460 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS an article which is an antiperspirant is a drug because it affects a structure or function of the body relating to perspiration. If the cosmetic-type article meets the definition of a new drug it is sub- ject to the new drug procedure, in spite of the fact that no such require.- ment exists for a new cosmetic. The Federal Food, Drug and Cosmetic Act prohibits the shipment in interstate commerce of any new drug until an application is effective for it. This gives the distributor of a cosmetic, when it is a new drug, a responsibility to acquire an effective new drug application before he markets the article. The purpose of this requirement of law is to insure that a new drug is adequately tested for safety before marketing. It is not sufficient for the distributor of a new drug to satisfy himself that it is safe, although this is an obvious first step. It is equally necessary under the law to satisfy the Food and Drug Administration that the new drug is safe. The term "new drug," as defined in the Act, may be paraphrased as any drug whose composition is such that it is not generally recognized, by ex- perts qualified by training and experience to evaluate safety of drugs, as safe for use as suggested in the labeling. The definition also includes a drug which has gained recognition of its safety as a result of studies but which has not otherwise been used for a material time or to a material ex- tent under the conditions suggested in its labeling. Under this definition safety may be recognized to the extent that one firm has an effective new drug application for a drug but, until it has been used to a material extent and for a material time, it is still a new drug, and other firms wishing to manufacture and distribute it must also obtain an effective new drug application. Now that we have considered the why and when to submit a new drug application, we may explore more fully the purpose and substance of an application. The Act provides that an application shall contain (1) full reports of investigations that have been made to show whether the drug is safe for use (2) a full list of the articles used as components of the drug (3) a full statement of the composition of the drug (4) a full description of the methods used in, and the facilities and controls used for, the manu- facture, processing, and packing of the drug (5) required samples of the drug and its components and (6) specimens of the proposed labeling for the drug. The significant purpose for the processing of new drug applications is contained in section 505(d) of the Act, which provides that an application may be refused, after giving the applicant notice and opportunity for a hearing, if it is found (1) that the submitted reports of investigations do not include adequate tests by all methods reasonably applicable to show whether the drug is safe for use or (2) the tests show that the drug is un- safe or fail to show that it is safe or (3) the methods, facilities and con-

NEW DRUGS AND THE COSMETIC CHEMIST 461 trols used for the manufacture, processing and packing of the drug are inadequate to preserve its identity, strength, quality and purity or (4) there is insufficieat information to determine whether the drug is safe for use under the conditions prescribed, recommended or suggested in the pro- posed labeling. This authority to refuse an application also gives the Food and Drug Administration the responsibility to refuse any application until it has been adequately demonstrated that the drug is safe according to the criteria out- lined above. Based upon our experience with cosmetic firms entering the new drug field, we believe that many pitfalls encountered are those which can be attributed to lack of background with respect to new drug application re- quirements. Therefore a few of the more common obstacles to obtaining an effective new drug application should be covered. Let us consider more specifically the contents of an application for a new drug. A new drug application form is available on request from the Food and Drug Administration. It furnishes a detailed outline which should be followed in assembling the data for the application, which must be submitted in duplicate. The investigations of the safety of the drug should include adequate tests by all methods reasonably applicable. The reports should contain detailed data derived from animal and clinical studies in which the methods used and the results obtained are clearly set forth. This usually means pharmacologic studies in animals and subsequent clinical investigations. The kind and the amount of information required will depend on several factors, such as the nature of the drug and its indications, and must be determined individually for each new drug. Cosmetic-type drugs may be employed daily or several times daily and during the greater portion of the individual's lifetime, that is, by the young, by the old and even by individuals in varying conditions of health. Al- though the risk of adverse effects is justified to seek the benefits of a life- saving drug, no significant risks should be tolerated from the administration of a product for essentially cosmetic purposes. A dogmatic statement cannot be mkde of•the requi'rements with respect to animal toxicity studies since such will vary with the drug and the nature of its use. If the intended use includes prolonged or continuous adminis- tration, then chronic experiments of from six months to a year or more are probably indicated. A useful guide in this c6nnection is a booklet, "Ap- praisal of the Safety of Chemicals in Foods, Drugs and Cosmetics," pre- pared by the staff of our Division of Pharma•c•logy and published in 1959 by the Association of Food and Drug Officials of the United States. Of particular interest in connection with 6osmetic-type preparations intended for external application is the chapter on "Dermal'Toxicity."