39096 Federal Register / Vol. 63, No. 139 /Tuesday, July 21, 1998 / Notices

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

[Docket No. 98N–0517]

Development of Antimicrobial Drug

Products; Development and Use of

FDA Guidance Documents; Request

for Comments

AGENCY: Food and Drug Administration,

HHS.

ACTION: Notice; request for comments.

SUMMARY: The Food and Drug

Administration (FDA), Center for Drug

Evaluation and Research (CDER), Office

of Drug Evaluation IV (ODE IV), is

providing notice to drug manufacturers

regarding its current plans for revising

existing guidance documents and

preparing new guidance documents on

the development of antimicrobial drug

products for the treatment of infections.

ODE IV is reviewing, updating,

consolidating, and revising its existing

guidance documents and identifying

topics for future guidance. The agency

is requesting public comment on topics

for future guidance development.

DATES: Written comments may be

submitted by October 19, 1998. General

comments on agency guidance

documents are welcome at any time.

ADDRESSES: Copies of agency guidance

documents can be obtained on the

Internet at ‘‘http://www.fda.gov/cder/

guidance/index.htm’’. Submit written

comments to the Dockets Management

Branch (HFA–305), Food and Drug

Administration, 5630 Fishers Lane, rm.

1061, Rockville MD 20852. Comments

are to be identified with the docket

number found in brackets in the

heading of this document.

FOR FURTHER INFORMATION CONTACT:

Renata Albrecht, Center for Drug

Evaluation and Research (HFD–590),

Food and Drug Administration, 9201

Corporate Blvd., Rockville, MD 20850,

301–827–2336.

SUPPLEMENTARY INFORMATION:

I. Background

In the Federal Register of February

27, 1997 (62 FR 8961), FDA published

a notice explaining its policy for

guidance document development,

issuance, and use. The notice included

an agency document entitled ‘‘Good

Guidance Practices’’ (GGP’s), which sets

forth agency policies and procedures for

developing, issuing, and using guidance

documents. The GGP’s emphasize the

importance of gaining public input early

in the guidance development process.

Since the 1970’s the agency has

issued guidance in a variety of forms to

the pharmaceutical industry to facilitate

the development of antimicrobial drug

products. In addition to advice and

guidance provided verbally during

various industry and FDA meetings and

other interactions between the regulated

industry and FDA, or in individual

letters written to sponsors, general

written guidance has also been

provided. In 1977, the agency issued

guidance on the development of

antimicrobial drug products entitled

‘‘Clinical Evaluation of Anti-Infective

Drugs (Systemic).’’ In fulfillment of a

contract from FDA, in November 1992,

the Infectious Disease Society of

America (IDSA) published its

‘‘Guidelines for the Evaluation of AntiInfective Drug Products’’ in the

supplement of ‘‘Clinical Infectious

Disease’’ (formerly, ‘‘Reviews of

Infectious Diseases’’). That same month,

FDA’s Division of Anti-Infective Drug

Products issued ‘‘Points to Consider:

Clinical Development and Labeling of

Anti-Infective Drug Products’’ (1992) on

issues related to evaluating new drug

applications for anti-infective drug

products. All of these documents

contain information helpful for

designing clinical trial protocols for

evaluating the safety and effectiveness

of new therapies to treat infections and

gaining approval for supplemental

indications.

In 1996, in an attempt to outline in

more detail the elements the agency

considers important when evaluating

clinical studies, the agency initiated

efforts to develop guidance that would

provide investigators, academia, and

industry with insight on those elements

(often referred to as ‘‘evaluability

criteria’’) considered important during

the evaluation of clinical studies for

antimicrobial drug products. In March

1997, an early draft guidance, entitled

‘‘Evaluating Clinical Studies of

Antimicrobials in the Division of AntiInfective Drug Products,’’ was discussed

at an Anti-Infective Drug Products

Advisory Committee meeting. That early

draft contained an introduction and

individual sections addressing 12

specific indications. Space was reserved

to provide guidance at some later date

on approximately 15 additional

indications.

Since the 1997 advisory committee

meeting, several events have occurred

that affect how clinical trials are

designed, conducted, evaluated, and

reported and that are relevant to the

revision and development of guidance

on antimicrobial drug products. ODE IV,

which includes the Division of AntiInfective Drug Products, the Division of

Special Pathogens and Immunologic

Drug Products, and the Division of AntiViral Drug Products, reviewed all of its

guidance documents and determined

that certain revisions were necessary. In

November 1997, the Food and Drug

Administration Modernization Act of

1997 (Modernization Act) was enacted

(Pub. L. 105–115); it contains several

provisions related to drug development

and will lead to additional agency

guidance documents on a variety of

subjects relating to clinical trial design

and evaluation. For example, section

119 of the Modernization Act addresses

meetings and agreements concerning the

design and size of clinical trials. In

addition, in May 1998, the agency

published a guidance for industry

entitled ‘‘Providing Clinical Evidence of

Effectiveness for Human Drugs and

Biological Products’’ (63 FR 27093, May

15, 1998) that fulfills certain

requirements in section 403(b) of the

Modernization Act and that also has

implications for antimicrobial drug

products.

ODE IV is continuing its efforts to

develop comprehensive guidance on

evaluability criteria by reviewing,

updating, consolidating, and revising its

existing guidance documents, taking

into account these broader agency

initiatives. Specifically, the office is

deciding which elements of current

guidance documents remain applicable,

which elements need to be removed,

which elements need to be updated, and

which elements need to be added. In the

process, all guidances are being

developed consistent with the agency’s

GGP’s.

Throughout the 1990’s, ODE IV has

approached the development of

guidance in an open forum as part of its

advisory committee process. It wishes to

continue this public and transparent

process for guidance document

development. ODE IV generally expects

to include advisory committee review as

part of the process of reviewing and

developing guidance for industry on

antimicrobial drug development.

II. Guidance Development Plan

ODE IV has reviewed all existing,

relevant documents. Within the next

few months, ODE IV expects to issue a

general draft guidance that addresses

issues common to all indications and a

series of companion draft guidances that

address the following individual

indications:

1. Uncomplicated urinary tract

infections,

2. Uncomplicated skin and superficial

skin structure infections,

3. Complicated skin and soft tissue

infections,

4. Community-acquired pneumonia,

5. Nosocomial pneumonia,
Federal Register / Vol. 63, No. 139 /Tuesday, July 21, 1998 / Notices 39097

6. Acute bacterial exacerbation of

chronic bronchitis,

7. Secondary bacterial infection of

acute bronchitis,

8. Acute otitis media,

9. Acute uncomplicated gonorrhea,

10. Acute sinusitus,

11. Complicated urinary tract

infections and pyelonephritis,

12. Bacterial prostatitis,

13. Early Lyme disease,

14. Empiric therapy of febrile

neutropenia,

15. Vulvovaginal candidiasis,

16. Streptococcal pharyngitis and

tonsillitis,

17. Bacterial meningitis, and

18. Bacterial vaginosis.

Key aspects of these draft guidances will

be discussed in a July 1998 advisory

committee meeting. After the meeting,

ODE IV will work toward finalizing

these guidances.

The next step will involve developing

draft guidance documents for the

following proposed indications:

1. Nongonoccocal urethritis/cervicitis,

2. Endocarditis,

3. Uncomplicated intra-abdominal

infections,

4. Complicated intra-abdominal

infections,

5. Gynecologic infections (except

sexually transmitted disease and pelvic

inflammatory disease),

6. Pelvic inflammatory disease,

7. Osteomyelitis (acute and chronic),

8. Acute bacterial arthritis, and

9. Helicobacter pylori infections.

Once developed, the agency expects that

it will release the guidances in draft for

review and comment, with key elements

discussed before the advisory

committee.

ODE IV also is considering developing

guidance during the next few years for

the following agents:

1. Agents to treat opportunistic

infections related to AIDS;

2. Antimycobacterial agents;

3. Antifungal agents;

4. Antiparasitic agents;

5. Immunologic/transplant agents;

6. Antiviral agents;

7. Dermatologic surgical scrubs, etc.;

8. Agents to treat sepsis/septic shock;

and

9. Agents used in surgical

prophylaxis.

As with the other guidances, it is

expected that these guidances will first

be issued in draft for review and

comment and discussed before the

advisory committee.

III. Comments

ODE IV is seeking suggestions and

recommendations for future guidance

development. Interested persons may

submit comments 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. Received comments may be

seen in the office above between 9 a.m.

and 4 p.m., Monday through Friday.

Dated: July 13, 1998.

William K. Hubbard,

Associate Commissioner for Policy

Coordination.

[FR Doc. 98–19319 Filed 7–20–98; 8:45 am]

BILLING CODE 4160–01–F

DEPARTMENT OF HEALTH AND

HUMAN SERVICES

Food and Drug Administration

[Docket No. 97E–0358]

Determination of Regulatory Review

Period for Purposes of Patent

Extension; FlowmaxTM

AGENCY: Food and Drug Administration,

HHS.

ACTION: Notice.

SUMMARY: The Food and Drug

Administration (FDA) has determined

the regulatory review period for

FlowmaxTM and is publishing this

notice of that determination as required

by law. FDA has made the

determination because of the

submission of an application to the

Commissioner of Patents and

Trademarks, Department of Commerce,

for the extension of a patent which

claims that human drug product.

ADDRESSES: Written comments and

petitions should be directed to the

Dockets Management Branch (HFA–

305), Food and Drug Administration,

5630 Fishers Lane, rm. 1061, Rockville,

MD 20852.

FOR FURTHER INFORMATION CONTACT:

Brian J. Malkin, Office of Health Affairs

(HFY–20), Food and Drug

Administration, 5600 Fishers Lane,

Rockville, MD 20857, 301–827–6620.

SUPPLEMENTARY INFORMATION: The Drug

Price Competition and Patent Term

Restoration Act of 1984 (Pub. L. 98–417)

and the Generic Animal Drug and Patent

Term Restoration Act (Pub. L. 100–670)

generally provide that a patent may be

extended for a period of up to 5 years

so long as the patented item (human

drug product, animal drug product,

medical device, food additive, or color

additive) was subject to regulatory

review by FDA before the item was

marketed. Under these acts, a product’s

regulatory review period forms the basis

for determining the amount of extension

an applicant may receive.

A regulatory review period consists of

two periods of time: a testing phase and

an approval phase. For human drug

products, the testing phase begins when

the exemption to permit the clinical

investigations of the drug becomes

effective and runs until the approval

phase begins. The approval phase starts

with the initial submission of an

application to market the human drug

product and continues until FDA grants

permission to market the drug product.

Although only a portion of a regulatory

review period may count toward the

actual amount of extension that the

Commissioner of Patents and

Trademarks may award (for example,

half the testing phase must be

subtracted as well as any time that may

have occurred before the patent was

issued), FDA’s determination of the

length of a regulatory review period for

a human drug product will include all

of the testing phase and approval phase

as specified in 35 U.S.C. 156(g)(1)(B).

FDA recently approved for marketing

the human drug product FlowmaxTM

(tamsulosin hydrochloride). FlowmaxTM

is indicated for the treatment of the

signs and symptoms of benign prostatic

hyperplasia (BPH). Subsequent to this

approval, the Patent and Trademark

Office received a patent term restoration

application for FlowmaxTM (U.S. Patent

No. 4,703,063) from Yamanouchi

Pharmaceutical Co., Ltd., and the Patent

and Trademark Office requested FDA’s

assistance in determining this patent’s

eligibility for patent term restoration. In

a letter dated November 7, 1997, FDA

advised the Patent and Trademark

Office that this human drug product had

undergone a regulatory review period

and that the approval of FlowmaxTM

represented the first permitted

commercial marketing or use of the

product. Shortly thereafter, the Patent

and Trademark Office requested that the

FDA determine the product’s regulatory

review period.

FDA has determined that the

applicable regulatory review period for

FlowmaxTM is 3,529 days. Of this time,

3,163 days occurred during the testing

phase of the regulatory review period,

366 days occurred during the approval

phase. These periods of time were

derived from the following dates:

1. The date an exemption under

section 505 of the Federal Food, Drug,

and Cosmetic Act (the act) (21 U.S.C.

355) became effective: August 19, 1987.

FDA has verified the applicant’s claim

that the date the investigational new

drug application became effective was

on on August 19, 1987.