Document ID: FDA-2008-N-0549-0001
Agency: fda
Document Type: Notice
Title: Opportunity for Hearing on a Proposal to Withdraw Approval of Prescription Polyethylene Glycol 3350 Abbreviated New Drug Applications
Posted Date: 2008-10-24T04:00Z

[Federal Register: October 24, 2008 (Volume 73, Number 207)]
[Notices]               
[Page 63491-63495]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr24oc08-92]                         

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2008-N-0549]

 
Opportunity for Hearing on a Proposal to Withdraw Approval of 
Prescription Polyethylene Glycol 3350 Abbreviated New Drug Applications

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is proposing to 
withdraw approval of the following abbreviated new drug applications 
(ANDAs) for drug products containing polyethylene glycol 3350 (PEG 
3350) labeled for prescription only use: ANDA 76-652 held by Schwarz 
Pharma, Inc.; ANDA 77-736 held by Kali Laboratories, Inc.; ANDA 77-706 
held by Nexgen Pharma Inc. (formerly known as Anabolic Laboratories, 
Inc.); ANDA 77-893 held by Coastal Pharmaceuticals, Inc.; and ANDA 77-
445 held by Teva Pharmaceutical Industries, Ltd. (collectively, the PEG 
3350 ANDAs). The proposal is based on the switch of MiraLax from 
prescription only (``Rx only'') to over-the-counter (OTC) use. This 
switch was pursuant to the submission of a new drug application (NDA) 
for MiraLax (NDA 22-015), which was approved by the agency on October 
6, 2006, establishing that PEG 3350 may be used safely and effectively 
without the supervision of a licensed healthcare professional. The 
Federal Food, Drug, and Cosmetic Act (the act) does not permit both Rx 
and OTC versions of the same drug product to be marketed at the same 
time. Under the act, a drug to which the prescription provisions of the 
act do not apply (i.e., an OTC drug) shall be deemed to be misbranded 
if at any time prior to dispensing the label of the product bears the 
``Rx only'' symbol. Because the PEG 3350 generic drug products are 
labeled as Rx only, they are misbranded and may not be legally 
marketed. Thus, FDA is proposing to withdraw their approval.

DATES: Submit written or electronic requests for a hearing by November 
24, 2008; submit data and information in support of the hearing request 
by December 23, 2008. Submit written or electronic comments by December 
23, 2008.

ADDRESSES: Submit written requests for a hearing, any data and 
information justifying a hearing, and any other comments identified 
with Docket No. FDA-2008-N-0549 to the Division of Dockets Management 
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, 
Rockville, MD 20852. Submit electronic requests for a hearing, any data 
and information justifying a hearing, and any other comments identified 
with Docket No. FDA-2008-N-0549 to http://www.regulations.gov.

FOR FURTHER INFORMATION CONTACT: Elizabeth Sadove, Center for Drug 
Evaluation and Research (HFD-7), Food and Drug Administration, 10903 
New Hampshire Ave., Bldg.51, rm. 6368, Silver Spring, MD 20993-0002, 
301-796-3601.

SUPPLEMENTARY INFORMATION:

I. Background

A. Original Approval of MiraLax NDA and Subsequent ANDA Products

    MiraLax is an osmotic laxative containing the active ingredient 
polyethylene glycol 3350. MiraLax was approved as a prescription drug 
on February 18, 1999, under Braintree Laboratories, Inc. (Braintree), 
NDA 20-698, for up to 14 days of use for the treatment of occasional 
constipation in adults. In patients with a history of constipation, 
MiraLax therapy increases the volume and frequency of bowel movements. 
The approved prescription dosing and administration regimen stated:
     ``The usual dose is 17 grams (about 1 heaping tablespoon) 
of powder per day (or as directed by physician) in 8 ounces of water. 
Each bottle of MiraLax is supplied with a measuring cap marked to 
contain 17 grams of laxative powder when filled to the indicated line.
     Two to 4 days (48 to 96 hours) may be required to produce 
a bowel movement.''
    Five ANDAs for PEG 3350 powder for oral solution, 17 gram (g)/
single-dose were subsequently submitted and approved based on this 
reference-listed drug MiraLax Powder for Oral Solution for Rx only use. 
These ANDAs were approved under the requirements of section 505(j) of 
the act (21 U.S.C. 355(j)) and Sec. Sec.  314.92 and 314.94 (21 CFR 
314.92 and 314.94). The approved labeling of these PEG 3350 ANDA 
products is the same as that of the reference-listed drug, NDA 20-698.

B. Switch of Innovator Product

    On October 6, 2006, FDA approved a new NDA for MiraLax (NDA 22-015) 
submitted by Braintree, switching its use from Rx only to OTC. By 
approving this NDA, FDA determined that PEG 3350 may be used safely and 
effectively OTC for the treatment of occasional constipation and that 
the Rx only limitation on PEG 3350 for occasional constipation was no 
longer necessary or appropriate. The sponsor was granted 3 years of 
exclusivity based on the studies necessary to establish that PEG 3350 
would be safe and effective when used OTC for the treatment of 
occasional constipation. According to FDA's Approved Drug Products With 
Therapeutic Equivalence Evaluations, NDA 22-015 is the subject of 
marketing exclusivity for the OTC use of MiraLax until October 6, 2009. 
Schering-Plough Corp. now holds NDA 22-015 and markets its PEG 3350 
product for OTC use under the brand name MiraLax[reg].

C. The Durham-Humphrey Amendments

    The distinction between prescription and OTC drugs was codified by 
the Durham-Humphrey Amendments, which were enacted in order to address 
the marketplace confusion that arose from the simultaneous marketing of 
identical or nearly identical drugs on a prescription and OTC basis for 
identical or equivalent uses (Public Law 82-215, 65 Stat. 648 (1951). 
See, e.g., H.R. Rep. No. 82-700, at 5 (1951); see also 70 FR 52050 at 
52051, September 1, 2005). Prescription drugs are defined as those 
which because of their toxicity or other potentiality for harmful 
effect, or the method of use, or the collateral measures necessary to 
their use, are not safe for use except under the supervision of a 
practitioner licensed to administer such drugs, or those drugs which 
are limited by an approved application under section 505 of the act

[[Page 63492]]

to use under the professional supervision of a practitioner licensed to 
administer such drugs (see section 503(b)(1) of the act). A drug that 
does not meet this definition is an OTC drug.
    The Durham-Humphrey Amendments prohibit marketing both Rx and OTC 
versions of the same drug product at the same time (21 U.S.C. 353(b)). 
Under section 503(b)(4)(B) of the act, a drug to which the prescription 
provisions of the act do not apply (i.e., an OTC drug) shall be deemed 
to be misbranded if at any time prior to dispensing the label of the 
drug bears the ``Rx only'' symbol. Once FDA determines that the 
prescription provisions of the act in section 503(b)(1) (21 U.S.C. 
353(b)(1)) do not apply a manufacturer is expressly prohibited from 
labeling the drug product as prescription only for the OTC uses under 
section 503(b)(4)(B) of the act. Specifically, such labeling would 
cause the drug to be misbranded under section 503(b)(4)(B) of the act. 
Under section 301(a) of the act (21 U.S.C. 331(a)), it is a prohibited 
act to introduce a misbranded drug product into interstate commerce.
    These provisions of the Durham-Humphrey Amendments apply to the PEG 
3350 drug products. PEG 3350 was initially approved as a prescription 
product under the requirements of section 503(b)(1) in NDA 20-698 
submitted by Braintree. The PEG 3350 ANDAs were approved based on 
reference to NDA 20-698 and FDA's determination that the products 
covered by the ANDAs contained the same active ingredient; were in the 
same dosage form, strength, and route of administration; and had the 
same labeling as the Braintree product. In approving NDA 22-015, FDA 
determined that MiraLax is safe and effective for OTC use and that the 
prescription provisions of section 503(b)(1) of the act no longer 
apply. Thus, no manufacturer of a PEG 3350 product that is the same as 
the OTC drug product can market its product for Rx only use under 
section 503(b)(4)(B) of the act. The manufacturers of PEG 3350 products 
approved in ANDAs that referenced NDA 20-698 are prohibited by sections 
301(a) and 503(b)(4)(B) of the act from labeling their PEG 3350 
products as Rx only for marketing in interstate commerce.

D. FDA's Notice to the PEG 3350 ANDA Holders

    On April 20, 2007, FDA sent to the five sponsors of the approved 
PEG 3350 ANDAs letters that articulated the agency's position regarding 
the legality of marketing of PEG 3350 for Rx use. FDA's letters 
explained that section 503(b) of the act does not permit both Rx and 
OTC versions of the same drug product to be marketed at the same time. 
FDA's letters informed the ANDA holders that their Rx products, which 
bear the ``Rx only'' symbol, are misbranded and may not be legally 
marketed. FDA's letters further explained that if an ANDA holder wished 
to continue marketing its product, the company must submit a new ANDA 
using the appropriate reference listed drug, NDA 22-015, and that such 
ANDA, among other things, must include the same OTC labeling as the 
reference listed drug.
    The letters noted that the sponsors could not simply supplement 
their existing ANDAs because section 505(j)(2)(D)(i) of the act does 
not allow an applicant to amend or supplement an application by 
referring to a different listed drug.

E. Grounds for Withdrawal Under the Standard of Section 505(e) of the 
Act

1. Statutory Authority
    Section 505(e) of the act states that the Secretary of Health and 
Human Services (the Secretary) may, after due notice and opportunity 
for hearing to the applicant, withdraw the approval of an application 
if the Secretary finds that ``on the basis of new information * * * the 
labeling of such drug, based on a fair evaluation of all material 
facts, is false or misleading in any particular and was not corrected 
within a reasonable time after receipt of written notice from the 
Secretary specifying the matter complained of.'' As stated previously, 
FDA sent letters on April 20, 2007, to the five sponsors of the 
approved PEG 3350 ANDAs informing them that their Rx products, which 
bear the ``Rx only'' symbol of the reference listed drug product in NDA 
20-698, are misbranded under section 503(b)(4)(B) of the act and may 
not be legally marketed because the same PEG 3350 drug as the reference 
listed drug was approved as safe and effective for OTC use in NDA 22-
015. Thus, in accordance with section 505(e) of the act, the ANDA 
holders have been given written notice that the Rx only labeling for 
their drugs is false and misleading, because FDA has determined that 
the drug product may be used safely and effectively OTC. The sponsors 
have failed to submit new ANDAs using the appropriate reference listed 
drug, NDA 22-015, including, among other things, the same OTC labeling 
as the reference listed drug. In addition, the applicants have not 
voluntarily sought withdrawal of the approval of their respective 
ANDAs.
    Therefore, FDA is proceeding with this notice of opportunity for a 
hearing on the agency's proposal to withdraw approval of these ANDAs 
for the Rx only PEG 3350 products. As explained previously, FDA is 
basing this proposal to withdraw approval under section 505(e) of the 
act on the ``false and misleading'' labeling of the Rx only products, 
which are misbranded under section 503(b)(4)(B) of the act because they 
bear the ``Rx only'' symbol and the same PEG 3350 product was approved 
for OTC use.
2. The Rx and OTC Products Are the Same Drug Under Section 503(b) of 
the Act
    In determining whether an Rx drug product and an OTC drug product 
are the same, FDA considers whether there are any meaningful 
differences between the OTC and Rx products that would justify the 
different marketing status of the products. When considering whether a 
drug switched from prescription to nonprescription status differs from 
the prescription drug in some meaningful way, the agency considers such 
factors as the indication, strength, route of administration, dosage 
form, or patient population (see 70 FR 52050 at 52051, September 1, 
2005). If there are no meaningful differences between the Rx version of 
the drug and the OTC version of the drug that would support the 
continued marketing of the Rx version of the drug, the drug with the Rx 
labeling is misbranded under section 503(b)(4)(B) of the act.
    The agency has determined that there is no meaningful difference 
between the Rx and OTC PEG 3350 drug products. There is no meaningful 
difference between the PEG 3350 prescription drug product that was 
approved under NDA 20-698 and the PEG 3350 switched to OTC status under 
NDA 22-015, nor is there a meaningful difference between the ANDAs 
referencing the PEG 3350 prescription drug product under NDA 20-698 and 
the OTC PEG 3350 product under NDA 22-015. There are no meaningful 
differences between the Rx and OTC products in any of the factors 
considered when evaluating meaningful differences, including the active 
ingredient, dosage form, strength, route of administration, 
indications, or patient population. The active ingredient in both drug 
products is polyethylene glycol 3350. Each is a powder for solution 
which is to be taken orally once daily by dissolving a 17-g dose in 4 
to 8 ounces of liquid. Both drugs are indicated for use in patients 
with constipation. Finally, both drugs are for patients 17 years of age 
or older. Thus, these products are the same. The

[[Page 63493]]

continued marketing of the same PEG 3350 drug product on both a 
prescription and nonprescription basis could result in the consumer 
confusion that Congress intended section 503(b)(4)(B) of the act to 
prevent.
3. Nonmeaningful Label Differences
    As explained previously, NDA 20-068 and NDA 22-015 are the same 
drug for purposes of determining Rx/OTC status under section 
503(b)(4)(B) of the act. There are, however, minor differences in the 
labeling between the Rx and OTC drugs that are based on the agency's 
practice under the OTC drug monograph system of having consistent 
labeling for lawfully marketed OTC laxative drugs. These differences 
are not meaningful for purposes of determining the appropriateness of 
continued Rx marketing under section 503(b)(4)(B) of the act.
    Specifically, there are minor, nonmeaningful differences in 
duration of use and in the wording of the indication between the Rx and 
OTC products.\1\ The labeling of NDA 20-068 states: ``For the treatment 
of occasional constipation. This product should be used for 2 weeks or 
less as directed by a physician.'' The NDA 22-015 (MiraLax OTC) label 
states: ``Relieves occasional constipation (irregularity). Generally 
produces a bowel movement in 1-3 days.'' Also, the MiraLax OTC label 
states: ``Use no more than 7 days.''
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    \1\ There have been numerous instances in which a drug has been 
switched from Rx to OTC status and there has been a change in its 
duration of use (e.g., ranitidine). In these cases, the drug 
remained prescription for one duration of use while becoming OTC for 
the other duration of use only when there was an additional and more 
fundamental difference between the products, such as a different 
indication, dose, duration of therapy, and/or target population. 
Often these drugs are initially approved as Rx and then subsequently 
switched to OTC for certain indications with corresponding different 
durations of use. The Rx version of the drug continues to be 
marketed with indications for which consumers cannot self-diagnose 
and treat the disease or condition, requiring physician supervision. 
The manner in which a particular drug is dosed or administered 
(e.g., dose titration, duration of use) may also require clinical 
judgment and physician supervision, and thus Rx status, while a 
corresponding OTC version of the drug can be available at a 
different dosing regimen or duration of use that does not require 
physician involvement. Therefore, for the Rx and OTC versions of 
other drugs (e.g., omeprazole, ibuprofen), there are meaningful 
differences that are distinguishable from the nonmeaningful 
differences between the Rx version (NDA 22-068) and the OTC version 
(NDA 22-015) of MiraLax.
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    These minor variations in labeling statements are not based on any 
differences in use necessitated by science or safety concerns, but 
rather are based on differences inherent in all OTC laxative drugs. The 
7-day duration of use for OTC laxatives is derived from advice from the 
advisory panel convened over 3 decades ago, when they considered 
appropriate labeling for laxatives to be regulated under the OTC 
Monograph for Laxative Drug Products for OTC Human Use (40 FR 12902 at 
12906, March 21, 1975). The panel noted a concern about the safety of 
labeling nonprescription laxatives for longer than 1 week, noting that 
a consistent message regarding duration of use of OTC laxatives (for a 
maximum of 7 days) helps to promote safety in case the consumer is 
constipated from a serious condition for which he or she should seek 
care from a physician. Also, the consistency of OTC laxative labeling 
for the maximum 7-day duration of use helps to avoid consumer confusion 
regarding how long to use different laxative products.
    In addition, the Tentative Final Monograph for Laxative Drug 
Products for OTC Human Use (50 FR 2124, January 15, 1985) uses the 
phrase ``For the relief of occasional constipation'' in the labeled 
indication statement. Thus, FDA approved the OTC MiraLax drug with a 
similar indication statement (relieves occasional constipation) for 
consistency with other OTC marketed laxative products. As noted 
previously, the consistency of OTC laxative labeling helps to avoid any 
consumer confusion that might arise from differences in wording of the 
indication statement between OTC laxative products. The limited 
duration of use and use of the word ``relieves'' instead of 
``treatment'' are factors inherent to all OTC laxative products and do 
not demonstrate a meaningful difference between a specific OTC drug and 
an Rx drug.
    The Rx-to-OTC switch of MiraLax was a full switch of the same drug 
for the same indication. The differences in labeling for the duration 
of use and the words ``relieves'' and ``treatment'' exist because of 
the need for OTC labeling statements across OTC laxative products to be 
consistent. These minor changes to the MiraLax labeling for OTC use do 
not constitute a meaningful difference for purposes of section 
503(b)(4)(B) of the act. If such differences in labeling were 
considered meaningful, no Rx and OTC laxative drug would be considered 
the same, and the prohibition of section 503(b)(4)(B) of the act would 
never apply to these products, and thus would be meaningless. Thus, 
there are no meaningful differences between the PEG 3350 Rx and OTC 
drugs or their indications.
4. Same Safety and Efficacy Profiles
    Moreover, the data in the MiraLax OTC NDA did not demonstrate there 
is a difference between the safety and efficacy profiles of the Rx and 
OTC drugs. To support its original NDA 20-698 for the Rx marketing of 
MiraLax, the sponsor submitted study data that demonstrated that the 
drug was safe and effective for Rx use. In patients with a history of 
constipation, FDA determined that MiraLax therapy increases the volume 
and frequency of bowel movements. To support its NDA 22-015 for an Rx-
to-OTC switch of the MiraLax drug, the sponsor submitted three studies 
evaluating the safety and efficacy of the drug in adults (including a 
subset of elderly subjects) for a period longer than the previously-
approved period of up to 14 days of use. Although OTC MiraLax is 
indicated for a period of up to 1 week, the submitted long-term safety 
studies allowed for a better assessment of whether the drug would be 
safe in the OTC environment, where repeated purchase and use is likely. 
The primary endpoints for these three studies were all longer term 
assessments of safety and efficacy and not the day to first bowel 
movement.
    The following summaries describe the studies that formed the basis 
for approval for NDA 20-698, MiraLax (PEG 3350).
     Study 851-3 was a single center, double-blind, triple-
crossover, study which randomized 50 constipated patients to a first 
period (10 days) of either 17 or 34 g of PEG 3350 therapy. 
Subsequently, without a washout interval, subjects were randomized to 
second or third periods (also 10 days) of placebo or the alternate PEG 
3350 dose. The primary endpoints of efficacy were stool frequency and 
stool weight. All 50 patients completed this trial. This study helped 
to define a dose-response for PEG 3350.
     Study 851-6 was a double-blind, parallel trial which 
enrolled 151 subjects who were randomized to placebo or PEG 3350 17 g. 
The treatment period lasted 14 days. The primary efficacy endpoint was 
bowel movement frequency with success defined as >3 bowel movements per 
7-day period, and failure defined as <3 bowel movements per 7-day 
period, use of a laxative or enema or withdrawal from the study. One 
hundred thirty three subjects completed this study.
    The studies submitted with NDA 22-015 to support the Rx to OTC 
switch are briefly described as follows:
     Study 851-CR1 was a randomized, double-blind, placebo-
controlled, multicenter study of 304 subjects comparing 6 months of 
treatment with PEG 3350 17 g/day to daily treatment with a matched 
placebo.
     Study 851-CR3 was an open-label, long term, multicenter 
study of 311

[[Page 63494]]

subjects using PEG 3350 17 g/day for 12 months.
     Study 851-ZCC was an open-label, randomized, parallel arm, 
multicenter study of constipated adult patients randomized to treatment 
with either 17 g/day PEG 3350 or Zelnorm (tegaserod maleate) for 28 
days.
    Eligible subjects were constipated, but otherwise healthy, adults 
with no documented organic cause for constipation who met protocol-
specified modified Rome Criteria for constipation. (Rome criteria are 
consensus criteria developed by the Rome Coordinating Committee (RCC) 
on various medical topics.) In study 851-CR3, all subjects were treated 
with MiraLax. In study 851-CR1, subjects who met study criteria were 
randomized 2:1 to PEG or placebo treatment. In study 851-ZCC, subjects 
were randomized 1:1 to PEG or Zelnorm. The primary endpoint(s) for 
these three studies were all longer term assessments of efficacy and 
safety and not the day to first bowel movement.
    There was no suggestion in any of the reviews that the drug MiraLax 
would act any differently in the OTC consumer than in a patient who 
would have previously taken the drug by a physician's prescription. 
There was no data in the three studies submitted in the OTC switch 
application that showed a different efficacy or safety profile in the 
treated populations. The three studies provided evidence that MiraLax 
would be safe if repeatedly used over time in an OTC setting. When 
considering the data from study 851-ZCC in conjunction with other 
efficacy data, one could reasonably conclude that MiraLax, whether a 
prescription or OTC drug, is efficacious for the vast majority of users 
with constipation within 7 days and generally produces a bowel movement 
by day 3. This information enabled FDA to inform consumers about the 
expectation of benefit on the OTC label.
    Based on its review of the study data for the Rx-to-OTC switch of 
MiraLax, FDA concluded that there was no indication that the MiraLax 
drug would act differently in the OTC consumer than in a patient who 
took the drug by a physician's prescription. In particular, there was 
no data in the three studies submitted in the OTC switch application 
that showed a different efficacy or safety profile between the 
populations taking the OTC drug and those taking an Rx drug. The three 
studies provided sufficient evidence that MiraLax would be safe if 
repeatedly used over time in an OTC setting. FDA concluded that OTC 
MiraLax is efficacious for the vast majority of users with constipation 
within 7 days and generally produces a bowel movement by day 3.
5. NDA 20-698, NDA 22-015, and the PEG 3350 ANDAs Are the Same Drug
    The fact that FDA approved the MiraLax OTC drug under a different 
NDA (22-015) than the MiraLax Rx NDA (20-698) does not demonstrate that 
there is a meaningful difference between the MiraLax Rx and OTC drugs. 
The data in the MiraLax OTC NDA did not demonstrate any differences 
between the safety and efficacy profiles of the Rx and OTC drugs. 
Whether the sponsor sought an Rx-to-OTC switch of the drug through a 
supplement to the original NDA, or by submission of a separate NDA, is 
a reflection of the sponsor's choice and administrative processes 
within the agency, and is irrelevant in determining whether the Rx and 
OTC products are the same for the purpose of section 503(b)(4)(B) of 
the act. The content of the applications to support such a switch would 
be the same, regardless of the form of the applications. All of the 
approved indications in NDA 20-698 were switched to OTC uses in 22-015.
    As explained previously, there are no meaningful differences 
between the drug approved in NDA 20-698 and NDA 22-015. With the 
exception of slight differences in labeling necessitated by the OTC 
switch, they are the same drug for purposes of section 503(b) of the 
act. Under section 503(b)(4)(B), the innovator (Schering-Plough Corp.) 
cannot legally market the misbranded Rx drug product that had been 
approved in NDA 20-698. Therefore, the manufacturers of the PEG 3350 Rx 
drugs approved in ANDAs, which are the same as the reference listed Rx 
drug approved in NDA 20-698, are also prohibited from marketing their 
misbranded Rx drugs.

II. Notice of Opportunity for a Hearing

    The Director has evaluated the information discussed previously 
and, on the grounds stated, is proposing to withdraw approval of ANDA 
76-652, ANDA 77-736, ANDA 77-706, ANDA 77-893, ANDA 77-445 and all 
amendments and supplements thereto, on the ground that the drugs 
covered by the applications are misbranded and the labeling for such 
drugs is false and misleading.
    In accordance with section 505 of the act and part 314 (21 CFR part 
314), notice is given to the sponsors of the PEG 3350 ANDAs, and to all 
other interested persons, that FDA is hereby providing the applicants 
an opportunity to request a hearing to show why the applications listed 
should not be withdrawn.
    Any applicant who decides to seek a hearing shall file: (1) On or 
before November 24, 2008, a written notice of appearance and request 
for a hearing and (2) on or before December 23, 2008, the data, 
information, and analyses relied on to demonstrate that there is a 
genuine and substantial issue of material fact that requires a hearing 
to resolve, as specified in Sec.  314.200.
    Any other interested person may also submit comments on this notice 
on or before December 23, 2008. The procedures and requirements 
governing this notice of opportunity for a hearing, notice of 
participation and request for a hearing, information and analyses to 
justify a hearing, other comments, and a grant or denial of a hearing 
are contained in Sec.  314.200 and in 21 CFR part 12.
    The failure of an applicant to file a timely written notice of 
participation and request for a hearing, as required by Sec.  314.200, 
constitutes an election by that applicant not to avail itself of the 
opportunity to request a hearing concerning the action proposed and 
constitutes a waiver of any contentions concerning the legal status of 
that applicant's drug products. In such instance FDA intends to 
withdraw approval of the applications and to take other appropriate 
action. Any new drug product marketed without an approved new drug 
application is subject to regulatory action at any time.
    A request for a hearing may not rest upon mere allegations or 
denials, but must present specific facts showing that there is a 
genuine and substantial issue of material fact that requires a hearing. 
If it conclusively appears from the face of the data, information, and 
factual analyses in the request that there is no genuine and 
substantial issue of material fact, or if a request for a hearing is 
not made in the required format or with the required analyses, the 
Commissioner of Food and Drugs will enter summary judgment against the 
person who requests the hearing, making findings and conclusions, and 
denying a hearing.
    All submissions under this notice of opportunity for a hearing must 
be filed in four copies. Except for data and information prohibited 
from public disclosure under 21 U.S.C. 331(j) or 18 U.S.C. 1905, the 
submissions may be seen in the Division of Dockets Management (see 
ADDRESSES) between 9 a.m. and 4 p.m., Monday through Friday.

[[Page 63495]]

    Dated: October 16, 2008.
Jeffrey Shuren,
Associate Commissioner for Policy and Planning.
[FR Doc. E8-25359 Filed 10-23-08; 8:45 am]

BILLING CODE 4160-01-S