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

NEW DRUGS AND THE COSMETIC CHEMIST 465 Idrug application, samples of the dosage forms the applicant proposes to Imarket representative of the drug employed in clinical studies, of the drug Iproposed for initial marketing, and of commercial scale production, to- igether with samples of the new drug substances used in producing the Ibatches of the drug represented by the foregoing samples, and such refer- lence standards and blanks as may be required to perform the assay proce- Idures described in the application. The new drug sample regulations were designed for the purpose of check- iing the adequacy of the proposed methods in a new drug application to Idetermine whether or not these methods to be employed are adequate Ito preserve the identity, strength, quality, and purity of the article to Ibe marketed, and to verify specifications, especially for new drug sub- Istances. Our experience to date with the drug sample regulations has brought •out some common faults which arise to cause difficulty in complying with Ithese regulations. We have received insufficient and inadequately identi- Ified samples. In some instances, applicants fail to submit their results ion the batches represented by their samples. As to the methods submitted Iby the applicant for the laboratory test procedures of the samples, many •are not given in sufficient detail. We can evaluate the adequacy of pro- Iposed drug controls only when an applicant submits adequately described Imethods and unambiguous laboratory reports. We would recommend Ithat you submit methods that can be employed routinely by our labora- Itories to assay your product without the necessity of having the blanks iinvolved in a particular batch. A demonstration of the stability of a proposed preparation should be isubmitted as a part of a new drug application. The potency of a drug is •most important at the time it is consumed. This suggests that prolonged 'stability may be even more important for an over-the-counter drug that may be used intermittently over a long time until exhausted than in the tcase of a prescribed drug entirely consumed as directed during a short I period of illness. There are a number of significant factors affecting the stability that I should be considered in designing studies of the shelf life of a formulation I but which are not always given the full consideration that they deserve. I For example, temperature, pH, particle size, moisture, air oxidation, dilu- lents, preservatives, containers, closures, light and the presence of certain I trace metals, are some of the important factors. It is most important in this day of new and different containers and t closures for packaging drugs that the samples for stability study be taken 'from material stored as it will be in the market package. Once the stability of a formulation of a drug in a specific market container I has been established, it does not follow that a change in formulation or