[Federal Register Volume 61, Number 223 (Monday, November 18, 1996)]
[Notices]
[Pages 58694-58695]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-29486]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES
[Docket No. 96N-0425]


Paclitaxel Drug Products; Environmental Information Needed in New 
Drug Applications, Abbreviated New Drug Applications, and 
Investigational New Drug Applications

AGENCY:  Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is issuing this 
document to clarify the environmental information that must be 
submitted to the Center for Drug Evaluation and Research (CDER) for 
drug products containing paclitaxel. Paclitaxel is an active moiety 
that may be obtained or derived from various wild or cultivated species 
of yews. Under the National Environmental Policy Act (NEPA), all 
Federal agencies are required to assess the environmental impacts of 
their actions and to ensure that the interested and affected public is 
informed of environmental analyses. This action is being taken to 
ensure that environmental factors regarding paclitaxel drug products 
are adequately assessed.

FOR FURTHER INFORMATION CONTACT: Nancy B. Sager, Center for Drug 
Evaluation and Research (HFD-357), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-594-5721.

SUPPLEMENTARY INFORMATION:

I. Background

    NEPA requires all Federal agencies to assess the environmental 
impacts of their actions and to ensure that the interested and affected 
public is informed of environmental analyses. FDA is required under 
NEPA to consider the environmental impacts of approving drug product 
applications as an integral part of its regulatory process. FDA's 
regulations in 21 CFR part 25 specify that environmental assessments 
(EA's) or abbreviated environmental assessments (AEA's) must be 
submitted as part of NDA's, antibiotic drug applications, ANDA's, 
AADA's, IND's, and for other various actions described under 
Sec. 25.22, unless the action qualifies for a categorical exclusion 
under Secs. 25.23 and 25.24. FDA's regulations at Sec. 25.23(c) provide 
that a person submitting an application for an action that falls within 
a class that qualifies for a categorical exclusion shall specify the 
provision that excludes the action from the requirement for an EA. FDA 
may require an applicant to provide information that establishes to the 
agency's satisfaction that the action requested is included within an 
excluded category and meets the criteria for the applicable exclusion 
(Sec. 25.23(c)). FDA will require an EA for any specific action that 
ordinarily is excluded if the agency has sufficient evidence to 
establish that the specific proposed action may significantly affect 
the quality of the human environment (Sec. 25.23(b)). In the Federal 
Register of January 11, 1996 (61 FR 1031), FDA announced the 
availability of a CDER guidance document entitled ``Guidance for 
Industry for the Submission of an Environmental Assessment in Human 
Drug Applications and Supplements'' (Guidance for Industry). The 
document was intended to provide guidance on how to prepare EA's for 
submission to

[[Page 58695]]

CDER in NDA's, antibiotic drug applications, ANDA's, AADA's, and IND's.

II. Paclitaxel Drug Products

    The following clarifies the environmental information that must be 
submitted to CDER for drug products containing paclitaxel. For the 
purposes of the following discussion, ``applications'' is defined as 
IND's that are expected to enroll cumulatively 200 or more subjects, 
NDA's, and ANDA's.
    In accordance with FDA's NEPA regulations (21 CFR part 25) and the 
Guidance for Industry, a person who submits an NDA, ANDA, or IND 
involving drug products containing paclitaxel shall include an EA for 
the requested action in the applicable format, unless the action 
qualifies for a categorical exclusion under Secs. 25.23 and 25.24. In 
accordance with Sec. 25.23(c), FDA will require those persons 
submitting applications involving drug products containing paclitaxel 
derived from natural sources to identify the sources of paclitaxel so 
that FDA can determine whether an EA is required.
    FDA will treat all applications involving paclitaxel derived from 
or otherwise involving Pacific yew trees (Taxus brevifolia) as 
requiring the preparation of EA's. Accordingly, FDA will require 
persons to prepare and submit to the FDA EA's for applications 
involving paclitaxel derived from or otherwise involving the Pacific 
yew. The EA's shall, among other things, identify all sources of 
Pacific yew which are expected to be harvested in connection with the 
manufacture of paclitaxel relating to the application. The EA's shall, 
among other things, include a discussion of the anticipated 
environmental impacts of such harvests, measures that may be taken to 
mitigate adverse impacts, and reasonable alternatives. See in 
particular, format items 4, 9, 10 and 11, at Sec. 25.31a. If the 
harvest took place prior to the issuance of this Federal Register 
notice, the EA's shall discuss, among other things, each such matter 
including mitigation measures that are still available. FDA will 
require this information in all future applications involving 
paclitaxel derived from or otherwise involving the Pacific yew and for 
all such applications which have not been finally acted upon by FDA by 
November 18, 1976.
    FDA will subject such EA's to the NEPA process, and will complete 
and issue an EA and finding of no significant impact (FONSI) in 
accordance with Secs. 25.32 and 25.42, or an environmental impact 
statement (EIS) and record of decision (ROD) in accordance with 
Secs. 25.34 and 25.42, as required by NEPA, before approving any NDA or 
ANDA involving paclitaxel derived from or otherwise involving the 
Pacific yew tree. FDA will also subject such EA's for IND's involving 
paclitaxel derived from or otherwise involving the Pacific yew to the 
NEPA process, provided that in cases in which the IND involves 
treatment of subjects with serious or life-threatening disease, as 
determined by the FDA, the FDA, where NEPA permits, will not place the 
IND on clinical hold pending the completion of environmental 
documentation required by NEPA.
    FDA is committed to assuring that assessment of environmental 
factors continues throughout the planning process and is integrated 
with other program planning at the earliest possible time to ensure 
that planning and decisions reflect environmental values (Sec. 25.10). 
As provided by FDA regulations under Sec. 25.22(b), ``Failure to submit 
an adequate EA, if one is required, . . . is sufficient grounds for FDA 
to refuse to file or approve the application or petition.''
    EA's, FONSI's, EIS's and ROD's for drug products containing 
paclitaxel and other pertinent environmental information relating to 
approvals of drug products containing paclitaxel will be filed in 
Docket No. 92N-0489. This docket was previously established as a 
repository of environmental information relating to the first approval 
of a paclitaxel drug product (Taxol, NDA 20-262).

    Dated: November 12, 1996.
William B. Schultz,
Deputy Commissioner for Policy.
[FR Doc. 96-29486 Filed 11-15-96; 8:45 am]
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