Trends and Considerations in Global Infectious Disease Drug Dev | Page 5

A crisis involving the deaths of 107 children who ingested an elixir of sulfanilamide, which used diethylene glycol, an antifreezelike poison, prompted the creation of liquid suspension suitable
for small children. This led to the Food, Drug and Cosmetic Act of
1938, which required the premarketing approval of all new drug
applications (NDAs) for safety only. Following the thalidomide
crisis of the early 1960s, in which a drug not approved in the US
was imported and used by pregnant women resulting in fetal loss
and major birth defects, Congress passed the Kefauver-Harris

The FDA guidelines have posed new challenges for
sponsors, such as requirements for better defined patient
populations and microbiologic identification of a pathogen,
superiority studies required for approval, the redefining of
clinical end points, and establishing an exact clinical and microbiologic diagnosis when the screening period is measured
in hours and the probable diagnoses are largely determined
clinically before a microbiological etiology is established.

drug amendment in 1962. This required all new drugs to be assessed for efficacy as well as safety based on adequate and wellcontrolled clinical trials, and all previously approved drugs were required to be assessed for efficacy or withdrawn from the market. The amendment was referred to as the Drug Efficacy Study Implementation (DESI) Review. DESI established the Investigational New Drug (IND) Application
process, which regulates how drugs are tested for safety and efficacy before NDA submission.
Clinical drug development for antimicrobial agents also underwent several stages prior to 2000. In the early days of antibiotic drug development,
NDA submissions and FDA approvals were focused on antimicrobials targeted to specific bacterial pathogens. Many important drugs used today,
such as penicillin and vancomycin, approved before 1962, were assessed for efficacy after 1962 through the DESI program, based on published
clinical data. Prior to 1962, efficacy was based on published observational cohorts of patients receiving the designated treatment. From 1962
until the late 1980s, the development target shifted from individual pathogens to organ systems where there was some commonality in
bacteriologic etiology, such as skin and skin structure indications, and grouped together as indications in the product labels. New guidelines for
the development of antimicrobial drugs, developed by the Infectious Disease Society of America, were published in 1992. More than 30 individual
treatment indications were identified for common infectious diseases in the US. Large pharmaceutical companies met the challenge and new
antimicrobials were approved with as many as 14 specific treatment indications. The Prescription Drug User Fee Act of 1992 offered the
advantage of a more rapid NDA review.
Drugs for infectious disease have had a significant impact on patient morbidity and mortality since their introduction in the 1930s. In the 1980s
there was a proliferation of antimicrobial drugs in development, which were major contributors to both disease control and improvement in
human lives, including second- and third-generation cephalosporins, newer amino glycosides and the fluoroquinolones.

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