Chemist Lee Geismer looking over an NDA in the 1960s
The 1906 Food and Drugs Act prohibited the adulteration or misbranding of pharmaceuticals, but that law did not require premarket approval of drugs. As long as drugs were properly labeled and conformed to the applicable standard compendia—the U. S. Pharmacopoeia or the National Formulary, there was no federal statute to prevent their commercialization, safe or hazardous, effective or useless.
Congress considered some bills to correct this and other elements in the 1906 law, beginning in the early 1930s. Support for legislation was inadequate until 1937, when a manufacturer introduced an untested formulation of sulfanilamide with a solvent that was responsible for the deaths of over 100. In June of the following year President Roosevelt signed the Food, Drug, and Cosmetic Act, which completely revamped oversight of food and drugs and included for the first time consumer protection over medical devices and cosmetics.
The foundation of the drug provisions of the new law required manufacturers to submit to FDA evidence of a drug's safety before it could go on the market, and the agency had two months to approve, reject, or request additional data from the firm (failure to act on the application would theoretically lead to automatic de facto approval of the drug). This mandate for premarket evidence of a drug's safety represented the birth of the new drug application, or NDA.
A congressional investigation and subsequent hearings launched by Senator Estes Kefauver in the late 1950s raised many questions about drugs, including drug effectiveness. Consequently, the drug application itself changed substantially in 1962 when Congress amended the drug provisions of the law to require, among many other items, that manufacturers establish not only the safety but also the effectiveness of the drug through adequate and well-controlled clinical trials prior to marketing. These data were responsible for the expansion of the drug application into a massive document of perhaps hundreds of volumes.
There are several qualifications to the tabulation of new drug applications below that are cited in the footnotes. Unless stipulated otherwise, all data are derived from FDA publications over the years, such as its annual reports. Included are new molecular entities, which essentially are structurally unique active ingredients that have never before been marketed. Occasionally the footnotes explain abrupt shifts in the numbers of drugs approved or received. Otherwise, no assessment of changes in the data over time has been attempted.
|Year||NDAs Approved a||New Molecular Entities||NDAs Rec'd a, b|
|1940||1782 (1938-40)||14 (1940 only)||2752 (1938-40)|
|1953||454 c||19||508 c|
|2004||119 e||36 e||115|
* Data through 1976 are reported for the fiscal year, 1 July through 30 June; data thereafter are reported for the calendar year. It is unknown if the de Haen data are based on calendar or fiscal years (see below).
a If both human and animal drugs are reported separately, only human drugs are listed.
b If data for original NDA submissions and NDA resubmissions are reported separately, only original NDA submissions are listed here.
c Reported as including both human and animal drugs; NDA approvals for this year are implied to include both as well.
d Includes 114 applications for radioactive drugs formerly regulated by the Atomic Energy Commission, and 94 applications for amphetamine drugs for obesity intended to demonstrate both safety and effectiveness.
e Approvals for 2004 and after include Biologic License Applications for therapeutic biologic products transferred from the Center for Biological Evaluation and Research to the Center for Drug Evaluation and Research.
Data on NDAs approved and NDAs received from 1938 through 1976 are drawn from: Federal Food, Drug and Cosmetic Law: Administrative Reports, 1907-1949 (Chicago: Commerce Clearing House, 1951); Food and Drug Administration, Annual Reports, 1950-1974 (Washington, D. C.: G. P. O., ca 1976); FDA Annual Report 1975 ([Rockville, MD.: FDA], ca 1976; and FDA Annual Report 1976 ([Rockville, MD.: FDA], ca 1977).
Data on approval of NMEs for 1940 through 1950 are from [Paul de Haen], "Compilation of New Drugs, 1940 thru 1975," Pharmacy Times 42, no. 3 (March 1976): 42.
Data on NMEs for 1951 through 1989 are from Document Management and Reporting Branch, Division of Management and Budget, Office of Management, Center for Drug Evaluation and Research, FDA, "Offices of Drug Evaluation: Statistical Report," typescript, 1989, pp. 152-199, FDA History Office Files, Rockville, Maryland. Note that the term "New Chemical Entity" was used instead of "New Molecular Entity" earlier in this period, but expressed the same concept.
Data on NDAs received, 1977 through 2006 are from "Number of NDAs Received by Calendar Year," 16 January 2007, www.fda.gov/cder/rdmt/numofndareccy.htm.
Data on approval of NDAs from 1977 through 2006, and NMEs from 1990 through 2006, are from Office of Management, Center for Drugs and Biologics, FDA, "New Drug Evaluation Statistical Report (Briefing Book)," unpublished typescript, 1985, p. 58, FDA History Office Files, Rockville, Maryland; Document Management and Reporting Branch, Division of Management and Budget, Office of Management, Center for Drug Evaluation and Research, FDA, "Offices of Drug Evaluation: Statistical Report," typescript, 1993, p. 33, FDA History Office Files, Rockville, Maryland; and www.fda.gov/cder/rdmt/NDAapps93-06.htm, 29 January 2007.
“Data on approved NDAs and NMEs, and original NDA and BLA applications received, from 2007 through 2011, are from Center for Drug Evaluation and Research 2007 Update, “Improving Public Health Through Human Drugs,” http://www.fda.gov/downloads/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/WhatWeDo/UCM121704.pdf; “Drug and Biologic Approval Reports: NDA and BLA Approvals,” and “Drug and Biologic Approval Reports: NME Drug and New Biologic Approvals,” http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/DrugandBiologicApprovalReports/default.htm; and “FY 2011 Performance Report to the President and Congress for the Prescription Drug User Fee Act,” p. 6, http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Reports/UserFeeReports/PerformanceReports/PDUFA/UCM294101.pdf (NDAs and BLAs received).”
Questions can be addressed to John P. Swann, Ph.D., FDA Historian, FDA History Office, White Oak Building 32, Room 3322, 10903 New Hampshire Avenue, Silver Spring, Maryland 20993, firstname.lastname@example.org