The US Food and Drug Administration (FDA) has sent a Warning Letter to USPlabs-at least the third in the last two years-regarding an ingredient used in one of its products, which regulators maintain falls afoul of US laws on marketing dietary ingredients.
USP, a Texas-based manufacturer widely known for its workout supplements, has been a frequent target for FDA enforcement actions in recent months.
A Warning Letter, dated 4 December 2012, was sent to the company regarding its Jack3D and Oxy Elite Pro products, as well as a third product known as Super Cissus. The letter focused on the good manufacturing practices used by the company's Dallas, TX manufacturing facility.
In April 2013, the company's Jack3D and Oxy Elite Pro supplements were again the target of an FDA Warning Letter after the agency said it contained dimethylamylamine (DMAA), an ingredient linked to cardiovascular adverse events.
"Ingestion of DMAA can elevate blood pressure and lead to cardiovascular problems ranging from shortness of breath and tightening in the chest to heart attack," FDA wrote in its warning. "Dietary supplements containing DMAA are illegal and FDA is doing everything within its authority to remove these products from the market. FDA has issued warning letters to companies notifying them products with DMAA need to be taken off the market or reformulated to remove this substance."
At issue for FDA in that letter was the company's contention that DMAA was a dietary ingredient, which would allow the product to avoid the premarket assessment process used for new drugs (Section 505 of the Federal Food, Drug and Cosmetic Act). Instead, such ingredients are regulated similarly to food, though with stricter manufacturing standards.
FDA contended that the ingredient's use was not supported by any information "demonstrating that [it] was lawfully marketed as a dietary supplement in the US before 15 October 1994," at which time it would have been grandfathered in as an existing dietary ingredient under federal law. Neither, FDA added, was DMAA known to science as a food item or being found in food in an unaltered state.
Under such conditions, DMAA would need to have approval from FDA as a new dietary ingredient (NDI) under 21 USC 350b(a)(2). Since it did not seek or receive approval from FDA, regulators said the product was therefore adulterated, and USPlabs subsequently pulled Jack3D off the market voluntarily.
Since then, USPlabs has remained in the scope of regulators.
In early October 2013, FDA issued a statement saying that it was coordinating with the Centers for Disease Control and Prevention (CDC) to investigate 29 cases of acute non-viral hepatitis associated with use of Oxy Elite Pro, which the company had since reformulated to remove DMAA.
FDA explained that at the time of its statement, one patient had already died from liver-related issues, while another two had received liver transplants and 11 had been hospitalized with acute hepatitis. As a result, FDA said it was in the process of re-inspecting USPlabs' manufacturing facility and distribution records to determine if the outbreak was caused by Oxy Elite Pro or by counterfeit versions of the product.
Third Warning Letter
Now, just weeks later, FDA is out with yet a third Warning Letter calling into question the safety of both Oxy Elite Pro and yet another product known as VERSA-1.
As with the April 2013 letter, FDA said the products' respective use of aegeline (N-[2-hydroxy-2(4-methoxyphenyl) ethyl]-3-phenyl-2-propenamide) was improper as it was neither natural nor marketed prior to 1994, and thus required registration and approval as a new dietary ingredient. In the absence of such registration, the products are both adulterated, FDA said.
In addition, FDA referenced its public warning on acute non-viral hepatitis, offering new clues that seem to indicate a higher degree of certainty by regulators that Oxy Elite Pro was to blame.
FDA said that 14 of the 20 patients whose records were referred to it by the Hawaii Department of Health had only one common risk factor: they were exposed to Oxy Elite Pro.
"Eight (8) patients reported Oxy Elite Pro as the sole dietary supplement they took prior to becoming ill, and most of these patients had been entirely healthy before they became ill," FDA explained. "Second, upon discontinuing Oxy Elite Pro following onset of illness, most patients recovered from their illness, implying Oxy Elite Pro was the cause of the illness."
The absence of other potential causes for the hepatitis-viruses, autoimmune conditions, hemochromatosis, Wilson's disease, excess acetaminophen ingestion, etc-"increases the likelihood that Oxy Elite Pro played a hepatotoxic role in these patients," regulators concluded.
FDA said the company is therefore ordered to "immediately cease distribution," and that failure to do so could result in immediate enforcement action on the part of the agency.
The company has meanwhile maintained that the ingredient is both safe for use and is appropriately categorized as a dietary ingredient (allegedly an alkaloid derived from the citrus fruit tree Bael). The company has nevertheless withdrawn Oxy Elite Pro from the market "out of an abundance of caution."
USPlabs has 15 days to respond to the letter.
FDA Warning Letter to USPlabs