The dietary supplement industry has been burgeoning since the 1990’s when the number of products on the US market was approximately 4,000. In 2015, the journal Drug Testing and Analysis estimated the number of US manufacturers to be approximately 15,000, accounting for more than 90,000 products and a $40-billion-dollar industry. The Lachman blog has extensively covered issues associated with dietary supplements that contain hidden drug ingredients, make false or drug claims, or are adulterated in some other manner (see here). The Dietary Supplement Health Education Act (DSHEA) was passed in 1994, and gave FDA the responsibility to develop and enforce Good Manufacturing Practices for the industry under 21 CFR Part 111. A Consumer Reports investigation found that since 2010, FDA has inspected, on average, 400 companies per year. This post addresses the requirement for meeting appropriate current good manufacturing requirements.
Recent unfortunate events linked to tainted supplements has once again put supplements in the cross-hairs of the Agency. In 2015, Congress called for increased oversight of the industry. The oversight was a strategic goal of FDA’s Office of Regulatory Affairs (ORA) in fiscal year 2016. And, an interesting crossroad with the Food Safety and Modernization Act (FSMA) is bringing the number of inspections up.
Under FSMA, entities that manufacture, process, pack, receive or hold food are subject to the regulations. The definition of “food” includes dietary supplements. As a result of FSMA, FDA is required to inspect facilities identified as “high risk” once every three years; and, those identified as “low risk” once every seven years. What makes a firm high risk or low risk is not necessarily clear. However, what is clear is that if a manufacturer has been quietly avoiding inspection, their time is going to come soon.
Most in the industry agree that the cGMP regulations set forth in 21 CFR Part 111 are more closely related to regulations for finished pharmaceuticals found in 21 CFR Part 211. As a result of such, FDA routinely sends investigators with a pharmaceutical background to conduct inspections of known or suspect supplement manufacturers, particularly for first time inspections. Further, specialization under ORA’s program alignment initiative is providing stronger training to food investigators working in this field.
Under FSMA, firms can expect that poor regulatory outcomes may result in the new enforcement tools of FSMA potentially being employed. This includes the use of Administrative Detention, preventing a manufacturer from distribution of products at the time that deficiencies are noted by the investigator, a power once wielded only by State enforcement agencies. Finally, an inspection resulting in a Warning Letter, recall, detention or mass destruction is a factor in moving a once “low risk” firm into the “high risk” category increasing the inspectional frequency. Under FSMA, the Agency may charge industry for the cost of follow up inspections necessary to confirm corrective actions and cGMP compliance.
Since January 2016, the FDA has issued more than 45 Warning Letters for adulterated/misbranded supplements. The issues range from failure to comply with cGMPs and/or drug claims associated with the supplement causing it to be considered an unapproved new drug.
The best way to ensure that you are not subject to regulatory action is to prepare well in advance. A regulatory review should be performed to ensure your products are marketed appropriately, not placing them in the category of unapproved new drugs. A compliance review should be conducted to determine if the quality system is robust enough to withstand inspection. Gaps should be evaluated and an action plan should be executed. Finally, if you’ve never been inspected by FDA, a solid plan for managing the inspection should be developed to ensure when the inspection happens, it goes smoothly.
