NEW DRUGS AND THE COSMETIC CHEMIST 463 some detail is omitted, such as the quantitative declaration of a perfume, which you may consider of no importance but which the law requires. In addition to the formula for the dosage form, a representative batch formula is required. This serves as a check on the quantitative composition and should disclose overages which are used in the manufacturing procedure. I will not attempt to discuss in detail all the requirements in Part Four of the new drug application, which deals with manufacturing procedures and controls. The new drug application form contains a detailed outline which is largely self-explanatory. Such procedures and controls are neces- sary in establishing the safety of a drug. They offer assurance that the product marketed will meet adequate and uniform standards. There are certain omissions and misunderstanding of our requirements which frequently occur. These merit some attention. The chemistry involved in the synthesis of new drugs, the use of outside manufacturers and laboratories in the preparation of a drug dosage form, the checking of specifications of raw materials, information derived from assay procedures and product stability studies are necessary information in a new drug application. Omissions or'inadequacies in these areas be- come the causes of delay in the handling of an application. When the specifications and controls of a new drug are inadequate in themselves to determine its identity, strength, quality and purity, the methods used in synthesis, extraction, isolation and purification must be described in detail. The method of preparation may be one of the most important points in establishing the identity of the product. Less detail is usually required in a description of the synthesis of a compound of known structure which has clearly defined specifications. Frequently the applicant does not perform all of the manufacturing pro- cedures himself. Some operations may be done by another firm. When such is the case, a signed description of all procedures conducted by the second firm should be submitted to the Administration, either directly or through the applicant, to be included in the application. Similarly, de- scriptions of control procedures performed by a consulting laboratory for an applicant should be prepared and signed by that laboratory. We be- lieve it is desirable for the applicant to check independently compliance of an article manufactured for him with its specifications. When this is the, case, it should be described in the application. Raw material control is an essential part of an over-all control program that is capable of maintaining the integrity of the product. In the Divi-. sion of New Drugs we adopt the view that adequate control must include defined standards for each raw material used in a drug and the use of appro- priate methods to insure compliance with the standards. Standards and methods adequate to determine the identity, strength, quality and purity of each raw material, and therefore its safety, are as important for any raw material, whether an active or inert substance.

464 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS The manufacturer is, of course, responsible for the integrity of his fin- ished product. Despite this, some manufacturers wish to rely to a lesser or greater extent on their suppliers of the raw materials going into the finished product. Sometimes the supplier may take short cuts, too. We believe that adequate control includes some rechecking of the supplier's representations in the laboratory of the applicant or an independent labor- atory of his choice. It is unwise to submit a new drug application that fails to show exactly who performs the laboratory tests insuring that a raw material meets the standards it professes. The Division of New Drugs may hold the application until it receives such information. The description of raw material or other control elaborated in a new drug application is a representation that these controls will be used for every batch as long as the article is a new drug. If the applicant fails to employ the standards and methods he describes in his application, it is subject to the suspension provisions of the Act. We are concerned with the indica- tions that some manufacturers fail to observe the commitments they made in an application. We recommend conscientious observance of the stan- dards the manufacturer writes into his new drug application, for though they are initially self-imposed, after the new drug application becomes effective, they become a legal obligation. Laboratory controls may be used during various stages of the manu- facturing process and are certainly required for the finished product as well as for the raw materials. It is necessary that control over the finished product be exercised to establish that the active ingredient (or ingredients) will be present in the finished dosage form within a reasonable range of the amount declared in its labeling. This means that the new drug applica- tion should contain limits of acceptance based upon the assays of the active components. In many instances, however, the applicant fails to give the standards or limits of acceptance for each batch. Without such a com- mitment in the application the whole procedure is relatively meaningless from our standpoint. The assays used to check the finished product should be described in the application in sufficient detail to permit duplication in our laboratories. I'he assays insofar as possible should be specific, or, if not specific for the component, an adequate identification test should be provided. The assays should be capable of yielding reasonably reproducible results, and data to this effect should be a part of the application. Of course, specifications other than control of the active component in the finished product should be established. These will depend upon the type product involved. In connection with assays and Part Five of a new drug application, the New Drug Regulations require that specific samples be submitted with a new drug application. These regulations require, as part of each new