOR FURTHER INFORMATION CONTACT:

Shiew-Mei Huang, Center for Drug

Evaluation and Research (HFD–

850), Food and Drug

Administration, 5600 Fishers Lane,

Rockville, MD 20857, 301–594–

5671; or

Martin D. Green, Center for Biologics

Evaluation and Research (HFM–

579), 1401 Rockville Pike,

Rockville, MD 20852–1448, 301–

827–5344.

SUPPLEMENTARY INFORMATION: FDA is

announcing the availability of a

guidance entitled ‘‘Pharmacokinetics in

Patients with Impaired Renal

Function—Study Design, Data Analysis,

and Impact on Dosing and Labeling.’’

The pharmacokinetics (PK) and

pharmacodynamics (PD) of drugs

primarily eliminated through the

kidneys may be altered by impaired

renal function to the extent that the

dosage regimen needs to be changed

from that used in patients with normal

renal function. Although the most

obvious type of change arising from

renal impairment is a decrease in renal

excretion (or possibly renal metabolism)

of a drug or its metabolites, renal

impairment also has been associated

with other changes, such as changes in

hepatic metabolism, plasma protein

binding, and drug distribution. These

changes may be particularly prominent

in patients with severely impaired renal

function and have been observed even

when the renal route is not the primary

route of elimination of a drug. Thus, for

most drugs that are likely to be

administered to patients with renal

impairment, PK characterization may

need to be assessed in subjects with

such impairment to provide appropriate

dosing recommendations.

The guidance provides specific

information on when studies of PK in

patients with impaired renal function

should be performed and when they

may be unnecessary. It also addresses

the design and conduct of PK studies in

patients with impaired renal function,

the design and conduct of PK studies in

end stage renal disease patients treated

with dialysis, the analysis and reporting

of the results of such studies, and

representation of these results in

approved product labeling.

In the Federal Register of June 16,

1997 (62 FR 32617), FDA announced the

availability of a draft version of this

guidance, entitled ‘‘Pharmacokinetics

and Pharmacodynamics in Patients with

Impaired Rental Function: Study

Design, Data Analysis, and Impact on

Dosing and Labeling.’’ The June 16,

1997, document gave interested persons

an opportunity to submit comments

through August 15, 1997. All comments

received through the end of September

have been carefully reviewed and

incorporated, where appropriate, in this

revised guidance.

This guidance is being issued as a

Level 1 guidance consistent with FDA’s

good guidance practices (62 FR 8961,

February 27, 1997). It represents the

agency’s current thinking on conducting

PK studies on patients with impaired

renal function. 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

requirement of the applicable statute,

regulations, or both.

Interested persons may, at any time,

submit written comments on the

guidance to the Dockets Management

Branch (address above). Comments

should be identified with the docket

number found in brackets in the

heading of this document. A copy of the

guidance is available for public

examination in the Dockets

Management Branch between 9 a.m. and

4 p.m., Monday through Friday.

Dated: May 8, 1998.

William K. Hubbard,

Associate Commissioner for Policy

Coordination.

[FR Doc. 98–12898 Filed 5–14–98; 8:45 am]

BILLING CODE 4160–01–F

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

National Institutes of Health

Government-Owned Inventions;

Availability for Licensing

AGENCY: National Institutes of Health,

Public Health Service, DHHS.

ACTION: Notice.

SUMMARY: The inventions listed below

are owned by agencies of the U.S.

Government and are available for

licensing in the U.S. in accordance with

35 U.S.C. 207 to achieve expeditious

commercialization of results of

federally-funded research and

development. Foreign patent

applications are filed on selected

inventions to extend market coverage

for companies and may also be available

for licensing.

ADDRESSES: Licensing information and

copies of the U.S. patent applications

listed below may be obtained by writing

to the indicated licensing contact at the

Office of Technology Transfer, National

Institutes of Health, 6011 Executive

Boulevard, Suite 325, Rockville,

Maryland 20852–3804; telephone 301/

496–7057; fax: 301/402–0220. A signed

Confidential Disclosure Agreement will

be required to receive copies of the

patent applications.

Molecular Computing Elements: Gates

and Flip-Flops

TD Schneider, PN Hengen (NCI)

DHHS Reference No. E–170–97/0 filed

Feb. 20, 1998

Licensing Contact: John Fahner-Vihtelic,

301/496–7735 ext. 270

The present invention is a method

and apparatus for molecular computing

which provides for molecular logic

devices analogous to those of electronic

computers, such as flip-flops, AND

gates, etc. Coupling of the gates allows

for molecular computing. The method

allows data storage, the transformation

of binary information and signal

readout. Possible applications include

encoding ‘‘read only’’ memory for

microscopic identifiers, digital control

of gene expression, and quantification of

analytes. The computing elements also

provide means for complex regulation of

gene expression.

Lipooligosaccharide-Based Vaccine for

the Prevention of Moraxella

(Branhamella) Catarrhalis Infections In

Humans

X–X Gu, JB Robbins (NIDCD)

Serial No. 60/071,483 filed Jan 13, 1998

Licensing Contact: Robert Benson, 301/

496–7056 ext. 267

This invention is a vaccine for the

prevention of disease caused by M.

catarrhalis, which is the third most

common causative agent of otitis media

(middle ear infection) and sinusitis in

children. The emergence of antibiotic

resistant bacteria has caused concern

that treatment of otitis media will

become more problematic. This

invention offers a new approach to

managing otitis media. The vaccine is

composed of lipooligosaccharide (LOS),

isolated from the surface of strains of M.

catarrhalis and detoxified by removing

esterified fatty acids to produce

detoxified LOS (dLOS), which is then

conjugated to an immunogenic protein

carrier such as tetanus toxiod. The

conjugates have been shown to be

nontoxic by the limulus amebocyte