4. Pantopaque, FDA warning, licence approval 1944

Dr. Burton November 2011, "In all cases Myodil caused toxic Chemical Meningitis leading to Adhesive Arachnoiditis," blog page 17.

A letter from Walton Van Winkle of the FDA to Lafayette (1944), he expresses concerns about quality control during manufacturing of Pantopaque, adverse reactions of animal tests and reports of the same in Humans.  He was also unhappy about the lack of testing for free Iodine in the product and other concerns.  These issues were never resolved and were forgotten, the bastards were determined to make money even if it meant killing people.

Lafayette Pharmacal Inc.         Jan 21 1944
15th & Ball Street
Lafayette, Indiana

Gentlemens,                          Attention of Mr. W. S. Bucks

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.

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 M.D.
Acting Chief, Drug Division.

Even though there were serious concerns about the safety of Pantopaque, below is a copy of a letter by the FDA to Lafayette in which the FDA grant permission for it's use.

Lafayette Pharmacal, Inc,                            Feb 22 1944
15th & Ball Street
Lafayette, Indiana

Gentlemen:                                                 Attention of Mr. W. B. Bucke,

We have your letter of February 15 with which you have submitted additional material for your pending application under section 505 of the Federal Food, Drug and Cosmetic Act for the preparation “Pantopaque.”

We have completed our study of this application and it has been concluded that no order will issue under section 505(d) of the Act to refuse to permit the application to become effective.

This application is effective with respect to the use of this drug only under the conditions prescribed, recommended and suggested in the application. Should you decide to alter the composition, or dosage, or method or duration of administration or application, or other condition of use, an appropriate amendment to the application should be submitted for consideration.

Your attention is directed to section 301(1), which prohibits the use in the labelling or in any advertising of any statement to the effect that an application with respect to this drug is effective under section 505 or that the drug complies with the provision of that section.

Section 505(e) of the Act provides for the suspension of the effectiveness of an application if further experience and tests with the article show it to be unsafe for use or if it is found that the application contains any untrue statement of a material fact.

The effectiveness of this application under section 505 in no way relieves you of the necessity of complying with the requirements of all other provisions of the Act applicable to the preparation.

We have no comment to offer on either the labels or proposed circular. As soon as available you should submit five copies of the printed labels together with five copied of the printed circulars.

Cc CD C                         Very Truly Yours,
Cc Drug Div                    R. P. Herwick, M.D.
WVW:mbc 2/21/44          Chief, Drug Division