Section 510 of the Federal Food, Drug, and Cosmetic Act at 21 U.S.C. § 360 Requires Every Person Who Owns or Operates an Establishment Engaged in the Manufacture of a Drug to Register With the Secretary, Section 201(g) at 21 U.S.C. § 321(g) Defines a Drug to Include Any Article Intended to Affect the Structure or Any Function of the Body, the Human Gut Microbiota Comprises an Estimated 38 Trillion Bacterial Cells That Synthesize Vitamin K2, B Vitamins, and Gamma-Aminobutyric Acid and Regulate the Body’s Own Production of Serotonin Around the Clock, the Agency Determined in 2013 That Fecal Microbiota Meets the Definition of a Drug and a Biological Product, No Establishment Has Ever Registered, No Current Good Manufacturing Practice Regulation Has Ever Been Observed, and the Largest Unregistered Drug Manufacturing Operation in America Operates Inside Approximately 341.8 Million Americans

I. The Registration Requirement

Section 510 of the Federal Food, Drug, and Cosmetic Act, codified at 21 U.S.C. § 360, provides that every person who owns or operates any establishment engaged in the manufacture, preparation, propagation, compounding, or processing of a drug or drugs shall register with the Secretary the person’s name, places of business, and all such establishments.¹ The requirement was added by the Drug Amendments of 1962 and has been in continuous effect for more than six decades. It is the instrument by which the Food and Drug Administration knows where drugs are made in the United States, who is responsible for making them, and where to send the inspectors.

The consequences of noncompliance are set out in the statute itself. Section 502(o), codified at 21 U.S.C. § 352(o), provides that a drug is deemed misbranded if it was manufactured, prepared, propagated, compounded, or processed in an establishment not duly registered under section 510.² Section 301(p), codified at 21 U.S.C. § 331(p), makes the failure to register a prohibited act.³ The introduction or delivery for introduction into interstate commerce of a misbranded drug is likewise prohibited under section 301(a). The scheme is comprehensive. Every establishment that manufactures drugs must register. Drugs made in unregistered establishments are misbranded. The introduction of misbranded drugs is unlawful. That is the theory.

The theory has an exception. It is microscopic, anaerobic, and located approximately three feet inside every American.

II. The Definition

Section 201(g) of the Act, codified at 21 U.S.C. § 321(g), defines a drug to include “articles (other than food) intended to affect the structure or any function of the body of man or other animals.”⁴ The definition turns on intended effect, not on the identity of the manufacturer. It does not require that the article be synthesized in a facility with a loading dock. It does not require that the article be sold. It does not require that the article be labeled. The agency determines intended use objectively, from all relevant evidence concerning the article and the circumstances of its distribution.

The articles under investigation in this matter are not labeled. They are not advertised. They carry no package insert and no National Drug Code. They are manufactured anyway, continuously, in quantities that affect the structure and function of the bodies in which they are produced. The statute says what it says.

III. The Facility

In 2016, Ron Sender, Shai Fuchs, and Ron Milo of the Weizmann Institute of Science and the Hospital for Sick Children published revised estimates for the number of human and bacterial cells in the body in PLoS Biology. Integrating MRI-based organ volume measurements with bacterial density data from the colon, they estimated the total number of bacteria in a 70-kilogram “reference man” at 3.8 × 10¹³, against 3.0 × 10¹³ human cells, for a total microbial mass of approximately 0.2 kilograms.⁵ Thirty-eight trillion bacterial cells. The facility’s workforce outnumbers its host’s own cells by a ratio of approximately 1.3 to 1.

The facility operates around the clock at a constant 37 degrees Celsius in an anaerobic environment. It has no shifts. It observes no holidays. It has no written standard operating procedures, no organizational chart, and no employee of the month program, but it has never shut down for maintenance in the recorded history of the species, which suggests a level of operational continuity that the licensed pharmaceutical industry has never achieved.

There is one such facility in every American. The Census Bureau puts the resident population at 341,784,857 as of July 1, 2025.⁶ That is approximately 341.8 million establishments, each engaged in the continuous manufacture of articles that affect the structure and function of the body, and not one of them has ever registered under section 510.

IV. The Product Line

The facility manufactures at least four product lines of regulatory significance.

Serotonin. Enterochromaffin cells of the gastrointestinal tract produce up to 95 percent of the body’s total serotonin, coordinating motility, secretion, sensation, and gut-brain communication.⁷ The gut microbiota itself regulates this production: spore-forming members of the gut community control host serotonin biosynthesis, and peer-reviewed reviews report direct evidence of serotonin production and turnover by the gut microbiome.⁸ Serotonin is the target of the most widely prescribed class of psychiatric drugs in human history. The facility manufactures the endogenous supply without a prescription, without a label, and without a manufacturing license.

Vitamin K2 and the B vitamins. Human gut commensals synthesize vitamin K2 as well as the water-soluble B vitamins: biotin, cobalamin, folic acid, niacin, pantothenic acid, pyridoxine, riboflavin, and thiamine.⁹ Metagenomic modeling has estimated that the gut microbiota could provide up to 86 percent of the daily reference intake for pyridoxine, 37 percent for folate, and 31 percent for cobalamin.¹⁰ Vitamin K regulates blood clotting. The B vitamins drive cellular metabolism. Each is an article that affects the structure or function of the body. Each is manufactured in situ, daily, in an unregistered establishment.

Gamma-aminobutyric acid. Barrett and colleagues demonstrated in 2012 that culturable bacteria from the human intestine, including strains of Lactobacillus and Bifidobacterium, produce gamma-aminobutyric acid, the principal inhibitory neurotransmitter of the mammalian nervous system, with reported production in the millimolar range.¹¹ Subsequent genomic surveys of more than a thousand Bifidobacterium genomes confirmed that the genetic machinery for GABA synthesis is prevalent among human gut isolates.¹² GABA exerts tranquilizing, antihypertensive, and immunomodulatory effects. It is, by the agency’s own definition, a drug. It is manufactured in the human colon by organisms that have never heard of the agency.

The product line affects the structure or function of the body in the most literal sense available. It regulates clotting, metabolism, motility, and neurotransmission. Under section 201(g), these articles are drugs. Under section 510, the establishments that manufacture them must register. None has.

V. The Quality System Failure

Registration is only the beginning of the regulatory scheme. The Act’s current good manufacturing practice regulations, codified at 21 CFR Parts 210 and 211, govern every aspect of drug production: facilities, equipment, personnel, components, production and process controls, packaging, labeling, laboratory controls, and records.

Section 211.22 requires every drug manufacturer to maintain a quality control unit with the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging material, labeling, and drug products.¹³ The gut microbiota has no quality control unit. It has never approved or rejected anything. Its release decisions are made by peristalsis.

Section 211.186 requires master production and control records for each drug product, and batch production and control records documenting the complete history of each batch.¹⁴ The facility has never issued a batch record. It has never assigned a lot number. It has never retained a sample. Its entire production history, spanning the lifetime of every human being who has ever lived, exists nowhere in documentary form.

Section 211.100 requires written procedures for production and process control. The facility has no written procedures. Section 211.166 requires stability testing. The facility has never tested stability; it simply continues. Environmental monitoring consists of the environment being 37 degrees and dark, which is maintained with perfect consistency but documented with perfect absence.

Section 704 of the Act, codified at 21 U.S.C. § 374, authorizes the agency to inspect any establishment in which drugs are manufactured, processed, packed, or held.¹⁵ The agency has never inspected a gut. No Form FDA 483, the agency’s official record of inspectional observations, has ever been issued to a colon. The largest drug manufacturing operation in the country has operated for the entire history of the species without a single inspectional observation, because there has never been a single inspection.

VI. The Double Standard

The agency’s position on this exact material, when it appears outside the body, could not be clearer. In 2013, the FDA determined that fecal microbiota meets the definition of a drug and a biological product, and that an investigational new drug application is required to conduct clinical studies of fecal microbiota transplantation in humans, even when investigators have no plan to develop a commercial product.¹⁶ The agency has since issued warning letters to firms marketing microbiota products without an approved biologics license or an IND in effect, informing them that their products are “both unapproved new drugs and unlicensed biological products” and that introducing them into interstate commerce violates the Act.¹⁷

Consider the regulatory geography. The same organisms, manufacturing the same compounds, are a drug the moment they cross the threshold of the body and an unregulated non-event while they remain inside it. The agency regulates the loading dock and ignores the factory. A company that packages these bacteria in a capsule faces a warning letter; the 38 trillion bacteria already manufacturing drugs inside the company’s own customers face nothing. The distinction has no basis in the statute. Section 201(g) does not say “articles intended to affect the structure or function of the body, provided the articles are first removed from the body and placed in commerce.” It says articles intended to affect the structure or function of the body. The articles inside the body affect the structure and function of the body more directly than any article the agency has ever regulated, because they never leave it.

VII. The Enforcement Arithmetic

Each unregistered establishment constitutes a prohibited act under section 301(p). Each article manufactured in an unregistered establishment is misbranded under section 502(o). The census count is 341,784,857 Americans.¹⁸ That is 341.8 million unregistered establishments, manufacturing misbranded drugs continuously, in every state, in every territory, in every time zone, including Alaska and Hawaii, which the agency has also never inspected for this purpose.

The agency maintains a public registry of every establishment that has complied with section 510. The gut microbiota appears on it zero times. The compliance rate for the largest drug manufacturing sector in the United States is therefore zero percent, a figure unmatched by any other regulated industry in the agency’s history, including the industries the agency has described as having compliance problems.

VIII. Conclusion

Section 510 of the Food, Drug, and Cosmetic Act requires every drug manufacturing establishment to register with the Secretary. Section 201(g) defines a drug to include any article intended to affect the structure or function of the body. The human gut microbiota comprises an estimated 38 trillion bacterial cells per person. It synthesizes vitamin K2, the B vitamins, and gamma-aminobutyric acid. It regulates the production of up to 95 percent of the body’s serotonin. These articles affect the structure and function of the body. They are drugs.

The establishments that manufacture them have never registered. They have never implemented current good manufacturing practice. They have never maintained a quality control unit, issued a batch record, or submitted to an inspection. The agency has determined that the same material is a drug when it leaves the body and has exercised enforcement discretion only for a single narrow indication. Inside the body, where the manufacturing actually occurs, the agency has done nothing.

The operation continues tonight. Approximately 341.8 million unregistered establishments will manufacture drugs while their owners sleep, without a single registration, without a single batch record, without a single inspection, in continuous violation of a statute that has been on the books for more than sixty years.

Ergo.