Guidance for Industry

Q & A

Content and Format of INDs for Phase 1 Studies

of Drugs, Including

Well-Characterized, Therapeutic,

Biotechnology-Derived Products

U.S. Department of Health and Human Services

Food and Drug Administration

Center for Drug Evaluation and Research (CDER)

Center for Biological Evaluation and Research (CBER)

October 2000

Pharmacology/Toxicology
Guidance for Industry

Q & A

Content and Format of INDs for Phase 1 Studies of

Drugs, Including Well-Characterized, Therapeutic,

Biotechnology-Derived Products

Additional copies are available from:

Office of Training and Communications

Division of Communications Management

Drug Information Branch, HFD-210

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Rockville, MD 20857

(Tel) 301-827-4573

(Internet) http://www.fda.gov/cder/guidance/index.htm

or

 Office of Communication, Training and

Manufacturers Assistance, HFM-40

Center for Biologics Evaluation and Research

 Food and Drug Administration

1401 Rockville Pike, Rockville, MD 20852-1448

Internet: http://www.fda.gov/cber/guidelines.htm.

Fax: 1-888-CBERFAX or 301-827-3844

Mail: the Voice Information System at 800-835-4709 or 301-827-1800

U.S. Department of Health and Human Services

Food and Drug Administration

Center for Drug Evaluation and Research (CDER)

Center for Biological Evaluation and Research (CBER)

October 2000

Pharmacology/Toxicology
Guidance for Industry1

Q & A on

Content and Format of INDs for Phase 1 Studies of Drugs,

Including Well-Characterized, Therapeutic,

 Biotechnology-Derived Products

I. INTRODUCTION

This guidance is intended to clarify when sponsors should submit final, quality-assured toxicology

reports and/or update the Agency on any changes in findings since submission of non-quality-assured

reports or reports based on non-quality-assured data.

In November 1995, FDA published a guidance for industry entitled Content and Format of

Investigational New Drug Applications (INDs) for Phase 1 Studies of Drugs, Including WellCharacterized, Therapeutic, Biotechnology-Derived Products. The guidance states that

If final, fully quality-assured individual study reports are not available at the time of

IND submission, an integrated summary report of toxicologic findings based on the

unaudited draft toxicologic reports of completed animal studies may be

submitted.... [...] full toxicology department individual study reports should be

available to FDA, upon request, and individual study reports should be available to

FDA, upon request, as final, fully quality-assured documents within 120 days of

the start of the human study... [emphasis added].

If the integrated summary is based upon unaudited draft reports, sponsors should

submit an update to their integrated summary 120 days after the start of the human

study(ies)....2

 

1

 This guidance has been prepared by the Pharmacology and Toxicology staff, Office of Review Management ORM),

Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) in

the Food and Drug Administration.

This guidance represents the Food and Drug Administration=s current thinking on this topic. 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

statutes, regulations, or both.
There has been some confusion over when the 120-day clock starts, specifically, whether it means 120

days after the start of the clinical trial, or 120 days after the submission of the toxicology information.

Q: How does FDA measure the start of the 120-day period within which sponsors should

submit updates to their integrated summaries?

A: The Agency measures the 120-day period based on the Agency's receipt (date of receipt

stamped on the IND submission) of the integrated summary report including the toxicology

information. If the sponsor does not submit the final, quality-assured report and update at this

time, the sponsor should make the final, quality-assured report available upon the request of the

Agency and update the Agency on any changes in the findings. In any case, the final, qualityassured report should be submitted with the NDA.

The Agency believes that 120 days from submission of an integrated toxicology summary should

provide sponsors with adequate time to complete a final, quality-assured document. Because the

Agency assumes that clinical studies will generally be initiated immediately following the initial 30-day

clock (or upon submission of the protocol for an existing IND), the intention of the 120-day allowance

is to encourage the initiation of clinical studies by, in effect, allowing earlier submissions of clinical

protocols based on unaudited reports.

 

2

 See guidance, section III(G)(2), Toxicology: Integrated Summary.