GMP Problems Red Flag Other Regulatory Issues

As the list of companies receiving warning letters related to FDA dietary supplement good manufacturing practice (GMP) inspections and found violations continues to grow, so too does the adjacent regulatory scrutiny of other areas of business, including adverse event reporting and claims. Three recent GMP-driven warning letters also highlighted other regulatory issues that run the companies involved afoul of the law and in need of urgent, multifaceted remedy to satisfy FDA and halt future enforcement action.

The Jan. 25 warning letter to Scilabs Nutraceuticals Inc. detailed several GMP violations increasingly common in the dietary supplement industry, including lack of in-process control specifications, master manufacturing records (MMRs), batch records, storage controls  and various documentation requirements. However, the Irvine, Calif-based contract manufacturer was also warned several of its products are considered misbranded due to failure to include a domestic address or phone number for the responsible party for submission of adverse event reports (AERs).

Exemplifying another problem common to cases of GMP violation, FDA noted in the letter the initial response from Scilabs to the 483 report issued by FDA GMP inspectors was inadequatethe company supplied standard operating procedures (SOPs)  without examples of documents that will serves as its MMR and batch record, and its promise to issue testing specs for incoming ingredients and update its supplier verification program was not accompanied by a proposed testing spec or supporting documents.

The Jan. 29 letter to MDR Fitness Corp. highlighted several equipment-related GMP violations, including written procedures and key documentation, but FDA also warned the company claims made on its website rendered several products as unapproved drugs. Claims made include some pretty typical diseases and conditions such as blood pressure, cholesterol, erectile dysfunction, infection, diabetes and cancer.

Again, FDA warned MDR its response to the 483 report was inadequatethe company said the equipment related procedures would be "redone" but did not specify how the specific violations would be brought into compliance, including copies of any written  procedures.

Most recently, Genesis Herb Co. received a warning letter outlining extensive GMP failures and noting several labeling deficiencies that render those products misbranded. Among the GMP violations FDA inspectors found were: failure to establish and follow written procedures for quality control, MMRs, batch records, production/in-process controls holding/distribution operations and identity testing of raw materials. While FDA noted the company told inspectors it was creating the necessary procedures, specifications and other requirements needed to become compliant, the company never responded to the inspection 483 report or provide any documentation of corrective actions planned or taken.

In pointing out the failure to identify several products as dietary supplements on their labels and the lack of nutrition labeling or Supplement Facts Panel on some of those same products, FDA failed to call the company out for product names, such as Seizure and Gout, that would seem to be implied disease claims. 

INSIDER's Take:

The recurring common, major failures found in FDA GMP inspections of dietary supplement companies have become concerning to both the agency and industry. Take a look at the three recent warning letters to see the specifics of the violations:

To some extent, there was always an expectation dietary supplement GMPs would raise the bar of entry to the industry and leave only the serious and responsible companies. While this may account for some of the extensive failures detailed in these and other warning letters, the companies receiving GMP warning letters aren't all fringe players.

MDR has been in business, in some form, for about three decades, about the same amount of time  Scilabs management has been in the industry, according to the company. Just last spring, Scilabs announced a partnership to manufacture Natrol's Prolab sports nutrition line.

For the established companies, the issue might be lack of a sense of urgency, education, or some combination of both. FDA has stressed education may be inadequate, especially on certain aspects of the regulation. The agency also feels not enough attention is being placed on equipment, and equipment suppliers are, so far, not involved enough to help manufacturers with those aspects of compliance.

These letters, as well as a few sent in 2012, clearly show once a company is on FDA's GMP radar, it is also subject to scrutiny in other areas including labeling, claims and AER matters. When a company has not only foundational GMP failures but also multiple claims or labeling violations, there justifiably should be questions about its regulatory affairs department. Are they utilizing all the industry education resources before and after inspections? FDA has reported many companies expect the agency to be their consultant on GMP specifics, but the agency is not in the business of consulting and has limited resources for its oversight and enforcement duties.

The other problem highlighted in these warning letters is inadequate responses to 483 reports and warning lettersin one case there was no response at all. I just looked at MDR's website and found many of the claims and marketing language noted in the warning letter still on the page (some were changed.)

Pat Riley, CEO and founder of MDR, told INSIDER her company has been dedicated to providing the highest quality products to promote public health for over 20 years and makes every attempt to provide accurate information. "We have corrected most of [FDA's] requests and will complete the others as soon as possible," she reported. Regarding the GMP inspection and violations, she said, "We were told that because we are a drug manufacturer, we are held to a higher standard and inspected more often than typical supplement companies."  Riley further noted MDR utilizes in-house staff to comply with regulations, but would welcome outside expertise to improve procedures.

Industry needs to take GMPs seriouslyexpect to be inspectedand invest time and resources into getting this right. FDA recently closed down a supplement company that repeatedly failed to comply and cooperate. The body count could be higher, and there is no reason to believe it won't be if this non-compliance and seeming defiance continues.