Viewed from a single moment in time, this debate can appear intractable, whether it concerns the pros and cons of generic steroids in 1961 or generic epilepsy medications in 2014. Viewed over time, however, conflicts over generic drugs form a shifting historical dialectic of similarity and difference. Consider the case of Parke-Davis’ blockbuster drug Chloromycetin, which in 1966 was one of the first broad-spectrum antibiotics to go off patent and face generic competition. To a host of consumer advocates and policymakers in the federal government, the chemically equivalent generic versions offered a remarkable opportunity to rein in the increasing amount of taxpayer dollars that, since the passage of Medicare and Medicaid two years earlier, were now being spent on brand-name drugs. To executives at Parke-Davis, generic competition meant the potentially disastrous loss of market share for their flagship product.

When generic Chloromycetin capsules emerged on the market, however, one of these newer and cheaper products did not dissolve in water. Further testing in human subjects (euphemistically labeled volunteers) at a series of military bases and prisons showed that some of these capsules passed through the human digestive tract completely unabsorbed. Even though these products had proven to be the same according to a series of stringent tests of chemical equivalence, they were not the same in their effects on the human body. In response, the FDA pulled the generic versions from the market and instituted a new proof of biological equivalence, requiring any generic version of this drug to demonstrate that it would be absorbed into the bloodstream of patients. A year later, a newer, bioequivalent generic version of Chloromycetin was approved by the FDA, and bioequivalence has since worked its way into the matrix of proofs required to sell all generic drugs in the United States.

Generic drugs are not marketed as identical to the brand but as the same in all ways that matter. They are allowed to be different from the brand name versions in some respects—in their price, color, size, shape, place of manufacture, the specific dyes used to create them, the filling agents that they contain, the chemical binders that hold their active components together, or the lacquered coatings that they employ—but key to their approval and marketing is the claim that the differences are trivial and the similarities are substantial. As the case of Chloromycetin reminds us, however, our understanding of what is trivial and what is significant in medical sciences is a moving target, a contested form of knowledge that emerges at the interface of interested claims to similarity and difference.

To speak of the chemistry or the biology of equivalence is to name only two of the many possible metrics of similarity and difference that emerge in contests over generic drugs. New sciences of similarity and difference continue to proliferate, and have only become more urgent as generic drugs have grown from roughly 10 percent of all drugs prescribed in 1960 to more than 80 percent of all drugs prescribed in 2010. The FDA has recently expanded funding for new regulatory sciences of generic similarity, with the understanding that new forms of potential difference continue to emerge, requiring new proofs of similarity. Should a different standard of proof be used to prove the similarity of high-stakes drugs (such as immunosuppressants and antiseizure medications) for populations (such as transplant recipients and persons living with epilepsy) for whom a single botched dosage could entail loss of livelihood or life? What new proofs can provide confidence that copies of large and complex biotech drugs are the same as the original versions when the precise molecular structure of the original drugs is not fully knowable?