The Secretary has decided not to enforce a list he has not written

The federal government keeps a list of raw drug ingredients that nobody has approved and that your pharmacist may mix into a medicine for you anyway. Congress ordered the list in 1997. The first entries arrived in 2019. There are six entries today, and the first one is a blue dye.

That is twenty-one years of rulemaking for six ingredients, or one every three and a half years, and five of the six are marked "for topical use only." Nothing has been added since. The regulation then says of its own six that "there are inadequate data to demonstrate the safety or efficacy of any drug product compounded using" them, and that anyone who says the FDA has approved or endorsed one of them has misbranded the drug. It is the only government list I know of that comes with a note asking you not to take it as a recommendation.

Meanwhile the country has discovered peptides. A peptide is a short chain of amino acids, and the popular ones have names like license plates: BPC-157, TB-500, KPV, MOTS-c. The first two are promoted, the Associated Press reports, to help heal injuries and build muscle. Buyers often order vials online, labeled for research use only. The Secretary of Health and Human Services, Robert F. Kennedy Jr., has called himself a "big fan." None of them is on the list. So on October 30 the Secretary published a notice in the Federal Register announcing that, for six of them, his department "does not intend to take enforcement action against a State-licensed pharmacy, Federal facility, or licensed physician" who compounds one. The public was given two weeks to comment. The docket closes Friday night at 11:59, and as of this morning it showed 115 comments posted.

I read the whole thing, which did not take long. The notice occupies two pages of the Federal Register by citation and rather less than one by the ruler. The policy behind it runs sixteen pages: four of policy and twelve of chemistry. There are ten conditions. The patient needs a prescription. The product may contain one peptide and no more. The powder has to come from an FDA-registered plant with a certificate of analysis. Serious side effects go to the FDA's MedWatch program. The only device in the box may be a cleared syringe, and the label must say, "This is a compounded drug product. Not for resale." The Secretary, it says, "has determined that the policy advances patient choice and freedom while appropriately protecting patient safety."

Then the notice adds that the policy "does not establish any rights for any person and is not binding on HHS or the public." Freedom, with no rights attached and nobody bound. I have had gym memberships with firmer terms. The notice also calls the document a "draft" in one paragraph and "this interim policy" in another, which leaves a pharmacist to guess whether he is being invited to comment or invited to start.

What is in the vial

For that you want the slides the FDA's own staff showed its Pharmacy Compounding Advisory Committee on July 23. BPC stands for Body Protection Compound, a name that sounds like something you would spray on a deck. It is fifteen amino acids long and was "first described in 1993." The staff evaluated it as a treatment for ulcerative colitis. The nominations that brought it to the agency had been withdrawn, and the FDA went ahead on its own. The pharmacology studies "have been limited to rodent models." The "mechanisms of action of BPC-157 are unknown." Injected into a vein, half of it is gone from a rat in 15.2 minutes and from a beagle in 5.3.

The human record, by the staff's count, is a handful of small studies and about 81 people. Roughly fifty of them received BPC-157 as an enema, and among the healthy volunteers in that group the side effects reported most often were "headache and flatulence." Seventeen had it injected into a knee, twelve into the bladder, and two got it by IV. The FDA found no study that gave it to a human being by mouth or under the skin. The Secretary's policy covers BPC-157 by mouth, under the skin, into the muscle and on the skin. The one route with fifty test subjects behind it did not make the appendix.

The staff's conclusion on BPC-157 was that "a balancing of the criteria weighs against" listing it. They reached the same conclusion, in nearly the same words, on all seven peptides the committee took up over two days. For MOTS-c, which the staff reviewed for obesity and osteoporosis, the slide reads, "No information on the use of MOTS-c-related BDSs administered in humans." BDS is bulk drug substance. The sentence is otherwise in English.

On six of the seven, the committee voted the other way. On BPC-157 the count was 8 to 6 with one abstention, ABC News reported that afternoon, in a vote that binds no one. Seven peptides went into the meeting and six came out on the Secretary's Appendix A.

Peptide	Amino acids	What the FDA staff reviewed it for	What HHS says it will leave alone
BPC-157	15	Ulcerative colitis	Injection under the skin or into muscle, oral and topical forms
TB-500	7	Wound healing	Injection under the skin or into muscle
KPV	3	Wound healing and inflammatory conditions	Topical and oral forms
MOTS-c	16	Obesity and osteoporosis	Injection under the skin or into muscle
Epitalon	4	Insomnia	Injection under the skin or into muscle, in intermittent courses
Semax	7	Cerebral ischemia, migraine and trigeminal neuralgia	Intranasal use

Appendix B takes the six one at a time, and each entry carries a version of the same sentence: the FDA's drug center "recommended against listing either form," and the committee "voted in favor." Then the department explains why its scientists should not trouble anyone. Their safety concerns about TB-500 are "inferential rather than observed." About Epitalon they are "mechanistic rather than based on observed harm." About KPV their conclusion "reflects an absence of information rather than an observed signal." Which is to say that nobody has looked, and so nobody has seen anything. By that standard my basement is free of radon. For MOTS-c the department reports that the evidence "points in one direction," and cites a trial of "a MOTS-c analogue," meaning a different molecule.

My favorite is condition eight. Peptides are hard to absorb through the gut, the policy concedes, so a pharmacy that makes an oral version "is expected to maintain documentation confirming that the specific formulation provided to a patient achieves an adequate level of oral bioavailability in humans." The FDA, with a building full of pharmacologists, could not find a study of BPC-157 swallowed by a person. The strip-mall compounder is to keep one in a drawer.

Why it came as a shrug

According to the AP, citing people familiar with the drafting, the department first wanted a regulation that would put BPC-157 and its cousins on the list. FDA officials warned that the agency's scientific staff "wouldn't support a regulation deeming them safe." So the department "moved to a different approach that would direct the FDA not to enforce its rules against pharmacies that compound the substances."

There is a famous case about that approach, and the FDA is in it. A group of men on death row in Oklahoma and Texas had asked the agency to move against the drugs the states planned to use on them, on the theory that nobody had approved the drugs for that purpose. The agency declined. In Heckler v. Chaney, decided in 1985, the Supreme Court held that an agency's decision not to enforce "should be presumed immune from judicial review." Justice Rehnquist left a door open in footnote 4 for an agency that has "consciously and expressly adopted a general policy" so extreme that it amounts to "an abdication of its statutory responsibilities." Whether a signed and published policy that names six drugs is that kind of policy is a question I leave to the people who will bill for it.

But you can see the appeal. A rule that adds a peptide to the list has to go through the advisory committee, a consultation with the United States Pharmacopeia, a public comment period, and then a courtroom, where someone will ask what the evidence was. A decision not to enforce goes through the Secretary. The doctrine that once let the FDA ignore the executioner's pharmacy now lets the Secretary ignore the gym's.

It does not let anyone else ignore anything. The statute has not changed, and it still says an ingredient like this must "appear on a list developed by the Secretary through regulations." The department "may revisit" the policy whenever a safety problem turns up, and the next Secretary may revisit it for no reason at all. The FDA's own second slide says this kind of compounding is "primarily overseen by state regulators," and a federal promise to look away is not addressed to a state board of pharmacy. The pharmacist who buys a clean room on the strength of this document, and the telehealth company that hires a sales force, are building on a promise that says on its face that it is not one.

And the rules they are being excused from were not written out of boredom. In 2012 a compounding pharmacy in Massachusetts shipped contaminated steroid injections. The Justice Department's account, as of 2021, is that 753 patients in 20 states were diagnosed with fungal infections and more than 100 died. Congress rewrote parts of the compounding section the next year.

Here is where I come out. I think a grown man ought to be able to buy fifteen amino acids with a rat study behind them, inject them into his own shoulder, and report back on the results. The burden of proof belongs to the regulator, and this regulator has not carried it. In twenty-nine years the FDA has formally listed six ingredients and formally refused four. Everything else, these peptides included, has waited in line. From September 2023 until this April they sat in something the FDA called Category 2. The AP's account is that in 2023 the agency added more than a dozen peptides, BPC-157 and TB-500 among them, to its list of substances that should not be compounded. The department now says that "neither the placement nor the removal changed" their legal status. A category whose entrances and exits change nothing is a waiting room, and you do not get to run a waiting room for the better part of three decades and then complain that people left through the window.

But the burden runs to the Secretary too, and he has more than a burden. He has a pen. The statute says "the Secretary shall" write the list, and the AP notes that federal law gives his department authority over essentially all drug regulation. He could put BPC-157 on it, sign his name, and defend the choice in court with whatever the committee heard. He has instead issued a note saying he will not enforce the absence of a rule he has not written, after FDA officials warned, by the AP's account, that the agency's scientists would not support one. That is not deregulation. Deregulation repeals something. This leaves the prohibition exactly where it was and asks the country to rely on the Secretary's mood.

Comments are due Friday. Mine is that six peptides deserve what the blue dye got, which is a line in the Code of Federal Regulations or a refusal with reasons a court can read. The list waited twenty-one years for its blue dye. At that pace the peptides will be legal just in time for none of us to need a longevity drug.

Columns are the views of their authors. They are not legal advice and not the position of the firm.