After a relatively quiet 2017-2018 marked mostly by noticeable decline in FDA inspections of dietary supplements for GMP (good manufacturing practices) compliance, anecdotal evidence indicates the agency has returned to the field and that many of the issues that existed before continue to be gnawing problems for the industry today. Recordkeeping, ingredient and finished product testing, and overall quality control continue to be cited as problems at both the manufacturer and own-label distributor level in warning letters and reports of inspectional observations (FDA 483s).
A new issue that seems to be looming is CBD; investigators have recently started to remind both manufacturers and own-label distributors that the agency does not consider it to be a lawful dietary ingredient. While this subject has only been raised in one warning letter that does not also cite unapproved/illegal drug claims, FDA may be taking steps to prepare industry for stepped-up enforcement in this area.
In light of this uptick in FDA enforcement activity, an overview of FDA’s authority and industry’s responsibilities are in order.
FDA's modern regulatory functions began with the passage of the 1906 Pure Food and Drugs Act (Wiley Act) which prohibited the movement of adulterated and misbranded food and drugs in interstate commerce. The law was enacted only after the publication of “The Jungle” by Upton Sinclair, which documented the horrific, unsanitary conditions in the meatpacking industry. Enforcement authority at this time was vested in the Bureau of Chemistry, which was previously part of the Department of Agriculture. The Pure Food and Drug Act did not have any requirement for drug efficacy.
The regulatory system as we know it was put into place by the Federal Food, Drug and Cosmetic Act (FD&C, 1938). This law created the first uniform federal standards for the safety of food, drugs and cosmetics in response to the Elixir Sulfanilamide tragedy that caused the death of 100 Americans. This Elixer was an untested antibacterial medication that included diethylene glycol (antifreeze) to make it more palatable. For the first time, the law required preapproval for new drugs, a government safety review and established the modern definition of drug: anything that is intended to treat, cure, prevent or mitigate disease in man or other animals. Enforcement of the law was vested solely in FDA, where it remains today.
Major amendments to FD&C have included:
- 1962 Kefauver Harris Amendment requiring drugs be both safe and effective (adopted following the Thalidomide tragedy);
- 1990 Nutrition Labeling Education Act creating nutrient-content claims and standardized label formats for foods;
- 1994 Dietary Supplement Health and Education Act (DSHEA) creating the category of dietary supplements, allowing structure/function claims and directing FDA to promulgate GMPs for supplements;
- 2006 Dietary Supplement and Nonprescription Drug Consumer Protection Act mandating the reporting of serious adverse events to FDA; and
- 2011 Food Safety Modernization Act (FSMA) revamping the way food, including the ingredients used in dietary supplements, is regulated with an emphasis on hazard analysis and risk-based preventive controls (HARPC).
Under FD&C, FDA may enter, at reasonable times, any factory, warehouse or establishment in which food, drugs, devices, tobacco products or cosmetics are manufactured, processed, packed or held, for introduction into interstate commerce or after such introduction, or to enter any vehicle being used to transport or hold such food, drugs, devices, tobacco products or cosmetics in interstate commerce for purposes of enforcing the law and any related regulations.
This means that any time a facility is operating, FDA has the authority to enter and conduct an inspection. If a company is running 24 hours a day, seven days a week, FDA can inspect because there is a presumption that if production or distribution of regulated product is taking place, there must be someone of adequate authority onsite to represent the company during the inspection. On the other hand, if the company operates on a standard 9:00 a.m. to 5:00 p.m. Monday to-Friday schedule, it is not reasonable to start an inspection at 4:00 p.m. on Friday afternoon.
The most common reason for inspections of supplement companies is to verify GMP compliance status.
Contract Manufacturers and Own-Label Distributor Responsibilities
In May 2013, FDA published a “draft” guidance for industry titled “Contract Manufacturing Arrangements for Drugs: Quality Agreements.” The key message delivered by this guidance is that FDA believes that “in all cases, the owner is responsible for assuring that drugs introduced for interstate commerce are neither adulterated nor misbranded as a result of the actions of their selected contracted facilities. All contracted facilities must assure compliance with applicable current good manufacturing practices for all manufacturing, testing or other support operations performed to make a drug(s) for the owner.”
This guidance was published just as FDA issued a series of warning letters to own-label distributors for failure to comply with cGMPs and exemplifies the agency’s thinking that concepts applicable to one area can apply across regulated industries and that it is incumbent upon industry to understand agency thinking at any given time.
For the past six years, warning letters issued to own-label distributors citing failure to properly understand how products made for them are manufactured have stated: “Although your firm may contract out certain dietary supplement manufacturing operations, it cannot, by the same token, contract out its ultimate responsibility to ensure that the dietary supplement it places into commerce (or causes to be placed into commerce) is not adulterated for failure to comply with dietary supplement cGMP requirements.”
The logic behind this approach is explained in the guidance:
“Because the agency considers contractors an ‘extension of the manufacturer’s own facility,’ both owners and contracted facilities are responsible for ensuring that their products are not adulterated or misbranded.
“With respect to contract manufacturing, both owners and contracted facilities must also work together to establish and maintain quality oversight of contracted manufacturing operations and the materials produced under contracted manufacturing arrangements.”
The unequivocal message from FDA to own-label distributors remains:
- Your name is on the label.
- You make the final release decision.
- You are ultimately responsible for ensuring compliance.
Companies that do not understand or accept this ultimate responsibility not only cannot answer the common-sense question, “How do you know the product is made properly and is suitable for release to your customers?” but also invite a warning letter and potentially other enforcement activity from FDA.
Marc S. Ullman, of counsel, Rivkin Radler (rivkinradler.com), represents clients in matters relating to all aspects of FDA and DEA matters, regulatory issues, FTC proceedings and litigation. He practiced with one of New York’s leading white-collar criminal defense firms for 10 years, where he represented clients in both federal and state prosecutions, as well as numerous related civil matters and other litigations.