By Bhavishya Mittal, Ph.D., Vice President, Product Development and Manufacturing, BioDuro-Sundia
In fall of 1962, the Kefauver–Harris Amendments to the Federal Food, Drug, and Cosmetic Act was signed into law by President Kennedy. Championed by Sen. Estes Kefauver and Rep. Oren Harris, the amendments established a framework that required drug manufacturers to prove scientifically that an experimental medication was not only safe but effective. Although the 1962 Kefauver-Harris Amendments were drafted in response to the thalidomide disaster and based on the groundbreaking research of Dr. Frances O. Kelsey (which prevented thalidomide from being marketed in the United States), the impact of this landmark legislation changed the modus operandi of the entire pharmaceutical industry.
Armed with this new legal mandate, the FDA enforced good manufacturing processes, strengthened its control of experimentation on humans, and changed how drugs are approved and regulated. The amendments granted the FDA the power to demand proof of efficacy — in the form of “adequate and well-controlled investigations”— before approving a new drug for the U.S. market. They also led to a retrospective review of all drugs approved between 1938 and 1962 (the Drug Efficacy Study Implementation program), which by the early 1970s had categorized approximately 600 medicines as “ineffective” and forced their removal from the market. These market-making and -unmaking powers were also tied to a new structure of knowledge generation: the orderly sequence of phase 1, phase 2, and phase 3 trials now seen as a natural part of any pharmaceutical life cycle (Greene and Podolsky 2012).
Over the last three decades, multiple amendments have been enacted to efficiently bring safer and more effective drugs and medical devices to market. For example, the 1997 Food and Drug Administration Modernization Act brought about the most wide-ranging reforms since 1938, including regulation of advertising for unapproved (off-label) uses for drugs and devices, a step that has resulted in a growing number of warning letters to manufacturers for off-label promotion. It also provided for accelerated reviews of drugs and medical devices using less stringent thresholds (e.g., use of surrogate markers to assess efficacy and requiring only one well-controlled trial to evaluate safety and efficacy) to allow new therapies to be brought to market sooner for products used to treat rare diseases (i.e., orphan drugs) or serious medical conditions for which there are no currently available treatment options (e.g., treatment-resistant malignancies). In addition, fees associated with product applications were imposed on manufacturers of drugs through the Prescription Drug User Fee Act of 1992 and for medical devices through the Medical Device User Fee and Modernization Act of 2002 to provide additional funding to the FDA for the new product review process (Sweet, Schwemm and Parsons 2011).
All these examples prove that pharmaceutical drug law is dynamic and aspires to address the various challenges that society faces. However, the regulatory process instituted by the Kefauver-Harris Amendments of 1962 is the unshakeable foundation of modern drug development. For this, we are eternally indebted to scientists and leaders such as Dr. Kelsey, Sen. Kefauver, Rep. Harris, and finally, JFK.
References
Greene, J. A. and S. H. Podolsky (2012). "Reform, regulation, and pharmaceuticals--the Kefauver-Harris Amendments at 50." N Engl J Med 367(16): 1481-1483.
Sweet, B. V., et al. (2011). "Review of the processes for FDA oversight of drugs, medical devices, and combination products." J Manag Care Pharm 17(1): 40-50.
Bhavishya Mittal is the Vice-President of Product Development and Manufacturing at BioDuro-Sundia (Irvine, CA), where he leads the strategy and operations for drug product development of all small molecule client-owned assets within the portfolio. Bhavi has 21+ years of industrial experience in the formulation design, process development, and project management of numerous drug products of small therapeutic molecules. He is the author of 3 published books (with 25 combined chapters), 4 granted US patents, 11 peer-reviewed manuscripts, and numerous conference papers and posters published/presented in various international journals and conferences.