Lost medicines: a longer view of the pharmaceutical industry with the potential to reinvigorate discovery

Abstract

It is widely understood that the 1962 Kefauver-Harris Amendment to the Food, Drug and Cosmetics Act ushered in the modern regulation of medicines requiring a combination of safety and efficacy. However, fewer appreciate the amendment was applied retroactively to virtually all medicines sold in the USA. For various reasons, many medicines faded into history. Here, we identify and analyze >1600 medicines (including over-the-counter drugs) and their innovators prior to the enactment of Kefauver-Harris. We report 880 of these past medicines are no longer accessible. This project also reveals new insight into the pharmaceutical enterprise, which reveals an industry already mature and beginning to retract before enactment of the legislation. Beyond its historical implications, the recollection of these medicines could offer potential starting points for the future development of much-needed drugs.

Figure 1.

Compounds and remedies used prior to enactment of Kefauver-Harris legislation. Shown is an overview of the 1401 different medicinal products used in the USA before 1963 according to medical and pharmaceutical sources. The source, current status and therapeutic application of each medicine is indicated. The products have been broadly divided into products first introduced before or after the year 1800. Abbreviations: OTC, over the counter (medicines); GRAS, generally regarded as safe (products).

Figure 2.

Pharmaceutical product introductions. (a) The annual rate of new product introduction is indicated for over the counter (OTC; red) and ‘forgotten’ (black) medicines from 1901 to 1962 (the final year before implementation of the Kefauver-Harris provisions). (b) The cumulative number of OTC and forgotten medicines is indicated over time, revealing >1200 pharmaceutical ingredients available to physicians by 1962. Note this graph does not include the 347 GRAS compounds.

Figure 3.

Growth and maturation of the pharmaceutical enterprise. (a) The cumulative number of available medicines was tracked over time, revealing a dramatic loss in products as a result of enactment of the Kefauver-Harris Amendment. (b) The number of new product introductions is shown on a year-to-year basis, revealing periodic waves of pharmaceutical industry productivity in the decades starting in the late 19th century and continuing to the present day. (c) The cumulative effect of over the counter (OTC), ‘forgotten’ and FDA-approved new molecular entities (NMEs) reveals that almost 3000 different molecules have been used in the USA at one time or another. Note the same color scheme is used as in Figure 2.

Figure 4.

Rise and fall of pharmaceutical innovators. (a) Shown is a summary of ‘successful’ private sector innovators, who pioneered at least one active pharmaceutical product. The positive axis reflects the year in which each company was founded (or entered the pharmaceutical enterprise; blue) whereas the negative axis indicates when the company had left research (defunct; black) or was subject to industry consolidation (acquired; red). (b) The net number of pharmaceutical innovators still active in the field of new drug R&D is indicated.