This is the second article in a three-part series on cGMP (current good manufacturing practice) inspections of dietary supplement firms.
Formulife Inc., a Texas-based manufacturer of sports supplements, has been on FDA’s radar for several years.
Since 2011, the federal agency has inspected Formulife’s dietary supplement facility five times—including the last three years in a row—and warned the company in two letters that it violated multiple regulations, causing its products to be adulterated and misbranded. Over the years, FDA officials have reported violations of labeling and manufacturing regulations, including neglecting to establish written procedures to review and investigate a product complaint, failure to test ingredients and marketing of steroids.
Three times since 2011, FDA has assigned a classification to Formulife that is associated with "significant objectionable conditions or practices" and warranted regulatory action. Despite the "official action indicated" (OAI) designation, U.S. prosecutors have not moved in federal court to seize Formulife’s products or obtain an injunction that would prohibit the company from manufacturing dietary supplements.
In 2014, FDA held a regulatory meeting with Formulife after the company was designated OAI for the third time, according to the agency. In 2015, following an inspection at Formulife’s Dallas facility, FDA assigned a designation to the company that reflected an improvement in its status: "voluntary action indicated," or VAI—what FDA describes as "when objectionable conditions or practices were found that do not meet the threshold of regulatory significance."
Formulife was most recently inspected in July 2016.
FDA investigators reported eight observations—or alleged violations—of the agency’s nine-year-old cGMPs. One observation reported failure to establish product specifications for the purity, strength and composition of the finished product. FDA investigators also alleged Formulife failed to conduct at least one proper test or examination to confirm the identity of a dietary ingredient prior to use. Several observations were repeat violations from previous inspections, the inspection report indicated.
Benjamin Misumi, who directs quality control (QC) and regulatory affairs for Formulife, reported "significant progress" with cGMP (current good manufacturing practice) compliance. For example, he explained the company tests every raw material that it receives and keeps such materials in a temperature-controlled warehouse.
Marianna Naum, an FDA spokeswoman, said the matter involving Formulife remains an open investigation.
"We are taking every measure we can to make sure that we don’t fall into the same noncompliance issues that we fell into in the past years," Misumi said in a phone interview on Nov. 8, 2016.
FDA Targets Noncompliant Supplement Manufacturers
While FDA critics have questioned the agency’s resolve to take swift enforcement action against a dietary supplement industry often mischaracterized as "unregulated," public records show FDA has devoted resources to monitor noncompliant firms. In fiscal year 2015 (FY15), of the 63 dietary supplement companies subject to FDA cGMP reinspections, 32—or roughly half—had been previously designated OAI by the agency, as INSIDER previously reported.
Through a Freedom of Information Act (FOIA) request, INSIDER reviewed FDA inspection reports of five supplement manufacturers that received an OAI designation: Abba Pharma Inc., Formulife, Nature’s Health LLC, Summit Beverage Group LLC and West Coast Labs Inc.
Of the three companies (Abba Pharma, Formulife and Nature’s Health) that responded to INSIDER’s requests for comment, all either cited significant progress with cGMP compliance or contended they had satisfactorily addressed FDA’s concerns. In December 2016, Naum confirmed FDA had not filed for court action against any of them related to cGMPs.
However, FDA—and the U.S. Department of Justice (DOJ)—had no comment when asked if FDA had ever recommended that federal prosecutors take court action against any of the above-mentioned firms. To move for an injunction or seizure of products in federal court, FDA needs the cooperation of DOJ since its lawyers are the ones who bring and prosecute the cases for violations of the Federal Food, Drug & Cosmetic Act (FD&C).
"As a matter of policy, the Department generally neither confirms nor denies whether a matter is under investigation, nor discusses internal deliberations," Nicole Navas, a DOJ spokeswoman, said in an emailed statement. "The Justice Department is committed to addressing the unlawful sale of dietary supplements, and we generally focus on those whose products cause harm and/or who have been warned that their conduct is unlawful."
Joy Joseph, a cGMP consultant who analyzed the five companies’ inspection reports, said she identified flagrant and repeated violations of the cGMPs. Under federal law, supplements that are prepared under conditions that don’t meet the cGMPs are considered adulterated.
"There is a serious lack of understanding by the companies of what is required by GMPs," Joseph said in a phone interview. "And the FDA, in my opinion, is very lenient with them insofar as they can still have the same violations, which fall into the top 10 violations across the nation, and they see the same things three years running, and the action that they [FDA] took was not severe enough so that these people have this stuff corrected."
Enter Nature’s Health, a dietary supplement manufacturer in Salt Lake City. The company was inspected by FDA three years in a row beginning in 2013. In a 2015 inspection report, or "483," FDA reported six observations.
For example, the inspection report alleged the company failed to perform any testing on finished dietary supplement products before releasing them for distribution. The testing observation was partially the same one reported during 2013 and 2014 inspections, an FDA investigator, Christine L. Williams, noted in the 483. In fact, the FDA investigator described all six alleged violations of the cGMPs in the 2015 inspection report as either "repeat" or "partial repeat" observations from prior inspections.
In 2015, FDA designated Nature’s Health OAI. That resulted in a warning letter for cGMP observations and other alleged violations of the FD&C.
Lawrence Lim, the owner of Nature’s Health, declined a request for a phone interview. "We are well aware of the inspections and take FDA regulations seriously," he said in an emailed statement. "All observations and concerns the FDA have made [have] since been addressed."
Summit Beverage Group
For three years in a row, FDA investigators also visited Summit Beverage Group, a company in Marion, Virginia that FDA has described as a dietary supplement contract manufacturer. In an eight-page inspection report dated May 15, 2015, two FDA investigators reported 13 observations related to the firm’s dietary supplement and food operations.
For instance, the fifth observation alleged the company failed to establish any specifications for the identity, purity, strength, composition or limits on contamination for several dietary supplement finished products. In 2014 and 2013, Summit Beverage Group also was cited for failure to establish product specifications.
Geoffrey Soares, CEO of Summit Beverage Group, didn’t respond to requests for comment.
FDA officials and cGMP consultants have characterized the setting of product specifications as a fundamental requirement that is integral to ensuring a supplement contains the ingredients declared on the bottle and is free of undeclared contaminants.
Abba Pharma, a dietary supplement manufacturer in Tampa, Florida, was designated OAI for three years in a row from 2010 to 2012. In a 2015 inspection, FDA reported four observations, including failure to qualify a supplier of a component by establishing the reliability of the supplier’s certificate of analysis (CoA) by confirming the results of its tests or exams.
Separately, FDA said Abba Pharma did not verify its contract labs could perform appropriate tests and had no documentation to establish the company qualified its labs. The observation was similar to those listed on 2011 and 2012 inspection reports, the FDA investigator, Jennifer A. Robinson, said.
FDA designated Abba Pharma VAI in 2015. Carlos Gomez, the president of Abba Pharma, declined a request for a phone interview. Daniel Caamano, an attorney representing the company, said he conferred with Gomez.
"The company is in good standing with the FDA, and there are no outstanding regulatory issues," Caamano said in a brief statement over the phone.
West Coast Labs
West Coast Labs in Gardena, California, is another dietary supplement manufacturer that garnered FDA’s attention. In a 2011 inspection, FDA reported 14 observations, including failure to test every batch of finished dietary supplement, a lack of training records, and failure to develop written procedures for preventing microbial contamination. West Coast Labs was inspected as a follow-up to consumer complaints involving illnesses from taking a weight loss supplement, Lipozene, according to the inspection report.
In 2014, the company was designated OAI, which resulted in a warning letter. In the letter, FDA revealed lab analyses verified the presence of undeclared active pharmaceutical ingredients (APIs) in certain products. Specifically, FDA contended West Coast Labs’ "Super ArthGold" and "Pro ArthMax" products contained one or more muscle relaxants, non-steroidal anti-inflammatory drugs (NSAIDs), and/or drugs that had not been approved for marketing. The letter also asserted the company failed to adequately respond to cGMP observations that were identified during a 2014 inspection. FDA cited an absence of supporting documentation to show corrections had been made.
On April 23, 2015, FDA issued a "close-out letter" that said West Coast Labs appeared to have addressed the violations the agency raised in the 2014 warning letter. Representatives for the company did not respond to requests for comment.
Losing Faith in Promises
Dean Cirotta, president and chief operating officer of EAS Consulting Group LLC, said clients often contact his consulting group because they have received a warning letter for failure to adequately respond to an inspection report.
"People don’t understand the key to addressing these things appropriately—whether it’s a 483 or a warning letter—is submitting the documentation, and the justification for what you did, and that you actually implemented it," he said in a phone interview. "You can’t say just what you are going to do. You have to prove to them that you actually did it, so that they can assess that what you did was acceptable."
But critics of the industry—and some insiders themselves—have questioned whether FDA gives supplement manufacturers like the ones noted above one too many bites at the apple to come into compliance with rudimentary regulations, such as the requirement to test dietary ingredients and establish product specifications.
Joseph, the cGMP consultant, observed FDA’s priority is on safety. Still, FDA—and the DOJ—don’t have unlimited patience and have filed for injunctions against supplement marketers even when there was not an imminent threat to the public health.
"You are going to get to the point where FDA is no longer going to have any faith that they will correct these things," Joseph said, commenting on the inspection reports she reviewed, "and this consultant feels like they need some help."
The Formulife Journey
Formulife captured FDA’s attention as early as 2011. In some ways, Formulife’s story of noncompliance is a microcosm of the various regulatory problems that have plagued the supplement sector.
In spring 2011, FDA inspected Formulife’s dietary supplement facility in Dallas. At the time, Formulife was an own-label distributor, meaning it contracted with a third-party to manufacture its products. In a 2012 warning letter to Formulife and Purus Labs Inc.—an affiliated brand of dietary supplements—following the 2011 inspection, FDA reminded Formulife it was "ultimately responsible for complying with the requirements related to manufacturing operations, even though you have hired another person to perform that job task."
During inspections of Formulife’s facility and an undisclosed manufacturing facility, FDA investigators identified several cGMP violations, rendering Formulife’s products adulterated, an FDA official in the Dallas District, Reynaldo R. Rodriguez Jr., wrote in the Jan. 18, 2012 letter. Additionally, Purus Labs’ website promoted supplements for conditions that caused the products to be drugs, Rodriguez observed in the six-page warning letter. Supplements also were misbranded because they failed to comply with food-labeling requirements, he said.
After returning to Formulife’s facility in summer 2012, an FDA investigator, Ashley N. Williams, stated in an inspection report that the company failed to submit a new dietary ingredient notification (NDIN) to FDA for the use of dimethylamylamine, or DMAA. FDA later described the substance as an unsafe food additive that was associated with cardiovascular risks.
The following year, FDA’s Rodriguez warned Formulife in a letter that failure to cease distribution of products containing DMAA could result in enforcement action without further notice. In the June 17, 2013 letter, Rodriguez cited additional problems, including unapproved drug and food misbranding violations.
FDA returned to Formulife’s facility in early 2014. In an inspection report that listed Formulife as a dietary supplement manufacturer, an FDA investigator, Jamie M. Bumpas, reported 10 observations. The alleged cGMP violations included failure to verify the identity of a dietary ingredient prior to its use through at least one appropriate test or exam, failure to confirm the finished batch of dietary supplement meets product specifications, and incomplete batch production records.
While Formulife acquired reference standards to verify the identity of certain dietary ingredients, the company failed to do identity testing for other dietary ingredients, including milk thistle, saw palmetto and coenzyme Q-10 (CoQ10), among others, according to Bumpas’ inspection report.
In 2015, after yet another visit to Formulife’s manufacturing plant, an FDA investigator, Andrew J. Lang, identified seven observations, including failure to perform at least one appropriate test or exam to confirm the identity of a dietary ingredient prior to use. Specifically, he said Formulife was unable to verify the identity of several dietary ingredients used in the manufacture of Purus brand dietary supplements, including Basella alba, bladderwrack, Tribulus Alatus, white button mushroom, S-adenosylmethionine (SAME) and magnesium creatine chelate.
Williams, the FDA investigator, and a colleague, Dana M. Lewis, reinspected Formulife’s facility in July 2016, reporting eight observations. Misumi, Formulife’s QC director, said he responded to FDA’s 2016 inspection with a corrective plan and has not heard back from the agency.
Misumi said he oversees three QC personnel, including a regulatory affairs person who examines raw ingredients, testing and standard operating procedures (SOPs).
However, at least one of the observations reported by FDA investigators in 2016 related to purported deficiencies in QC oversight. The eighth observation asserted, "Your quality control personnel did not conduct a material review and make a disposition decision when a batch deviated from the master manufacturing record."
Misumi said Formulife has come a long way since he joined the company in January 2016. He has developed Formulife’s SOPs, while the company has purchased reference standards for raw materials, qualified its suppliers, and tests every single raw material, Misumi explained.
Formulife recently moved to a new 42,000-square-foot facility in Allen, Texas. Misumi said the new building affords the company an opportunity to handle greater capacity and be more cGMP-compliant. He added the company was debating whether to work with NSF International or the Natural Products Association (NPA), which both offer services including audits to facilitate compliance with cGMPs.
Asked why it has taken the company so long to implement QC measures, Misumi responded in part, "They didn’t just have someone with that knowledge of everything that needs to be done to keep the whole entire company compliant."
However, Misumi asserted Formulife was now "absolutely compliant" with FDA’s cGMPs. Finally, he said Formulife would move forward with third-party certification, which could add further assurance that the company was following FDA regulations and taking QC seriously.