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Included in the first portion of this section should be an overall tabulated summary of all in vivo biopharmaceutical studies carried out on the drug grouped by type of study. The study number, route of administration, dosage form, batch number, plant and date of manufacture, number of subjects, IND or NDA number under which the study was conducted or study submitted, date of submission, conclusions regarding the study, and previous agency response on the study or the protocol together with the date of the correspondence should be included. 

Goldberg and Rubin [Ind. Eng. Chem. Proce.s.s Des. Dev., 6 195 (1967)] showed in tests with a disk spinning vertically to the foam layer that most mechanical procedures, whether centrifugation, mixing, or blowing through nozzles, consist basically of the application of shear stress. Subjecting foam to an air-jet impact can also provide a source... 

For determination of the aerodynamic diameters of particles, the most commonly apphcable methods for particle-size analysis are those based on inertia aerosol centrifuges, cyclones, and inertial impactors (Lundgren et al.. Aerosol Measurement, University of Florida, Gainesville, 1979 and Liu, Fine Paiiicles—Aerosol Generation, Measurement, Sampling, and Analysis, Academic, New York, 1976). Impactors are the most commonly used. Nevertheless, impactor measurements are subject to numerous errors [Rao and Whitby, Am. Ind. Hyg. A.s.soc.]., 38, 174 (1977) Marple and WiUeke, "Inertial Impactors, in Lundgren et al.. Aerosol Measurement and Fuchs, "Aerosol Impactors, in Shaw, Fundamentals of Aerosol Sci-... 

The maximum ground concentration of stack gases subjected to atmospheric diffusion occurs about 5-10 effective stack heights dow tiw ind from the point of emission. 

Once the FDA receive the initial submission, an IND reference number is assigned. The application is then passed on to the appropriate review centre either the Center for Drug Evaluation and Research (CDER), or the Center for Biologies Evaluation and Research (CBER). Various experts will then review the submitted documents, the purpose being to ensure that the safety of subjects is not compromised and, in the case of Phase II and III studies, that the quality of study design is scientifically adequate. The FDA are allowed 30 days to complete the initial review, after which the study can commence, provided that it has been approved by an Institutional Review Board (IRB). 

Bartonicek V. 1962. Metabolism and excretion of trichloroethylene after inhalation by human subjects. Br J Ind Med 19 134-141. 

Stopps GJ, McMaughlin M. 1967. Psychophysiological testing of human subjects exposed to solvent vapors. Am Ind Hyg Assoc J 28 43-50. 

CFR - Part 312.33 discusses what is required for an Investigational New Drug (IND) application. Part 312.33 discusses the requirements for the annual reporting for the IND. This reporting requires you to create adverse event, death, and subject dropout summaries annually for any drug under an IND application. 

Cavalleri A, Minoia C, Pozzoli L, et al. 1978. Determination of plasma lead levels in normal subjects and in lead-exposed workers. Br J Ind Med 35 21-26. 

CFR 312.32 Safety reports for investigational products subject to an IND application (published 1987). 

Ikeda M, Ohtsuji H. 1969. Hippuric acid, phenol, and tricholoacetic acid levels in the urine of Japanese subjects with no known exposure to organic solvents. Br J Ind Med 26 162-164. 

With an approved IND, the drug company can place me in humans at lower doses, mainly to observe any overt symptoms of toxicity and to evaluate my PK characteristics, and the study may use 10 to 20 healthy subjects. These data are then resubmitted to FDA (Phase 1). After my Phase I is completed, drug testing begins for my clinical efficacy, with trials at different doses and given to different populations under strict supervision. A successful study may require a few thousand patients and the involvement of several study centers across the country (or perhaps across the world) to collect extensive data. It is not unusual to have 100,000 patients take me before the data are submitted to the FDA for drug approval — the so-called marketing approval. 

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