Physicians are permitted to prescribe drugs off-label. By off-label, I really mean “silent label.” Silent label implies the manufacturer has not received FA approval to market the drug as safe and effective for treating the off-label condition.


An example: some antibiotics have been approved for those 18 or older. The label granted by the FDA likely reflects the submission. The manufacturer might have wanted to keep costs down and only test adults. Most manufacturers know that if a drug is approved for adults, some physicians will prescribe the medication for younger patients. And the law generally allows physicians to do precisely that. (We are aware of only a narrow class of restrictions where the federal government dictates the uses for which a drug can be prescribed – anabolic steroids and human growth hormone). Eventually, the literature will accumulate data about the safety and efficacy of the antibiotic’s use in minors.


So doctors have had significant latitude to prescribe medications off-label.

But, pharmaceutical manufacturers have had their hands tied. They are allowed to market the drugs only for the indications which have been approved by the FDA. So, in the example above, a pharmaceutical rep was not legally entitled to say that the antibiotic can safely be prescribed in children – even if the literature supports that conclusion.


Pharma had several safe harbors. They could send some medical literature about a drug’s off-label use. This was “codified” in 2009 with the inviting title: “Good Reprint Practices for the Distribution of Medical Journal Articles and Medical or Scientific Reference Publications on Unapproved New Uses of Approved Drugs and Approved or Cleared Medical Devices.” That draft guidance focused on what types of literature may be distributed to health care providers as well as the conditions under which such literature may be provided.


Here are a few of the conditions:


The article must be: 1) unabridged; 2) not marked, summarized or characterized by the manufacturer in any way; 3) accompanied by the product’s approved labeling; 4) accompanied by a comprehensive bibliography; 5) accompanied by a representative opposing article that reaches a different conclusion (if one exists); and 6) separate from information that is promotional in nature.


And there are more.


Which brings us to 2012. And USA v. Caronia. Caronia was a pharmaceutical representative who promoted the drug Xyrem for off-label use. Xyrem contains gamma-hydroxy-butyrate (“GHB”) and was indicated for some types of narcolepsy. (GHB has also been implicated in date rape – clearly not an “indicated use.”) In 2009, a federal court found Caronia guilty of criminal conspiracy to introduce a misbranded drug into interstate commerce. He allegedly told a doctor (the conversation was taped) Xyem could be used for “daytime fatigue and excessive sleepiness.” And so on.

The penalty included potential jail sentence – although the judge sentenced him to one year probation, 100 hours of community service, and a $25 special assessment.


A federal appeals court just reversed the conviction. And now a lot has changed.


The appellate court concluded the FDA cannot prevent a pharmaceutical representative from speaking the truth about off-label indications. The court noted that the outcome – physicians prescribing off-label – is allowed. But, speaking about that outcome – a representative’s promotion of off-label – is not allowed. The court believed this did not make sense.


The court acknowledged the FDA has a substantial interest in securing the drug approval process in supporting safety and efficacy of drugs. But,


if the government is concerned that off-label promotion may mislead physicians, it could guide physicians and patients in differentiating between misleading and false promotion, exaggerations and embellishments, and truthful or non misleading information. The government could develop its warning or disclaimer systems, or develop safety tiers within the off-label market, to distinguish between drugs. The government could require pharmaceutical manufacturers to list all applicable or intended indications when they first apply for FDA approval, enabling physicians, the government, and patients to track a drug’s development. To minimize off-label use, or manufacturer evasion of the approval process for such use, the government could create other limits, including ceilings or caps on off-label prescriptions. The FDA could further remind physicians and manufacturers of, and even perhaps further regulate, the legal liability surrounding off-label promotion and treatment decisions. Finally, where off-label drug use is exceptionally concerning, the government could prohibit the off-label use altogether. The possibilities are numerous indeed.


The court continued:


prohibiting off-label promotion by a pharmaceutical manufacturer while simultaneously allowing off-label use “paternalistically” interferes with the ability of physicians and patients to receive potentially relevant treatment information; such barriers to information about off-label use could inhibit, to the public’s detriment, informed and intelligent treatment decisions.


In sum, the court concluded “the government cannot prosecute pharmaceutical manufacturers and their representatives under the [Federal Food, Drug, and Cosmetic Act] for speech promoting the lawful, off-label use of an FDA-approved drug.


I guess there will be much more to discuss next time a pharmaceutical representative brings lunch.