[Federal Register Volume 60, Number 122 (Monday, June 26, 1995)]
[Notices]
[Pages 32982-32986]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-15539]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 95N-0182]
KV Pharmaceutical Co.; Proposal To Withdraw Approval of Two
Abbreviated New Drug Applications and One Abbreviated Antibiotic Drug
Application; Opportunity for a Hearing
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 two abbreviated new drug applications (ANDA's) and
one abbreviated antibiotic application (AADA) held by KV Pharmaceutical
Co., 2503 South Hanley Rd., St. Louis, MO 63144 (KV). The grounds for
the proposed withdrawals are (1) that the applications contain untrue
statements of material fact; and (2) that based upon new information
evaluated together with the evidence available when the applications
were approved, there is a lack of substantial evidence that the drugs
will have the effect they purport or are represented to have under the
conditions of use prescribed, recommended, or suggested in their
labeling.
DATES: A hearing request is due on July 26, 1995; data and information
in support of the hearing request are due August 25, 1995.
ADDRESSES: A request for a hearing, supporting data, and other comments
should be identified with Docket No. 95N-0182 and submitted to the
Dockets Management Branch (HFA-305), Food and Drug Administration, rm.
1-23, 12420 Parklawn Dr., Rockville, MD 20857.
FOR FURTHER INFORMATION CONTACT: Harry T. Schiller, Center for Drug
Evaluation and Research (HFD-366), Food and Drug Administration, 7500
Standish Pl., Rockville, MD 20855, 301-594-2041.
SUPPLEMENTARY INFORMATION:
I. Background
On February 4, 1992, FDA attempted to inspect KV to determine
whether or not the firm was following current good manufacturing
practice (CGMP) regulations. The firm, however, refused to provide
necessary records as required under the Federal Food, Drug, and
Cosmetic Act (the act). (See sections 505(k) and 704 of the act (21
U.S.C. 355(k) and 21 U.S.C. 374).) The agency, therefore, obtained
inspection warrants and inspected KV between March 11 and April 23,
1992. Despite the inspection warrants, KV failed to provide all of the
documents requested. FDA conducted another inspection of KV between
July 31 and November 3, 1992.
During the two 1992 inspections, the agency compared documents and
data found at the firm with records previously submitted to FDA in
support of KV's AADA and ANDA applications. The agency discovered that
KV had submitted false and misleading information in the following
applications:
1. AADA 62-047, Erythromycin Ethylsuccinate Oral Suspension, 200
and 400 milligrams (mg);
2. ANDA 71-929, Disopyramide Phosphate Extended Release Capsules,
100 mg; and
3. ANDA 86-538, Nitroglycerin Extended Release Capsules, 2.5 mg.
In support of the AADA and the two ANDA's listed above, KV
submitted analytical data necessary for approval and continued approval
of the applications, including stability data. During its inspections
of KV, the agency discovered documents that showed that KV had made
untrue statements in some of the stability data it had submitted in
supplements and amendments to the applications. The documents also
showed that KV had made untrue statements concerning stability data in
annual reports submitted to the applications.
In letters dated June 1, 1993, and November 12, 1993, FDA informed
KV that the agency intended to downgrade the therapeutic equivalency
rating of the products listed above in the agency's publication
``Approved Drug Products with Therapeutic Equivalence Evaluations''
(the ``Orange Book'') and to begin the administrative procedures
necessary to withdraw approval of the products. Accordingly, as
explained below, the Director of the Center for Drug Evaluation and
Research (the Director) is proposing to withdraw approval of the
products' applications.
II. Evidence That the Applications Contain Untrue Statements of
Material Fact
The first ground for withdrawing the AADA and two ANDA's listed
above is that the applications contain untrue statements of material
fact (21 U.S.C. 355(e)(5)). This section presents FDA's general
comments on untrue statements and materiality, and then sets forth the
specific false and misleading information in the three abbreviated
applications.
A. Untrue Statements
The untrue statements submitted by KV in its drug applications
include both stability test results that are inconsistent with
stability test results retained by the firm and selective or incomplete
reporting of stability date.
1. Conflicts Between Information Submitted to the Agency and
Information Retained by the Firm
The first type of untrue statement submitted in the drug
applications listed above consists of data that differ from data and
other primary source information discovered at the firm. The agency
concludes in such cases that, in the absence of a satisfactory
explanation, the discrepant information in the application is untrue.
Information in an AADA or ANDA, including the facts and data
covered by this notice, is generally derivative information. Such
information is often a restatement, summary, or copy of original data
or other underlying information such as that found in laboratory
notebooks not specifically included in the application. The agency
believes that original or underlying data generally have a higher
degree of reliability because they are the primary sources of the
information that are usually created contemporaneously with the event
the information describes. Restated, summarized, or copied information
submitted in the [[Page 32983]] application is transcribed, calculated,
or otherwise derived from the original or underlying sources and is
prepared after the events actually occurred and, therefore, is
generally less reliable in the event of a discrepancy or inconsistency.
Errors in the original or underlying data, even if discovered during
the preparation of an application, should be corrected with a proper
explanation.
2. Selective Reporting
The second type of untrue statement in the KV applications listed
above consists of selective or incomplete reports of stability data.
Selective reporting refers to reports that contain certain passing
results only. Selective reporting does not consistently contain failing
results and does not consistently contain a scientific justification
for rejecting the failing data. Selective reporting thus misrepresents
results, introduces bias into the studies' analysis, and may result in
erroneous conclusions about the stability of the product.
B. Material Fact
KV's ANDA's and AADA, filed under sections 505(j), 505(b), and 507
of the act and implementing regulations, did not require for their
approval the submission of animal toxicity studies, human safety
studies, and adequate and well-controlled clinical effectiveness
studies. Rather, the approval of an abbreviated application is based on
a showing that the generic drug is equivalent to the innovator drug on
certain key chemical and pharmacologic parameters, and, thus, will be
therapeutically equivalent to the innovator drug throughout the shelf
life of the generic product.
A finding that the generic and innovator drugs are chemically
equivalent with respect to the active ingredient and bioequivalent with
respect to the extent and rate of absorption of the active ingredient
includes adequate proof that the generic product will remain stable
throughout its labeled shelf life. Stability is demonstrated by showing
that the drug product will remain within specifications established to
ensure its identity, strength, quality, and purity throughout its
specified shelf life. The stability data help, therefore, to provide
assurance that a generic product will retain its physical, chemical,
and bioequivalent characteristics throughout its labeled shelf life.
To obtain FDA approval, an application for a generic drug must
demonstrate with reliable data and information (including stability
data) that the generic drug is equivalent to the innovator drug so that
the toxicity, safety, and effectiveness studies supporting the approval
of the innovator drug also support approval of the generic drug.
Moreover, FDA must have a reasonable basis on which to conclude that
data based on test batches of a generic product are representative of
the proposed commercial batches of that generic product.
To maintain continued approval of a drug, the sponsor must, among
other things, comply with various post-marketing reporting
requirements. Under 21 CFR 314.81, a sponsor must file annual reports,
which then become a part of the application; the failure to file such
annual reports may be grounds for withdrawing approval of the
application.
A fact is material if it has the natural tendency to influence or
be capable of affecting or influencing a government function. (See U.S.
v. Brittain, 931 F.2d 1413, 1415 (10th Cir. 1991); Gonzales v. United
States, 286 F.2d 118, 122 (10th Cir. 1960), cert. denied, 365 U.S. 878
(1961); Weinstock v. United States, 231 F.2d 699, 701-702 (D.C. Cir.
1956)). The statements submitted by KV about stability data are
required information for the approval or continued approval of an ANDA
or AADA (see 21 U.S.C. 355(j)(2)(A)(vi), 355(b)(1)(C), 355(b)(1)(D); 21
CFR 314.50(d)(1), 314.94(a)(9), 314.94(c), and 314.81).
Statements pertaining to stability are among the many statements in
an abbreviated application on which FDA relies when deciding whether or
not to approve an application for a generic product (see 21 U.S.C.
355(j)(3)(A) and 355(j)(3)(F); 21 CFR 314.94 and 314.125). Similarly,
when allowing a proposed tentative expiration dating period, FDA relies
on the manufacturer's written commitment in the application to conduct
or continue shelf life stability studies on at least the first three
production batches to establish the actual expiration dating period
(see 21 CFR 314.94(a)(9), 314.94(c), and 314.50(d)(1)). Moreover, FDA
relies on data submitted in annual reports to determine whether an
application should continue to be approved (see 21 U.S.C. 355(e),
355(k); 21 CFR 314.81, 433.1).
Because the statements in the applications that are the subject of
this notice were capable of affecting or influencing FDA's review of
the applications, they are material.
C. Specific Untrue Statements of Material Fact Contained in Each
Application
The specific untrue statements of material fact found in each
application are described below. KV received written notice of many of
these untrue statements in inspectional observations on Forms FDA-483
after FDA's inspections of March 11 through April 23, 1992, and July 31
through November 3, 1992.
1. AADA 62-047, Erythromycin Ethylsuccinate Oral Suspension, 200 and
400 mg
KV was not the original holder of this AADA. KV purchased the
original holder and its approved applications, including AADA 62-047,
the AADA for erythromycin ethylsuccinate oral suspension (EES). EES is
a drug recognized in the United States Pharmacopeia (U.S.P.), and,
therefore, the drug must meet the specifications regarding strength,
quality, and purity prescribed in the U.S.P. unless the deviations are
stated on the label. KV's EES product is labeled to indicate
conformance with such U.S.P. specifications, not deviations.
On August 2, 1989, KV submitted to FDA two supplements to AADA 62-
047, seeking approval for manufacturing changes (supplement S-006 for
its 200 mg EES and supplement S-007 for its 400 mg EES). After
evaluating KV's submissions, FDA issued a deficiency letter on
September 14, 1989, regarding a number of issues, including KV's
failure to provide adequate stability data for EES manufactured by KV's
proposed new process. KV amended these supplements on August 14, 1990,
and again on December 19, 1990. FDA approved the supplements in a
letter dated April 12, 1991.
Subsequently, during the inspections of March 11 through April 23,
1992, and July 31 through November 3, 1992, FDA compared the data
submitted in these supplements with records found at the firm. The
comparisons demonstrated that the data submitted in response to FDA's
1989 deficiency letter omitted failing stability results and falsely
reported failing results as passing. These data were false and
misleading and material to the approval of the AADA supplements.
In the August 14, 1990, amendment to its then pending AADA
supplement, KV provided results from freeze/thaw cycle stability
studies for lot L2072 (200 mg) and lot L2071 (400 mg), which were
performed by an independent contractor. Records discovered at KV,
however, showed that KV did not report failing freeze/thaw results done
by KV's lab. The selectively reported data submitted to FDA are
misleading because they do not reflect all of the stability testing
results of the lots, and, [[Page 32984]] thus, constitute untrue
statements of material fact.
In the August 14, 1990, amendment to its then pending supplement,
KV also selectively reported only a passing result for a 12-month
stability test for lot L2071 (400 mg) for methylparaben, an inactive
ingredient, although KV's records showed an initial unreported result
in which the lot failed to meet the firm's specifications approved in
the AADA for methylparaben.
In the August 14, 1990, amendment to its then pending supplement,
KV falsely reported that lot L2072 (200 mg) passed a 6-month stability
test for methylparaben. However, KV's records for the same time and
storage conditions showed that L2072 failed to meet the firm's
specifications as approved in the AADA.
FDA's inspection also established that KV made untrue statements in
certain annual reports by submitting false stability study results and
by omitting failing stability results for EES 200 mg and 400 mg. In
KV's April 30, 1991, annual report for its 200 mg EES product, the firm
falsely stated that lot L2510 passed an erythromycin assay at 3 months.
However, records from the outside contract laboratory that conducted
the 3-month assay show that the erythromycin assay results for lot
L2510 were below the U.S.P. specifications.
In KV's September 26, 1991, annual report for EES 400 mg, the firm
falsely reported that the assay of the active ingredient in lot L2071
passed stability testing at 18 months. Records at the firm, however,
showed that lot L2071 failed testing at 18 months because the results
were below U.S.P. specifications.
Records from KV show that EES lot L1791 (200 mg) failed assays for
erythromycin and for an inactive ingredient at 18 months. KV, however,
did not report these failures in its April 30, 1991, annual report as
required under 21 CFR 314.81. On April 28, 1992, KV recalled both
strengths of EES because of recurrent stability problems. Only after
this recall, in the firm's June 2, 1992, annual report, did KV report
the stability test failures of EES lot L1791.
The stability failures in 1990 and 1991 were capable of affecting
FDA's continued approval of the AADA because they provide evidence
directly relevant to the product's safety and effectiveness. KV's
omission in the April 30, 1991, annual report of the available
information about the 1990 and 1991 failures misrepresented the
product's quality at that time and, therefore, the applications contain
untrue statements of material fact.
2. ANDA 71-929, Disopyramide Phosphate Extended Release Capsules, 100
mg
FDA's inspections of KV revealed that the firm made untrue
statements about the stability of its Disopyramide Phosphate Extended
Release Capsules (100 mg) in its September 10, 1992, annual report, as
explained below. Disopyramide Phosphate Extended Release Capsules must
meet the specifications regarding strength, quality, and purity
prescribed in the approved ANDA, as amended. The stability data
submitted in the annual reports and discussed below are false and
misleading and are material to the continued approval of the ANDA
application.
First, KV reported that in December 1991, lot V1040 passed ANDA
specifications for 18-month drug release testing at 1, 4, and 8-hour
intervals. Records at the firm, however, showed that the six capsules
tested by KV on December 11, 1991, failed the 4-hour test both
individually and collectively. These failing data were lined through
and the notation ``Inconsistent with history and retest'' was added. No
other notation or explanation of KV's December 11, 1991, test results
was recorded. KV did not report this failure in the September 10, 1992,
annual record or record an explanation for omitting this failure from
the annual report. Five days later, on December 16, 1991, KV tested
another six capsules, which passed the 4-hour specifications. KV
selectively reported only the average of the passing test results in
the annual report, and the omission of failing data in the annual
report was misleading.
KV also reported in the September 10, 1992, annual report that in
April 1991, the 3-month drug release test for lot V1377 passed ANDA
specifications at the 4-hour interval. Records at the firm, however,
showed that on April 18, 1991, the aggregate average value of the six
capsules tested was below drug release specifications for the 4-hour
interval. Five of the six individual capsules were also below
specifications at 4 hours. These failing data were not reported in the
September 10, 1992, annual report.
Four months later, on August 18 and 19, 1991, KV reassayed the lot
three times and selectively reported only the results from the first
reassay. Furthermore, in the September 10, 1992, annual report, KV
falsely reported that the drug release test result had been obtained at
3 months, but KV's records showed that it had been obtained at 7
months.
KV also reported in the September 10, 1992, annual report that lot
V1497 passed both 4 and 8 hour, 12-month drug release tests in May
1992. KV's records, however, showed that a set of six capsules failed
the 8 hour, 12-month ANDA drug release test on July 21, 1992. On August
3, 1992, a second set of six capsules passed both 4 and 8 hour drug
release tests. However, these results were crossed out on the firm's
stability data report form. A handwritten note next to these results
reads ``Void. See recal using correct shell factor.'' On August 8,
1992, KV recalculated both the 4-hour and 8-hour drug release test
results. The aggregate averages for both 4 hour and 8 hour tests passed
specifications. However, two of the six capsules failed at 4 hours and
two of the six capsules failed at 8 hours. The notation ``Recal'' is
written beside this third set of data. KV selectively reported only the
passing 4 and 8 hour aggregate average results in the September 1992,
annual report.
3. ANDA 86-538, Nitroglycerin Extended Release Capsules, 2.5 mg
FDA's inspections of KV revealed that the firm made untrue
statements in certain annual reports about the stability of its
Nitroglycerin Extended Release Capsules. These untrue statements
consisted of false reporting and selective reporting of stability data,
including content uniformity data, which are material to the continued
conditional approval of the application.
In its April 29, 1988, annual report, KV reported that on July 28,
1987, the content uniformity test data for lot V8715 were not available
at 24 months. KV's records, however, included content uniformity test
results for this lot, which showed that lot V8715 failed to meet U.S.P.
specifications at 24 months. Although Nitroglycerin Extended Release
Capsules is not listed in the U.S.P., the standard test for content
uniformity of any product is described in the U.S.P., and KV's
submissions stated that it met the U.S.P. test.
In its June 6, 1989, annual report, KV reported that the 12-month
assay for nitroglycerin in lot V8648 tested within the ANDA
specifications. KV's records, however, showed that an assay result was
outside the ANDA assay limits. The passing result KV reported was an
average of the failing result and two additional assays it performed.
In the June 6, 1989, annual report, KV reported that a
nitroglycerin assay purportedly conducted at 9 months after lot V9527
was within ANDA specifications. KV's records, however, showed that the
KV lab test result, [[Page 32985]] which was dated March 3, 1988,
failed to meet ANDA specifications. KV records also showed that the
stability test result KV reported in its annual report was the average
of two retests performed by KV on April 19, 1988.
In the June 6, 1989, annual report, KV falsely reported that lot
V9133 conformed to U.S.P. specifications in a content uniformity test
conducted 6 months after the lot was manufactured. KV's records,
however, showed that the first 10 capsules of the lot failed U.S.P.
relative standard deviation (RSD) specifications and contained no
evidence that KV tested an additional 20 capsules. Without further
testing of an additional 20 capsules, the batch failed to meet U.S.P.
specifications. Therefore, lot V9133 did not conform to U.S.P.
specifications.
In its May 8, 1990, annual report KV reported that lot V9432 passed
a 24-month stability test in April 1989. Records at the firm, however,
show that the lot failed its stability test on May 15, 1989. During
retesting on June 5, 1989, the lot passed stability testing and met
assay specifications twice. KV averaged the passing tests and then
improperly averaged that resultant average with the failing result.
This final average was reported as a passing result in the May 8, 1990,
annual report.
KV reported in its May 8, 1990, annual report that lot V9527 met
ANDA assay specifications, purportedly in an 18-month stability test of
nitroglycerin conducted in February 1989. Records at the firm, however,
show that the lot failed the first stability test on May 15, 1989. The
lot passed the second and third stability tests, done on June 5, 1989.
KV improperly averaged the three test results and reported in the
annual report the average as a passing result. Furthermore, the retests
were conducted 21 and 22 months after the batch was manufactured, but
KV reported in the annual report that the tests were conducted at 18
months.
KV reported in an August 6, 1992, letter to the agency that lot
V9991 passed the 24-month content uniformity test and conformed to
U.S.P. specifications. Records at the firm, however, showed that the
group of capsules tested failed because its RSD was above U.S.P. RSD
specifications. In addition, the results of two individual capsules
were below U.S.P. specifications. According to U.S.P. specifications,
such failing results require testing an additional 20 capsules, which
KV did not do. Therefore, this lot did not conform to U.S.P.
specifications.
KV reported in an August 1, 1990, supplement that lot V9527 passed
a 12-month stability test for nitroglycerin. Records at the firm,
however, show that the lot failed a stability test on September 22,
1988, and thus did not meet the ANDA assay specifications. KV then
conducted two retests on October 4, 1988. KV selectively reported the
result of only one of the passing retests, and also falsely reported
the date of the test as August 15, 1988, which was 2 months before the
actual test date.
D. Conclusion
On the basis of the foregoing findings, the Director finds that KV
submitted untrue statements of material fact in the AADA and two ANDA's
listed above, and, therefore, proposes to withdraw the approval of
these applications under section 505(e)(5) of the act.
III. Evidence That the Drugs Lack Substantial Evidence of Effectiveness
Sction 505(e)(3) of the act provides that approval of an AADA or an
ANDA shall be withdrawn if, on the basis of new information, evaluated
together with the evidence available when the application was approved,
there is a lack of substantial evidence that the drug will have the
effect it purports or is represented to have. Because KV submitted
untrue statements regarding the stability of its product in annual
reports, supplements, and amendments to its applications, the agency
cannot be assured of the products' stability. Moreover, the agency can
no longer be assured as to the accuracy and validity of any of the data
used to support approval and continued approval of these applications.
Thus, the discovery of these untrue statements constitutes new
information demonstrating that there is a lack of substantial evidence
that the drugs will have the effects they purport or are represented to
have under the conditions of use prescribed, recommended, or suggested
in their labeling.
The reliability of stability data is of particular concern when, as
here, the results of multiple stability tests, both reported and
unreported, indicate a significant history of stability problems.
Without reliable stability data, FDA cannot be assured that a drug will
maintain the efficacy upon the basis of which the drug was approved.
Similarly, in the case of stability problems with generic drugs, FDA
cannot be assured that the drug will continue to be bioequivalent to
the innovator drug over a given period of time. In either case, an
unstable drug product may be more or less potent than the efficacy
parameters that the agency approved.
Because there are no reliable data or information to demonstrate
the stability and bioequivalence of these products to the listed drugs,
the three products listed above lack substantial evidence of
effectiveness.
IV. Proposed Action and Notice of Opportunity For a Hearing
The Director has evaluated the information discussed above
concerning the filing of untrue statements of material fact by KV and,
on the grounds stated, is proposing to withdraw approval of the
following AADA and ANDA's:
1. AADA 62-047, Erythromycin Ethylsuccinate Oral Suspension, 200
and 400 mg;
2. ANDA 71-929, Disopyramide Phosphate Extended Release Capsules,
100 mg; and
3. ANDA 86-538, Nitroglycerin Extended Release Capsules, 2.5 mg.
Notice is hereby given to the holder of the AADA and ANDA's listed
above and to all other interested persons that, based upon the
information discussed above concerning the filing of untrue statements
by KV and, on the grounds stated, the Director proposes to issue an
order under section 505(e) of the act withdrawing approvals, including
conditional approvals, of the foregoing AADA and ANDA's, and all
amendments and supplements thereto. The Director finds that: (1) The
applications contain untrue statements of material fact; and (2) on the
basis of new information before her with respect to the drugs,
evaluated together with the evidence available to her when the
applications were approved, there is a lack of substantial evidence
that the drugs will have the effects they purport or are represented to
have under the conditions of use prescribed, recommended, or suggested
in their labeling.
In accordance with section 505(e) of the act and 21 CFR part 314,
the applicant is hereby given an opportunity for a hearing to show why
approval of the AADA and ANDA's should not be withdrawn.
An applicant who decides to seek a hearing shall file: (1) On or
before July 26, 1995, a written notice of appearance and request for a
hearing, and (2) on or before August 25, 1995, the data, information,
and analyses relied on to demonstrate that there is a genuine issue of
material fact to justify a hearing. Any other interested person may
also submit comments on this notice. The procedures and requirements
governing this notice of opportunity for a hearing, a notice of
appearance and request for a hearing, submission of information
[[Page 32986]] and analyses to justify a hearing, other comments, and a
grant or denial of a hearing, are contained in 21 CFR 314.200 (except
that the limitations imposed by 21 CFR 314.200(d)(1) and (d)(2) do not
apply) and in 21 CFR part 12.
The failure of the applicant to file a timely, written notice of
appearance and request for a hearing, as required by 21 CFR 314.200,
constitutes an election by that person not to use the opportunity for a
hearing concerning the action proposed, and a waiver of any contentions
concerning the legal status of that person's drug products. 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 fact that requires a hearing. In order
to raise a genuine and substantial issue of fact justifying a hearing
on the issue of whether the application contains untrue statements, the
applicant must specifically identify new evidence that supports its
position. Mere allegations and denials, arguments by counsel, or the
unsupported articulation of possible alternate inferences will not
suffice to obtain a hearing. See 21 CFR 12.24(b)(2); see also Cooper
Laboratories, Inc. v. Commissioner, Federal Food and Drug
Administration, 501 F.2d 772, 785 (D.C. Cir. 1974); Pineapple Growers
Ass'n v. Food and Drug Administration, 673 F.2d 1083-1085 (9th Cir.
1982); Weinberger v. Hynson, Westcott & Dunning, Inc., 412 U.S. 609,
620-621 (1973).
In order to obtain a hearing, the new evidence must do more than
reaffirm the applicant's belief that the information in the application
is true. As explained above, the Director's conclusion that the
applications contain an untrue statement of material facts is based on:
(1) Selective reporting of stability data without justification, (2)
omission of failing stability test results, and (3) actual conflicts
between stability data reported to FDA and stability data retained by
the firm.
In order to raise an issue of fact about whether the application
contains truthful information, the applicant's evidence should be
directed toward the basis of the Director's conclusion that the
statements in the application are untrue. The applicant's failure to
present evidence identifying a genuine and substantial issue of fact
with respect to the Director's conclusion that the applications listed
in this notice contain untrue statements of material fact, leaves the
basis for the conclusion intact, and will result in the denial of a
hearing on those issues.
In addition, the submission of truthful information to replace
untrue statements will not result in a finding that the previously
identified untrue statements are no longer material. If corrective
information could nullify the materiality of untrue statements, then
applicants could simply correct all untrue statements as soon as they
were discovered.
Should a hearing be held on these issues, the participants
requesting the hearing will bear the burden of proof with respect to
whether the applications contain untrue statements of material fact
and, ultimately, whether the drugs that are the subject of the
applications listed in this notice have been shown to be safe and
effective (21 CFR 12.87(d)).
If it conclusively appears from the face of the data, information,
and factual analyses in the request for a hearing that there is no
genuine and substantial issue of fact that precludes the withdrawal of
approval of the applications, or when a request for 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(s) who
request the hearing, making findings and conclusions, and denying a
hearing.
Section 505(j)(6)(C) of the act requires that FDA remove from its
approved product list contained in FDA's publication the Orange Book
any drug that was withdrawn for grounds described in the first sentence
of section 505(e) of the act. If the agency determines that withdrawal
of the drugs subject to this notice is appropriate, FDA will announce
the removal of the relevant drugs from the list in the Federal Register
notice announcing the withdrawal of approval of the drugs.
All submissions pursuant to this notice of opportunity for hearing
are to 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 Dockets Management Branch
(address above) between 9 a.m. and 4 p.m., Monday through Friday.
This notice is issued under the Federal Food, Drug, and Cosmetic
Act (sec. 505 (21 U.S.C. 355)) and under authority delegated to the
Director of the Center for Drug Evaluation and Research (21 CFR 5.82).
Dated: June 13, 1995.
Murry A. Lumpkin,
Deputy Director, Center for Drug Evaluation and Research.
[FR Doc. 95-15539 Filed 6-23-95; 8:45 am]
BILLING CODE 4160-01-P
