Developing Standardized Testing Methods: An Industry Priority

Material identity and quality of raw materials have been increasing priorities in the natural products industry. Even prior to the 1994 passage of the Dietary Supplement Health and Education Act (DSHEA), industry members debated the importance of active constituents and marker compounds in botanicals, and grappled with how to ensure that label claims matched a product's contents.

As the industry heads into the new millennium, media reports and manufacturer concerns about the consistency of raw materials have raised a red flag on the industry's quality assurance practices.

The industry has taken steps to address this problem, which the Institute for Nutraceutical Advancement (INA) summed up as: "The consistency of raw materials has become an issue for virtually every major player in the natural products industry. Even companies with conscientious and responsible quality control procedures have found it difficult to ensure consistency in their products, due to the lack of published standards for analysis."

Independent media analyses and organizations such as ConsumerLab.com (CL) have brought a great deal of attention to testing methods. For example, articles in the Los Angeles Times and Boston Globe have examined St. John's wort products, using the HPLC method published in 1991, and found that almost all the products failed to meet label claims. However, the American Herbal Products Association (AHPA) has continued to recommend use of the 1986 photometric method for testing. If the St. John's wort products were tested using that method, they did meet label claims, according to Joe Betz, AHPA's vice president of scientific and technical affairs.

"These media reports have gotten a lot of publicity, but they're not using standardized, validated methods," said John Cardelina, vice president of botanical science and regulatory affairs for the Council for Responsible Nutrition (CRN). "All these reports come out with negative findings, but I haven't seen one in which the method used for testing hasn't been questionable." CL stated that it determines its testing methods for product reviews by getting input from manufacturers, looking at published materials like the German Commission E and talking with groups such as U.S. Pharmacopoeia (USP). (For more about ConsumerLab.com, see this hyperlinked story.)

Published, validated methods are the key, according to industry members, to ensuring truth and consistency in labeling. "The idea of standardized testing methods is important because you can get different kinds of values for the same marker compound with different testing methods," said Mark Blumenthal, executive director of the American Botanical Council (ABC). Ginseng, for example, can show 17% or 7% ginsenosides depending on whether a UV or HPLC method is used. Using that older UV method could give a company a competitive advantage by showing 17% ginsenosides when other products show only 7%. What would a consumer do if she is assuming that ginsenosides are the active component she wants?

"Our responsibility as an industry is to assure that we are providing customers with the highest quality products possible," said Michelle Zollner with Banner Pharmacaps, which is an INA sponsor. "Without these analytical methods being in place, the results of these tests can be disputed."

The two main organizations working to standardize testing methods are INA and the USP. INA, a non-corporate division of Denver-based Industrial Laboratories, launched its Methods Validation Program (MVP) in 1998. The industry-funded project has a scientific and advisory committee and a mission of selecting, validating and publishing scientific methods for analyzing raw botanical products.

INA's advisory committee determines which compounds have the greatest need for a uniform test method as well as the appropriate marker compound for that botanical. Its scientific review panel reviews submitted methods and selects one for scientific basis, availability of validation data, cost effectiveness and reasonable analysis time. INA then submits the method for publication by the USP's National Formulary (NF) or by AOAC International, an independent scientific association of analytical scientists that validates analytical methods and QA procedures for laboratories in a variety of fields.

"INA's MVP is a rare bird," said Mark Lange, who heads up the program. "Our sponsors recognize the value of validated test methods and are willing to financially invest in this program."

MVP has published more than a dozen methods, including kavalactones in Piper methysticum by HPLC, ginkgoterpenoids in Ginkgo biloba by HPLC and flavonol glycosides in Ginkgo biloba by HPLC.

USP, meanwhile, has been the standard setter for the pharmaceutical industry since the 1800s. It was established in 1820 to promote the availability of unadulterated and appropriately named and prepared therapeutic products. It has been moving forward on a quality seal program, and has published several of INA's methods as industry standards. [Editor's note: At press time, USP had not yet submitted answers to questions about this topic. Look for more at www.naturalproductsinsider.com or in a future issue of the Insider.]

Companies are also developing new testing methods and working with organizations like INA to come to consensus. However, industry-wide agreement on a single project has been lacking. Cardelina noted that a meeting was scheduled for late January to bring industry associations, INA, AOAC and other interested parties together with NSF International to look at developing a single group effort. USP had also been invited to the meeting, but had not yet confirmed its attendance, according to Cardelina. "We think a marriage of INA and NSF, together with other bodies such as AOAC and USP, is a strong approach," Cardelina said.

In addition to developing new methods, many companies have stepped up to financially support INA and USP activities. "The industry has been supportive of this movement," Zollner said. "As a company, we continue to validate test methods internally with our on-site laboratories as well as assisting organizations such as USP when they call for analytical methods."

Part of the challenge in developing standardized testing methods, particularly for botanicals, is the discussion of using straight marker compounds or determining each active constituent and testing for a level of that component.

"When a chemist looks at a plant, the analysis can be challenging, but not controversial," Betz said. "That comes in when you figure what to use it for." Commission E worked backwards, finding out the clinical efficacy of ingredients, and then determining the amounts of active components in the botanicals to set a baseline standard.

Financial concerns and the expanse of the task have made it difficult to come up with clinicals on single botanical efficacy and which active components are responsible for the result. One project funded by the National Institutes of Health (NIH) has ethnobotanist Norman Farnsworth studying how black cohosh works and which compounds are responsible. "That's expensive research and the result is not something you can patent," Betz said.

Even when the active components are determined, it can still be quite difficult to agree upon testing methods. If a plant has a single active component, that can be easy. Kava, for example, has kavalactones that can be separated and measured using a single analytical method. But other botanicals have a host of active components, some of which are not even fully understood. With St. John's wort, for example, .3-percent hypericin has been assumed to be the active compound. Now, more research is showing that hyperforin (5-percent) is necessary and has a more direct influence on the anti-depressant activity. There are also questions about flavonoid content and its influence on activity. What this means is there could be up to three separate testing methods needed for validation of a single botanical. "These types of botanicals are more akin to testing a multivitamin mixture than a straight vitamin C," Cardelina said.

Other tests use marker compounds that may or may not influence the activity of the plant. "Often, marker compounds have some relationship to the pharmacological activity of the plant," Lange said. "This is not always the case, however, and in these situations marker compounds are still used to monitor consistency in a manufacturing process. Whether the true active is known, marker compound analysis gives a snapshot of the overall extract's composition." Cardelina noted that companies could use easier marker compound methods to determine the botanical profile of a raw material for internal quality control, but would still need to make sure it could also pass any published, standardized test.

One past hindrance to industry cooperation on standardizing testing methods was the proprietary nature of some tests. There remains a concern that standardized testing methods could stifle competition and innovation with botanical products. One possible solution could be for manufacturers to list on their labels the analytical method used to arrive at the botanical label claim. "Companies should let people know what method they're using to be honest," Blumenthal said. "That's truth in labeling."

"Over the past three years, the industry has made real progress in methods development," Lange said. "Competing laboratories are now willing to openly discuss testing approaches, and trade organizations are facilitating communications."

Ultimately, the industry's determination and use of standardized methods could help turn the negative media tide. Media reports that state 40 percent of products fail to meet label claims undermine consumer confidence, and could continue to slow down sales. "We aren't losing our core consumers," Cardelina said. "But the wave that came in during the growth in the 90s is susceptible to the negative blitz. So to stop the current sales downturn and grow the industry, we have to put the question of quality to bed."

--Heather Granato