[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]



-----------------------------------------------------------------------

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.

-----------------------------------------------------------------------

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