NDA 5319
AF 15702
JAN 21 1944
Lafayette Pharmacal Inc.
15th & Ball Street
Lafayette, Indiana.
Gentlemen,
Attention of Mr. W. S. Bucke.
Further consideration has been given to your application
under section 505 of the Federal Food, Drug and Cosmetic
Act for the preparation "Pantopaque". From the
description of control procedures contained in this application,
we are somewhat in doubt as to the extent of the test to
be made on each batch of the drug. In discussing the preparation
of the active ingredient, we note that certain physical
constants are mentioned and that the drug is essayed biologically
on dogs. It also appears that a total iodine content determination
is made. We assume that these examinations are made either
by the Eastman Kodak Company or by the University of Rochester.
It does not appear that
you exert any chemical control over the drug after you receive
the raw materials. In our opinion, it will be highly desirable
for some further check to be made on the finished packaged
product. We, of course, are not in a position to state what
sort of a test is most desirable, but we feel that the manufacturer
should assure himself that the product, before distribution
in the channels of commerce, meet the criteria for quality
and purity as specified in this application.
It is also suggested that
in addition to the tests proposed in the application a test
for free iodine be included. This is particularly desirable
in that no information has been furnished concerning the
stability of this product, other than the fact that the
color changes on exposure to light.
The clinical reports which
have been submitted leave one with the impression that a
rather large number of reactions of varying degrees of severity
have been observed with the use of this material. We
are aware that some of these reactions may be accounted
for by the fact that investigators failed to remove the
material following examination of the patient.
However, on the basis of
the reports contained in the application and without additional
data, we hesitate to permit this application to become
effective on the basis of its safety for use. It is
suggested that additional reports be obtained from some
of the investigators mentioned in the application to whom
material has been sent but who have not submitted reports.
We would be particularly interested in having them state
their opinion of the safety of this preparation as compared
to Lipiodol and to discuss the nature and severity of the
reactions observed by them as compared to those observed
when Lipiodol is used.
In our opinion, the
proposed circular setting forth the indications and method
of administration of this product is not wholly satisfactory.
Because of the severity of reactions observed in patients
in whom the product is not removed after injection, we feel
that considerable stress should be laid upon the necessity
for removing this material on completion of the radiologic
examination.
It might be well for the
label of the product to bear a caution calling this fact
to the physician attention. The entire circular creates
the impression that reactions are infrequent and are of
a minor character. We suggest, therefore, that a more thorough
discussion on the side reactions and potential toxicity
be given in the circular and that it be stressed that these
reactions appear almost uniformly if the product is not
removed following examination of the patient.
It is also suggested that
the circular state that the product is not intended for
use in the bronchial or in the uterine cavity. At the time
you submit the additional data regarding controls and toxicity,
you should also submit a draft of a proposed revised circular
and labels.
Very truly yours,
Walton Van Winkle, Jr.,
M.D.
Acting Chief, Drug Division.
c.c. CD C
c.c. Drug Div
WVW:mbc
1/20/44
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