NEW DRUGS AND THE COSMETIC CHEMIST 467 list of drug warning statements published in the Federal Register of March 25, 1960, which is available from the Food and Drug Administration on request, may be helpful. Generally a new drug application for an over-the- counter drug may not be made effective unless it bears the substance of the recommended warnings in that list, when applicable to the product. If the preparation is a prescription drug, the labeling on or within the Ipackage should include full information for its professional use as well as I the prescription legend. The label of a prescription drug should bear a Iquantitative statement of its composition. It is not necessary to undertake the expense of preparing proposed Ilabeling in final printed form fbr submission with a new drug application. ITypewritten or other draft copies of labeling are acceptable for conditional •consideration of an application. It may be noted in this connection that Ithe preparation of a large supply of expensively labeled containers in ad- dvance of clearance of a new drug application may lead to a total loss of that iinvestment. Unsatisfactory labeling will not be cleared on the grounds I that there is a substantial investment in it. Another area which may be of interest to you and which became a part •of the New Drug Regulations last year deals with establishment inspections. IThese regulations explicitly recognize that the marketing of a new drug Imay be delayed or prevented until inspectors of this Administration have !been furnished an adequate opportunity to verify the adequacy of manu- I facturing, processing and packing methods, facilities, and controls, and Irecords pertaining to them. These regulations also recognize that in tmost cases an adequate inspection can be completed during the time other ,aspects of an application are undergoing study. We strongly recommend that you inspect the general controls of the ,plant to assure that they are in accord with those set forth in an applica- I tion. We believe that general controls by a firm are as important to the uniform production of a new drug as those described in the new drug .application for that particular article. They are, in essence, insep- , arable. When an applicant obtains an effective new drug application he can .revise his application to reflect changes and improvements in his product. This can be done by supplementing his application. The applicant should i submit full information regarding the proposed change to the Division of I New Drugs for our review and appropriate action. There is an important point I would like to emphasize in connection with i supplements. Cosmetic and drug manufacturers as well as the Food and 'Drug Administration know that occasionally adverse effects are found in the course of extensive distribution of a product under marketing condi- tions, although they were not encountered during the more limited investi- gational use. Further, marketing experience may yield significant informa-

468 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS tion with respect to the incidence of adverse effects found but not accurately assessed as to incidence during the investigational period. Over the years responsible manufacturers have promptly submitted such information to this Administration on a wholly voluntary basis. In some cases this had led to labeling changes with respect to conditions of use, such as dosage, indications, precautions, and the disclosure of ad- verse effects. In other cases it has been necessary to remove the drug from the market. We think the prompt reporting of such adverse information with respect to a drug is essential. We are very much concerned with evidence that in some cases it is not being done. We have encountered from time to time information with respect to untoward reactions with new drugs in reports in the literature or through correspondence with physicians. We have followed up these leads only to learn in some cases that these reactions, and even additional cases, were known to the manufacturer but were never submitted as part of his new drug application. We view the failure to: submit such information as a serious violation of the intent and the pur- pose of the entire new drug application procedure. If information going to the very essence of the safety question is not made available to users of the product through informative labeling or is not used to remove the drug from the market, the essential purpose for the existence of the new drug provision of the Act is completely defeated. A supplement is not an entity in itself but only a part of the new drug application which it incorporates. The failure to disclose any vital inform- ation available to the applicant, such as an adverse reaction, an unstable lot, or difficulty with an assay, is indeed, in our opinion, sufficient grounds for an application to be suspended on the basis that it contains an untrue statement of a material fact. I hope I have clarified the requirements in the field of new drugs by this brief description of our activities in handling new drug applications. Many of the areas discussed are open to a diversity of opinions. I would remind you that we welcome your opinions in this new drug area and recognize that an exchange of ideas is the healthiest atmosphere for all of us. (Received May 8, 1962)