466 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS container, no matter how minor, will not change the stability of the prepar- ation. Changes in the container, closure, excipients, flavor and manufac- turing and processing operations may affect the stability adversely, requir- ing additional studies of stability. It should be emphasized that almostl any changes in process or composition require evaluation as to their effect l on the stability of the product. In interpreting the results of stability studies many firms have found to• their disadvantage that the carrying over of stability data from one formu-I lation to another is not acceptable. In general, the results of any stabilityl study are applicable only to the formulation under the test conditions im-i posed, such as temperature, diluents, container, moisture, pH, closures,I etc., employed on a particular article. The chemical assay methods on which stability studies are based shouldl be sufficiently specific to differentiate between the unaltered drug and itsl possible degradation products. A method that does not differentiate thel original product from the degradation products is of no value in reaching I a conclusion that the preparation is stable. Too often we are expected to evaluate the stability of a product on thel basis of data derived from a single batch. In addition, we are continually I being asked by members of firms about how long their firm should run--orl be required to run--stability studies of a preparation for acceptance in al new drug application. They seem to ignore the fact that we must be as. guided as they by what the data indicate. A preparation may be stable, apparently, in the hands of one pharma- ceutical firm under the conditions of his own manufacture. The prepara- tion of the same composition in another's hands, using different raw mater- ials, different equipment, different containers, and variation in technique, may not be stable. Frequently, we find that an applicant, when his formu- lation is the same as that of another firm, relies entirely on the other firm's stability studies. He finds to his disadvantage that studies of the stability of his formulation are an essential part of his own new drug application. I do not propose to discuss in detail all the requirements in Part Six of the new drug application which deals with labeling. A drug must be safe for use as labeled, so that evaluation of labeling is another vital step in the consideration of the safety of a new drug. The information derived from the animal and clinical Studies provides knowledge regarding the indica- tions, dosage, contraindications, precautions and side effects of a newl drug. Generally the labeling of cosmetic-type drug preparations will be similar' to the pattern of labeling'employed on other drugs, with perhaps a fewl unique characteristics. If the drug is to be sold over-the-counter, that is, without prescription, the package should includ• among'other things ade- quate directions for use in self-medication and adequate warnings. The

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-