Kohlstaedt, Kenneth G., M.D., executive director, medical research, Eli Lilly & Co., Indianapolis, Ind.... Larrick, George P., Commissioner of Food and Drugs; accompanied by Winton Rankin, Assistant Commissioner; R. C. Brandenburg, staff officer; Dr. Ralph G. Smith, Director, Division of New Drugs; Dr. Bert J. Vos, Director, Division of Toxicological Evaluation; and William W. Goodrich, Assistant General Counsel, Department of Health, Education, and Welfare... McNinch, Dr. Joseph H., Chief Medical Director, Department of Medicine and Surgery, Veterans' Administration; accompanied by Dr. Oreon K. Timm, Assistant Chief Medical Director for Pro- fessional Services; Dr. Edward Dunner, Director, Research Service; and Vernon Trygstad, Director of Pharmacy Services... Mider, Dr. G. Burroughs, Director, Laboratories and Clinics, National Institutes of Health, Public Health Service, Department of Health, Rankin, Winton B., Assistant Commissioner for Planning, Food and Drug Administration; accompanied by R. C. Brandenburg, staff officer; Dr. Ralph G. Smith, Director, Division of New Drugs; Dr. Bert J. Vos, Director, Division of Toxicological Evaluation; and William W. Goodrich, Assistant General Counsel, Department of Health, Education, and Welfare.. Sjoerdsma, Dr. Albert, Chief, Experimental Therapeutics Branch, Zbinden, Gerhard, M.D., vice president, research division, Hoffmann- La Roche, Inc., Nutley, N.J.; accompanied by Dr. V. D. Mattia, vice president for marketing, Hoffmann-La Roche, Inc.. Zubrod, Dr. C. Gordon, Director of Intramural Research, National Letters, statements, etc., submitted for the record by- Axelrod, Dr. Julius, Laboratory of Clinical Sciences, National Insti- 441 Brodie, Dr. Bernard B., Chief, Laboratory of Chemical Pharmacol 421 CONTENTS Letters, statements, etc.-Continued Fountain, Hon. L. H., a Representative in Congress from the State of Page Excerpt from new drug applications for Flexilon... 605 736 462 791 Excerpt of letter from FDA, to McNeil Laboratories, April 6, 645 674 717 731 Excerpt of letter from George_P. Larrick, Commissioner, Food August 19, 1964.. Gray, W. Donald, senior investigator, Intergovernmental Relations Excerpt from letter submitted with original new drug application Excerpt from statement re description of the animal data Excerpt of memorandum from Dr. Bert J. Vos, Director, Division Kohlstaedt, Kenneth G., M.D., executive director, Medical Research, Chart Birth of a new drug for FDA........... Developing and testing of new drugs by the pharmaceutical Letter from George P. Larrick, Commissioner, Food and Drugs, 558 "The Early Life History of a New Drug," by S. O. Waife, M.D. Larrick, George P., Commissioner, Food and Drugs: 525 Answers to questions submitted for the record by the subcommittee. 653 592 575 Excerpt from supplemental new drug application to FDA for 574 History of a New Drug Application... 632 Letter from John L. Harvey, Deputy Commissioner, Food and 615 Numbers of medical officers and veterinarians requested in the 618 McNinch, Dr. Joseph H., Chief Medical Director, Department of Directive, part of Veterans' Administration Services Manual, Memorandum No. 10-63-29-Central Office Procedure on Ad- Samples of adverse drug reaction reports: Veterans' Administration Hospital, Bronx, N.Y., March 31, Veterans' Administration Center, Whipple, Ariz., March 31, 377 Veterans' Administration Hospital, Memphis, Tenn., March 378 CONTENTS Letters, statements, etc.-Continued Mider, Dr. G. Burroughs, Director, Laboratories and Clinics, National Boards of scientific counselors of the National Institutes of Excerpt from the Federal Food, Drug, and Cosmetic Act, as Part 6-Inventions and patents (general). Part 7-Employee inventions....... Part 8-Inventions resulting from research grants, fellow- Part 6-Patents and inventions, Manual: General Admin- Page 444 450 448 472 473 475 478 Miscellaneous amendments, December 4, 1957....... 477 477 Patent policy applicable to cancer chemotherapy industrial 480 Moss, Hon. John E., a Representative in Congress from the State of 746 Rankin, Winton B., Assistant Commissioner for Planning, Food and ̧ Excerpt from original Orabilex labeling... 726 689 Summary of reports of kidney damage associated with Orabilex.. 791 646 434 Timm, Dr. Oreon K., Assistant Chief Medical Director for Profes- Information re reporting of adverse drug reactions.. 373 387 Trygstad, Vernon, Director of Pharmacy Services, Veterans' Admin- 389 428 Vos, Bert J., M.D., Director, Division of Toxicology Evaluation, Excerpt from evaluation by Dr. Geoffrey Woodard of animal 592 745 Excerpt from summarization of Dr. Deichmann's evaluation of 759 Letters, statements, etc.-Continued Zbinden, Gerhard, M.D., vice president, Research Division, Hoffmann- Conclusions reached in 1963 re need for more toxicological studies. Pag! 515 Chart Standardized death rate per 100,000 from pneu- 516 Table 1-Toxicological tests in animals. 494 Table 2-Drug-related toxic manifestations in humans.. 497 498 Zubrod, Dr. C. Gordon, Director, Intramural Research, National 403 EXHIBITS Exhibit 1-Memorandum from Robert L. McNeil, Jr., vice president, 567 568 Exhibit 3A-Excerpt from draft of proposed Flexin brochure, without change re jaundice.... 569 Exhibit 3B-Excerpt from draft of proposed Flexin brochure containing change re jaundice... 570 Exhibit 4-Page on adverse reactions, from supplemental new drug application for Flexin, June 11, 1958. Exhibit 5-Excerpt re adverse reactions to Flexin from proposed brochure Exhibit 7-Excerpt from supplemental new drug application for Flexilon. 571 572 573 574 575 Exhibit 9-Excerpt re side effects from proposed brochure submitted with 577 Exhibit 10-Draft of proposed physicians index card from Triurate new drug application.... 578 Exhibit 11-Memorandum from Robert L. McNeil, Jr., chairman of the 579 581 Exhibit 13-Revised labeling proposed for Flexin....... 581 582 583 Exhibit 16-Letter from Robert J. Robinson, M.D., medical officer, New Drug Surveillance Branch, Division of New Drugs, Bureau of Medicine, to McNeil Laboratories, Inc., re effectiveness of Parafiex, August 6, 1964 Exhibit 17-Descriptions of Paraflex products from 1962 physician's desk reference. 585 586 Exhibit 18-Descriptions of Parafiex products from 1963 physician's desk reference. 588 Exhibit 19-Descriptions of Paraflex products from 1964 physician's desk reference. 589 Exhibit 20-Letter from A. J. Donnelly, Institute for Cancer Research, Exhibit 23-Letter from Barbara Moulton, M.D., medical officer, New CONTENTS Exhibit 24-Intraagency memorandums re Triurate new drug application and letter making the application effective..... Exhibit 25 Report of Special Committee advisory to the Secretary of Health, Education, and Welfare to review the policies, procedures, and decisions of the Division of Antibiotics and the New Drug Branch of the Food and Drug Administration. Exhibit 26-Correspondence concerning reports of bone marrow depression Exhibit 27-Memorandum from James M. Shaffer, M.D., director, Exhibit 28B-Hepatotoxicity during Zoxazolamine (Flexin) therapy: Exhibit 29 Synopsis of reports and inquiries re hepatic injury-Flexin.. Exhibit 31-Letter from Henry S. McNeil, president, McNeil Laboratories, Exhibit 32A-Letter from Hon. L. H. Fountain, chairman, Intergovern- Exhibit 34-Original physician's brochure for Orabilex. Exhibit 35-Letter from Sydney F. Thomas, M.D., associate professor of Exhibit 36-Letter from Sydney F. Thomas, M.D., associate professor of Exhibit 37-Post card questionnaire from Sydney F. Thomas, M.D., asso- VII Page 626 637 650 654 656 657 665 671 672 673 673 674 679 686 686 687 689 Exhibit 38B-Proposed warning letter from E. Fougera & Co., Inc., to doctors, re drug dosage-Precautions and contraindications in cholecystography, January 1963.. 692 Exhibit 39-Proposed labeling changes for Orabilex.. 693 Exhibit 40-Notice of hearing in the matter of Orabilex capsules... Exhibit 41-Warning letter from E. Fougera & Co., Inc., to doctors, March 1963, re dosage-Precautions and contraindications in cholecystography with Orabilex. 696 698 Exhibit 42-Revised labeling, Orabilex.. 699 Exhibit 43-Telegram from M. L. Weinstein, M.D., and N. E. Roberti, M.D., Martin Luther Hospital, Anaheim, Calif., to Hon. Anthony Cele brezze, April 12, 1963.. 709 Exhibit 44-Letter from Sydney F. Thomas, M.D., to William B. Seaman, 710 Exhibit 45-Letter from E. Fougera & Co., Inc., to doctors re Orabilex recall, January 27, 1964. 712 Exhibit 46-Letter from E. Fougera & Co., Inc., to the drug buyer re 712 Exhibit 47-Letter from E. Fougera & Co., Inc., to the accessories buyer re 713 Exhibit 48-Letter from E. Fougera & Co., Inc., to the pharmacist re 713 Exhibit 49A-Telegram from E. Fougera & Co., Inc., to drug wholesalers re Orabilex recall, February 14, 1964.. 714 |