OR WAIT null SECS
The herbal product category has had a difficult year. First came the ephedra ban. Then came new studies questioning the efficacy of several common extracts. And in case you missed those items, there was also the article on 'dangerous supplements still at large' in the May issue of Consumer Reports.Despite the steady stream of bad news, manufacturers are optimistic that the category will survive, and even prosper, in the years ahead.
The herbal product category has had a difficult year. First came the ephedra ban. Then came new studies questioning the efficacy of several common extracts. And in case you missed those items, there was also the article on 'dangerous supplements still at large' in the May issue of Consumer Reports.
Despite the steady stream of bad news, manufacturers are optimistic that the category will survive, and even prosper, in the years ahead. As a sign of confidence, many companies have invested heavily in new manufacturing facilities and equipment. Others have launched new products and sponsored research.
Alex Moffett, president of Renaissance Herbs Inc. (Chatsworth, CA), notes that news coverage of controversial herbs and unscrupulous companies has left a bad impression. But he predicts that the growing number of baby boomers reaching retirement age, spiraling healthcare costs, and new research on herbal ingredients will create and support long-term demand.
'For a number of years, our industry has suffered through a barrage of negative reports in the media,' Moffett says. 'However, there are far larger and broader trends that indicate long-term growth of herbal products.'
QUALITY, SAFETY, AND EFFICACY
Negative media stories on herbal products tend to focus on three areas: quality, safety, and efficacy. Although the new good manufacturing practices (GMPs) for dietary supplements will help manufacturers address the first area, they may only have a limited impact on the second and third.
The GMPs are intended to achieve quality and safety by ensuring that what is on the label is what is in the bottle, and by keeping adulterants and contaminants out of products. But other safety issues, such as an herb's potential to cause side effects or interfere with other compounds, can only be addressed through clinical testing. Similarly, questions about efficacy are likely to be resolved only through clinical research.
According to Tod Cooperman, MD, president of ConsumerLab.com (White Plains, NY), most herbal products that fail quality testing do so because they fall short on specific ingredients.
'Most commonly, this occurs with expensive ingredients,' Cooperman says. 'We have had many cases where once it is made aware of the shortfall, a company figures out that it has been buying low-quality raw materials.'
Cooperman adds that other problems uncovered by ConsumerLab.com include contamination with heavy metals and pesticides, pills that don't disintegrate, and doses that are too low to be effective. Doses that are too high can also be an issue.
'With vitamin and mineral supplements, we also find products with too much of an ingredient-for example, 175% of the claimed amount,' Cooperman says.
As mentioned before, the new GMPs are intended to eliminate many of these problems. Strict process controls and testing can help keep dosing accurate and prevent contamination with unwanted compounds. On the other hand, while GMPs may help ensure that quality remains consistent batch to batch, they don't necessarily ensure that manufacturers will decide to use only high-quality materials.
'Manufacturers should emphasize quality at all phases of the manufacturing process, from quality raw-material sourcing to finished-product packaging,' says Qun Yi Zheng, president and COO of Pure World Inc. (South Hackensack, NJ). 'Every company in our industry should comply with the GMPs.'
Safety is an even bigger issue. FDA (Rockville, MD) banned the herb ephedra in December, citing safety concerns, and also expressed its intention to go after ephedra alternatives like bitter orange (Citrus aurantium). Moreover, in its May issue, Consumer Reports listed 10 herbs among 12 supplements that it said were dangerous. Although Consumer Reports acknowledged in the article that most supplements 'are fairly benign,' it warned that potential side effects from some of the herbs on the list include liver damage, cancer, and heart problems.
The information about these supplements was not new and had appeared before, says Cooperman. 'It was fair to bring it to consumers' attention,' he says. 'Most of these, other than bitter orange, are not popular supplement ingredients.'
Efficacy is another factor. Many herbs have a long history of use, but sometimes clinical data are lacking. In some cases, marketers may overstate the efficacy of a product based on limited clinical research. In others, more long-term, double-blind, placebo-controlled studies may be needed to verify the efficacy or safety of a product, even one with a long history of use. For instance, in a review published in the April 1 issue of the American Journal of Medicine, researchers wrote that they could find evidence to support the use of only four herbs: garlic, ginkgo, St. John's wort, and saw palmetto. On the other hand, their findings don't preclude the possibility that better-designed trials in the future could provide more evidence for other herbs.
This situation is changing, as more companies have begun to fund clinical research. While many of the studies are still in the pilot stage, much of the early research can be used to set up larger trials later.
For instance, Renaissance's Moffett says the company has submitted the results of a small double-blind, placebo-controlled study on the East Indian herb Brahmi (Bacopa monniera) for publication.
'Increased primary research on the effects of herbal materials, well-designed clinical trials, and solid quality control at the manufacturing level are vital to provide the credibility required to grow our industry,' Moffett says. 'The public, the healthcare system, and regulatory agencies demand and deserve our best efforts to deliver pure, safe, and efficacious products.'
INVESTING IN QUALITY
Manufacturers are well aware of these issues and have come up with several strategies for dealing with them. Over the past few years, many companies have invested heavily in new state-of-the-art manufacturing facilities and equipment. Others have launched new products backed by more research.
Sonya Cropper, director of operations and communications at Geni Herbs (Noblesville, IN), explains that Geni's decision to open a new ISO 13000-certified factory in March was fueled in part by consumer demand for product safety and efficacy.
'As manufacturers of ingredients, we must adhere to strict GMPs, as well as provide product research-both of which require large investments in equipment and process controls,' says Cropper. 'With our new factory that began operations last month, we have the ability to develop, test, and manufacture higher volumes of premium ingredients in adherence with the new FDA guidelines.'
Another new factory, Renaissance's 8000-sq-ft facility, houses a variety of QA/QC equipment, including high-performance liquid-layer chromatography, thin-layer chromatography, and flamephotometer devices. According to Moffett, the company plans to install additional machines, including Fourier transform infrared spectroscopy, ultraviolet/visible spectroscopy, gas chromatography, and atomic-absorption equipment. Renaissance earned a Gold award from the Nutrition Business Journal in January 2003 for the facility.
'Renaissance is extremely proud of our new manufacturing facility and appreciative of the public recognition of our investment,' Moffett says. 'That investment was made based on our strong belief that natural and herbal alternatives to traditional Western healthcare will experience strong growth in the next 20 years.'
Another approach taken by manufacturers involves purifying their raw materials. Pure World, for example, received a patent in January for its new sterilization process, which removes microcontaminants without using irradiation or ethylene oxide (EtO). According to Paul Koether, chairman of Pure World, the technology is environmentally friendly and cost-effective.
'Quality control is one of the most critical issues in our industry,' explains Pure World's Zheng, adding that the new patent provides a useful option for the industry. 'Companies now can have a choice of using herbs that are not only free of microbial contamination but also free of irradiation or EtO treatment. We have received a great deal of interest, and many new projects and products related to this technology are ongoing.'
Similarly, Pharmline Inc. (Florida, NY) has developed validated QC methods for its raw materials. In March, the company announced that it had acquired a pulsed photo stimulated luminescence system from the Scottish Universities Research and Reactor Centre (SURRC) in Glasgow.
The system is an EU-validated method that tests raw materials for irradiation. In the system, herb samples are stimulated with a pulsed infrared source that causes them to produce a specific signal if they have been irradiated.
Pharmline also invested in employee training for the new system. After sending its QC manager to the SURRC for training, the company conducted an extensive in-house study to test the equipment and protocols. The process involved gamma irradiating more than 24 botanical extracts, cultivating herbs in a greenhouse and planting them in certified organic soil as a control, and validating the equipment and methodology.
A third approach is the development of products that are backed by research. Karen Todd, RD, senior marketing manager for new ingredients and business development at DSM Nutritional Products (Parsippany, NJ), notes that DSM completed several efficacy studies for its Teavigo green tea extract and presented three at the Experimental Biology 2004 conference held in April in Washington, DC.
'Safety is a critical factor in bringing any new product to market,' Todd explains, adding that DSM has an extensive research profile to document the safety of Teavigo. 'Manufacturers need to be up-front with the information they share. The information should be balanced and cover all aspects of an ingredient or a compound. We don't want to go down the road of marketing a product and then find out that there are issues, nor would we invest our time in a product that had such issues. It's just not worth it.'
Although the new GMPs will be a good first step toward improving quality, they shouldn't be thought of as the only step. Testing raw materials, using high-quality ingredients, conducting clinical research, and investing in new equipment are also important.
'Raw materials are often the source of trouble and should be tested by the manufacturer,' notes ConsumerLab.com's Cooperman. 'However, many manufacturers don't know the proper methods and standards for testing supplement ingredients-and some don't even care and will accept anything that looks like a certificate of analysis from an ingredient supplier.' He adds that supplements should be tested for disintegration and that herbs should also be analyzed to ensure that they contain the proper amounts of key marker compounds.
International Harmonization Is One Approach
to Improving Standards
Differences in natural-products regulations in the United States, Europe, and Canada may be one problem hindering the growth of effective, high-quality herbal supplements.
At an April 2 seminar at the first annual Integrative Medicine Conference and Natural Healthcare Expo in Miami, delegates from Indena (Milan, Italy) noted that quality and safety standards vary among countries that permit the use of herbal products.
'It would be highly desirable to obtain a common set of rules applicable on a worldwide basis,' Edward Croom, PhD, scientific and regulatory consultant for Indena USA (Seattle), said at the conference. 'This would allow the consumer to benefit from easier access to products of certified quality, safety, and benefit.'
Croom added that it would be difficult to achieve international regulatory harmonization because of varying cultural and legislative approaches to herbs and other supplements.
'The first achievable step should be the definition and adoption of higher common quality standards,' Croom explained, with the overall goal being the establishment of adequate standards for quality, safety, and benefit.
One way to do this could be to focus on standardizing the manufacturing process. Paolo Morazzoni, PhD, Indena's scientific director, emphasized the importance of standardization in producing quality extracts.
'Standardization involves every step of the production process, from plant material quality to the manufacturing process to the in-process control,' Morazzoni said. 'To reach higher quality standards, validated standard operating procedures must be established, as well as good agricultural and collection practices and good manufacturing practices.
Additionally, funding clinical research should be a part of the strategy. More research is needed to verify the safety and efficacy of many herbal supplements. And recent FDA and FTC (Washington, DC) actions suggest that many herbs are being sold for uses that as yet cannot be supported by clinical research.
Following up on these issues may not be easy. But manufacturers predict that those who do will see benefits in the long run.
'We are positive that the confidence in our ingredients will pass on to researchers and consumers, eventually coming full circle by adding prosperity and integrity to the industry,' says Geni's Cropper.