If you’re a supplement manufacturer, the date June 25, 2010 may be etched into your memory. It’s the date by which all supplement makers must comply with the U.S. Food and Drug Administration (FDA)’s good manufacturing practices (GMPs) guidelines for dietary supplements.

The three stages of compliance have been rolling out since 2008, and several companies have already been visited by FDA inspectors. Once an inspection is completed, inspectors file a Form 483, which cites any deficiencies in a company’s quality systems and any ways the firm is out of compliance with GMPs.

Analysis of these 483s, such as that offered by FDA’s Carl C. Reynolds at a recent industry event*, offers insight into the key areas of interest from FDA investigators and how industry companies can meet their expectations.

Surprising Findings from FDA
First, Reynolds, a senior advisor for the Center for Food Safety and Applied Nutrition, noted that there have been few inspections of dietary supplement manufacturers’ plants. There were 12 in FY2008 and 28 in FY2009, which resulted in one warning letter and one untitled letter, though several more are under review for possible action. While it’s too early to draw any hard-and-fast conclusions, some general trends can be identified.

Overall, most plants were in compliance. But Reynolds felt the inspectors’ findings of those that were not were surprising. The agency is finding that companies are out of compliance with some very basic rules, which is “troubling,” he stated.

• The first observation was shocking: insect and rodent activity in storage and manufacturing areas. Part of the reason for this citation is that companies don’t have well-documented plans for dealing with pests, if they are found. “You must have procedures in place…companies aren’t going far enough,” he added.

• Another surprising lapse in GMP compliance was that some companies weren’t formulating to meet 100% of the label specifications. He noted that some products were formulated to 90% because that is what the U.S. Pharmacopeia indicates. Reynolds stated this is not applicable for GMP compliance.

• Reynolds stated that many companies had incomplete identity testing records (or lacked them completely!). “That’s a biggie,” he said.

• In addition, companies were missing or had incomplete master manufacturing or batch records. A main reason why was because the firms didn’t have a basic understanding of what these records should entail. “The controlling document is the master,” he said, noting that batches are faxes of the master.

• Companies aren’t following their quality control (QC) procedures and their staffs are making errors. “Some QC personnel haven’t been adequately trained in their duties,” Reynolds stated. For example, they are failing to collect representative samples. Another basic problem: departments other than the quality unit (like production) are responsible for the final release of a batch. Only quality control/assurance personnel should take care of this duty.

• Some manufacturers aren’t properly qualifying their ingredient suppliers. “You must test the identity of all components,” he stated. You can only rely on certificates of analysis if you have qualified the supplier for certain non-active ingredients.

• Another red flag noted by Reynolds was that some companies’ standard operating procedures (SOPs) haven’t been changed in years. “They aren’t stagnant,” he said, “[They] should be regularly reviewed and revised.” If a company hasn’t changed them in years, the agency often found they were out of compliance with their written SOPs. “Changes must be documented and approved,” he stated.

Overall Trends
In summary, companies aren’t understanding some basic terminology (such as the term “specification”) and concepts found in the GMPs. He suggested reading the preamble to put the rules in perspective, and stated that the FDA will publish a guide to help industry better interpret the rules. This document is currently under review at FDA.

There are two additional items that are not directly in the GMPs that are important to note. First, FDA wants to see how companies are handling adverse events; they want manufacturers to look into complaints. Second, during an inspection, FDA wants investigators to select two products and trace their history. Often, the products they choose are the ones that are manipulated the most. And, they are looking for data to support shelf life dating.

So how’s industry doing with GMP compliance so far? It seems some companies get a passing grade while others have areas that need improvement. WF

* Presentation delivered at SupplySide East, Secaucus, NJ, April 27, 2010.


Published in WholeFoods Magazine, July 2010 (Published online ahead of print, June 21, 2010)