winkle1944

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 assayed Mologically 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 if 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 of 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, meets 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 colour 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 degree 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 the 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 becomes 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 lipidol and to discuss the nature and severity of the reactions observed by them as compared to those observed when lipidol 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 radiologists examination. It might be well for the label to bear a caution calling this fact to the physicians attention. The entire circular created the impression that reactions are infrequent and are of a minor character. The reports which have been submitted do not confirm this impression. We suggest, therefore, that a more thorough discussion of 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 bronchi or in the uterine cavity.