[Federal Register Volume 67, Number 206 (Thursday, October 24, 2002)]
[Notices]
[Pages 65358-65359]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 02-27096]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 01E-0363]


Determination of Regulatory Review Period for Purposes of Patent 
Extension; MIFEPREX; Amendment

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice; amendment.

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SUMMARY: The Food and Drug Administration (FDA) is amending a previous 
determination of the regulatory review period for MIFEPREX that 
appeared in the Federal Register of January 25, 2002 (67 FR 3724). The 
agency is taking this action in response to received comments. FDA is 
publishing notice of that amendment as required by law.

ADDRESSES: Submit written comments to the Dockets Management Branch 
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852. Submit electronic comments to http://www.fda.gov/dockets/ecomments.

FOR FURTHER INFORMATION CONTACT: Claudia V. Grillo, Office of 
Regulatory Policy (HFD-007), Food and Drug Administration, 5600 Fishers 
Lane, Rockville, MD 20857, 301-827-4565.

SUPPLEMENTARY INFORMATION: In the Federal Register of January 25, 2002 
(67 FR 3724), FDA published its determination of the regulatory review 
period for MIFEPREX. On June 10, 2002, Corcept Therapeutics, Inc., 
(Corcept) filed a request for revision of the regulatory review period. 
On July 2, 2002, the applicant filed a comment, disagreeing with 
Corcept's request and maintaining that FDA's initial determination was 
correct.
    The basis of Corcept's request is that August 4, 1994, is not the 
correct date an investigational new drug application (IND) covering the 
approved drug product became effective. Corcept asserts that June 13, 
1983, is the appropriate date. FDA has re-examined its records and has 
determined that Corcept is correct. The date an exemption under section 
505 of the Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 
355) became effective is June 13, 1983.
    The agency, the applicant, and Corcept agree that the relevant IND 
is IND 22,047. All agree that IND 22,047 became effective in 1983.
    The applicant's argument for keeping the initial determination is 
based on the claim that August 4, 1994, represents the date the IND 
first covered the ``approved human drug product.'' While acknowledging 
that IND 22,047 became effective in 1983, the applicant observes that 
during the next several years the only studies conducted were studies 
of mifepristone alone, that is, not in conjunction with the 
administration of other drugs. The 1994 date is when the applicant 
submitted an amendment to IND 22,047 to initiate studies of 
mifepristone when followed by the later

[[Page 65359]]

administration of misoprostol. The final approved MIFEPREX labeling 
recommends that patients taking mifepristone take 400 micrograms of 
misoprostol 2 days after taking mifepristone unless a complete abortion 
has already been confirmed before that time. The applicant argues from 
these facts that the submission of the 1994 amendment represents the 
first time an IND for the ``approved human drug product,'' as set forth 
in 21 CFR 60.22(a)(1), became effective.\1\
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    \1\ For purposes of part 60 (21 CFR part 60), ``human drug 
product'' is defined as ``the active ingredient of a new drug or 
human biologic product (as those terms are used in the act and the 
Public Health Service Act), including any salt or ester of the 
active ingredient, as a single entity or in combination with another 
active ingredient.'' (See 21 CFR 60.3(b)(10).)
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    The investigational path of a new drug is rarely straightforward. 
From the time of the first submission of an IND to the time, usually 
years later, of final approval for marketing, the course of drug 
investigation goes up many blind alleys and frequently takes off in new 
directions. Rarely, if ever, is a drug approved under precisely the 
same conditions (i.e., indication(s), patient population(s), dosing 
regimen(s), duration of treatment, use in conjunction with other drugs, 
etc.) for which it is initially investigated. The decision to 
investigate MIFEPREX in conjunction with misoprostol under certain 
circumstances is typical of the kind of change that can occur in the 
investigation of a new drug.\2\
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    \2\ The applicant tries to characterize MIFEPREX as mifepristone 
``in combination with another active ingredient'' in an attempt to 
take advantage of portions of the definition of ``human drug 
product'' in 35 U.S.C. 156(f), that is, a human drug product means 
``the active ingredient of a new drug * * * as a single entity or in 
combination with another active ingredient.'' The applicant points 
to the definition of ``combination product'' at 21 CFR 3.2(e)(3) in 
this effort. A more useful description of a drug ``in combination 
with another active ingredient'' is found at 21 CFR 300.50 (two or 
more drugs combined in a single dosage form). MIFEPREX is not 
mifepristone ``in combination with another active ingredient.'' 
MIFEPREX is single entity mifepristone.
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    The applicant misperceives the nature of FDA's task in this kind of 
proceeding, one FDA has performed hundreds of times since 1984. A 
determination of the regulatory review period under 35 U.S.C. 
156(g)(1)(B) is straightforward and largely ministerial in nature. Our 
role is not to probe a drug's investigational course and determine at 
what point in that course emerges the ``approved human drug product.'' 
To do so would be to insert into a purely ministerial function an 
arbitrary element of uncertainty that would clearly subvert the purpose 
of the statute.\3\
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    \3\ Indeed, using the kind of scrutiny recommended by the 
applicant, one could argue that the testing phase should be entirely 
disregarded for purposes of regulatory review period determinations 
because final labeling of any product, an essential element of an 
approved human drug product, is not established until well after the 
testing phase is complete.
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    The relevant IND became effective on June 13, 1983. That fact, upon 
which everyone agrees, is all that FDA need or should find in 
conducting the relevant portion of its regulatory review determination 
of MIFEPREX.\4\
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    \4\ In our initial determination, we did not take into account 
the effect of 35 U.S.C. 156(g)(4)(C) and, instead, accepted as 
harmless the applicant's request for a later date.
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    Therefore, FDA has determined that the applicable regulatory review 
period for MIFEPREX is 6,318 days. Of this time, 4,662 days occurred 
during the testing phase of the regulatory review period, while 1,656 
days occurred during the approval phase.
    These periods of time were derived from the following dates, 
summarized from the January 25, 2002, notice and modified by this 
amendment:
    1. The date an exemption under section 505 of the act (21 U.S.C. 
355) became effective: June 13, 1983. The applicant claims August 3, 
1994, as the date the IND became effective. However, for the reasons 
discussed previously, FDA has determined the IND effective date was 
June 13, 1983.
    2. The date the application was initially submitted with respect to 
the human drug product under section 505 of the act: March 18, 1996. 
FDA has verified the applicant's claim that the new drug application 
(NDA) for MIFEPREX (NDA 20-687) was initially submitted on March 18, 
1996.
    3. The date the application was approved: September 28, 2000. FDA 
has verified the applicant's claim that NDA 20-687 was approved on 
September 28, 2000.
    This determination of the regulatory review period establishes the 
maximum potential length of a patent extension. In its application for 
patent extension, the applicant seeks 1,825 days of patent term 
extension. However, the U.S. Patent and Trademark Office applies 
several statutory limitations in its calculations of the actual period 
for patent extension.

    Dated: October 16, 2002.
Jane A. Axelrad,
Associate Director for Policy, Center for Drug Evaluation and Research.
[FR Doc. 02-27096 Filed 10-22-02; 8:45 am]
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