The US Food and Drug Administration (FDA) issued a Federal Register notice on April 6, 2009, requesting public comments regarding economically motivated adulteration (EMA).1 Comments were requested on “ways in which the food (including dietary supplements and animal food), drug, medical device, and cosmetic industries, regulatory agencies, and other parties can better predict and prevent economically motivated adulteration with a focus on situations that pose the greatest public health risk.”1 The deadline to submit comments was early August 2009.
Some examples of EMA mentioned in the notice have involved serious health risks. Melamine added to some milk-based infant formulas (to increase nitrogen levels and give the impression of higher protein content) was responsible for the death of 6 infants in China.1 There were also 150 deaths in the United States between 2007–2008 associated with the intravenous anticoagulant drug heparin, which was contaminated with oversulfated chondroitin sulfate that was not detected during the original quality tests (these tests have now been updated to recognize this contaminant). The illegal substitution of diethylene glycol for glycerine was responsible for the death of 70 children in 1996 in Haiti and 50 children in Nigeria between 2008 and 2009. An example of an EMA in a dietary supplement, not mentioned in the notice, was the FDA’s discovery in 2009 of unapproved steroids added to body-building products of American Cellular Lab of Pacifica, California.2 These products were being illegally marketed as dietary supplements.
The FDA notice called for suggestions on how to combat this mounting problem as well as ways to clarify the agency’s working definition of EMA. The current working definition is as follows:
EMA [is] the fraudulent, intentional substitution or addition of a substance in a product for the purpose of increasing the apparent value of the product or reducing the cost of its production, i.e., for economic gain.1 EMA includes dilution of products with increased quantities of an already present substance (e.g., increasing inactive ingredients of a drug with a resulting reduction in strength of the finished product, or watering down of juice) to the extent that such dilution poses a known or possible health risk to consumers, as well as the addition or substitution of substances in order to mask dilution.
On August 3, 2009, the American Herbal Products Association (AHPA) submitted comments to the FDA, including a suggested revision of the above EMA definition. AHPA suggested the replacement of the word “product” with “ingredient, component, or product” to clarify that a product should be considered adulterated when it contains an adulterated ingredient or component.3,4 AHPA also pointed out in its comments that a definition of adulteration should not be limited to a situation that poses a health risk: “Whether or not any specific instance of EMA presents a health risk should not be a factor in defining intentional adulteration for economic gain as economically motivated adulteration.”4
AHPA also suggested the addition of the following sentence to the revised definition of EMA, to discourage the addition of substances that can cheat quality tests, as well as highlight the problem of products that achieve certain desired effects by substituting illegal undeclared drugs: “EMA also includes, but is not limited to, the addition or substitution of substances in order to allow an adulterated ingredient or product to conform to identity and other quality tests used for genuine articles, or in order to have a physiological effect that is dependant upon the added or substituted substance.”
“I believe the definition we’ve provided will assist [the FDA] because it’ll make it clearer what is meant by economically motivated adulteration,” said AHPA President Michael McGuffin (oral communication, September 15, 2009).
“They’re not doing this because of big problems with herbs. They’ve recognized that adulteration is rampant,” said McGuffin, pointing out that adulterated herbs and supplements were not even mentioned among the FDA’s examples of EMAs in the Federal Register notice. “Deliberate adulteration does no one any good except the cheater.”
In comments submitted to the FDA by the Council for Responsible Nutrition (CRN), Andrew Shao, PhD, vice-president of scientific and regulatory affairs at CRN, referred to EMA as a “‘two-way street.’ If there are willing buyers of sub par raw materials, whose true actives are substituted with or ‘cut’ by less expensive (and at times dangerous) materials, there will always be willing sellers. Manufacturers that knowingly accept economically adulterated raw materials, whether through failure to qualify suppliers, failure to properly identify materials by using outdated, nonspecific assays, or by just turning a blind eye, should be reprimanded by FDA…FDA can only hold these companies accountable by increasing the frequency and intensity of inspections of manufacturers’ facilities.”5 He further wrote that CRN encourages the FDA to work collaboratively with the dietary supplement industry to develop guidelines for ingredient supplier qualification, as this would likely reduce instances of EMA.
According to Shao, “EMA is a serious, and in some instances, dangerous issue. At a minimum, it undermines consumer confidence and, at the extreme, costs lives.”
It is unclear at press time when the FDA plans to have a revised definition of EMA or what new policies may be implemented to combat this problem.
–Kelly Saxton Lindner
- Food and Drug Administration. Economically motivated adulteration; public meeting request for comment. 74 Federal Register 64; April 6, 2009.
- Lindner K. Drugs illegally marketed as supplements also mislabeled by media. HerbalEGram: September 2009; 6(9).
- AHPA urges FDA to address ‘spiking’ in EMA definition [press release]. Silver Spring, MD: American Herbal Products Association. August 5, 2009.
- McGuffin M, Young A. Comments of the American Herbal Products Associations on Economically Motivated Adulteration. Silver Spring, MD: American Herbal Products Association; August 3, 2009.
- Shao A. Response to Docket No. FDA–2009–N–0166. Economically Motivated Adulteration. Washington, DC: Council for Responsible Nutrition; July 31, 2009.
GMP Standards and Experiences Elsewhere in the WorldOther countries have implemented their own GMP standards and procedures for dietary supplement companies. In 2003, Health Canada approved the Natural Health Products Regulations (NHPR), Part 3 of which includes GMP regulations for natural health products, such as dietary supplements.1 Under this rule, manufacturers, packagers, labelers, and importers must qualify for and obtain a site license by demonstrating that they meet GMP requirements. NHPR resulted from extensive and ongoing consultation with the industry, which probably prevented potential confusion over the regulation, said Robin Marles, PhD, director of the Bureau of Clinical Trials and Health Sciences at the Natural Health Products Directorate at Health Canada (oral communication, August 27, 2009). Before implementing the rule, the government held meetings, discussions, and workshops with industry from 2000 until 2003. The rule was phased in over 2 years, about 900 site licenses were issued, and the inspection process is now getting under way, said Marles. He added that the government continues to consult with the industry, hold nation-wide workshops, and release and revise guidance regularly as issues are identified. The herbal industry in Australia is also GMP-regulated. The Australian Code of GMP for Medicinal Products, which includes complementary medicines such as herbs,2 is generally the same as GMP regulations for pharmaceutical manufacturers. Those regulations are therefore considered to be superior to GMP regulations in countries where herbal preparations are regulated as foods (e.g., dietary supplements), said Robert Forbes, founding director of Robert Forbes & Associates, a regulatory consultancy firm in Australia specializing in complementary medicines (dietary supplements), foods, and cosmetics. References
- Health Canada. Good manufacturing practices guidance document. August 2006: Version 2.0. Available at: http://www.hc-sc.gc.ca/dhp-mps/alt_formats/hpfb-dgpsa/pdf/prodnatur/gmp-bpf-eng.pdf. Accessed September 3, 2009.
- The regulation of complementary medicines in Australia-an overview. Therapeutic Goods Administration Website. Available at: http://www.tga.gov.au/cm/cmreg-aust.htm. Accessed September 4, 2009.