The Durham-Humphrey Amendment of 1951

On Oct. 26, 1951, President Truman signed a two-page amendment to the Food, Drug, and Cosmetic Act, Public Law 82-215¹. It rewrote one subsection, 503(b), to say which drugs “shall be dispensed only” on a practitioner's prescription. Before then, as a North Carolina state history² puts it, “drug manufacturers decided for themselves whether their drugs could be sold with or without the supervision of medical professionals.”

The Durham-Humphrey Amendment, named for Representative Carl T. Durham of North Carolina and Senator Hubert Humphrey of Minnesota, gave the country a legal line between prescription and over-the-counter medicine. A 2016 review of prescription-to-OTC switches³ describes it as the law that “created two classifications of drugs: prescription and nonprescription.”

That line shows up on every generic sold today, from the “Rx only” symbol on a stock bottle to the details a pharmacy prints on a patient's label. It also decides which copies of a drug can sit on an open shelf. FDA is still adjusting where it falls.

Prescription drugs before 1951

Under the 1938 act⁴, drug labels had to carry “adequate directions for use,” though the government could exempt drugs from that rule by regulation. Its original section 503(b) also exempted a drug dispensed on a written prescription from some labeling rules if the label carried the pharmacy's name, the prescription's serial number and date, and the prescriber's name.

FDA used the exemption quickly. Within two months of the act's passage, the agency began identifying drugs, the sulfas among them, that “simply could not be labeled for safe use directly by the patient,” according to its history of the act's amendments⁵. A 2006 Milbank Quarterly history⁶ says 1938 regulations required exempted drugs to carry the warning “Caution: to be used only by or on the prescription of a physician, dentist, or veterinarian,” and that by 1941 FDA officials had identified more than 20 drugs or groups of drugs they considered too dangerous to sell without a prescription.

Still, the statute did not say which drugs needed one. FDA later summarized the result in a 2024 final rule⁷. “Until 1951, the FD&C Act did not contain criteria for determining when to limit a drug's approval to prescription use. As a result, different manufacturers made different decisions about whether to market a drug as prescription or nonprescription.” Pharmacists and patients were left unsure which products were safe without a physician.

What the 1951 amendment said

Congress's new section 503(b)¹ named three kinds of drugs that required a prescription: habit-forming drugs covered by the act's habit-forming drug labeling rule; drugs that, “because of its toxicity or other potentiality for harmful effect, or the method of its use, or the collateral measures necessary to its use,” were not safe without a licensed practitioner's supervision; and drugs limited to prescription use by their new drug application.

It also set out how those drugs could be dispensed: on a written prescription, on an oral prescription “reduced promptly to writing and filed by the pharmacist,” or by a refill the prescriber authorized. Dispensing in any other way made the drug misbranded. A drug dispensed this way was spared most labeling rules if the pharmacy label showed the dispenser's name and address, the prescription's serial number and date, the prescriber's name, the patient's name if given, and the prescriber's directions and cautions.

Every prescription drug had to carry the legend “Caution: Federal law prohibits dispensing without prescription,” and a drug that did not require a prescription was misbranded if it carried that legend. The government could move drugs out of the prescription category by regulation. The amendment took effect six months after enactment.

According to FDA's 2024 rule⁷, which cites the 1951 Senate report, the amendment had two aims, “to protect the public from abuses in the sale of potent prescription drugs” and “to relieve retail pharmacists and the public from burdensome and unnecessary restrictions on the dispensing of drugs that are safe for use without the supervision of a physician.”

How the text has changed since 1951

Most of the 1951 language is still in the current statute⁹, 21 U.S.C. 353(b). The amendment notes there record the main edits.

Congress made the 1997 changes in the FDA Modernization Act (Pub. L. 105-115). The pharmacy label fields listed in the law are the ones explained in GxRadar's guide to reading a prescription label. Which manufacturer's version goes into the bottle is a separate question, governed by the state substitution laws covered elsewhere on the site.

Spending shifted toward prescriptions over the same decades. The Milbank history⁶, citing earlier research, reports that the share of consumer drug spending going to physician-prescribed drugs rose from 32 percent in 1929 to 57 percent in 1949, and that prescription drugs made up 83 percent of consumer drug spending by 1969.

Switches, generics and the “meaningful difference” rule

Because the law sorts drugs by whether they are safe to use without supervision, the same molecule can change sides. A company that wants to move a prescription product to nonprescription status must show it no longer meets the section 503(b)(1) criteria, FDA says in its 2024 rule⁷. Familiar generics such as famotidine and omeprazole are now sold both ways, in different strengths or for different labeled uses, and many end up as the store-brand OTC products on pharmacy shelves.

The two versions can coexist only if they differ in a way that matters. FDA wrote that without a meaningful difference, selling the same active ingredient as both a prescription and a nonprescription product “would result in one of the two products being misbranded.” The agency has pointed to indication, strength, route of administration, dosage form and patient population as examples.

Generics feel this directly. The 2024 rule⁷ recounts FDA's decision to withdraw approval of generic prescription versions of a polyethylene glycol 3350 laxative powder after the product they referenced was fully switched to nonprescription status. A generic must match its reference product, including which side of the 1951 line it sits on.

The newest category, an OTC drug with a condition

In December 2024, FDA finalized a rule creating a “nonprescription drug product with an additional condition for nonprescription use,” or ACNU. Such a product could be sold without a prescription if the applicant adds a condition, such as a questionnaire a consumer must complete, to make sure buyers can select and use it appropriately. The rule's effective date was delayed twice⁸ under a January 2025 regulatory freeze and was set for May 27, 2025.

FDA said an ACNU can itself count as a meaningful difference, so a prescription product and a nonprescription ACNU version of the same drug could be sold at the same time. The agency tied that view to the second goal of the 1951 amendment, relieving the public of unnecessary restrictions. It also said it has “not created a finite list of what may constitute a meaningful difference” and will keep deciding such questions drug by drug.