Perhaps you’ve noticed on the bottom of a prescription form the words “may substitute” below the doctor’s signature. Maybe you’ve seen your generic medication change color or size when you’ve gotten a prescription renewed. But have you ever wondered about the history of the multi-billion-dollar generic
? Should we take these products for granted? Should we worry if they are really the same as brand name medications? How does the federal government determine that
are equivalent and how has that definition changed over time? We know that the Affordable Care Act includes
and allows insurers to only cover generics when they are available.
Generic drugs are copies of brand name drugs and the Food and Drug Administration says they must demonstrate the "same high quality, strength, purity and stability" as brand name drugs. What is the history of generic drug?
Greene: The rise of the modern generic drug industry over the past 50 years required new ways of making knowledge about drugs—not based on proofs of efficacy or safety but rather a series of emerging sciences of similarity. These proofs and protocols are over the course of the 20th century used to demonstrate that one medicine is good enough to take the place of another, and they are still evolving today. Ways of knowing can take many forms—physical, chemical, biological, epidemiological, and managerial—and emerged in turn at a distinct moment and amid significant political controversy and economic interest. For each established protocol of similarity, there are new potential sciences of difference that may yet emerge. We see this now with the problem of regulating biosimilarity in off-patent biotech drugs.
What is the history of the generic drug industry and what role does it play in health care today?
Greene: There has been a market for cheaper copies of expensive drugs for centuries, but I begin my history of the modern generic drug industry in the postwar United States. By the early 1960s, all the "wonder drugs" patented in the 1940s and 1950s were beginning to go off-patent. Consumer groups and private and public insurers were looking for ways to reduce their increasingly expensive pharmacy bills. Looking at the ways that companies interacted with the FDA, I saw that there were many different ways of making and selling products that claimed to be the same. Some firms sought FDA approval for their products, others mixed up batches of imitative drugs in the pharmacological equivalent of a bathtub and sold them without approval until the FDA ordered them to shut down. The trajectory of the generic industry from 1964 to 2014 is both a story of increasing transparency, legitimacy, and penetration of FDA regulation and one of changing scope and scale. The "little pharma" companies of mid-century became multinational corporations with global sales volume every bit as large as the "Big Pharma" firms.
You mentioned in a recent interview that generic drugs look different from brand name drugs because of trademark rather than patent protection. Can you explain this?
Greene: Unlike patents, which expire after a period of 17 (or 20) years, trademarks can be maintained in perpetuity. And trademark law protects more than just the brand name—it extends to the color, size, shape, taste, and feel of a product, as long as those attributes are not considered to be relevant to how the product functions. This explains why your pills look the same each month when you consume a brand-name drug but may change appearance month by month when your prescriptions are generically filled. There have been legal cases, since the 1950s, about whether the appearance of a drug might affect its therapeutic function. Current FDA regulations treat appearance as a trivial difference. But is it? Colleagues at the Brigham & Women's Hospital in Boston demonstrated that patients discharged from the hospital on a standard cocktail of preventive medicines after suffering a heart attack did a substantially better job at taking their medicines if they stayed the same size, shape, and color from month to month. The FDA is pursuing further studies to determine when appearance may be a nontrivial factor in a drug's functionality and to use the findings to ensure that generic drugs are the same in all important respects.
Looking ahead, what problems and potentials do you see in the arena of generic drug prescribing?
Greene: There are many challenges in generic drug prescribing. In the case of epilepsy, organ transplant recipients, and persons living with HIV/AIDS, patient advocacy groups have been arguing that some drugs should require higher standards of similarity than others, and they have been successful in changing state generic substitution laws in some states to that effect. Additionally, generic competition doesn't always produce the kind of cost-savings we hope for: lucrative pay-for-delay deals, rising prices of some generic drugs made by only one or two manufacturers, and increasing waves of generic drug shortages show there are costs as well as benefits to finding private-sector solutions to public health problems. As the supply chain for active pharmaceutical ingredients becomes increasingly globalized, it has become harder to maintain regulatory access to all sites of pharmaceutical production. And as the "large molecule" biotech drugs of the 1980s and 1990s go off patent in the 2010s, it is far from clear that a competitive generic marketplace will emerge for these products. Nevertheless, generic drugs remain one of the few success stories in several decades of otherwise failed attempts to provide high quality health care in the United States for less money. The history of generic drugs offers many lessons for policymakers, practitioners, and consumers of health care for the present and future.
Jeremy Greene, M.D., Ph.D. is Associate Professor of Medicine and Elizabeth Treide and A. McGehee Harvey Chair in the History of Medicine at Johns Hopkins University.