Guidance for Industry1
Q & A
Content and Format of INDs for Phase 1 Studies of Drugs, Including Well-Characterized,
Therapeutic, Biotechnology-Derived Products
[PDF version of this document]
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
Additional copies are available from:
Office of Training and Communications
Division of Communications Management
Drug Information Branch, HFD-210
5600 Fishers Lane
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
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.
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 Well-Characterized,
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
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, quality-assured 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.
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.
2 See
guidance, section III(G)(2), Toxicology: Integrated Summary.
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Last Updated: March 08, 2001
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